Monte Rosa Therapeutics, Inc. (GLUE) Business

Item 1. Business

Overview

We are a clinical-stage biotechnology company developing a portfolio of novel and proprietary molecular glue degraders, or MGDs. MGDs are small molecule drugs that employ the body’s natural protein destruction mechanisms to selectively degrade therapeutically relevant proteins, in effect editing the human proteome. MGDs function by inducing the engagement of an E3 ligase, such as cereblon, with defined structural features on surfaces of target proteins. These target proteins are also referred to as neosubstrates. The E3 ligase then tags the target protein for degradation by adding a molecular mark known as ubiquitin. We believe our MGDs provide significant advantages over existing therapeutic modalities, including other protein degradation approaches.

We have developed a proprietary and industry leading discovery engine, called QuEENTM (an abbreviation for “Quantitative and Engineered Elimination of Neosubstrates”) to enable our unique target-centric MGD discovery and development approach and our rational design of MGD product candidates.

To date, our QuEENTM discovery engine has identified numerous proteins for potential targeting by our MGDs, including those targeted by product candidates in our pipeline. We combine our artificial intelligence or “AI” / machine learning or “ML” engines with multiple proprietary experimental tools to identify therapeutically relevant target proteins amenable to degradation by our MGDs. We are continuously increasing our understanding of how MGDs function and we are using this understanding to develop design principles for the engineering of new MGDs. This growing expertise manifests in our expanding MGD library as well as our discovery and development pipeline. Using our insights, knowhow, and technology platform we have generated a library of MGDs that forms the basis for our MGD programs. At present, our library comprises a diverse set of rationally designed small molecules representing more than 1000 unique low molecular weight scaffolds and over 75,000 different MGD molecules. We also use our insights and learnings to continuously update and improve QuEENTM and our MGD library, consistently increasing the power of the discovery engine.

We prioritize our product development to address therapeutic targets backed by strong biological and genetic rationales. We are focused on developing solutions to clinically important indications, including indications in immunology, inflammation, cardiology, oncology, and others. To date, our discovery engine has resulted in three programs in clinical development: MRT-6160, a VAV1-directed MGD for immune-mediated diseases; MRT-8102, a NEK7-directed MGD for inflammatory diseases driven by IL-1β, IL-6, and the NLRP3 inflammasome; and MRT-2359, a GSPT1-directed MGD for metastatic castration resistant prostate cancer (mCRPC).

MRT-6160 is a VAV1-directed MGD being developed for immune-mediated diseases. Our preclinical studies showed that targeted degradation of VAV1 protein via an MGD modulates both T- and B-cell receptor activity. Our VAV1 MGD, MRT-6160, showed promising activity in preclinical models of neurologic and systemic autoimmune and inflammatory diseases and thus we believe has the potential to provide therapeutic benefit in multiple immune-mediated diseases, such as inflammatory bowel disease, rheumatoid arthritis, dermatological disorders, and multiple sclerosis.

In October 2024, we announced a global exclusive development and commercialization license agreement with Novartis under which we granted to Novartis an exclusive license to develop, manufacture, and commercialize VAV1-directed MGDs including MRT-6160, starting with Phase 2 clinical studies. We received from Novartis an upfront payment of $150 million and are eligible to receive up to $2.1 billion in development, regulatory, and sales milestones, beginning upon initiation of Phase 2 studies and including potential development and regulatory milestone payments, exceeding $1.5 billion if multiple indications achieve regulatory approval in multiple territories. We and Novartis also agreed to a net profit and loss sharing arrangement, in which we will co-fund any global clinical development from Phase 3 onwards and will share 30% of any profits and losses associated with the manufacturing and commercialization of the licensed products in the United States. We are eligible to receive from Novartis potential sales milestone payments and tiered royalties in connection with sales outside of the United States. We were responsible for costs associated with the now completed Phase 1 clinical study and Novartis will be responsible for costs associated with any subsequent clinical studies except for the Phase 3 costs covered by us under the profit and loss sharing agreement.

In March 2025, we announced initial clinical results from our Phase 1 study of MRT-6160, demonstrating deep VAV1 degradation of greater than 90%, significant T and B cell functional inhibition, including profound inhibition

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of cytokine release from T and B cells ex-vivo, and a generally favorable safety and tolerability profile. We believe these data support a clear path to multiple Phase 2 studies and broad potential applications in immune-mediated diseases. We expect that our collaborator, Novartis, will initiate multiple Phase 2 studies of MRT-6160 in immune-mediated diseases in 2026.

MRT-8102 is a NEK7-directed MGD targeting diseases and inflammatory conditions driven by the NLRP3 inflammasome, IL-1, and IL-6. The NLRP3 inflammasome is a multi-protein complex that serves as a central node for integrating signals from pathogens, damage, and stress, and triggers the production of pro-inflammatory cytokines. Aberrant NLRP3 inflammasome activation and the subsequent release of active interleukin-1β (IL-1β) and interleukin-18 (IL-18) have been implicated in multiple inflammation-driven diseases, including atherosclerotic cardiovascular disease (ASCVD), gout, hidradenitis suppurativa, pericarditis, osteoarthritis, and obesity. NEK7, functioning as a scaffolding protein, facilitates assembly and activation of the NLRP3 inflammasome in a kinase-independent manner, suggesting that degradation of NEK7 with an MGD molecule would be a potentially attractive therapeutic approach to preventing NLRP3 inflammasome activation and associated downstream cytokine production.

In January 2026, we announced positive interim data from an ongoing Phase 1 clinical study (now called GFORCE-1) evaluating MRT-8102. In subjects with elevated cardiovascular disease (CVD) risk, MRT-8102 demonstrated rapid and durable reductions in systemic inflammation. After four weeks of MRT-8102 treatment in subjects with elevated CVD risk, C-reactive protein (CRP) levels were reduced by 85%, and 94% of study participants achieved CRP values below 2 mg/L, a threshold associated with reduced CVD risk. The single ascending dose (SAD) and multiple ascending dose (MAD) cohorts demonstrated deep and sustained NEK7 degradation at doses from 5 mg to 400 mg. A favorable safety profile was observed with mild to moderate adverse events (AEs) and no evidence of increased infection risk.

Our ongoing GFORCE-1 Study of MRT-8102 in subjects with elevated CVD risk has been expanded to multiple dose levels to accelerate development in ASCVD. We anticipate results from this study in H2 2026. We plan to initiate a Phase 2 ASCVD study, GFORCE-2, (in elevated CVD risk patients defined by Stage 3/4 chronic kidney disease and elevated CRP) in H2 2026, a Phase 2 study of MRT-8102 in patients with gout flares, GFORCE-3, in Q4 2026 or Q1 2027, and a Phase 2 study in patients with hidradenitis suppurativa, GFORCE-4, in H1 2027. Furthermore, we expect to submit an IND application for a next-generation NEK7-directed MGD in 2026.

MRT-2359 is an orally bioavailable MGD targeting the translation termination factor protein GSPT1 and is currently in clinical development for potential use in MYC-driven tumors, with a focus on metastatic castration-resistant prostate cancer, or mCRPC. GSPT1 (also known as eRF3a) is a translation termination factor that helps catalyze the termination of protein synthesis, facilitating the release of mRNA and newly synthesized protein from the ribosomal protein synthesis machinery. We have identified GSPT1 as a potential therapeutic vulnerability for MYC-driven cancers, including mCRPC. MRT-2359, our GSPT1-directed MGD, was designed to preferentially affect growth and survival of cancer cells addicted to protein translation, such as those driven by high expression and activity of MYC family transcription factors. Our preclinical studies showed that once-daily oral dosing of MRT-2359 led to potent antitumor activity in MYC-driven cell-line- and patient-derived xenograft models, and pointed to mCRPC as a potential indication for MRT-2359.

In December 2025, we announced positive interim data from an ongoing Phase 1/2 clinical study evaluating MRT-2359 in combination with enzalutamide in heavily pretreated patients with metastatic castration-resistant prostate cancer (mCRPC). We provided further updates from this ongoing clinical study in February 2026, including at the ASCO Genitourinary Cancers Symposium held in San Francisco on February 26-28, 2026. In our February 2026 update we showed that in the subset of mCRPC patients with androgen receptor (AR) mutations, treatment with MRT-2359 in combination with enzalutamide led to a 100% PSA response rate in patients identified as having AR mutations (5 out of 5 patients). In addition, MRT-2359 plus enzalutamide demonstrated a 100% disease control rate in this patient subset, per RECIST criteria, including 2 RECIST partial responses and 3 with stable disease. In total, our study included 15 evaluable patients, including the 5 patients identified as having AR mutations. Across those 15 evaluable patients, the overall disease control rate was 67% (10 of 15), with 10 of 15 patients showing tumor size reductions of target lesions, including the 2 RECIST partial response patients that were also identified as having AR mutations.

Based on the success of our reported Phase 1/2 studies in mCRPC patients, we plan to initiate a Phase 2 study of MRT-2359 in combination with a second-generation AR inhibitor in mCRPC patients with AR mutations, with potential to expand the study into additional patient subsets, including patients naive to 2nd generation AR inhibitors. The study is anticipated to start in 2026.

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We are also advancing programs directed at cyclin E1 (CCNE1) and cyclin-dependent kinase 2 (CDK2), key drivers of cell cycle progression in cancer.

Cyclin E1 is a protein that plays a crucial role in the cell cycle, and is a frequently amplified non-enzymatic driver oncogene relevant in multiple solid tumors that has not been druggable by conventional modalities. We believe that our proprietary Cyclin E1 MGDs represent a potential novel therapeutic approach for treatment of such solid tumors by directly and selectively targeting Cyclin E1. We believe our cyclin E1 MGDs could provide a highly differentiated alternative and additional approach to other cell-cycle focused therapeutics currently in development.

We expect to submit an IND application for a cyclin E1-directed MGD in 2026.

Our CDK2-directed MGDs have demonstrated superior selectivity for CDK2 in preclinical models as compared to several clinical-stage small molecule CDK2 ATP-site inhibitors, which we believe will be important to mitigate toxicity limitations reported for CDK2 inhibitors in development. In preclinical models of ER+ breast cancer our CDK2 MGDs reduced tumor burden when added to standard of care therapy. We believe our preclinical data supports further clinical evaluation of our CDK2 MGDs as a potential improvement over current standard of care therapies in ER+ breast cancer, and potentially without the toxicity limitations reported for CDK2 inhibitors currently in development.

Our proprietary QuEENTM discovery engine uniquely enables us to rationally design and develop our diverse library of MGDs and to deploy them against target proteins identified through our QuEENTM discovery engine. Uniquely, many of these target proteins are considered inadequately drugged or completely undruggable by other therapeutic modalities. We actually consider a target protein’s lack of druggability as one of our key criteria for our discovery and development selection and prioritization process. Our resulting MGDs are designed to reprogram the E3 ligase to bind to and induce the degradation of a therapeutically relevant target protein. Central to our QuEENTM discovery engine is a detailed understanding of the molecular interactions promoted by our MGDs between E3 ligases and structural features on the surface of therapeutically relevant proteins, which we refer to as degrons.

Key components of our QuEENTM discovery engine are:

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AI/ML engines: Our focus on protein surface characterization sets us apart, enabling us to identify reprogrammable E3 ligases as well as potential target proteins amenable to our approach. We have developed sophisticated and proprietary AI-powered algorithms to mine databases of protein sequences and structures, including structures determined from x-ray crystallography and cryoEM, and structures from predicted protein folding. Our proprietary geometric deep learning engine for surface characterization continuously learns from our expanding MGD library, identifying new degrons and surface features (“glueprints”) in targetable proteins across the proteome.

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High throughput screening, structural biology and proteomics capabilities: We have developed a suite of high-throughput assays that rapidly assess our proprietary MGD library and MGDs generated during specific programs. Coupled with customized automation and robotic systems, our assays can measure ternary complex formation in both a biochemical and cellular format, as well as measure degradation of target proteins in cells, which we use to screen, identify and rapidly optimize our MGDs.

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Proprietary MGD library: We have built a wholly-owned, proprietary, diverse, and continuously growing chemical library of currently over 75,000 MGDs that we have rationally designed based on our growing expertise in molecular glue anatomy and design, our large proteomics and screening databases, and AI/ML algorithms. Library compounds currently represent more than 1000 unique low molecular weight scaffolds with favorable binding affinities for an E3 ubiquitin ligase.

By capturing our insights and experience with the identification of target proteins amenable to our approach as well as the discovery and development of MGDs through QuEENTM, we are constantly increasing the power of our discovery engine.

Our QuEENTM discovery engine continues to generate discovery stage programs targeting therapeutically relevant proteins otherwise considered undruggable or inadequately drugged. We are progressing our discovery stage programs for multiple other undisclosed target proteins. Our focus is on target proteins that have been considered undruggable or insufficiently drugged, that are highly credentialed preclinically or clinically, and that can potentially move quickly into clinical development in indications with high unmet need and substantial commercial potential.

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In October 2023, our wholly-owned subsidiary, Monte Rosa Therapeutics AG, or Monte Rosa AG, entered into a strategic collaboration and licensing agreement with F. Hoffmann-La Roche Ltd., or Roche Basel, and Hoffmann-La Roche Inc., or Roche US, and together with Roche Basel referred herein as Roche. Pursuant to the License Agreement, the parties will seek to identify and develop MGDs against cancer or neurological disease targets using our proprietary drug discovery platform for an initial set of targets in oncology and neuroscience selected by Roche, with each target being subject for a limited time to certain substitution rights owned by Roche. We will lead preclinical discovery and research activities until a defined point. Upon such point, Roche gains the right to exclusively pursue further preclinical and clinical development activities. Under the terms of the agreement, Monte Rosa received an upfront payment of $50 million, and is eligible to receive future preclinical, clinical, commercial and sales milestone payments that could exceed $2 billion, including up to $172 million for achieving preclinical milestones. We are also eligible to receive tiered percent royalties ranging from high-single-digit to low- teens on any products that are commercialized by Roche as a result of the collaboration.

In September 2025, we and Novartis entered into a collaboration, option, and license agreement, under which Monte Rosa granted to Novartis an exclusive, royalty-bearing, sublicensable and transferable license to degraders for one immunology and inflammation, or I&I program, or the First Licensed Program, and the exclusive option to obtain exclusive, royalty-bearing, sublicensable and transferable licenses with respect to two programs from the Company’s growing preclinical immunology portfolio, or the Options, and the programs, or the Optioned I&I Programs. Such Options are individually exercisable at Novartis’ discretion until a program meets criteria for investigational new drug application-filing-readiness. On a program-by-program basis, if Novartis does not exercise an Option, all rights with respect to such program are retained by the Company; if Novartis does exercise its Option, such program becomes a Licensed Program, or together, with the First Licensed Program, the Licensed Programs. Under the 2025 Novartis Agreement, the Company will apply its proprietary AI/ML-enabled QuEEN™ product engine for the discovery and development of degraders for the First Licensed Program and the Optioned I&I Programs. The Licensed Programs will be further developed and commercialized by Novartis, unless otherwise agreed to by the parties in accordance with the 2025 Novartis Agreement. Research activities for the Licensed Programs governed by the Agreement will be overseen by a Joint Research Committee.

Under the agreement, the Company received a $120.0 million non-refundable upfront payment from Novartis. The Company is entitled to receive further payments from Novartis to maintain the Options totaling up to $60.0 million, and is also eligible to receive from Novartis (1) preclinical milestone payments relating to the First Licensed Program and option exercise payments related to the Options of up to $180.0 million, (2) up to $5.4 billion in clinical development, regulatory, and sales milestones relating to the First Licensed Program and the two Optioned I&I Programs, beginning upon initiation of Phase 1 studies, including (a) potential development and regulatory milestone payments of up to $2.2 billion if regulatory approval is achieved for multiple indications in multiple territories and (b) potential sales milestone payments of up to $3.2 billion, allocated across licensed products, and (3) tiered royalties on global net sales in the high-single to low double-digit range for the First Licensed Program and in the low double-digit range for the two Optioned I&I Programs. The Company will be responsible for costs related to research activities, while Novartis will be responsible for costs related to development and commercialization activities.

We are led by an experienced team of drug discovery and development experts with deep experience in targeted protein degradation, molecular glues, chemistry, structural biology, data science, disease biology, translational medicine, and clinical development.

Monte Rosa Therapeutics AG, a Swiss operating company, was incorporated under the laws of Switzerland in April 2018. Monte Rosa Therapeutics, Inc. was incorporated in the State of Delaware in November 2019. The Company is headquartered in Boston, Massachusetts with research operations in both Boston and Basel, Switzerland. Our principal executive office is located at 321 Harrison Avenue, Suite 900, Boston, MA 02118 and our telephone number is (617) 949-2643. Information about us is available on our corporate websites at www.monterosatx.com. Information available on our website is not a part of, and is not incorporated into, this Annual Report. We trade on the Nasdaq Global Select Market under the ticker symbol “GLUE”.

Our product pipeline

We have leveraged our QuEENTM discovery engine to generate our pipeline of product candidates with the potential to treat a diverse range of diseases through targeted protein degradation. Our current programs are focused on delivering therapies to target proteins that have been considered undruggable or inadequately drugged in well-characterized biological pathways across clinical indications in immunology, inflammation, cardiovascular diseases, oncology, and other diseases with high unmet needs. We currently retain exclusive

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worldwide rights to the programs shown in Figure 1 below, except for MGDs directed against VAV1 including MRT-6160, which we licensed to Novartis in October 2024, and the targets included in the Roche and Novartis relationships.

Figure 1: Monte Rosa Pipeline

Over the next several years, we plan to expand our early-stage product portfolio into our current therapeutic areas of focus and additional therapeutic areas, leveraging the ability of our QuEENTM discovery engine to degrade therapeutically relevant proteins in areas including immunology & inflammation, cardiovascular, metabolic, and genetic diseases.

Our strategy

Our mission is to discover and develop a portfolio of novel small molecule MGDs that selectively eliminate therapeutically relevant proteins. We believe our MGDs have the potential to benefit patients in a broad range of indications with significant unmet medical need. We believe the product candidates identified through our proprietary QuEENTM discovery engine can provide distinct advantages over other modalities, including the ability to address target proteins that have been considered undruggable or inadequately drugged. We intend to fully develop certain programs internally, while also utilizing collaborations to advance programs in areas where we believe that external expertise and financial resources may enable us to more fully realize the therapeutic and commercial potential of a program.

MGDs provide for therapeutic opportunities not constrained by some of the key limitations of conventional small molecule inhibitor drugs. MGDs provide an opportunity to target the vast universe of target proteins without a defined binding pocket, in a highly selective way, due to the diversity of surfaces that can be targeted, resulting in reversible elimination of a target protein. More specifically, because MGDs work by inducing protein-protein interactions between target proteins and an E3 ligase, they do not require a defined binding pocket on the target protein of interest. Thus, MGDs offer a unique opportunity to unlock significant target space and enable us to address target proteins that have been considered undruggable or inadequately drugged. The interaction surfaces we utilize are often not conserved within protein classes and families, allowing us to potentially achieve significant selectivity for our MGD product candidates that we believe is superior to classical small molecule inhibitor drugs. Lastly, we focus on target proteins where experimental evidence suggests that removal of the target is superior to transiently inhibiting it, in particular proteins that have a scaffolding function.

Through our ability to produce potentially highly selective MGDs with fine-tuned speed and depth of degradation, we believe we can generate MGD product candidates with a wide therapeutic window and other therapeutic advantages that may be beneficial in a broad range of indications, including immunology, inflammation, cardiovascular diseases, oncology, metabolic diseases, genetic diseases, and diseases of the central nervous

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system (CNS). We believe our platform has the capability to produce MGDs suitable for distribution into any tissue, including MGDs designed to be CNS-penetrant.

In immunology and inflammation, we are uniquely able to target highly credentialed immune signaling proteins in pathologically relevant immune pathways. We prioritize target proteins that are validated through preclinical or clinical (including human genetic) evidence. We have shown that we are able to optimize our MGD product candidates to induce deep and selective degradation of immune-pathway relevant proteins. Our precision oncology programs are focused on the elimination of proteins that are highly validated driver oncogenes in cancer cells (“oncogene addiction”), that define a cancer lineage dependence (“lineage addiction”), or that create a vulnerability specific to tumor cells (“synthetic lethality”).

Key elements of our strategy include:

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Continue to advance our NEK7-directed MGD, MRT-8102, for the treatment of NLRP3/IL-1/IL-6 driven inflammatory diseases through completion of the GFORCE-1 trial in elevated CVD risk subjects and initiate the GFORCE-2 study of MRT-8102 in ASCVD. MRT-8102 is a potent, highly selective, and orally bioavailable investigational MGD that targets NEK7 for the treatment of inflammatory diseases linked to the NLRP3 inflammasome, IL-1, and IL-6 dysregulation. NEK7 has been shown to be required for NLRP3 inflammasome assembly, activation and IL-1β release both in vitro and in vivo. Aberrant NLRP3 inflammasome activation and the subsequent release of active IL-1β and interleukin-18 (IL-18) has been implicated in multiple inflammatory disorders, including ASCVD, gout, hidradenitis suppurativa, osteoarthritis, asthma, neurodegenerative diseases, and metabolic disorders including metabolic dysfunction-associated steatohepatitis (MASH) and obesity. In January 2026, we reported interim results from our Phase 1 study of MRT-8102. In subjects with increased CVD risk, MRT-8102 demonstrated rapid and durable reductions in systemic inflammation. Specifically, after four weeks of MRT-8102 treatment in subjects with elevated CVD risk and high levels of CRP, CRP levels were reduced by 85%, and 94% of study participants achieved CRP values below 2 mg/L, a threshold associated with reduced CVD risk. We expect to initiate a study of MRT-8102 in in elevated CVD risk patients defined by Stage 3/4 chronic kidney disease and elevated CRP in H2 2026, a Phase 2 study of MRT-8102 in patients with gout flares in Q4 2026 or Q1 2027, and a Phase 2 study of MRT-8102 in patients with moderate to severe hidradenitis suppurativa, in H1 2027.

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Continue to support Novartis's clinical development of our VAV-directed MGD MRT-6160 in immune-mediated disease. Pursuant to our Agreement with Novartis, Novartis will be responsible for all further clinical development and commercialization of MRT-6160. We believe our global license agreement with Novartis will accelerate and broaden the scope of clinical development of MRT-6160 while retaining substantial value for us, including through milestone payments and our share of the US P&L for MRT-6160 provided under our Agreement;

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Advance our GSPT1-directed MGD program by initiating a signal-confirming Phase 2 study of MRT-2359 in mCRPC patients with AR mutations. In December 2025, we announced positive interim clinical data from our study of MRT-2359 in combination with enzalutamide in heavily pretreated mCRPC patients, including patients with AR mutations. We presented additional positive data at the ASCO Genitourinary Cancers Symposium in February 2026. In mCRPC patients with AR mutations, treatment with MRT-2359 in combination with enzalutamide led to a 100% PSA response rate in all 5 patients identified as having AR mutations. In addition, MRT-2359 plus enzalutamide demonstrated a 100% disease control rate in this patient subset, per RECIST criteria, including 2 RECIST partial responses and 3 with stable disease. In total, our study included 15 evaluable patients, including the 5 patients identified as having AR mutations. Across those 15 evaluable patients, the overall disease control rate was 67% (10 of 15), with 10 of 15 patients showing tumor size reductions of target lesions, including the 2 RECIST partial response patients that were also identified as having AR mutations. We plan to initiate a Phase 2 study of MRT-2359 in combination with a second-generation AR inhibitor in mCRPC patients with AR mutations, with potential to expand the study into additional patient subsets, including patients naive to 2nd generation AR inhibitors. The study is anticipated to start in 2026;

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Advance our cell cycle program to IND submission. We believe our programs directed at CCNE1 and CDK2, key drivers of cancers with cyclin dependent kinase pathway alterations, have the potential to achieve greater selectivity for the CCNE/CDK2 complex versus conventional CDK ATP-site inhibitors. We also believe they have the potential to provide more sustained pathway inhibition compared to ATP-site inhibitors. We expect to submit an IND application for a cyclin E1-directed MGD in 2026;

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Continue to advance and develop our pipeline of rationally designed MGDs to transform the treatment of diseases in multiple therapeutic areas including immunology & inflammation, cardiology, and oncology. Through our QuEENTM discovery engine, we have identified a variety of additional degron-containing proteins that are amenable to our approach and are either undruggable or insufficiently drugged and we continue to build MGDs against these proteins. We continue to advance programs in preclinical development, and to identify new degron-containing target proteins as well as MGDs. We will continue to prioritize therapeutically relevant target proteins backed by strong biological and genetic rationale with the goal of producing novel precision medicines;

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Continue to enhance and expand the capabilities of our QuEENTM discovery engine to unlock the full therapeutic potential of our MGDs in our targeted therapeutic areas. We employ a core set of drug discovery and development principles to guide our target protein selection across various protein classes and therapeutic areas. We are specifically focused on delivering therapies to target proteins that have been considered undruggable or inadequately drugged, and that are situated in preclinically and clinically well-characterized and validated biological pathways;

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Expand and protect our proprietary know-how and intellectual property. We continue to innovatively expand our intellectual property around our innovations in the field of targeted protein degradation and in particular MGDs. Our intellectual property, which includes proprietary know-how, patent applications and issued and expected patents, as well as trade secrets, applies not only to our product candidates, but also to all of our various innovations, including, for example, our drug discovery processes including our QuEENTM discovery engine; our AI-based E3 ligase characterization algorithms, AI-based degron discovery algorithms, AI-based novel MGD design algorithms, and in silico screening algorithms; our drug development tools; our growing library of MGDs; the innovative methods and approaches we have developed to rationally design MGDs to expand our library, and to certain biomarkers and therapeutic applications for our potential product candidates;

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Execute our discovery collaboration with Roche in the areas of cancer and neurology. Under the terms of the agreement, Monte Rosa will lead discovery and preclinical activities against multiple select cancer and neurological disease targets to a defined point. Upon such point, Roche gains the right to exclusively pursue further preclinical and clinical development of the compounds. We believe this collaboration will enable and accelerate expansion of our platform into neuroscience and additional areas of oncology; and

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Execute our collaboration with Novartis for degraders to treat immune-mediated diseases. Under the terms of the agreement, Monte Rosa’s scientists will apply our proprietary AI/ML-enabled QuEEN™ product engine for the discovery and development of degraders to be further developed and commercialized by Novartis. Monte Rosa’s publicly disclosed pipeline programs are outside the scope of this agreement.

Background on targeted protein degradation and molecular glue degraders

Proteins drive nearly all biochemical reactions in the body and many diseases stem from abnormal intracellular protein activity. Proteins, including those inside the cell and on its surface, are attractive therapeutic targets; nevertheless, despite advances in therapeutic modalities, approximately 75% of human proteins remain undruggable by traditional small molecule inhibitors.

Challenges with druggable vs. undruggable proteins

Traditional small molecule inhibitors target proteins by binding to a pocket on the protein’s surface. The absence of a binding pocket presents a challenge to the discovery and development of traditional small molecule inhibitors. Indeed, many proteins, including key disease-driving proteins such as transcription factors, scaffolding proteins, and enzyme modulators, often lack druggable pockets, making them undruggable by conventional small molecule inhibitor approaches. Other therapeutic modalities that can target such proteins, such as therapeutic antibodies, oligonucleotide-based therapies, and genetic therapies, are limited in their ability to address aberrant protein behavior. Although these therapies have improved patient outcomes, they face challenges in delivery, scalability, and therapeutic application. A summary of characteristics of various therapeutic modalities compared to MGDs is shown in Figure 2.

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Figure 2: Characteristics of Therapeutic Modalities, Including MGDs, the Next Generation of Precision Medicine-Based Small Molecule Drugs

Molecular glues: our expanding approach to protein degradation

Protein degradation is one of the body’s natural processes by which proteins are eliminated from human cells through the attachment of a molecular tag, called ubiquitin, to a protein by any of the approximately 600 human E3 ligases, marking the protein for degradation by the proteasome in the cell. Targeted protein degradation can be mediated by two small molecule classes: MGDs and PROTACs (proteolysis-targeting chimeras, also known as heterobifunctional degraders) (illustrated in Figure 4).

We believe our targeted protein degradation approach offers many features that make it an attractive therapeutic modality:

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Removal of a target protein: partial or complete removal of a target protein can lead to more complete inhibition of signaling and metabolic pathways, thus resulting in more profound and longer lasting pharmacodynamic effects than traditional reversible or irreversible inhibition can induce.

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Targeting intracellular proteins: small molecule-based protein degraders, in particular MGDs, readily cross cell membranes or can be optimized to do so.

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Ease of delivery: small molecule-based protein degraders, in particular MGDs, can be delivered through various routes of administration, including orally.

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Systemic and tissue distribution: since most small molecule-based degraders, in particular MGDs, are low molecular weight compared to other therapeutic modalities, tissue distribution, such as into the CNS or tumor tissues, poses less of an issue.

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Catalytic mode of action: after inducing degradation of a target protein molecule, the small molecule-based protein degrader-E3 ligase complex is able to induce the degradation of additional target protein molecules. Thus, the small molecule-based protein degrader acts catalytically, unlike protein inhibition, causing the removal of many target protein molecules with a single MGD molecule, thereby editing the cellular proteome.

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Event driven pharmacology: unlike with inhibitors where prolonged engagement of the drug with the protein is required for efficacy, small molecule-based protein degraders only require engagement with the E3 ligase and the target protein long enough to induce tagging for degradation.

As described above, there are multiple potential advantages of the protein degradation approach, but one of the most intriguing is the potential to achieve greater therapeutic benefits resulting from the durable but reversible removal of a target protein from the cellular proteome.

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Figure 3: Molecular Glue Degraders; Expanding Target Space, Fostering a New Generation of Drugs

Our approach

MGDs are small molecule-based protein degraders designed to modify an E3 ligase’s binding specificity and thus can employ the body’s natural mechanisms of protein destruction to selectively eliminate therapeutically relevant proteins.

Our QuEENTM discovery engine was built for the rational, target-centric discovery of potent and selective MGDs with favorable drug-like properties, thus potentially systematically overcoming common challenges of MGD discovery, as illustrated in Figure 4

Figure 4: QuEENTM is Redefining the Rules of MGD Discovery

We believe our discovery engine has the potential to continue to deliver MGD product candidates, including product candidates that could address target proteins that have been considered undruggable or inadequately drugged, while possessing attractive pharmaceutical properties. As shown in Figure 6, our initial programs utilize

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cereblon as the E3 ligase system to tag target proteins. Through our generation of data-at-scale, AI/ML platform and proprietary MGD library we have expanded and continue to expand chemical and target space, and have now begun to leverage other E3 ligase systems.

Figure 5: Our Rational Approach to Unleash the Full Potential of MGDs

We have built our discovery engine on the insight that deep knowledge and understanding of features of protein surfaces drives MGD discovery. Surfaces and their unique features, which we call “glueprints”, mediate protein-protein interactions and targeted protein degradation. As shown in Figure 7, interrogating surfaces using geometric deep learning enables us to identify reprogrammable ligases and the matching target protein space, creating broad potential opportunities to eliminate undruggable, disease-driving proteins through “only-in-class” MGDs.

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Figure 6: Surface Interactions Drive "Only-in-Class" MGD Designs

QuEENTM Discovery Engine

We design and develop MGDs in a rational and iterative approach using our industry-leading and dynamic QuEENTM discovery engine, encapsulating our team’s proprietary knowledge and discovery capabilities across biology, chemistry and computational sciences, and from which we are generating our library and pipeline of MGD product candidates. Through our discovery engine, we have built intellectual property that allows us to induce a high degree of surface complementarity between an E3 ligase and a target protein, potentially leading to high potency and selectivity of MGDs for the therapeutically relevant target proteins we select.

The QuEENTM discovery engine was built to support our approach to the discovery and development of MGD product candidates that degrade a wide landscape of therapeutically-relevant target proteins by (i) systematically identifying degrons and other surface features on target proteins that may enable ternary complex formation and consequential degradation initiated by E3 ligases, (ii) understanding how to reprogram the surface of endogenous E3 ligases using small molecule-based MGDs; and (iii) rationally designing MGDs that can be optimized towards high potency and selectivity, with favorable pharmaceutical properties. Our process of degron discovery and MGD design is highly iterative and interdisciplinary. Our quantitative mass-spectrometry-based proteomics and high throughput screening capabilities allow us to screen our library at scale to facilitate our discovery efforts. Powerful AI modeling learns from and guides our high throughput screening and chemo-proteomics, which in turn feed information back to the AI engine, and the accumulated knowledge is used to guide our MGD discovery programs and library expansion. For example, MGD discovery and development for a protein target can pass from degron identification, to MGD hit identification, to in silico improvement, to a round of chemo-proteomics validation, to chemical library alterations and back, until we reach the desired selectivity and degradation.

Our Proprietary MGD library

We discover and develop lead MGDs for degron-containing target proteins by screening our MGD library of currently over 75,000 MGD molecules, and applying proximity screening tools and our chemo-proteomic capabilities in QuEENTM. We continue to expand our highly diverse library of MGDs based on our growing expertise in MGD design, our knowledge of the cereblon-binding surface, and variations in target surface features and degrons. We have developed unique and innovative synthetic chemistry approaches to access over 1,000 scaffolds, each designed to probe three-dimensional structural and chemical property space differently. These scaffolds are being utilized as building blocks to generate our proprietary library of highly diverse compounds. The modular construction of our library allows us to explore different areas of chemical space and follow-up rapidly on hits from our library. Our highly diverse library of MGDs leverages different areas of the cereblon surface to

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engage diverse degrons and surface features on target proteins. Our library has given rise to multiple series of MGDs for each of the target proteins currently being studied across our disclosed and undisclosed portfolio.

Our AI/ML engine identifies reprogrammable E3 ligases and E3 ligase-accessible target proteins

Our focus on protein surface characterization sets us apart, enabling us to identify reprogrammable E3 ligases as well as potential target proteins amenable to our approach. We have developed sophisticated and proprietary AI-powered algorithms to mine databases of protein sequences and structures, including structures determined from x-ray crystallography and cryoEM, and structures from predicted protein folding. fAIceit – our proprietary geometric deep learning engine for surface characterization - continuously learns from our expanding MGD library, identifying new degrons and surface features (“glueprints”) in targetable proteins across the proteome.

High throughput screening of our proprietary library identifies active MGDs

We have developed a suite of high-throughput assays that rapidly assess our proprietary MGD library and MGDs generated during specific programs. Coupled with customized automation and robotic systems, our assays can measure ternary complex formation in both a biochemical and cellular format, as well as measure degradation of target proteins in cells, which we use to screen, identify and rapidly optimize our MGDs.

Our quantitative proteomics profiling assays for neosubstrate identification and MGD optimization

Utilizing mass-spectrometry-based proteomics, we have developed a suite of unbiased high throughput quantitative profiling assays to assess cellular protein degradation, selectivity of degradation, target ubiquitination, and ternary complex formation. Combined with our end-to-end instrument, automation and computational infrastructure, the platform enables us to screen our library, identify new targets amenable to our approach, and drive our drug discovery programs rapidly from hit identification to development candidate.

Our structural biology platform enables the rational design of our MGDs

Leveraging high-throughput crystallization and cryo-electron microscopy, we have established a robust pipeline for generating high resolution protein structures. We use structural insights derived from these to support the design of our MGD library, rationally optimize our MGDs during lead optimization programs, and validate novel binding modes target proteins that are highly diverse with regards to the protein-protein interface involved.

Our QuEENTM discovery engine has enabled us to discover novel degrons, protein surface features and binding modes, some of which have been published in scientific journals such as Science, dramatically expanding our addressable target space. We have used our AI engine and a rational design approach to discover MGDs that are exquisitely selective, enabling us to potentially eliminate therapeutically relevant target proteins in pathways that are highly relevant for diseases with high unmet need in immunology, inflammation, cardiovascular diseases and oncology as well as other diseases.

QuEENTM expansion

Our QuEENTM discovery engine was originally focused on identifying and developing MGDs that induce the binding of degron-containing neosubstrates to cereblon as a means of targeting them for degradation. Using our established tools, we are expanding the scope of QuEENTM to further grow the cereblon target space, to leverage additional E3 ligases for targeted protein degradation, and to potentially extend the utility of our degraders to target multiple therapeutic targets.

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Expand chemical space: We are expanding the diversity and the chemical space covered by our MGD library based on our understanding of protein surfaces. Using structure-based design and AI-driven algorithms we have identified more than 1000 unique scaffolds which form the basis of our MGD library of over 75,000 compounds;

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Activate new E3 ligases: We believe that we will be able to reprogram other E3 ligases through the discovery of ligase specific MGDs as well as specific ligase-accessible degrons, thus enabling us to generate ternary complexes with a further subset of the approximately 600 E3 ligases;

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Grow target space: We believe expanding degron identification, identification of other protein surface features, E3 ligase activation, and MGD chemical space will unlock previously undruggable proteins for therapeutic intervention;

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Explore modality expansion: We believe our experience and capabilities enable us to expand the utility of small-molecule based induced-proximity for unique clinical applications.

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Our Approach for Immunologic and Inflammatory Diseases

MRT-6160, a highly selective and orally bioavailable VAV1-directed MGD in development for the treatment of immune-mediated diseases

Overview

VAV1 is a Rho-family guanine nucleotide exchange factor that plays a critical role in T- and B-cell receptor signaling and activity. As many immune-mediated diseases are thought to be driven by an underlying dysregulation or hyperactivation of T- and/or B-cells, a VAV1-directed MGD, which we believe will ameliorate aberrant responses from both cell types, has broad potential application for immune-mediated diseases.

There are multiple published studies providing preclinical data supporting VAV1’s potential as an attractive target for attenuating T- and B-cell activity, as shown in Figure 7. Studies report that VAV1 knockout mice are viable and fertile, but display various loss-of-function T- and B-cell phenotypes, and are protected from experimentally induced autoimmune diseases. In addition, it was shown using whole-genome CRISPR screens in primary human T cells that VAV1 plays a key role in T-cell function and that genetic loss of VAV1 confers loss of IL-2 secretion, amongst other functional consequences.

We believe our VAV1-directed MGDs have the potential to modulate both T- and B-cell function as well as the cross talk between these cell types when activated in autoimmune disease. Despite being a preclinically validated target for attenuating T- and B-cell activity, VAV1 has remained undruggable to date using small molecule inhibitor approaches due to the lack of an appropriate binding pocket for small molecule inhibitor design. Therefore, targeting VAV1 with a VAV1-directed MGD and eliminating its activity through protein degradation could provide therapeutic benefits in multiple T- and/or B-cell mediated autoimmune diseases.

Figure 7: VAV1 is a Highly Validated Target for Attenuating T-cell and B-cell Activity

In October 2024, we and Novartis entered into a License Agreement under which we granted to Novartis an exclusive license to develop, manufacture, and commercialize VAV1-directed MGDs including MRT-6160. We were responsible for completing the Phase 1 clinical study and Novartis is responsible for all subsequent development and commercial activities starting at Phase 2. We received from Novartis an upfront payment of $150 million and are eligible to receive up to $2.1 billion in development, regulatory, and sales milestones, beginning upon initiation of Phase 2 studies and including potential development and regulatory milestone payments, exceeding $1.5 billion if multiple indications achieve regulatory approval in multiple territories. We and Novartis also agreed to a net profit and loss sharing arrangement, in which we will co-fund any global clinical development from Phase 3 onwards and will share 30% of any profits and losses associated with the manufacturing and commercialization of the licensed products in the United States. We are eligible to receive from Novartis potential sales milestone payments in connection with sales outside of the United States, and tiered royalties on sales outside of the United States. Novartis will be responsible for costs associated with any

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subsequent clinical studies except for the Phase 3 cost covered by us under the profit and loss sharing agreement.

We have demonstrated, in vivo, that once daily oral dosing of MRT-6160 inhibited disease progression in well-established models of multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease, and spontaneous autoimmune disease such as systemic lupus erythematosus and Sjogren’s disease, as shown in the Figures and discussion below. We believe the public literature, coupled with our data package, summarized herein, provides strong support for use of a VAV1-directed MGD in a broad range of systemic and CNS autoimmune diseases. Based on this support, we advanced our VAV1 development candidate, MRT-6160 into clinical studies. In August 2024, we announced initiation of our MRT-6160 Phase 1 single ascending dose/multiple ascending dose (SAD/MAD) study. Results from the Phase 1 study are provided herein.

Development of VAV1-directed MGDs

A summary of the VAV1 intracellular signaling pathway is illustrated in Figure 8.

Figure 8: VAV1 is a Key Regulator of T- and B-cell Receptor Activity

VAV1 is an upstream signaling node associated with multiple clinically validated pathways impacting immune cell functions, as shown in Figure 9. These include T cell activation, B cell activation and plasma cell differentiation, Th17 response, and pro-inflammatory cytokine production. Therapies targeting these pathways individually have been approved for multiple autoimmune and inflammatory diseases.

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Figure 9: VAV1 is an Upstream Targeting Node Associated with Clinically Validated Pathways

MRT-6160 is a first-in-class molecular glue degrader of VAV1. MRT-6160 forms a strong ternary complex with VAV1 and cereblon through a newly characterized non-canonical degron which was unveiled through application of our QuEENTM discovery engine technologies. The unique character of the VAV1 degron and its interaction with cereblon induced by MRT-6160 result in a high degree of selectivity over commonly degraded neosubstrates and other closely related VAV family proteins. Our studies show that MRT-6160 degrades human VAV1 with a DC50 of 7 nM and Dmax of 97%, is orally bioavailable across species, and displays favorable in vitro ADMET properties. The favorable drug-like profile of MRT-6160 is summarized in Figure 10.

Figure 10: MRT-6160 is a Potent, Selective VAV1 MGD Development Candidate with a Favorable Drug-Like Profile

Degradation of VAV1 in peripheral immune cells was observed following MRT-6160 oral administration. Additionally, MRT-6160 has brain penetrance with anticipated dose dependent degradation of VAV1 in the CNS. Non-clinical safety profiling showed a clean profile with respect to mutagenicity (mini-Ames), hERG activity, CYP inhibition and induction, and broad off-target screening (CEREP panel).

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Preclinical 28-day GLP toxicology studies in rats and non-human primates (cynomolgus macaque or cyno) demonstrated a highly favorable profile. The no-observed-adverse-effect-level (NOAEL) was set at the highest doses tested in both species. The exposure at NOAEL for rats was approximately 1000-fold over the projected human efficacious exposure, and the exposure at NOAEL for cynos was approximately 600-fold over the projected human efficacious exposure. In healthy cynos, no adverse immunotoxicity or impact on peripheral immune compartments was observed. There was no observed impact on bone marrow and peripheral hematopoietic cell counts. No gastrointestinal toxicity was observed. Furthermore, there were no off-target effects identified in in-vitro safety profiling, no genotoxicity, no phototoxicity, and no hERG activity.

The potency and selectivity profile of MRT-6160 was evaluated in primary human peripheral mononuclear blood cells (hPBMCs). As shown in Figure 11, left panel, MRT-6160 elicited dose-dependent degradation of VAV1 in primary human T and B cell subsets. As shown in Figure 11, right panel, tandem mass tag (TMT)-global proteomics assessment revealed selective degradation of VAV1 over its closely related family members VAV2 and VAV3 in addition to other proteins expressed in hPBMCs and detectable in the assay.

Figure 11: MRT-6160 Selectively Degraded VAV1 in Primary Human Immune Cells

MRT-6160 was further characterized for anticipated on-target pharmacodynamic and functional activity in primary human T and B cells. As shown in Figure 12, in primary human T cells (top panel), VAV1 degradation by MRT-6160 resulted in inhibition of TCR-mediated pharmacodynamic (CD69) and functional activity (IL-2 secretion and proliferation). In primary human B cells (bottom panel), VAV1 degradation by MRT-6160 resulted in inhibition of BCR-mediated pharmacodynamic (CD69) and functional activity (IL-6 and soluble IgG secretion) demonstrating expected on-target activity in disease-relevant cell types.

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Figure 12: VAV1 degradation by MRT-6160 Resulted in Inhibition of T- and B-cell Receptor Signaling and Activity

In vivo validation of VAV1 MGD MRT-6160

MRT-6160 was evaluated in various well-established T- as well as T- and B-cell mediated in vivo models of autoimmune disease. In a T-cell-mediated experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis (Figure 13, left panel), daily oral dosing of MRT-6160 following disease onset inhibited disease progression in a dose-dependent manner comparable to that of supratherapeutic doses of dexamethasone, a corticosteroid used broadly in autoimmune disease. After 6 days of dosing, samples from mice were assessed by western blot for murine (m) VAV1 levels in diseased tissue. Shown in the right panel of Figure 13, MRT-6160 induced dose-dependent degradation of mVAV1 commensurate with inhibition of disease progression.

Figure 13: MRT-6160 Elicited Dose-Dependent Activity in a T-cell mediated Multiple Sclerosis Autoimmune Disease Model

MRT-6160 was also evaluated in a T- and B-cell mediated collagen-induced arthritis (CIA) model of rheumatoid arthritis. Mice were orally administered MRT-6160 daily following disease onset and scored for clinical signs of disease. As shown in Figure 14, left panel, 1 mg/kg MRT-6160 inhibited disease progression comparably to 10 mg/kg anti-TNF-Alpha antibody. The right panel of Figure 14 shows that treatment with MRT-6160 reduced the

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serum levels of anti-collagen II IgG1 and total anti-collagen II IgG antibodies, demonstrating inhibition of auto-antibody production.

Figure 14: MRT-6160 Inhibited Disease Progression and Auto-Antibody Production in the Collagen-Induced Arthritis Disease Model

MRT-6160 was also evaluated in a T-cell transfer-induced model of colitis, as shown in Figure 15. In a prophylactic model shown in the left panel, mice were orally administered vehicle or MRT-6160 daily following T-cell transfer. Anti-TNF-Alpha antibody was administered intraperitoneally every third day as a standard of care control. Oral dosing with 1 mg/kg MRT-6160 demonstrated superior disease inhibition compared to 10 mg/kg anti-TNF-Alpha antibody. In a therapeutic model shown in the right panel, mice were orally administered MRT-6160 starting on Day 17 following disease induction. MRT-6160 was compared to two commonly used oral therapies for rheumatoid arthritis, a JAK inhibitor and a S1PR antagonist, as well as vehicle control. MRT-6160 was superior in controlling clinical signs of disease as compared to both active comparators.

Figure 15: MRT-6160 Ameliorated T Cell Transfer-Induced Colitis Equal to or Better than Standard of Care

Figure 16, left panel, shows reduction of inflammation-mediated damage and swelling of the colon following MRT-6160 treatment in the prophylactic T-cell transfer-induced model of colitis. The right panel of Figure 16 shows mesenteric lymph node and colon CD4+ T cell assessment by flow cytometry where MRT-6160 reduced the

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frequency of IL-17A+, TNF-Alpha+, and IL-6+ CD4+ T cells, known drivers of inflammatory bowel disease in humans.

Figure 16: MRT-6160 Inhibited Inflammation-Mediated Damage and Cytokine Production in a Model of Inflammatory Bowel Disease

In a preclinical autoimmune disease model characterized by chronic inflammation, autoantibody production, and multi-organ involvement (Figure 17) administration of MRT-6160 resulted in broad activity across an array of disease markers, including attenuated autoantibody levels and reduced skin and kidney pathology. MRT-6160 was equivalent or superior to prednisone or anti-CD40L monoclonal antibody treatments across multiple metrics of disease pathology.

We believe these findings reinforce the breadth of MRT-6160's potential across multiple immune-mediated diseases, including systemic lupus erythematosus, Sjögren’s disease, rheumatoid arthritis, and others.

Figure 17: MRT-6160 Inhibited Disease Progression, Autoantibody Production, and Nephritis in the MRL-Faslpr Lymphoproliferative Autoimmune Model

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In summary, these data further highlight the potential of MGDs to potently degrade otherwise ‘undruggable’ proteins such as VAV1, providing an opportunity to treat immune-mediated diseases with a novel, orally dosed modality capable of blocking multiple pathogenic immune and cytokine receptor pathways in parallel, thereby potentially providing greater clinical benefit, a strategy we are planning to continue to pursue through our portfolio of MGDs.

MRT-6160 Phase 1 Study

In a Phase 1 study of healthy volunteers, MRT-6160 was dosed in five SAD dose level cohorts and three MAD dose level cohorts, as shown in Figure 18. All cohorts were randomized and placebo controlled, and over 70 subjects were enrolled in total. The primary endpoint of the study was safety and tolerability of MRT-6160. The secondary endpoints were pharmacokinetic and pharmacodynamic assessments using various readouts in multiple different analytes.

Figure 18: MRT-6160 Phase 1 Healthy Volunteers Study Design and Objectives

VAV1 degradation was assessed by flow cytometry of CD3+ T cells and CD19+ B cells, as shown in Figure 19. In addition, ex vivo activation of whole blood was performed to assess T and B cell functions, including CD69 upregulation on T and B cells measured by flow cytometry, and cytokine secretion measured by immunoassay.

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Figure 19: In-Vitro Assay Validation of PD and Immune Cell Functional Testing

Analysis of plasma concentrations of MRT-6160 over time demonstrated a dose dependent human pharmacokinetic profile, as shown in Figure 20. MAD dosing resulted in an approximately two-fold increase in exposure at steady state. No food effect was observed.

Figure 20: MRT-6160 Displayed a Dose-Dependent Human Pharmacokinetic Profile

As shown in Figure 21, MRT-6160 achieved degradation exceeding 90% at all but DL1 of the SAD cohorts and at all MAD cohorts, based on analysis of peripheral blood T cells. Reduction of VAV1 protein levels was sustained, with dose-dependent recovery following cessation of treatment. Similar results were observed in peripheral blood B cells.

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Figure 21: MRT-6160 Achieved Dose-Dependent Degradation 90% in Peripheral Blood T cells After Single and Multiple Dose Administration

VAV1 degradation by MRT-6160 resulted in significant functional inhibition of T and B cells following ex vivo activation of T and B cell receptors in cells derived from whole blood, as shown in Figure 22 for all SAD cohorts. MRT-6160 treatment significantly attenuated CD69 upregulation (a marker of immune cell activation) on T and B cells following TCR stimulation, reflecting functional inhibition of both cell types. In addition, MRT-6160 treatment significantly inhibited IL-2, IFN-γ and IL-17A secretion from whole blood derived T cells following ex-vivo activation of T cell receptor signaling, demonstrating reductions of up to 99% from pre-dose levels. MRT-6160 also attenuated IL-6 production by 60-90% across dose levels, and over 80% at all but the lowest dose level, following B cell activation. Alignment with the pharmacodynamic studies above suggests robust functional effects on cytokine production can be achieved with 80% and higher degradation of VAV1.

Figure 22: VAV1 Degradation by MRT-6160 Resulted in Significant Functional Inhibition of T and B Cells

Suppression of CD69 upregulation following single or multiple doses of MRT-6160 and subsequent ex vivo TCR stimulation of whole blood derived cells was significant (90%) as well as sustained during post treatment observation periods, as shown in Figure 23 (data for selected SAD and MAD dose shown as example). Similar results were observed in peripheral blood B cells following BCR-stimulation.

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Figure 23: MRT-6160 Resulted in Sustained Suppression of TCR-mediated CD69 Activation following Single or Multiple Doses of MRT-6160

MRT-6160 demonstrated a sustained effect on TCR-mediated cytokine production following single and multiple dose administration and ex vivo stimulation of whole blood derived cells, as shown in Figure 24. MRT-6160 treatment resulted in significant and sustained suppression of IL-2, IL-17A and IFN-γ secretion from whole blood derived T cells following ex-vivo activation of T cell receptor signaling (data for selected SAD and MAD dose shown as example).

Figure 24: MRT-6160 Resulted in Sustained Suppression of TCR-mediated Cytokine Production following Single or Multiple Doses of MRT-6160

MRT-6160 was well tolerated with no serious adverse events, or SAE, observed. Observed treatment-emergent adverse events, or TEAEs, were mild (82%) or moderate (18%) and self-limiting. Overall TEAE frequency was similar between MRT-6160 and placebo. TEAEs observed in 2 or more subjects treated with MRT-6160 were: in the SAD cohorts, pain from vessel puncture (2); in the MAD cohorts, cough (2), diarrhea (3), feeling hot (4), headache (5), nasal congestion (2), oropharyngeal pain (3) and pyrexia (2).

In summary, the pharmacodynamic and functional ex-vivo studies suggest significant effects on cytokine production can be achieved following treatment with MRT-6160. Furthermore, we believe the levels of VAV1

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degradation observed clinically are consistent with levels of degradation required to induce efficacy in the preclinical models tested so far. The functional impact on cytokine production is also consistent with levels predicted to be required to achieve efficacy in humans, based on benchmark clinical data from other compounds.

In summary, we believe the Phase 1 data described here as well as our chronic toxicology package support a clear path into Phase 2 studies and broad potential applications of MRT-6160 in multiple immune-mediated diseases.

NEK7-directed MGDs for the treatment of inflammatory disease

Overview

The NLRP3 inflammasome is a multi-protein complex that functions as a central signaling hub integrating stimuli derived from pathogens, cellular damage, metabolites and metabolic stress, ultimately triggering the production of pro-inflammatory cytokines, and is implicated in numerous inflammatory diseases. Activation of the NLRP3 inflammasome critically depends on NIMA-related kinase 7, or NEK7, a serine/threonine kinase that is essential to trigger the assembly of the active NLRP3 inflammasome complex in a NEK7 kinase-independent manner. As depicted in Figure 25, aberrant NEK7-dependent activation of the NLRP3 inflammasome leads to the release of highly inflammatory mediators, including the cytokines IL-1α, IL-1β, and IL-18, through a form of cell death known as pyroptosis. The NLRP3 inflammasome and above mentioned cytokines have been implicated in multiple inflammation-driven diseases, including ASCVD, gout, hidradenitis suppurativa, pericarditis, osteoarthritis, and obesity. Given the central role of NEK7 in pathological NLRP3 inflammasome activation and in disease initiation and progression, targeted degradation of NEK7 with a highly selective MGD, such as our product candidate MRT-8102, may effectively suppress NLRP3 inflammasome activity at the most upstream intervention point, thus leading to the broadest downstream inhibition of inflammatory signaling possible, thereby potentially inducing more effective disease resolution than currently approved agents.

Figure 25: NEK7 Enables NLRP3 Inflammasome Assembly and Activation, Pyroptotic Cell Death and Release of Highly Inflammatory Cytokines and DAMPs

Extensive clinical data support the relevance of IL-1 and NLRP3 inflammasome signaling across multiple diseases in large therapeutic areas spanning cardiovascular, rheumatologic, respiratory, dermatologic, neurologic, and metabolic conditions. Cytokine-targeting agents that act downstream of the NLRP3 inflammasome, such as rilonacept (an IL-1α/β blocker) and canakinumab (an IL-1β blocker), have demonstrated clinical activity across several of these inflammatory diseases, including recurrent pericarditis and ASCVD, respectively, as illustrated in Figure 26. Despite the reported activity of IL-1 targeting agents like rilonacept and canakinumab, we believe that upstream therapeutic degradation of NEK7 will drive more complete suppression of the full spectrum of inflammasome-driven signals and thus, may offer even greater benefit to patients.

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Figure 26: The NLRP3 Inflammasome and IL-1 Signaling are a Clinically Validated Pathway for Inflammatory Diseases

Below, we describe our internal in vitro and in vivo studies supporting the essential role of NEK7 in cytokine production downstream of NLRP3 inflammasome activation across multiple species, including mouse, rabbit, and cynomolgus monkey. We present evidence that MRT-8102 and related NEK7 MGDs can potently and selectively suppress NLRP3 inflammasome activity in disease models, leading to meaningful improvements in disease burden. Finally, we provide data suggesting that existing therapeutics, such as the GLP-1 receptor agonist semaglutide, may partially function through downregulation of NEK7 expression, although sub-optimally, to achieve anti-inflammatory activity and efficacy, further confirming the crucial role NEK7 plays in the pathological activation of the NLRP3 inflammasome.

Identification of a NEK7 degron and NEK7-directed MGDs

The kinase-independent, scaffolding function of NEK7 in activating the NLRP3 inflammasome suggests that degradation of NEK7 could be an effective way to block NLRP3 inflammasome activation. Indeed, we have demonstrated experimentally that removal of NEK7 by MGD-mediated degradation is an efficient way to prevent NLRP3 inflammasome formation and therefore has the potential for deep pathway inhibition through disassembly of the NLRP3 inflammasome.

Our discovery efforts resulted in the identification of MRT-8102 as a first-in-class NEK7 MGD. As shown in Figure 27, MRT-8102 induces a strong ternary complex of NEK7 with cereblon via a canonical G-loop degron (left panel), resulting in profound NEK7 degradation (DC50 10 nM and Dmax 89%; right panel). MRT-8102 is highly selective against known cereblon neosubstrates and more importantly, against other NEK family members (also see below), is orally bioavailable across multiple species tested, and displays favorable in vitro ADMET properties. Non-clinical safety profiling showed a clean profile with respect to mutagenicity (mini-ames), hERG activity, and broad off-target screening (CEREP panel).

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Figure 27: MRT-8102 is a Potent and Selective Investigational NEK7 MGD with a Favorable Drug-Like Profile

The amino acid sequence of the NEK7 degron is unique among the NEK family members, indicating the potential to identify MGDs that are highly selective for NEK7. As shown in Figure 28, human peripheral blood mononuclear cells (PBMC) were treated with MRT-8102 for 24 hours, followed by TMT-global proteomic profiling. Profound and highly selective degradation of NEK7 is evidenced by a several-fold decrease in NEK7 protein, without significant changes in other detected proteins. Other NEK family members are highlighted on the volcano plot and were not degraded. Several other cell lines and types, including U937, MM1S, iPSCs, and PBMCs derived from cynomolgus monkeys revealed similarly selective proteomic profiles when treated with MRT-8102.

In a PK/PD study in cynomolgus monkeys, a single oral dose of 10 mg/kg of MRT-8102 was sufficient to achieve deep and sustained NEK7 degradation beyond the PK exposure window of the compound (Figure 28, right panel).

Figure 28: MRT-8102, a Potent and Highly Selective NEK7-directed MGD, Induces Durable Pharmacodynamic Modulation In Vivo

MRT-8102 is differentiated from existing NLRP3-IL-1-IL-6 targeting agents

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MRT-8102 is an orally bioavailable molecular glue degrader that is designed to selectively and catalytically degrade NEK7 to suppress NLRP3 inflammasome activity. As compared to small molecule inhibitors of the NLPR3 inflammasome, NEK7 degradation by MRT-8102, as shown schematically in Figure 29, leads to long-lasting inflammasome disassembly and sustained inhibition of cytokine release, most importantly without the on/off pathway inhibition characteristic of inhibitors. Moreover, MRT-8102 is exquisitely selective for NEK7, as confirmed by our proteomics work, which may help minimize the risk of off-target effects.

Figure 29: MRT-8102 Induces Catalytic NEK7 Degradation, Long-lasting Inflammasome Disassembly, and Sustained Inhibition of Cytokine Release

Beyond deeper and more sustained pathway inhibition, we believe targeting NEK7 will provide safety advantages over NLRP3 inhibitors, as NLRP3 has been shown to have inflammasome-independent functions, potentially impacting safety. Toxicities with NLRP3 inhibitors have been reported preclinically and clinically and several NLRP3 inhibitors have been discontinued, potentially due to lack of selectivity and resulting toxicities.

Given that MRT-8102 prevents inflammasome assembly and activation, it is highly effective at suppressing pyroptosis, the pathological event that is ultimately responsible for the release of disease-promoting cytokines, such as IL-1α, IL-1β and IL-18, as well as damage-associated molecular patterns (DAMPs), which are known to be important drivers of the inflammatory process. Although various mono- and bi-specific biologics currently under investigation can robustly target one or more of these cytokines downstream of pyroptosis, ultimately, these classes of therapeutics may be limited by their inability to suppress the full spectrum of disease-relevant cytokines and more importantly the release of DAMPs as highlighted in Figure 30. Furthermore, whereas MRT-8102 selectively reduces the pool of cytokines driven by NLRP3 inflammasome activation, biologics, like IL-1 and IL-6 targeting antibodies may indiscriminately inhibit this pool of cytokines, irrespective of their source, and thus potentially elevate infection risk by impacting immune pathways beyond the NLRP3 inflammasome pathway. Such pathways might include other inflammasomes (e.g. AIM2, NLRC4, NLRP1), protease-mediated IL-1 activation, alternative inflammasome activation downstream of TLR4 and passive release from dying cells.

As shown in Figure 30, right panel, whereas MRT-8102 effectively prevented pyroptosis and DAMP release, anti-IL-1 and IL-6 agents failed to significantly inhibit these processes in stimulated human monocyte-derived macrophages (hMDM), suggesting that mono- and potentially bispecific biologics may incompletely block the multitude of pathological drivers of disease.

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Figure 30: MRT-8102 Potently Inhibits Pyroptotic Cell Death in Stimulated hMDM

NEK7 MGDs Demonstrate Compelling Efficacy Across a Number of Disease Models and Species

We showed that sustained NLRP3 inflammasome inhibition through NEK7 MGDs drives compelling improvements in disease severity across multiple models and species. Models tested in the course of our NEK7 program include two independent mouse models of cardiovascular disease (Figure 31, left panel) looking at reductions in cardiac damage, a rabbit-based gout model (Figure 31, middle panel) investigating whether MRT-8102 treatment leads to a decrease in severity of monosodium urate (MSU)-induced flares, and a cynomolgus monkey-based diet-induced obesity model (Figure 31, right panel) investigating the potential of a NEK7 MGD to reduce body weight and liver inflammation as a monotherapy or in combination with semaglutide.

Figure 31: MGD-Mediated NEK7 Degradation Improved Disease Burden Across a Wide Range of Disease Models Spanning Multiple Species

Mouse models of cardiac damage

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In an acute myocardial infarction (AMI) study conducted in CRBN-I139V mice (Figure 31, left panel), i.e. mice with a partially humanized CRBN protein sequence, the effects of prophylactic dosing with MRT-8102 were compared with an anti-IL-1R antibody and the NLRP3 inhibitor MCC950. Outcomes were evaluated histologically to assess infarct size. Coronary arterial ligation (60 min), followed by reperfusion led to significantly sized infarcts in vehicle-treated animals at the 24-hour timepoint. In contrast, prophylactic treatment with MRT-8102, an anti-IL-1R antibody and MCC950 significantly reduced infarct size. Collectively, these data support the pathological role of aberrant NLRP3 inflammasome activity in myocardial infarction and the therapeutic value of targeting NEK7 as a differentiated approach.

In a pericarditis model, also established in CRBN-I139V mice, the effects of prophylactic dosing with the same agents evaluated in the AMI model were assessed (Figure 31, middle panel). As neutralization of IL-1 and inhibition of IL-1 signaling is a clinically approved approach to treat recurrent pericarditis, treatment with an anti-IL-1R antibody served as a positive control in this study. Administration of zymosan, a potent immunostimulant, to the pericardium resulted in a significant increase in pericardial effusion relative to sham controls. In contrast, prophylactic treatment with MRT-8102, an anti-IL-1R antibody, or MCC950 significantly reduced pericardial effusion. Notably, MRT-8102 demonstrated superior efficacy compared with anti-IL-1R antibody treatment. Since the anti-IL-1R antibody blocks the action of both IL-1α and IL-1β (as does rilonacept, which is clinically approved for use in recurrent pericarditis), these data suggest that the activity of MRT-8102 in a model of pericarditis is in fact broader than blockade of the downstream IL-1 cytokines alone.

Rabbit rheumatology model of gout

In addition to inflammatory diseases of the heart, MRT-8102 also demonstrated activity in a rabbit model of gout. Following intra-articular injection of MSU crystals, marked joint swelling was observed, peaking at approximately 24 hours. Despite achieving only ~40% degradation of NEK7 in rabbits, due to limited homology between human and rabbit CRBN, prophylactic administration of MRT-8102 on Day -1 resulted in a three-fold reduction in peak joint swelling and accelerated resolution of inflammation, with swelling returning to baseline levels, comparable to rabbits not injected with MSU crystals, by days 3 - 6 (Figure 31, right panel).

Cynomolgus monkey diet-induced obesity model

In addition to acute inflammatory indications, MGD-mediated NEK7 degradation also demonstrated activity in chronic metabolic diseases such as obesity. In a cynomolgus monkey model of diet-induced obesity, animals with body mass index ≥ 40 kg/m2 were selected from a colony of animals maintained on a high-fat diet and randomized across treatment groups. A NEK7 MGD with similar properties to MRT-8102 was used for this study. Following single-agent NEK7 MGD treatment for 11 weeks, an approximately 8% reduction in body weight was observed relative to vehicle. When combined with the GLP-1 receptor agonist semaglutide, 23% body weight loss was achieved relative to vehicle treatment (Figure 32, left panel). In addition to monitoring total body weight, dual-energy X-ray absorptiometry (DEXA) body composition analysis was also performed. Notably, the combination treatment demonstrated preferential activity in central abdominal fat, a region associated with elevated metabolic risk, with proportionally greater reductions observed relative to other fat depots such as the gynoid region (Figure 32, middle, right panels).

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Figure 32: NEK7 MGD, Alone or in Combo with Semaglutide, Drives Preferential Abdominal Fat Loss While Sparing Lean Mass in a DIO Cyno Monkey Model

Intriguingly, while, as expected, 90% degradation of NEK7 was observed by Western blotting in PBMCs in the NEK7 MGD treatment arms, a significant reduction in NEK7 levels of about 40 – 50% was also detected in the semaglutide single agent treatment arm (Figure 33, left panel). These findings may suggest a mechanism through which GLP-1R agonists suppress NLRP3 inflammasome activity analogous to NEK7 MGD treatment, albeit less potently and reliably. Consistent with the central role of NEK7 in NLRP3 inflammasome signaling, NEK7 levels across treatment arms correlated with changes in plasma IL-18, a canonical inflammatory cytokine associated with NLRP3 inflammasome activity (Figure 33, right panel).

Figure 33: Anti-inflammatory Activity of NEK7 MGD and Semaglutide May Partially Overlap at the Level of NEK7 Degradation/Downregulation and NLRP3 Inflammasome Inhibition

Collectively, we believe these studies demonstrate that targeted degradation of NEK7 by MRT-8102 or other NEK7-directed MGDs enables deep and sustained suppression of NLRP3 inflammasome activity across multiple

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species and disease models, including cardiovascular injury, gout, and metabolic diseases. We believe these studies validate a broad and pivotal role of NEK7 in the pathogenic activation of NLRP3 inflammasomes.

In conclusion, by intervening upstream of where cytokine blocking biologics act, we believe that NEK7 degradation may offer the potential for broader and more durable therapeutic benefit across a wide range of inflammation-driven diseases and potentially carry less risk of infections.

Market Opportunities for NEK7-directed MGDs

ASCVD

We believe there are multiple attractive opportunities for NEK7-directed MGDs across a wide range of NLRP3 inflammasome-driven indications, including a particularly attractive opportunity in ASCVD. While LDL cholesterol lowering agents are a well-established part of the treatment paradigm, patients that achieve their LDL-C targets still experience up to a 40% chance of life-threatening cardiovascular events (Holtrop et al. European Journal of Preventive Cardiology, 2024). We believe this demonstrates the substantial residual risk not fully addressed by LDL-C lowering and speaks to the promise and importance of complementary approaches such as targeting the NEK7/NLRP3 pathway.

The role of the NLRP3 inflammasome and IL-1β in ASCVD has been well established through various approaches, including through the key findings of the landmark CANTOS clinical trial. In this study, canakinumab, a monoclonal antibody targeting IL-1b was dosed in over 10,000 patients with prior myocardial infarction and high sensitivity C-reactive protein (hsCRP, a marker of inflammation) levels of 2 mg/L, a threshold above which there is higher risk of cardiovascular events and mortality. Treatment led to a significant reduction in hsCRP and a significantly lower rate of recurrent cardiovascular events than in placebo treated patients, independent of lipid lowering. Despite the significant efficacy noted, canakinumab was also associated with a higher incidence of fatal infections than was placebo, which ultimately yielded an unfavorable risk-benefit profile. The higher risk of infections is likely due to the above-mentioned indiscriminate and deep suppression of an NLRP3 inflammasome-independent pool of IL-1b, a cytokine that plays a critical role in host protective immunity elicited by multiple different pathways.

We believe upstream targeting of the NEK7/NLRP3 pathway may have greater potential than downstream IL-6 biologics in ASCVD. Figure 34 shows how monocytes, upon uptake of oxidized LDLs, become the initiator and driver of disease through chronic activation of NLRP3 inflammasomes and consequential pyroptosis. This pathological activation of NLRP3 inflammasomes promotes plaque destabilization and downstream CV events through contribution of cellular debris, lipids and further recruitment of bone marrow derived macrophages to the growing plaques. Given the essential involvement of the NLRP3 inflammasome in this process, we believe that suppression of pyroptosis through degradation of NEK7 and disassembly of the NLRP3 inflammasome with MRT-8102 could be an effective means by which to stabilize plaques and hence reduce cumulative incidence of MACE.

Figure 34: NLRP3 Inflammasome Activation Promotes Plaque Growth, Destabilization and CV Events

As shown in Figure 35, an unbiased analysis using an in-house generated NLRP3 inflammasome activity signature, using our proprietary BreakthruTM data science engine across more than 1000 datasets spanning

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hundreds of diseases identified ASCVD as one of the top-ranking conditions with strong NLRP3 inflammasome activation. As expected, cryopyrin-associated periodic syndromes (CAPS), a group of rare and hereditary autoinflammatory disorders, also scored highly in our analysis. CAPS is known to be driven by constitutively active NLRP3 mutants, providing a positive control to this analysis. Interestingly, in addition to CAPS and ASCVD, we noted other diseases, such as gout and hidradenitis suppurativa (HS), also scored highly in our analysis, suggesting MRT-8102 or next generation molecules could offer broad therapeutic value across these indications.

Figure 35: ASCVD, HS and Gout Rank Amongst Top NLRP3 Inflammasome Activated Indications

Consistent with the transcriptomic study, an unbiased genetic association analysis, also performed through our BreakthruTM data science engine and shown in Figure 36, found an NLRP3 gain-of-function single nucleotide polymorphism, or SNP, to be significantly associated with increased downstream CV events including stroke, coronary artery disease, and peripheral artery disease, further supporting the role of the NLRP3 inflammasome in driving disease pathology. By comparison, although IL-6 signaling was also associated with CV outcomes, the effects were weaker than those observed for NLRP3, implying that upstream targeting of NLRP3 inflammasome activity may have the potential for greater efficacy than targeting downstream cytokines such as IL-6. In summary, these data strongly support an opportunity for MRT-8102 in the treatment of CV indications and the management of elevated CVD risk.

Figure 36: Human Genetics Supports Causal Relationship Between NLRP3 and ASCVD

Gout

Gout is a painful, chronic inflammatory arthritis driven by elevated uric acid levels that result in MSU crystal deposition in joints. These crystals potently activate NLRP3-inflammasome-mediated inflammation, leading to recurrent flares with intense pain. Nearly 30% of gout patients are comorbid with stage 3/4 chronic kidney disease (CKD), a condition that both elevates uric acid levels and increases gout risk. Current treatment options present significant limitations in this population. Many therapies are contraindicated in CKD or lack long-term safety data, often requiring dose titration and close monitoring. The anti-IL-1β antibody canakinumab, approved for treatment

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of gout patients including those with CKD comorbidity, has demonstrated efficacy in resolving acute flares, further validating the role of the NLRP3 inflammasome in the disease pathology of Gout. However, due to safety concerns, such as the risk of serious infections, canakinumab is not approved for prophylactic use.

Conversely, the urate-lowering therapy pegloticase is approved for chronic, refractory gout as a prophylactic treatment. Yet nearly 70% of patients experience flares within the first three months of therapy. Together, these examples highlight the persistent treatment challenges in the prophylactic setting, coupled with safety concerns in CKD patients, underscoring the need for new and safer therapeutic approaches capable of resolving acute flares while also preventing recurrent flares.

Our studies demonstrated that MRT-8102 significantly reduced MSU crystal–induced caspase-1 activation and downstream pyroptosis, with greater potency than the NLRP3 inhibitor selnoflast, as shown in Figure 37. By blocking pyroptosis, MRT-8102 may not only attenuate inflammatory severity but also preserve macrophage viability, potentially enhancing phagocytic clearance of MSU crystals, the underlying trigger of disease pathology. Consistent with these in vitro findings, MRT-8102 demonstrated robust activity in a rabbit model of gout as previously described in Figure 31 (middle panel). In addition to improving joint swelling, MRT-8102 treatment also led to statistically significant reductions in pathologic musculoskeletal ultrasound findings and histopathology scores at the end of the study, further supporting a robust resolution of gout flares (Figure 36; bottom right).

Collectively, these data, together with the clinical validation of IL-1 pathway inhibition through canakinumab, support a compelling potential development opportunity for MRT-8102 as a differentiated therapeutic for gout—either as a single agent or in combination with standard-of-care urate-lowering therapies.

Figure 37: MRT-8102 Inhibits NEK7/NLRP3 Pathway and Has Potential to Resolve and Prevent Gout Flares

Hidradenitis suppurativa (HS) Hidradenitis suppurativa (HS) is a chronic, complex inflammatory skin disease characterized by painful, recurrent nodules and abscesses that may progress to sinus tract formation and fistulae. Molecular profiling of HS lesions has identified several signaling pathways that contribute to disease pathogenesis, leading to the approval of targeted therapies such as anti-TNF agents (adalimumab) and anti-IL-17 therapies (secukinumab and bimekizumab). Despite these advances, physicians estimate that approximately 55% of patients remain inadequately controlled on current standards of care, suggesting that additional inflammatory pathways contribute meaningfully to disease pathology.

HS is strongly associated with metabolic syndrome, including dyslipidemia, obesity, and insulin resistance, highlighting a potential role for metabolically driven inflammation in disease pathogenesis. In this context, the NLRP3 inflammasome is thought to be an important mediator of disease pathology, as it can be activated by metabolic danger signals such as elevated free fatty acids and hyperglycaemia. Consistent with published findings, our internal data science analyses demonstrate that NLRP3 inflammasome activity is markedly elevated in HS lesions, at levels comparable to or exceeding those observed in atherosclerotic plaques (Figure 35).

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Notably, NLRP3 inflammasome activity remains significantly higher in anti-TNF non-responders compared with responders, suggesting that NLRP3-mediated inflammation may represent one of the dominant pathogenic drivers in this subset of patients (Figure 38). Further supporting this concept, the dual anti-IL-1α/β antibody lutikizumab recently demonstrated positive Phase 2 results in moderate-to-severe HS, particularly among patients who had previously failed anti-TNF therapy. Treatment with 300 mg every other week resulted in significantly higher HiSCR75 response rates (≥75% reduction in abscesses and inflammatory nodules) compared with placebo, along with meaningful reductions in skin pain at Week 16.

Figure 38: NLRP3-IL-1b Axis is Significantly Active in HS Lesions, Particularly in the Anti-TNF Non-responder Setting

Collectively, these data support a pathological role for aberrant NLRP3 inflammasome activation in HS and highlight a compelling development opportunity for MRT-8102 in both anti-TNF–naïve and anti-TNF–refractory settings, either as monotherapy or in combination with currently approved agents. Moreover, given the efficacy observed for NEK7 MGDs in diet-induced obesity models (Figure 32), MRT-8102 may reduce upstream metabolic danger signals, further reinforcing NLRP3 inhibition and potentially enabling more durable disease control.

MRT-8102 toxicology studies suggest considerable safety margin

In 28-day repeat-dose GLP toxicology studies in male and female rats and cynomolgus monkeys, no MRT-8102 related clinical signs, nor changes in immunophenotyping, and no gross or clinical pathology findings were observed at any dose level. Therefore, the no-observed-adverse-effect levels (NOAEL) were established at the highest doses tested in these studies, respectively. Additional IND-enabling GLP safety studies did not indicate significant safety concerns related to in vitro off-targets, mutagenicity, phototoxicity, hERG, or in vivo respiratory or CNS safety pharmacology (assessed in rats) and cardiovascular safety pharmacology (assessed in cynomolgus monkeys).

In a long-term toxicology study in cynomolgus monkeys, deep and sustained pathway inhibition was well tolerated following daily dosing of MRT-8102 for three months. There were no test-article related findings, and the NOAEL was determined as the highest dose tested. No body weight loss, unscheduled deaths, or clinically meaningful changes in hematology or clinical chemistry parameters were observed. Furthermore, no gross pathological findings were identified throughout the duration of the study.

In totality, our preclinical safety assessments suggest an at least 200 to 300 fold therapeutic margin over the projected human dose.

MRT-8102 Phase 1 SAD and MAD Study Interim Clinical Results

Based on the promising preclinical profile of MRT-8102, in July 2025, we initiated dosing in a Phase 1 combined SAD and MAD study (Figure 39). The primary endpoint was safety and tolerability. Key secondary and exploratory endpoints included pharmacokinetics and inflammatory markers, including assessment of NEK7

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degradation in peripheral blood T cells by flow cytometry, changes in the acute-phase reactants hsCRP and fibrinogen, levels of endogenous IL-6 in blood and cerebrospinal fluid, and IL-1β levels following ex vivo stimulation.

Interim results were based on a data cut-off date of December 23, 2025. In the SAD cohorts, we enrolled 48 participants across 5 dose levels ranging from 40 mg to 400 mg, and in the MAD cohorts, we enrolled 40 participants across 5 dose levels ranging from 5 mg to 200 mg. The 40 mg dose cohort of the ongoing Part 3 of the study, which evaluates MRT-8102’s activity at 40 mg for 28 days in subjects with elevated CVD risk, is expected to enroll approximately 36 subjects. As of the data cutoff date, 24 subjects had completed 4 weeks of dosing and CRP assessment.

Figure 39: MRT-8102 Phase I Study – Dose Levels and Endpoints

Consistent with our preclinical studies, we observed rapid and marked degradation of NEK7 in peripheral blood T cells following a single administration of MRT-8102 (Figure 40). Using flow cytometry, approximately 80-90% NEK7 degradation was noted at 6 hours post a single dose of MRT-8102, a level that was sustained following multiple administrations, ranging from 7 days in the MAD portion of the trial to up to 4 weeks in the Part 3 portion of the study. In the MAD portion, a dose as low as 5 mg achieved considerable degradation of NEK7 24h after the last of 7 doses, and levels of degradation at 5 mg where similar to those at the higher doses tested. These results were consistent with preclinical data from our cyno PK/PD studies, which also suggested that at these levels of NEK7 degradation deep pathway inhibition, including suppression of IL1b upregulation on ex vivo stimulation, can be achieved.

Figure 40: MRT-8102 Achieved 80 – 90% NEK7 Degradation in Peripheral Blood T Cells After Single and Multiple Dose Administration

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In light of achieving NEK7 degradation of 80 to 90% across all dose levels, we analyzed downstream inflammatory markers, including hsCRP, in aggregate across all SAD dose level cohorts. In this analysis, we observed a significant reduction in high-sensitivity CRP after a single dose of MRT-8102, as shown in Figure 41. Across all subjects treated with a single dose of MRT-8102, most of whom had normal CRP levels at baseline, we observed a 52% reduction in CRP at 96 hours post-dose. As expected, the reduction in CRP was greater in subjects with higher median baseline CRP, with median CRP reductions at 96 hours of 72% and 78% in the subsets with baseline CRP ≥ 1 mg/L and ≥ 2 mg/L, respectively. Comparable activity was noted across all SAD dose levels, ranging from 40 to 400 mg, suggesting the potential for a wide range of doses to be available for future development.

Figure 41: Single Dose of MRT-8102 Led to Significant Reduction in Serum hsCRP

Comparable results were obtained from the MAD (7 days of dosing) portion of the study, detailed in Figure 42. Similar to the SAD part of the study, we were able to analyze all MAD dose level cohorts in aggregate, based on comparable NEK7 degradation levels achieved across 5 to 200 mg. Through this analysis, we observed a 61% reduction in CRP in all subjects treated with MRT-8102, and greater reductions in subjects with elevated baseline median CRP levels, approaching nearly 80% in subjects with median baseline CRP of ≥1, ≥2, or ≥3 mg/L. Of note, individuals with CRP levels of 2 mg/L or higher are at greater risk of CV events; lowering CRP levels below this threshold is crucial for reducing CV morbidity and mortality.

Figure 42: Multiple Daily Doses of MRT-8102 Led to Significant and Sustained Reduction of Serum hsCRP

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Based on 7 days of treatment, 7 of 9 (78%) subjects with baseline CRP ≥ 2 mg/L achieved hsCRP suppression to 2 mg/L, indicative of the potential to lower CV risk, as shown in Figure 42. The frequency of subjects’ hsCRP value dropping to 2 mg/L was 67% and 78% depending on whether a baseline level of = 3 mg/L or = 2 mg/L was used as a cut off (Figure 43).

Figure 43: Multiple Daily Doses of MRT-8102 led to significant proportion of subjects achieved hsCRP reduction to 2 mg/L*

To gain a deeper, mechanistic understanding of MRT-8102’s impact on CRP, we monitored plasma levels of the pro-inflammatory cytokine IL-6, a well-characterized stimulator of CRP production and secretion from the liver, as detailed in Figure 44. Consistent with the previously noted reduction in CRP, MRT-8102 treatment significantly reduced IL-6 by 55% in the 14 MAD subjects with a median baseline CRP ≥ 1 mg/L. Importantly, the absolute levels of IL-6 were reduced below the threshold of 1.65 pg/mL defined by the previously mentioned CANTOS study, a level below which a significant decrease in the risk of CV events and mortality was reported.

Knowing that the NLRP3/IL-1b axis stimulates IL-6 production, we also investigated the impact of MRT-8102 on IL-1β production and secretion in ex vivo whole-blood stimulation experiments. Consistent with the strong reduction in CRP observed in subjects with elevated baseline CRP, and despite relatively modest induction levels under the assay conditions used, we observed a comparable, near 80% inhibition of IL-1β secretion in whole-blood ex vivo assays from these subjects following multiple administrations of MRT-8102. Importantly, we observed a correlation between NEK7 degradation and IL-1β levels throughout the dosing period, as shown here for a representative subject that displayed about 80% degradation and close to 90% inhibition of IL-1β (80.6% and 87%, respectively) at day 5 post dosing. In summary, MRT-8102, during the MAD portion of our Phase 1 study,

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effectively inhibited the entire NLRP3-IL-1β-IL-6-CRP axis, reducing critical biomarkers to levels associated with a significantly reduced risk of CV events and mortality.

Figures 44: Multiple Daily Doses of MRT-8102 Led to Reductions of IL-6 and IL-1β

We sought to characterize the impact of MRT-8102 on CSF inflammatory markers, including CRP and IL-6, following administration of MRT-8102 at a single dose level of 100mg (Figure 45). CSF levels of MRT-8102 were consistent with levels needed to be active against NEK7 (data not shown). Importantly, in two subjects with elevated IL-6 in cerebrospinal fluid at baseline, MRT-8102 administration resulted in reduced CSF IL-6 levels after 7 days of dosing. Plasma IL-6 levels at baseline in these two subjects were low, suggesting a centrally (CNS)-driven mechanism for the elevation as well as the suppression of CSF IL-6 levels.

Figure 45: MRT-8102 Treatment Reduced IL-6 Levels in CSF Consistent with CNS Penetration

Part 3 of the study (CRP PoC cohort) evaluated a cohort of subjects with elevated CVD risk. The study design, shown in Figure 46, included 36 subjects randomized 3:1 to MRT-8102 at a dose of 40mg once daily or placebo. Subjects were defined as having elevated CVD risk based on measures of obesity and elevated plasma CRP levels. The primary endpoints were safety and tolerability, with secondary endpoints including changes in CRP levels and pharmacokinetics. Endpoints for hsCRP included absolute reduction and frequency of reduction to 2 mg/L, a threshold that defines lower CVD risk, as discussed earlier. We also measured pharmacodynamic markers, including NEK7 degradation (see above), as well as levels of IL-6, IL-18, and fibrinogen in plasma.

Figure 46: CRP PoC (Part 3) Study of MRT-8102 in Subjects with Elevated CVD Risk

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Data analysis included data from 24 subjects (including both MRT-8102 and placebo) who had completed 4 weeks of dosing as of the data cutoff date. As shown in Figure 47, the interim data suggests that MRT-8102, dosed at 40 mg once daily, induced rapid and deep reductions of hsCRP and fibrinogen. The panel on the left shows that median CRP declined by 80% after one week, consistent with our observation from the MAD portion of the Phase 1 study, and by 85% after four weeks of dosing. Also, 94% of subjects reached hsCRP levels below 2 mg/L, meaning their hsCRP values returned to levels associated with lower CVD risk, as shown in the middle panel. Lastly, there was a 31% reduction in fibrinogen, an independent atherosclerotic risk factor, observed during the treatment period.

Figure 47: Analysis of CRP PoC Cohort Suggested MRT-8102 Induced Rapid Reductions of hsCRP and Fibrinogen

As of the data cut-off of December 23, 2025, 112 subjects had completed dosing across the SAD, MAD, and Part 3 portions of the study. Across this sample of patients, blinded review showed a favorable safety profile with no SAEs. Treatment-emergent AEs were mild to moderate. There was no evidence of increased infection risk or dose-dependent AEs. The evaluation and data collection are ongoing for Part 3 of the study. Of note, one participant in Part 3 was diagnosed with asymptomatic, acute infectious hepatitis A while on study. Because the data were blinded, it was not known whether the participant received MRT-8102 or placebo. The participant experienced a transient ALT elevation equivalent to a Gr 3 that improved while continuing on treatment for several days.

Review of unblinded data from 88 participants from the SAD/MAD cohorts confirmed that single and multiple doses of MRT-8102 were safe and well tolerated up to and including the highest dose level. No SAEs were noted,

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and no TEAEs were over grade 2. The treatment arm reported TEAEs in 29% of participants and the placebo arm reported TEAEs in 32% of participants. The most frequent TEAE was headache, which was reported in 9% of participants in both the placebo and treatment arms.

Based on these highly encouraging initial data, the MRT-8102 Phase 1 study, now named GFORCE-1, was expanded to include additional dose exploration of MRT-8102 in subjects with elevated CVD risk (Figure 48). We are enrolling subjects in 3-dose cohorts, randomized 3:1 to active drug vs. placebo, for a total of approximately 108 subjects. The ongoing cohort at 40 mg will be one of the 3 dose levels. Based on the interim clinical data suggesting that effects on CRP levels can be induced early and were sustained over the course of 4 weeks, we believe our 28-day study can provide valuable information on the dose levels necessary to achieve therapeutic benefit and guide our subsequent GFORCE-2 Phase 2 study in ASCVD, which we anticipate will initiate in 2026. Lastly, we believe our expanded GFORCE-1 study will also provide key insights for development of MRT-8102 and other potential NEK7 MGD product candidates in additional indications.

Figure 48: GFORCE-1 Study: Dose Exploration of MRT-8102 in Subjects with Elevated CVD Risk

We believe MRT-8102 has strong therapeutic potential in a broad range of inflammation-driven diseases and we are planning for broad development of our NEK7 MGDs, including MRT-8102 and potentially other NEK7 MGD product candidates, across this space. We plan to prioritize development of MRT-8102 in ASCVD and then to expand development of MRT-8102 or a next generation NEK7 MGD product candidate into other indications that meet our internal criteria, including unmet medical need as well as self-developability.

We are planning our next study of MRT-8102 in elevated CVD risk patients defined by Stage 3/4 chronic kidney disease and elevated CRP, as shown in Figure 48, and we have named this study GFORCE-2. This is a proposed trial design subject to review by FDA. GFORCE-2 is expected to initiate in H2 2026 and will evaluate the effect of MRT-8102 treatment for up to 12 weeks (followed by open label extension of 12 weeks) on CRP levels, as well as impact on liver fat, liver inflammation, and obesity, as illustrated in Figure 49. GFORCE-2 aims to generate additional safety data with longer dosing of MRT-8102, and to confirm the effects on CRP levels seen in data from GFORCE-1. Also, we believe the trial has the potential to generate data useful for understanding MRT-8102’s potential in other, related indications such as MASH and obesity.

Figure 49: GFORCE-2: Phase 2 Study in Elevated CVD Risk Patients Defined by Stage 3/4 Chronic Kidney Disease and Elevated CRP

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We are also planning to initiate a Phase 2 study of MRT-8102 in patients with acute gout flares, as shown in Figure 50. This is a proposed trial design subject to review by FDA. We anticipate this study to initiate in either Q4 2026 or Q1 2027. The study is expected to randomize approximately 40 patients with recurrent single joint gout flares to 12 weeks of treatment with one of two doses of MRT-8102. Outcome measures include reduction of pain Visual Analogue Scale (VAS) by 72 hours and frequency of new flares.

Figure 50: Phase 2 Study in Acute Gout Flares

We expect to initiate a Phase 2 study of MRT-8102 in patients with moderate to severe hidradenitis suppurativa in H1 2027. Outcome measures are expected to include HiSCR75 after 16 weeks of MRT-8102 treatment relative to placebo. This is a proposed trial design subject to review by FDA.

Our Precision Medicine Approach for Cancer

MRT-2359, a highly selective and orally bioavailable GSPT1-directed MGD in development for the treatment of AR and MYC-driven Prostate Cancer

Overview

GSPT1 (also known as eRF3a) is a translation termination factor that catalyzes protein synthesis termination, facilitating the release of mRNA and newly synthesized protein from the ribosomal machinery. We have identified GSPT1 as a potential therapeutic vulnerability in MYC-driven cancers with high protein translation activity, including androgen receptor (AR)-positive prostate cancer.

MRT-2359 is an orally bioavailable MGD that, through extensive in vitro and in vivo studies, we have shown to induce the degradation of GSPT1. MRT-2359 is designed to preferentially affect the growth and survival of MYC family transcription factor-driven cancer cells addicted to protein translation. In vivo, once-daily oral dosing of MRT-2359 led to potent antitumor activity in MYC-driven cell-line-derived and patient-derived xenograft models. MRT-2359 is currently in a Phase 1/2 clinical trial (ClinicalTrials.gov Identifier: NCT05546268). Based on our

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preclinical and clinical work to date, we are developing MRT-2359 in metastatic castration resistant prostate cancer (mCRPC).

Development of GSPT1-directed MGDs to Target Downstream Vulnerabilities of MYC Activation

It is well established that abnormal activation of MYC, for example through translocation or high expression, results in uncontrolled cell growth, associated with increased protein synthesis and a ramp-up of the protein translation machinery. MYC-driven tumors are therefore widely believed to be addicted to protein translation, which creates an inherent dependence on critical components of the translation machinery, such as GSPT1, as illustrated in Figure 51. As part of our research program, we identified GSPT1 as a potential novel vulnerability in MYC-driven cancers, demonstrating that degradation of GSPT1 leads to inhibition of the MYC pathway and downregulation of the expression of critical oncogenic signaling molecules and pathways, in particular in AR-positive prostate cancer cells.

Figure 51: Targeting MYC-driven Tumors and Their Addiction to Protein Translation Through GSPT1 Degradation

Targeting GSPT1 with MRT-2359 (preclinical data)

MRT-2359 is a potent and selective GSPT1-directed MGD discovered and rationally designed using our QuEENTM discovery engine. Key features and various pharmaceutical parameters of MRT-2359 are shown in Figure 52.

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Figure 52: MRT-2359 is a Selective and Orally Bioavailable GSPT1-directed MGD Rationally Designed Using our QuEENTM Discovery Engine

As shown in Figure 53, MRT-2359 displays preferential activity in MYC-high cancer cells by optimally reducing protein translation through degradation of GSPT1 by 60-70% (left panel, top right). In contrast, higher levels of GSPT1 degradation, as achieved with MRT-2136, lead to a more pan-toxic behavior with narrowed preferential activity in MYC high versus MYC low expressing cells (left panel, bottom right).

Figure 53: MRT-2359 has Optimized Depth of Degradation to Achieve Preferential Activity in MYC High Cancer Cells

Prostate Cancer as an Attractive Target Indication for MRT-2359

Prostate cancer is the second leading cause of cancer-related death among men. The androgen receptor (AR) signaling axis, widely recognized as an important driver of prostate cancer growth, has long been targeted through castration and other systemic therapies. Although androgen deprivation therapy (ADT) is initially effective, resistance almost invariably develops, leading to a more aggressive disease state known as castration-resistant

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prostate cancer (CRPC). A defining feature of metastatic CRPC (mCRPC) is the persistent activation of AR signaling through mechanisms such as AR gene amplification or overexpression, the emergence of constitutively active AR splice variants, and AR mutations. While second-generation AR-directed therapies, including enzalutamide, have improved overall survival and radiographic progression-free survival in mCRPC in both pre- and post-chemotherapy settings, responses remain limited in patients harboring AR alterations, underscoring the need for novel therapeutic strategies for this patient population.

Beyond AR signaling, multiple oncogenic pathways are known to contribute to prostate cancer progression and survival. Notably, MYC plays a central role in several aspects of prostate cancer biology (Figure 54), including activation of E2F and AR transcriptional programs, and has been implicated in resistance to multiple therapeutic modalities, including AR inhibitors and radioligand therapies. Given the complex and redundant oncogenic landscape of prostate tumors, therapeutic approaches capable of simultaneously targeting multiple oncogenic nodes may enhance treatment responses and help overcome mechanisms of therapy resistance.

Early in our discovery and preclinical development efforts, we identified mCRPC as a promising indication for MRT-2359. MRT-2359 demonstrated robust inhibition of tumor cell growth and viability in prostate cancer cell lines, including both those sensitive and resistant to anti-androgen therapies. Mechanistically, MRT-2359 reduced the expression of MYC and other key oncogenic proteins through GSPT1 degradation and inhibition of translation. We therefore hypothesized that rational combination strategies incorporating MRT-2359 with second-generation AR inhibitors or other approved agents, such as radioligand therapies, may enhance therapeutic efficacy and maintain activity against CRPC tumors, including those harboring AR mutations or other alterations.

Figure 54: MRT-2359 Exploits Key Therapeutic Vulnerabilities in Therapy-Resistant CRPC

Supporting our mechanistic hypothesis is data evaluating hundreds of cancer cell lines spanning multiple tumor lineages, demonstrating that prostate cancer lines co-expressing high levels of MYC and AR present much greater sensitivity to MRT-2359 than prostate cancer cells that are low or negative for MYC or AR, or neuroendocrine prostate cancer cell lines (Figure 55). Furthermore, in addition to baseline expression of the above mentioned oncoproteins, MRT-2359 treatment also led to significant down-modulation of MYC, AR and E2F signaling selectively in AR and MYC high expressing cell lines but not in PC3 cells (AR negative and MYC low), as assessed by RNAseq.

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Figure 55: Pharmacogenomic Profiling Identified AR/MYC-positive Prostate Cancer Cell Lines as Exquisitely Sensitive to MRT-2359

In support of the above-mentioned transcriptomic analysis that showed significant down-modulation of multiple oncogenic pathways selectively in MRT-2359 responsive cell lines, an unbiased global proteomics analysis across the responsive lines revealed significantly reduced cellular abundance of AR (wild type [WT] and the genetic variant AR-V7), MYC and Cyclin D1 proteins, potentially shedding light on the biological mechanism through which MRT-2359 treatment reduces signaling output through these oncoproteins and their downstream pathways (Figure 56). Notably, MRT-2359, as a single agent, demonstrated deeper reductions in AR activity than the AR antagonist enzalutamide in the cell lines tested in vitro within the 24 hour timeframe of the experiment, suggesting MRT-2359 activity toward this critical lineage-defining pathway may be achieved more rapidly than with the currently approved AR-directed therapeutic.

Figure 56: Proteomics Analysis Revealed Modulation of AR and MYC/E2F Pathway by MRT-2359

Consistent with pharmacogenomic screening and in vitro validation studies, MRT-2359 demonstrated encouraging single-agent as well as combination activity with enzalutamide across a number of prostate cancer cell line-derived xenograft (CDX) models, as shown in Figure 57. These models include LNCaP, a cell line characterized by high-level expression of the homozygous T878A mutation in AR, and VCaP, a cell line with amplification of AR WT and low-level expression of the constitutively active V7 isoform. In both models, suboptimal dosing of MRT-2359, when combined with enzalutamide, drove significant tumor regressions and substantially outperformed enzalutamide single agent treatment. Since MYC can promote expression of DNA repair genes, potentially blunting response to radioligand therapy, we also tested the potential for MRT-2359 to improve activity of a PSMA-based radioligand therapy, as shown in the right graph. Whereas single-agent

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treatments achieved stasis at best, combination treatment led to significant regressions, suggesting strong synergy between MRT-2359 and the PSMA-based radioligand.

Figure 57: MRT-2359 in Combination with Enzalutamide or Pluvicto Demonstrated Increased Activity Over Monotherapies in Xenograft Models

MRT-2359 Phase 1/2 Clinical Study Design and Preliminary Results

Based on our encouraging preclinical data demonstrating that MRT-2359 combined well with both AR inhibitors and radioligand therapy to improve preclinical activity across CDX models spanning multiple AR alterations, we assessed the potential of MRT-2359 to benefit patients with metastatic CRPC post multiple lines of prior treatment.

Figure 58 outlines the design of our Phase 1/2 clinical study. We conducted robust dose exploration in the monotherapy arms to confirm multiple safe dose levels and to determine our initial recommended Phase 2 starting dose of 0.5 mg daily on a 21-day on-drug, 7-day off-drug schedule.

Figure 58: MRT-2359 Phase 1/2 Clinical Study Design

We initiated the Phase 2 expansion cohort in heavily pretreated, metastatic CRPC patients and reported results for 23 patients that had been enrolled as of the January 30 2026 data cut-off. Notably, we required RECIST measurable disease for all patients entering the trial, a more stringent requirement than is typical for prostate cancer studies, which results in enrollment of a more severe, and often more heavily pretreated patient population with extensive metastatic disease.

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For our metastatic CRPC expansion cohort, we applied a multipronged approach to characterize tumors at the molecular level, including the identification of key AR alterations in all enrolled patients. To do so, we employed RNA and DNA sequencing of tumor biopsies, and molecular testing of circulating tumor DNA and circulating tumor cells to detect AR alterations such as AR mutations and/or splice variants (Figure 59). We also verified adenocarcinoma biology through RNA sequencing, which allowed us to exclude from the efficacy analysis tumors that had transformed to primarily neuroendocrine status.

Figure 59: Biomarker Profiling of Tumor and Liquid Biopsies

Figure 60 details the patient demographics, clinical characteristics and prior therapies of patients in the study. Patients in this study were more heavily pretreated than in comparable studies in mCRPC patients. In our study, 78% of patients had been previously treated with second generation androgen receptor inhibitors, 83% with chemotherapy, and 57% with Pluvicto. Of the 23 patients enrolled as of the data cutoff, 15 were evaluable for efficacy. 1 patient had not yet received an on-treatment scan prior to the data cutoff date, 2 patients were non-evaluable due to early consent withdrawal, 1 patient was not evaluable due to investigator decision, 1 patient was non-evaluable due to early clinical progression, and 3 patients were excluded from data analysis based on molecular profiling of their baseline biopsies showing transformation to neuroendocrine differentiation.

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Figure 60: Patient Demographics, Clinical Characteristics, and Prior Therapies

Figure 61 highlights the safety and tolerability profile of MRT-2359 in combination with enzalutamide, as of the data cut-off date. The combination was generally well tolerated, and the safety profile observed was favorable when our data was compared with third-party data on other drugs emerging as combination agents for metastatic CRPC, including EZH2 inhibitors. One patient had a dose-limiting toxicity (DLT) (grade 3 stomatitis associated with pain). The most common treatment-related AEs for MRT-2359 plus enzalutamide were fatigue (N=12, 52%), diarrhea (N=11, 48%), and nausea (N=8, 35%) which were classified as mild or moderate and were manageable and not therapy limiting. No dose discontinuations were observed due to AEs.

Figure 61: Treatment-related Adverse Events Occurring in 20% of Patients

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Figure 62 shows the waterfall plot for PSA responses, a frequently used marker of therapeutic benefit in prostate cancer, as of the data cut-off date. Patients were categorized by their AR status (WT, gray; V7, blue; mutant, purple). Of note, among the 15 evaluable patients, 5 had AR mutations, and all 5 achieved a PSA response. This includes 2 PSA90 responses and 3 PSA50 responses.

Figure 62: Best Change in PSA in AR-wild type, AR-V7 and AR-mutant Patients

Figure 63 shows the RECIST waterfall plot for the 15 evaluable patients as of the data cut-off date. Two of the 5 AR mutant patients achieved a RECIST partial response (PR), one confirmed and one unconfirmed, and the other 3 presented stable disease (SD), resulting in a disease control rate (DCR) of 100% in this patient subset. Of all 15 evaluable patients, the overall RECIST DCR was 67% (10 of 15), with 10 of 15 patients presenting tumor size reductions of target lesions versus baseline scans, including all 5 patients whose tumors were harboring AR mutations (including the 2 patients with a RECIST PR).

Figure 63: Best Change in RECIST in AR-wild type, AR-V7 and AR-mutant Patients

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As shown in the swimmer plot in Figure 64 displaying months on treatment as of the data cut-off date, treatment effects in these heavily pretreated patients were durable in several patients. In the AR mutant subset, 2 patients remained on therapy for 10 cycles or longer and 2 of 5 patients remained on drug as of the data cutoff on January 30, 2026.

Figure 64: Swimmer Plot of All Evaluable Patients

Figure 65 provides additional data on the 5 patients with AR mutations, as off the data cutoff date, where the MRT-2359/enzalutamide combination led to robust and durable PSA and RECIST responses. Looking at these patients in isolation, all patients previously received abiraterone, 3 of 5 previously received a second-generation AR inhibitor, 4 of 5 received the PSMA-targeting radioligand therapy Pluvicto, and 5 of 5 were previously treated with chemotherapy. Consistent with the 100% PSA response rate and 100% disease control rate in this subset of patients, mutant allele frequency in ctDNA and total circulating tumor cell counts were also significantly decreased in 4 of 5 patients, with data unattainable for the fifth patient due to poor sample quality.

Figure 65: Best % Change in PSA, Sum of Diameters of Target Lesions, Variant Allele Frequency and CTC Counts in AR-mutant Patients

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To identify signaling pathways associated with tumor size reductions and RECIST responses, we performed an unbiased analysis of pre-treatment biopsies (Figure 66, left panel). Consistent with our therapeutic hypothesis, we found that MYC, E2F, and AR signaling were among the top upregulated pathways associated with the magnitude of tumor size reductions, results that align clinically with what we had seen in preclinical experiments and further support the proposed therapeutic mechanism.

We also assessed whether combination treatment could suppress signaling through these pathways. Consistent with preclinical observations, we observed a significant decrease in output through these oncoproteins and pathways, as shown in Figure 66 (right panel), with, for example, reduced E2F signaling in 5 of 6 on-treatment biopsies.

Figure 66: Analysis of Tumor Biopsies Provides Proof-of-Modulation of Target Oncogenic Pathways

Figure 67 provides a case study of a patient with an AR H875Y mutation, including data as of the data cut-off. This patient had previously been treated with several therapeutics with multiple mechanisms of action, including chemotherapy, radioligand therapy, and an investigational bispecific antibody. Despite the number of prior treatments, MRT-2359, when combined with enzalutamide, led to a RECIST response that correlated with rapid and sustained decreases in blood PSA and in the AR H875Y allele frequency in ctDNA. While PSA values began to rebound at ~cycle 8 of treatment, tumor target lesion size continued to decrease, consistent with the mechanism of action of MRT-2359 described above, which extends to modulation of non-AR pathways such as the MYC and E2F pathways.

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Figure 67: Confirmed RECIST PR and PSA90 Response in mCRPC Patient with Activating AR Mutation

In Figure 68, we highlight the treatment journey of a second patient with an AR mutation, including data as of the data cut-off. At baseline, this patient harbored the AR L702H mutation. This patient was also heavily pretreated, having received chemotherapy, enzalutamide, Provenge and several other therapies. Despite these treatments and the advanced stage of disease, the patient responded favorably to the MRT-2359/enzalutamide combination. Blood PSA and mutant allele frequency in ctDNA were significantly decreased after 3 months of treatment, correlating with a decrease in the sum of target lesions. Interestingly, as with the prior patient case study, although PSA began to rebound at cycle 6, tumor regression, as assessed by RECIST, was maintained until cycle 10 of treatment. We believe this supports the conclusion that MRT-2359, at least in part, exerts its activity through an AR-pathway-independent mechanism.

Figure 68: Confirmed RECIST SD and PSA50 Response in mCRPC Patient with Activating AR Mutation

Based on the data we have obtained to date, we plan to conduct a signal-confirming Phase 2 study of MRT-2359 in combination with a second-generation AR inhibitor in patients with AR-mutant tumors. The study, planned to

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begin in 2026, will enable further efficient evaluation of MRT-2359 in metastatic CRPC using a Simon two-stage design. Based on the favorable AE profile and clinical activity observed to date in the Phase 2 arm of our Phase 1/2 study, we intend to evaluate a 0.5mg dose of MRT-2359 administered on a 21-day-on, 7-day-off schedule. The study is expected to enroll up to 25 patients with metastatic CRPC harboring AR mutations in their tumors, and there is potential to evaluate additional patient subsets, including patients naïve to 2nd-generation AR inhibitors, if activity in the AR-mutant patient population is confirmed. The primary Phase 2 study endpoints will be PSA response, RECIST response, duration of response, radiographic progression-free survival, and safety. Data from this study could confirm MRT-2359’s clinical activity in relevant patient groups, further clarify its role in the metastatic CRPC treatment landscape, and position the program for advancement into registrational studies.

Cyclin E1-directed MGD molecules for the treatment of cancer

Cyclin-dependent kinase protein complexes (cyclin-CDK) regulate progression through the cell cycle, whereby different combinations of the two subunits control different stages of the cell cycle. They are formed by an association of a regulatory subunit, a cyclin, with an inactive catalytic (kinase) subunit, a cyclin-dependent kinase (CDK). Once the complex is formed, it transitions into an active state, whereby the catalytic or CDK subunits become productive and can phosphorylate downstream effector substrates.

Cyclin E proteins, encoded by the CCNE1 and CCNE2 genes, complex with CDK2 to form an active cyclin E-CDK2 complex, regulating G1-to-S transition of the cell cycle and initiation of DNA replication, as shown in Figure 69. Under normal conditions, cyclin E expression is tightly regulated and restricted to the G1-S phase of the cell cycle. However, many cancer types, including ovarian, endometrial, gastric, and breast cancers, bear frequent amplification or overexpression of the CCNE1 gene, resulting in increased cyclin E1 protein expression and aberrant regulation of cell growth. As such, cyclin E1 represents a genuine oncogenic driver and cyclin E1 amplified cancers are greatly dependent on sustained high levels of cyclin E1 for their continued growth and survival. Hence, pharmacologic suppression of high cyclin E1 protein levels, for example through MGD induced degradation is expected to inhibit tumor growth, in line with the classical “oncogene addiction” paradigm.

Figure 69: CCNE1 (Cyclin E1) Drives Multiple Hallmark Cancer Mechanisms and is a Target for Solid Tumors with Deregulated Cyclin E1

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As a regulatory subunit with no catalytic activity, cyclin E1 has been considered “undruggable” to date. We have identified multiple MGD molecules that selectively promote the association of cyclin E1 and cereblon in vitro, while sparing the cyclin E2 paralog. These compounds have shown the ability to robustly and selectively induce cyclin E1 degradation in multiple cancer cell lines in vitro and in disease relevant models in vivo. In addition, they suppress cancer cell line proliferation preferentially when CCNE1 is amplified and/or overexpressed, suggesting robust biomarker-driven activity.

In vitro data

As shown in Figure 70, the cyclin E1-directed MGD MRT-55811 selectively degraded cyclin E1, led to downstream pathway suppression, and induced robust G1/S cell cycle arrest.

Figure 70: MRT-55811 is highly selective and showed biological activity in CCNE1-amplified cell lines

As shown in Figure 71, in addition to concentration-dependent cyclin E1 degradation, MRT-55811 treatment also led to parallel reduction of both phosphorylated and unphosphorylated forms of CDK2, as well as the downstream RB phosphorylation. Mass spectrometry assessment of ubiquitinated peptides following MRT-55811 treatment revealed that both cyclin E1 and the associated CDK2 protein were ubiquitinated, suggesting co-degradation of both components of the cyclin E1-CDK2 holoenzyme.

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Figure 71: MRT-55811 Induced CCNE1-CDK2 Holoenzyme Degradation in CCNE1 Amplified Cell Lines

MRT-55811 showed superior differential suppression of tumor growth in CCNE1 dependent cell lines compared to clinical development-stage CDK2 inhibitors and S-phase protein kinase inhibitors (WEE1 inhibitor azernosertib and PKMYT1 inhibitor lunresertib),or clinical stage CDK4/6 inhibitors, as shown in Figure 72. Unlike MRT-55811, several tested clinical stage CDK2, WEE1, or PKMYT1 inhibitors did not fully recapitulate genetic dependency, potentially indicating off-target activity.

Figure 72: MRT-55811 Exhibits Superior Selectivity for Cancers with High CCNE1

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In vivo data

When dosed orally as a single agent in preclinical cell line-derived xenograft models of CCNE1-amplified ovarian cancer, gastric cancer, and breast cancer, the cyclin E1-directed MGD MRT-55811 induced robust tumor growth suppression and regression in all three models, as shown in Figure 73.

Figure 73: MRT-55811 Treatment Resulted in Tumor Regression in CCNE1 Amplified Models

We expect to submit an IND application in 2026 for a cyclin E1-directed MGD.

CDK2-directed MGD molecules for the treatment of cancer

Cyclin dependent kinases, or CDKs, are a family of closely related kinases that regulate progression through the cell cycle. CDK activity is modulated by specific cyclins. For example, cyclin E1 binding activates CDK2, as shown in Figure 74. Importantly, increased activity and reliance on CDK2 due to cyclin E1 overexpression is thought to be one of the key mechanisms of resistance occurring in ER+ breast cancer patients when treated with CDK4/6 inhibitors such as ribociclib. Therefore, we believe that selective elimination of CDK2 using CDK2-directed MGDs may provide benefit to these patients. Previously reported small molecule inhibitors and PROTACs of CDK2 have been limited in their selectivity due to the high degree of similarity among the active sites of kinases, in particular within the CDK family itself. We have identified multiple MGD molecules that selectively promote the association of CDK2 and cereblon in vitro, while avoiding other CDKs. Through ongoing lead optimization chemistry, the most advanced compounds are orally bioavailable and can robustly and selectively induce CDK2 protein degradation in multiple cancer cell lines in vitro and in disease relevant models in vivo, leading to strong tumor growth inhibition.

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Figure 74: CDK2 is One of the Key Regulators of the Cell Cycle

Lead optimization towards orally bioavailable CDK2-directed MGDs

Our CDK2-directed MGDs form a strong ternary complex with CDK2 and cereblon through a newly characterized non-canonical degron which was unveiled through application of our QuEENTM discovery engine technologies. The unique character of the CDK2 degron interaction with cereblon, and the optimized features of our MGDs provide a high degree of selectivity over closely related proteins such as CDK1, CDK4, and CDK9. Our MGDs are designed to be orally bioavailable with favorable in vitro ADMET properties and preclinical safety profiles.

In vitro data

Our lead CDK2-directed MGD MRT-51443 has shown the ability to selectively degrade CDK2 and reduce E2F pathway proteins in vitro, with no significant effect on other CDKs or other kinases, as shown in Figure 75. Our data also support that our CDK2 MGD MRT-51443 can block DNA replication during S phase in CDK2 dependent cells and inhibits cellular proliferation in a concentration-dependent manner.

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Figure 75: CDK2-directed MGD MRT-51443 is Selective and Showed Biological Activity in a CDK2 Dependent Cell Line

MRT-51443 displayed superior selectivity compared to clinical CDK2 inhibitors, as shown in Figure 76. Clinical-stage CDK2 inhibitors show off-target activity in biochemical kinome profiling. CDK2 inhibitors, but not a CDK2 MGD, display CDK2-independent activity, as demonstrated by their suppression of cell proliferation in the absence of their primary target, CDK2.

Figure 76: CDK2-directed MGD Displayed Superior Selectivity Compared to CDK2 Inhibitors

Increased activity and reliance on CDK2 due to cyclin E1 overexpression is thought to be one of the key mechanisms of resistance occurring in ER+ breast cancer patients when treated with CDK4/6 inhibitors such as ribociclib. As shown in figure 77, the combination of MRT-51443 and ribociclib delayed resistance onset in in-vitro long term culture assays using a ER+ breast cancer cell line, suggesting that addition of a CDK2 MGD to standard of care therapy might have the potential to delay the occurrence of relapses in patients.

Figure 77: CDK2 MGD/Ribociclib Combination Delayed Resistance Onset

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In vivo data

As shown in Figure 78, when dosed orally in preclinical models of ER-positive/HER2-negative breast cancer, MRT-51443 drove deep tumor regression in a triple combination with a CDK4/6 inhibitor (ribociclib) and endocrine therapy (fulvestrant) and substantially reduced tumor burden versus ribociclib + fulvestrant combination therapy alone.

Figure 78: CDK2 MGD Demonstrated Activity in Combination with CDK4/6 Inhibitor and Fulvestrant in ER+ Breast Cancer Model

Other programs

We are specifically focused on developing product candidates for target proteins that have been deemed undruggable or inadequately drugged. Our QuEENTM discovery engine was purpose-built to support the discovery

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and development of drugs that degrade a wide landscape of therapeutically relevant proteins by (i) systematically identifying therapeutically relevant target proteins that may be amenable to molecular glue-based degradation; and (ii) rationally designing MGD molecules that can be optimized towards high potency and selectivity, with properties that we believe to be favorable, so to become MGD product candidates. Our pipeline includes programs in I&I indications as well as in oncology. We also have early-stage efforts in areas including cardiovascular, metabolic and genetic diseases.

We believe that the strengths of MGDs align very well with requirements for I&I drugs, as shown in Figure 79. Namely, we have shown that MGDs can achieve deep degradation of target proteins in immune and blood cells as cereblon is expressed highly in those cells and in immune relevant sites and organs; the catalytic mechanism of action of MGDs drives a sustained pharmacodynamic effect, potentially allowing for dose regimens that are convenient for patients; the exquisite selectivity of MGDs enables a high therapeutic index; and MGDs have the potential to deplete both membrane receptors and intracellular signaling nodes critical for immune cell regulation.

Figure 79: MGD Strengths Align with I&I Requirements

We are advancing novel discovery programs for I&I targets that we believe have the potential to be highly differentiated, by designing oral MGD product candidates that are degrading undruggable targets in critical I&I

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pathways. These may include programs to degrade multiple undisclosed targets in Th1, Th2, and Th17-driven autoimmune conditions, as illustrated in Figure 80.

Figure 80: Degrading Undruggable Targets in Critical I&I Disease Pathways

Our services, collaboration and licenses agreements

Roche agreement

On October 16, 2023, Monte Rosa AG entered into a Collaboration and License Agreement with Roche Basel and Roche US, and together with Roche Basel, Roche, or the “Roche Agreement”. Pursuant to the Roche Agreement, the parties will seek to identify and MGDs against cancer or neurological disease targets using our proprietary drug discovery platform for an initial set of targets in oncology and neuroscience selected by Roche, with each target being subject for a limited time to certain substitution rights owned by Roche. We will lead preclinical discovery and research activities until a defined point. Upon such point, Roche gains the right to exclusively pursue further preclinical and clinical development activities.

Under the Roche Agreement, Roche will have a worldwide, exclusive license under patents and know-how controlled by us to develop and commercialize products directed to applicable targets. The research collaboration activities governed by the Roche Agreement will be overseen by a joint research committee.

Unless earlier terminated, the Roche Agreement will remain in effect for each product licensed under the Roche Agreement until expiration of the royalty term for the applicable product. The parties have included customary termination provisions in the agreement, allowing termination of the Roche Agreement in its entirety, on a country-by-country or a target-by-target basis.

Under the terms of the agreement, we received an upfront payment of $50 million, and are eligible to receive future preclinical, clinical, commercial and sales milestone payments that could exceed $2 billion, including up to $172 million for achieving preclinical milestones. We are also eligible to receive tiered royalties ranging from high-single-digit percent to low-teens percent on any products that are commercialized by Roche as a result of the collaboration.

To date through December 31, 2025, the Company has received $9.0 million and recorded a $7.0 million receivable related to Roche's decision to pay preclinical milestones. The Company has also received $3.0 million related to Roche's decision to exercise its option rights to replace certain targets for research and development services. The related payments are initially classified as deferred revenue in the accompanying consolidated balance sheet and recognized in revenue as the related research and development services are performed.

2024 Novartis agreement

On October 25, 2024, Monte Rosa AG and Novartis entered into a global exclusive development and commercialization license agreement, or the Novartis Agreement. Pursuant to the Novartis Agreement, we granted to Novartis an exclusive, royalty-bearing, sublicensable and transferable license to develop, manufacture,

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and commercialize VAV1 MGDs, including MRT-6160. We were responsible for completing the Phase 1 clinical studies and Novartis is responsible for all subsequent development and commercial activities starting at Phase 2. Development and commercial activities governed by the Novartis Agreement will be overseen by a Development Committee and a Commercialization Committee.

Pursuant to the Novartis Agreement, in December 2024, we received from Novartis a non-refundable upfront payment of $150 million, and we are eligible to receive from Novartis (1) up to $2.1 billion in development, regulatory, and sales milestones, beginning upon initiation of Phase 2 studies including (a) potential development and regulatory milestone payments, exceeding $1.5 billion if multiple indications achieve regulatory approval in multiple territories, (b) potential sales milestone payments in connection with sales outside of the United States, and (2) tiered royalties on sales outside of the United States. Novartis will be responsible for costs associated with Phase 2 clinical studies. We and Novartis also agreed to a net profit and loss sharing arrangement, pursuant to which we will co-fund any global clinical development from Phase 3 onwards and will share 30% of any profits and losses associated with the manufacturing and commercialization of the licensed products in the United States. We have defined opportunities to opt out of the net profit and loss sharing arrangement, in such case, sales in the United States would be entitled to the potential sales milestone payments and tiered royalties on sales available outside of the United States. Any costs for any co-funded development and commercialization activities are subject to budgets reviewed by the Development Committee and Commercialization Committee, respectively. The Novartis Agreement includes customary termination provisions, including Novartis’ ability to terminate the Novartis Agreement in its entirety.

2025 Novartis License Agreement

In September 2025, Monte Rosa AG entered into a collaboration, option, and license agreement with Novartis, or the 2025 Novartis Agreement. Pursuant to the 2025 Novartis Agreement, we granted to Novartis an exclusive, royalty-bearing, sublicensable and transferable license to degraders for one I&I program, or the First Licensed Program, and the exclusive option to obtain exclusive, royalty-bearing, sublicensable and transferable licenses with respect to two programs from our growing preclinical immunology portfolio, or the Options, and the programs, or the Optioned I&I Programs. Such Options are individually exercisable at Novartis’ discretion until a program meets criteria for investigational new drug application-filing-readiness. On a program-by-program basis, if Novartis does not exercise an Option, all rights with respect to such program are retained by us; if Novartis does exercise its Option, such program becomes a Licensed Program, or together, with the First Licensed Program, the Licensed Programs. Under the 2025 Novartis Agreement, we will apply its proprietary AI/ML-enabled QuEEN™ product engine for the discovery and development of degraders for the First Licensed Program and the Optioned I&I Programs. The Licensed Programs will be further developed and commercialized by Novartis, unless otherwise agreed to by the parties in accordance with the 2025 Novartis Agreement. Research activities for the Licensed Programs governed by the Agreement will be overseen by a Joint Research Committee.

Under the agreement, the Company received a $120.0 million non-refundable upfront payment from Novartis. The Company is entitled to receive further payments from Novartis to maintain the Options totaling up to $60.0 million, and is also eligible to receive from Novartis (1) preclinical milestone payments relating to the First Licensed Program and option exercise payments related to the Options of up to $180.0 million, (2) up to $5.4 billion in clinical development, regulatory, and sales milestones relating to the First Licensed Program and the two Optioned I&I Programs, beginning upon initiation of Phase 1 studies, including (a) potential development and regulatory milestone payments up to $2.2 billion if regulatory approval is achieved for multiple indications in multiple territories and (b) potential sales milestone payments up to $3.2 billion, allocated across licensed products, and (3) tiered royalties on global net sales in the high-single to low double-digit range for the First Licensed Program and in the low double-digit range for the two Optioned I&I Programs. We will be responsible for costs related to research activities, while Novartis will be responsible for costs related to development and commercialization activities.

Competition

The biotechnology industry is extremely competitive in the race to develop new products and the industry is characterized by a high level of innovation and strong emphasis on proprietary products and intellectual property rights. While we believe we have significant competitive advantages due to our management team’s years of expertise in protein degradation, molecular glues and clinical and preclinical development of precision medicines in general, coupled with our unique scientific expertise and our growing portfolio of intellectual property rights, we currently face and will continue to face competition for our development programs from other companies that develop heterobifunctional degraders, similar MGDs or have protein degradation development platforms and their own associated intellectual property. Our competition will also include companies focused on existing and novel

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therapeutic modalities such as small molecule inhibitors antibodies and gene therapies. The competition is likely to come from multiple sources, including large and specialty pharmaceutical companies, biotechnology companies and academic institutions that are in the business of research, development, manufacturing and commercialization. Moreover, the existence of large numbers of patents and frequent allegations of patent infringement is typical in our industry.

The main competitors in our efforts to develop targeted protein degraders or MGD therapeutics for patients include, but are not limited to, C4 Therapeutics, Inc., Nurix Therapeutics, Inc., Kymera Therapeutics, Inc., Bristol-Myers Squibb, and Novartis, all of whom have reported having TPD or MGD product candidates in preclinical or clinical development. Several other large pharmaceutical companies have disclosed investments in the TPD field. In addition to competition we face in developing TPD or MGD therapeutics, we will also face competition in the indications we expect to pursue with our GSPT1, NEK7, and CCNE1/CDK2 programs, including, but not limited to, programs from AstraZeneca, Roche, Novo Nordisk, Novartis, Ventyx Biosciences, BioAge Labs, NodThera, Pfizer, Merck, BeOne Medicines, and Incyte Corporation.

In addition to the competitors we face in developing small molecule-based protein degraders, we will also face competition in the indications we expect to pursue with our MGD programs. Many of these indications already have approved standards of care which may include existing therapeutic modalities. In order to compete effectively with these existing therapies, we will need to demonstrate that our MGDs perform favorably when compared to existing therapeutics.

Manufacturing

We do not own or operate manufacturing facilities for the production of our product candidates and we currently have no plans to build our own clinical or commercial scale manufacturing capabilities. We currently contract with third-party contract manufacturing organizations, or CMOs, for the manufacture of our product candidates and we intend to continue to do so in the future. We rely on and expect to continue to engage with third-party manufacturers for the production of both drug substance and finished drug product. We currently obtain our supplies from these manufacturers on a purchase order basis and do not have long-term supply arrangements in place. Should any of these manufacturers become unavailable to us or their services to us become delayed for any reason, we believe that there are a number of potential replacements, although we may incur some delay in identifying and qualifying such replacements.

Intellectual property

We are an innovation-driven company and we seek to aggressively protect the innovations, intellectual property, and proprietary technology that we generate that we consider important to our business, including the pursuit of patent applications that cover our product candidates and methods of using the same, innovations around our industry leading QuEENTM discovery engine and our proprietary library of MGDs, as well as any other relevant innovations, inventions, and improvements that are considered commercially relevant to the development of our business and to maintain our perceived competitive advantages. We also rely on trade secrets, know-how and continuing technological innovation to develop and maintain our proprietary and intellectual property position. For our product candidates, we generally pursue patent protection covering compositions of matter, pharmaceutical compositions, methods of use, including combination therapies, methods of administration including dosing methods, methods for monitoring potential clinical events, compositions and methods for personalizing, monitoring, and potentially refining clinical use, including biomarkers, processes of manufacture and process intermediates, where relevant. For our QuEENTM discovery engine, we pursue patent protection covering our approaches, methods, and research and development tools. We continually assess and iteratively refine our intellectual property strategies as we develop new innovations and product candidates. We continue to invest in filing additional patent applications based on our intellectual property strategies to build value in our business and/or to improve our business and partnering opportunities, where appropriate.

Our commercial success depends, in part, on our ability to obtain, maintain, enforce and protect our intellectual property and other proprietary rights for the technology, inventions and improvements we consider important to our business, and to defend any patents we may own or in-license in the future, prevent others from infringing any patents we may own or in-license in the future, preserve the confidentiality of our trade secrets, and operate without infringing, misappropriating or otherwise violating the valid and enforceable patents and proprietary rights of third parties.

As with other biotechnology and pharmaceutical companies, our ability to maintain and solidify our proprietary and intellectual property position for our product candidates and technologies will depend on our success in obtaining

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effective patent claims and enforcing those claims if granted. However, our pending provisional and Patent Cooperation Treaty, or PCT, patent applications, and any patent applications that we may in the future file or license from third parties, may not result in the issuance of patents and the validity and/or enforceability of any of our issued patents may be challenged by third parties. Further, as with other companies, the patents we may obtain do not guarantee us the right to practice our technology in relation to the commercialization of our products. With respect to obtaining issued patents, here in the United States as well as in other jurisdictions of interest to our business, the patent positions for biopharmaceutical companies like us are generally uncertain and can involve complex legal, scientific, and factual issues. Further, the laws governing the protection of intellectual property may change over time due to the issuance of new judicial decisions or the passage of new laws, rules or regulations. In addition, the coverage claimed in a patent application can be significantly reduced before a patent is issued and its scope can be reinterpreted and challenged even after issuance. As a result, we cannot guarantee that any of our product candidates will be protected or remain protected by valid, enforceable patents. We also cannot predict whether the patent applications we currently pursue will issue as patents in any particular jurisdiction or whether the claims of any issued patents will provide sufficient proprietary protection from competitors. Any patents that we hold may be challenged, circumvented, or invalidated by third parties.

The exclusivity terms of our patents depend upon the laws of the countries in which they are obtained. In the countries in which we file, the patent term is 20 years from the earliest date of filing of a non-provisional patent application. The term of a U.S. patent may be extended to compensate for the time required to obtain regulatory approval to sell a drug (referred to as a patent term extension) or by delays encountered during patent prosecution that are caused by the United States Patent and Trademark Office (referred to as patent term adjustment). For example, the Hatch-Waxman Act permits a patent term extension for FDA-approved new chemical entity drugs of up to five years beyond the ordinary expiration date of one patent that covers the approved drug or its use. The length of the patent term extension is related to the length of time the drug is under regulatory review and diligence during the review process. Patent term extensions in the United States cannot extend the term of a patent beyond a total of 14 years from the date of product approval and only one patent covering an approved drug or its method of use may be extended. A similar kind of patent extension, referred to as a Supplementary Protection Certificate, is available in Europe. Legal frameworks may also be available in certain other jurisdictions to extend the term of a patent. We currently intend to seek patent term extensions for our products on any of our issued patents in any jurisdiction where we have a qualifying patent and the extension is available; however, there is no guarantee that the applicable regulatory authorities, including the FDA in the United States, will agree with our assessment of whether extensions of this nature should be granted and, even if granted, the length of these extensions. Further, even if any of our patents are extended or adjusted, those patents, including the extended or adjusted portion of those patents, may be held invalid or unenforceable by a court of final jurisdiction in the United States or a foreign country.

Patents and Patent Applications

As of December 31, 2025, we solely owned a patent portfolio that included fifty-three (53) pending patent families, including pending patent applications filed under the PCT, national and regional phase patent applications, and multiple pending United States provisional patent applications. Our portfolio is built to cover our MGDs product candidates and various uses thereof, and our industry-leading QuEENTM discovery engine, as further described below. Patent prosecution related to our portfolio is currently in the early stages and, as such, only four patent applications have proceeded to grant in the United States.

Wholly Owned Product Candidates

With respect to our GSPT1 program, as of December 31, 2025, our portfolio included two granted US patents, two pending PCT patent applications, ten pending non-provisional patent applications in the United States, and pending patent applications in Australia, Canada, Chile, China, Europe, Israel, India, Japan, Mexico, Nigeria, New Zealand, Singapore and South Africa, and two U.S. provisional patent applications. These patents and patent applications cover various GSPT1-directed MGDs and uses thereof, including methods of treatment, pharmaceutical formulations of a GSPT1-directed MGD, processes for making GSPT1-directed MGDs, combinations comprising various GSPT1-directed MGDs, and biomarkers related to use of our GSPT1-directed MGDs. The earliest scheduled expiration of any U.S. or foreign patent covering our GSPT1-directed MGDs, if such patent is issued, would be 2040, excluding any additional term available for patent term adjustment or patent term extension, and assuming timely payment of all applicable maintenance or annuity fees.

With respect to our NEK7 program, as of December 31, 2025, our portfolio included one granted U.S. patent, three pending PCT patent applications and four U.S. provisional patent applications that cover various NEK7-directed MGDs and uses thereof, including methods of treatment, processes for making various NEK7-directed

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MGDs, combinations comprising various NEK7-directed MGDs, and pharmaceutical formulations of a NEK7-directed MGD. The earliest scheduled expiration of any U.S. or foreign patents issuing from these patent applications, if such patents are issued, would be 2044, excluding any additional term available for patent term adjustment or patent term extension, and assuming timely payment of all applicable maintenance or annuity fees.

With respect to our CDK2 program, as of December 31, 2025, our portfolio included four pending PCT applications, three pending non-provisional patent applications in the United States, and pending patent applications in Australia, Canada, Chile, China, Europe, Israel, India, Japan, Korea, Mexico, New Zealand, Singapore and South Africa that cover various CDK2-directed MGDs and uses thereof, and combinations comprising various CDK2-directed MGDs. The earliest scheduled expiration of any U.S. or foreign patents issuing from these patent applications, if such patents are issued, would be 2042, excluding any additional term available for patent term adjustment or patent term extension, and assuming timely payment of all applicable maintenance or annuity fees.

With respect to our CCNE1 program, as of December 31, 2025, our portfolio included one pending PCT patent application that covers CCNE1-directed MGDs. The earliest scheduled expiration of any U.S. or foreign patents issuing from this PCT application, if such patents are issued, would be 2045, excluding any additional term available for patent term adjustment or patent term extension, and assuming timely payment of all applicable maintenance or annuity fees.

With respect to our VAV1 program, on October 25, 2024, the patent rights protecting our VAV1 MGDs were exclusively licensed to Novartis Pharma AG.

QuEENTM discovery engine

With respect to our QuEENTM discovery engine, as of December 31, 2025, our portfolio included two pending PCT patent applications, seven pending U.S. non-provisional patent applications, three U.S. provisional patent applications, and three pending European patent applications, that protect our QuEENTM discovery engine and uses thereof for the design, discovery, and development of MGD product candidates. The earliest scheduled expiration of any U.S. or foreign patent issuing from these U.S. provisional patent applications, if such patents are issued, would be 2042, excluding any available additional term for patent term adjustment or patent term extension.

Trademarks

As of December 31, 2025, we owned various registered and unregistered trademarks in Australia, Canada, China, Japan, Switzerland and the United States, including Monte Rosa, Monte Rosa Therapeutics and our housemark ‘M’ logo.

Trade secrets and know how

As an innovation driven biotechnology company, we rely on trade secrets, technical know-how and continuing innovation to develop and maintain the competitive advantage relevant to our business. Under the agreements we enter into with our employees and consultants, full rights in any intellectual property are assigned to us. We also rely on confidentiality or other agreements with our employees, consultants, other advisors and business partners to protect our proprietary information. Our policy is to require third parties that receive material confidential information to enter into confidentiality or other agreements with us that contain appropriate protections for our confidential and trade secret information.

Government regulation

The FDA and other regulatory authorities at federal, state and local level, as well as in foreign countries and local jurisdictions, extensively regulate among other things, the research, development, testing, manufacture, quality control, sampling, import, export, safety, effectiveness, labeling, packaging, storage, distribution, record-keeping, approval, advertising, promotion, marketing, post-approval monitoring and post-approval reporting of drugs. We, along with our vendors, contract research organizations, or CROs, and contract manufacturers, will be required to navigate the various preclinical, clinical, manufacturing and commercial approval requirements of the governing regulatory agencies of the countries in which we wish to conduct studies or seek approval of our product candidates. The process of obtaining regulatory approvals of drugs and ensuring subsequent compliance with appropriate federal, state, local and foreign statutes and regulations requires the expenditure of substantial time and financial resources.

In the U.S., the FDA regulates drug products under the Federal Food, Drug, and Cosmetic Act, or FD&C Act, as amended, its implementing regulations and other laws. If we fail to comply with applicable FDA or other

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requirements at any time with respect to product development, clinical testing, approval or any other legal requirements relating to product manufacture, processing, handling, storage, quality control, safety, marketing, advertising, promotion, packaging, labeling, export, import, distribution, or sale, we may become subject to administrative or judicial sanctions or other legal consequences. These sanctions or consequences could include, among other things, the FDA’s refusal to approve pending applications, issuance of clinical holds for ongoing studies, withdrawal of approvals, warning or untitled letters, product withdrawals or recalls, product seizures, relabeling or repackaging, total or partial suspensions of manufacturing or distribution, injunctions, fines, civil penalties or criminal prosecution.

The process required by the FDA before a drug may be marketed in the U.S. generally involves the following:

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completion of extensive preclinical studies in accordance with applicable regulations, including studies conducted in accordance with good laboratory practice, or GLP, requirements;

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submission to the FDA of an IND application, which must become effective before clinical trials may begin;

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approval by an IRB or independent ethics committee at each clinical trial site before each trial may be initiated;

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performance of adequate and well-controlled clinical trials in accordance with applicable IND regulations, good clinical practice, or GCP, requirements and other clinical trial-related regulations, to establish the safety and efficacy of the investigational product for each proposed indication;

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submission to the FDA of a NDA;

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a determination by the FDA within 60 days of its receipt of a New Drug Application, or an NDA, to accept the filing for review;

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satisfactory completion of one or more FDA pre-approval inspections of the manufacturing facility or facilities where the drug will be produced to assess compliance with current Good Manufacturing Practice, or cGMP, requirements to assure that the facilities, methods and controls are adequate to preserve the drug’s identity, strength, quality and purity;

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potential FDA audit of the clinical trial sites that generated the data in support of the NDA;

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payment of user fees for FDA review of the NDA; and

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FDA review and approval of the NDA, including consideration of the views of any FDA advisory committee, prior to any commercial marketing or sale of the drug in the U.S.

Preclinical studies and clinical trials for drugs

Before testing any drug in humans, the product candidate must undergo rigorous preclinical testing. Preclinical studies include laboratory evaluations of drug chemistry, formulation and stability, as well as in vitro and animal studies to assess safety and in some cases to establish the rationale for therapeutic use. The conduct of preclinical studies is subject to federal and state regulations and requirements, including GLP requirements for safety/toxicology studies. The results of the preclinical studies, together with manufacturing information and analytical data must be submitted to the FDA as part of an IND. An IND is a request for authorization from the FDA to administer an investigational product to humans and must become effective before clinical trials may begin. Some long-term preclinical testing may continue after the IND is submitted. The IND automatically becomes effective 30 days after receipt by the FDA, unless the FDA, within the 30-day time period, raises concerns or questions about the conduct of the clinical trial, including concerns that human research patients will be exposed to unreasonable health risks, and imposes a clinical hold. In such a case, the IND sponsor and the FDA must resolve any outstanding concerns before the clinical trial can begin. Submission of an IND may result in the FDA not allowing clinical trials to commence or not allowing clinical trials to commence on the terms originally specified in the IND.

The clinical stage of development involves the administration of the product candidate to healthy volunteers or patients under the supervision of qualified investigators, generally physicians not employed by or under the trial sponsor’s control, in accordance with GCP requirements, which include the requirements that all research subjects provide their informed consent for their participation in any clinical trial. Clinical trials are conducted under protocols detailing, among other things, the objectives of the clinical trial, dosing procedures, subject selection and exclusion criteria and the parameters and criteria to be used in monitoring safety and evaluating effectiveness. Each protocol, and any subsequent amendments to the protocol must be submitted to the FDA as part of the IND. Furthermore, each clinical trial must be reviewed and approved by an IRB for each institution at

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which the clinical trial will be conducted to ensure that the risks to individuals participating in the clinical trials are minimized and are reasonable related to the anticipated benefits. The IRB also approves the informed consent form that must be provided to each clinical trial subject or his or her legal representative, and must monitor the clinical trial until completed. The FDA, the IRB or the sponsor may suspend or discontinue a clinical trial at any time on various grounds, including a finding that the patients are being exposed to an unacceptable health risk or that the trial is unlikely to meet its stated objectives. Some studies also include oversight by an independent group of qualified experts organized by the clinical study sponsor, known as a data safety monitoring board, which provides authorization for whether or not a study may move forward at designated check points based on access to certain data from the study and may halt the clinical trial if it determines that there is an unacceptable safety risk for subjects or other grounds, such as no demonstration of efficacy. There also are requirements governing the reporting of ongoing clinical trials and completed clinical trials to public registries. Information about applicable clinical trials, including clinical trial results, must be submitted within specific timeframes for publication on the www.clinicaltrials.gov website.

A sponsor who wishes to conduct a clinical trial outside of the U.S. may, but need not, obtain FDA authorization to conduct the clinical trial under an IND. If a foreign clinical trial is not conducted under an IND, the sponsor must submit data from the clinical trial to the FDA in support of an NDA. The FDA will accept a well-designed and well-conducted foreign clinical trial not conducted under an IND if the trial was conducted in accordance with GCP requirements, and the FDA is able to validate the data through an onsite inspection if deemed necessary.

Clinical trials to evaluate therapeutic indications to support NDAs for marketing approval are typically conducted in three sequential phases, which may overlap or be combined.

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Phase 1—Phase 1 clinical trials involve initial introduction of the investigational product into healthy human volunteers or patients with the target disease or condition. These studies are typically designed to test the safety, dosage tolerance, absorption, metabolism and distribution of the investigational product in humans, excretion the side effects associated with increasing doses, and, if possible, to gain early evidence of effectiveness. In the case of some products for severe or life-threatening diseases, such as cancer, especially when the product may be too inherently toxic to ethically administer to healthy volunteers, the initial human testing is often conducted in patients.

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Phase 2—Phase 2 clinical trials typically involve administration of the investigational product to a limited patient population with a specified disease or condition to evaluate the preliminary efficacy, optimal dosages and dosing schedule and to identify possible adverse side effects and safety risks.

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Phase 3—Phase 3 clinical trials typically involve administration of the investigational product to an expanded patient population to further evaluate dosage, to provide statistically significant evidence of clinical efficacy and to further test for safety, generally at multiple geographically dispersed clinical trial sites. These clinical trials are intended to establish the overall risk/benefit ratio of the investigational product and to provide an adequate basis for product approval and physician labeling. Generally, two adequate and well-controlled clinical trials have been required by the FDA for approval of an NDA, although there are known exceptions, particularly for rare diseases. FDA leadership announced in February 2026 that the FDA will, going forward, adopt the default position that one adequate and well-controlled trial, combined with confirmatory evidence, can serve as the basis of approval for novel products.

Post-approval trials, sometimes referred to as Phase 4 clinical trials, may be conducted after initial marketing approval. These trials are used to gain additional experience from the treatment of patients in the intended therapeutic indication and are commonly intended to generate additional safety data regarding use of the product in a clinical setting. In certain instances, the FDA may mandate the performance of Phase 4 clinical trials as a condition of approval of an NDA.

Progress reports detailing the results of the clinical trials, among other information, must be submitted at least annually to the FDA. Written IND safety reports must be submitted to the FDA and the investigators fifteen days after the trial sponsor determines the information qualifies for reporting for serious and unexpected suspected AEs, findings from other studies or animal or in vitro testing that suggest a significant risk for human volunteers and any clinically important increase in the rate of a serious suspected adverse reaction over that listed in the protocol or investigator brochure. The sponsor must also notify the FDA of any unexpected fatal or life-threatening suspected adverse reaction as soon as possible but in no case later than seven calendar days after the sponsor’s initial receipt of the information.

Concurrent with clinical trials, companies usually complete additional animal studies and must also develop additional information about the chemistry and physical characteristics of the product candidate and finalize a

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process for manufacturing the drug product in commercial quantities in accordance with cGMP requirements. The manufacturing process must be capable of consistently producing quality batches of the product candidate and manufacturers must develop, among other things, methods for testing the identity, strength, quality and purity of the final drug product. Additionally, appropriate packaging must be selected and tested, and stability studies must be conducted to demonstrate that the product candidate does not undergo unacceptable deterioration over its shelf life.

U.S. marketing approval for drugs

Assuming successful completion of the required clinical testing, the results of the preclinical studies and clinical trials, together with detailed information relating to the product’s chemistry, manufacture, controls and proposed labeling, among other things are submitted to the FDA as part of an NDA requesting approval to market the product for one or more indications. An NDA must contain proof of the drug’s safety and efficacy in order to be approved. The marketing application may include both negative and ambiguous results of preclinical studies and clinical trials, as well as positive findings. Data may come from company-sponsored clinical trials intended to test the safety and efficacy of a product’s use or from a number of alternative sources, including studies initiated by investigators. To support marketing approval, the data submitted must be sufficient in quality and quantity to establish the safety and efficacy of the investigational product to the satisfaction of the FDA. FDA approval of an NDA must be obtained before a drug may be marketed in the U.S.

The FDA reviews all submitted NDAs before it accepts them for filing and may request additional information rather than accepting the NDA for filing. The FDA must make a decision on accepting an NDA for filing within 60 days of receipt, and such decision could include a refusal to file by the FDA. Once the submission is accepted for filing, the FDA begins an in-depth substantive review of the NDA. The FDA reviews an NDA to determine, among other things, whether the drug is safe and effective and whether the facility in which it is manufactured, processed, packaged or held meets standards designed to assure the product’s continued safety, quality and purity. Under the goals and polices agreed to by the FDA under the Prescription Drug User Fee Act, or PDUFA, the FDA targets ten months, from the filing date, in which to complete its initial review of a new molecular entity NDA and respond to the applicant, and six months from the filing date of a new molecular entity NDA for priority review. The FDA does not always meet its PDUFA goal dates for standard or priority NDAs, and the review process is often extended by FDA requests for additional information or clarification.

Further, under PDUFA, as amended, each NDA must be accompanied by a user fee. The FDA adjusts the PDUFA user fees on an annual basis. Fee waivers or reductions are available in certain circumstances, including a waiver of the application fee for the first application filed by a small business. Additionally, no user fees are assessed on NDAs for products designated as orphan drugs, unless the product also includes a non-orphan indication.

The FDA also may require submission of a Risk Evaluation and Mitigation Strategy, or REMS, program to ensure that the benefits of the drug outweigh its risks. The REMS program could include medication guides, physician communication plans, assessment plans and/or elements to assure safe use, such as restricted distribution methods, patient registries or other risk-minimization tools.

The FDA may refer an application for a novel drug to an advisory committee. An advisory committee is a panel of independent experts, including clinicians and other scientific experts, which reviews, evaluates and provides a recommendation as to whether the application should be approved and under what conditions. The FDA is not bound by the recommendations of an advisory committee, but it considers such recommendations carefully when making decisions.

Before approving an NDA, the FDA typically will inspect the facility or facilities where the product is manufactured. The FDA will not approve an application unless it determines that the manufacturing processes and facilities are in compliance with cGMP requirements and adequate to ensure consistent production of the product within required specifications. Additionally, before approving an NDA, the FDA may inspect one or more clinical trial sites to assure compliance with GCP and other requirements and the integrity of the clinical data submitted to the FDA.

After evaluating the NDA and all related information, including the advisory committee recommendation, if any, and inspection reports regarding the manufacturing facilities and clinical trial sites, the FDA may issue an approval letter, or, in some cases, a complete response letter. A complete response letter generally contains a statement of specific conditions that must be met in order to secure final approval of the NDA and may require additional clinical or preclinical testing in order for the FDA to reconsider the application. Even with submission of this additional information, the FDA ultimately may decide that the application does not satisfy the regulatory

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criteria for approval. If and when those conditions have been met to the FDA’s satisfaction, the FDA will typically issue an approval letter. An approval letter authorizes commercial marketing of the drug with specific prescribing information for specific indications.

Even if the FDA approves a product, depending on the specific risk(s) to be addressed it may limit the approved indications for use of the product, require that contraindications, warnings or precautions be included in the product labeling, require that post-approval studies, including Phase 4 clinical trials, be conducted to further assess a drug’s safety after approval, require testing and surveillance programs to monitor the product after commercialization or impose other conditions, including distribution and use restrictions or other risk management mechanisms under a REMS, which can materially affect the potential market and profitability of the product. The FDA may prevent or limit further marketing of a product based on the results of post-marketing studies or surveillance programs. After approval, some types of changes to the approved product, such as adding new indications, manufacturing changes and additional labeling claims, are subject to further testing requirements and FDA review and approval.

Orphan drug designation and exclusivity

Under the Orphan Drug Act, the FDA may grant orphan designation to a drug intended to treat a rare disease or condition, which is a disease or condition that affects fewer than 200,000 individuals in the U.S., or if it affects 200,000 or more individuals in the U.S., there is no reasonable expectation that the cost of developing and making the product available in the U.S. for the disease or condition will be recovered from sales of the product. Orphan designation must be requested before submitting an NDA. After the FDA grants orphan designation, the identity of the therapeutic agent and its potential orphan use are disclosed publicly by the FDA. Orphan designation does not convey any advantage in or shorten the duration of the regulatory review and approval process, though companies developing orphan products are eligible for certain incentives, including tax credits for qualified clinical testing and waiver of application fees.

If a product that has orphan designation subsequently receives the first FDA approval for the disease or condition for which it has such designation, the product is entitled to a seven-year period of marketing exclusivity during which the FDA may not approve any other applications to market the same therapeutic agent for the same indication, except in limited circumstances, such as a subsequent product’s showing of clinical superiority over the product with orphan exclusivity or where the original applicant cannot produce sufficient quantities of product. Competitors, however, may receive approval of different therapeutic agents for the indication for which the orphan product has exclusivity or obtain approval for the same therapeutic agent but for a different indication than that for which the orphan product has exclusivity. Orphan product exclusivity could also block the approval of one of our products for seven years if a competitor obtains approval for the same therapeutic agent for the same indication before we do, unless we are able to demonstrate that our product is clinically superior. If an orphan designated product receives marketing approval for an indication broader than what is designated, it may not be entitled to orphan exclusivity. Further, orphan drug exclusive marketing rights in the U.S. may be lost if the FDA later determines that the request for designation was materially defective or the manufacturer of the approved product is unable to assure sufficient quantities of the product to meet the needs of patients with the rare disease or condition.

Expedited development and review programs for drugs

The FDA maintains several programs intended to facilitate and expedite development and review of new drugs to address unmet medical needs in the treatment of serious or life-threatening diseases or conditions. These programs include Fast Track Designation, Breakthrough Therapy Designation, Priority Review and Accelerated Approval, and the purpose of these programs is to either expedite the development or review of important new drugs to get them to patients earlier than under standard FDA development and review procedures.

A new drug is eligible for Fast Track Designation if it is intended to treat a serious or life-threatening disease or condition and demonstrates the potential to address unmet medical needs for such disease or condition. Fast Track Designation provides increased opportunities for sponsor interactions with the FDA during preclinical and clinical development, in addition to the potential for rolling review once a marketing application is filed, meaning that the agency may review portions of the marketing application before the sponsor submits the complete application, as well as Priority Review, discussed below.

In addition, a new drug may be eligible for Breakthrough Therapy Designation if it is intended to treat a serious or life-threatening disease or condition and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development. Breakthrough Therapy Designation provides

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all the features of Fast Track Designation in addition to intensive guidance on an efficient drug development program beginning as early as Phase 1, and FDA organizational commitment to expedited development, including involvement of senior managers and experienced review staff in a cross-disciplinary review, where appropriate.

Any product submitted to the FDA for approval, including a product with Fast Track or Breakthrough Therapy Designation, may also be eligible for additional FDA programs intended to expedite the review and approval process including Priority Review designation and Accelerated Approval. A product is eligible for Priority Review if it has the potential to provide a significant improvement in safety or effectiveness in the treatment, diagnosis or prevention of a serious disease or condition. Under priority review, the FDA targets reviewing an application in six months after filing compared to ten months after filing for a standard review.

Additionally, products are eligible for Accelerated Approval if they can be shown to have an effect on a surrogate endpoint that is reasonably likely to predict clinical benefit, or an effect on a clinical endpoint that can be measured earlier than an effect on irreversible morbidity or mortality which is reasonably likely to predict an effect on irreversible morbidity or mortality or other clinical benefit, taking into account the severity, rarity or prevalence of the condition and the availability or lack of alternative treatments. Accelerated Approval is usually contingent on a sponsor’s agreement to conduct additional post-approval studies to verify and describe the product’s clinical benefit and, under the Food and Drug Omnibus Reform Act of 2022, or FDORA, the FDA may require, as appropriate, that such trials be underway prior to approval or within a specific time period after the date of approval for a product granted Accelerated Approval. Under FDORA, the FDA has increased authority for expedited procedures to withdraw approval of a drug or indication approved under Accelerated Approval if, for example, the confirmatory trial fails to verify the predicted clinical benefit of the product. In addition, for products being considered for accelerated approval, the FDA generally requires, unless otherwise informed by the agency, that all advertising and promotional materials that are intended for dissemination or publication within 120 days following marketing approval be submitted to the agency for review during the pre-approval review period, and that after 120 days following marketing approval, all advertising and promotional materials must be submitted at least 30 days prior to the intended time of initial dissemination or publication.

Even if a product qualifies for one or more of these programs, the FDA may later decide that the product no longer meets the conditions for qualification or the time period for FDA review or approval may not be shortened. Furthermore, Fast Track Designation, Breakthrough Therapy Designation, Priority Review and Accelerated Approval do not change the scientific or medical standards for approval or the quality of evidence necessary to support approval but may expedite the development or review process.

Pediatric information and pediatric exclusivity

Under the Pediatric Research Equity Act, or PREA, as amended, certain NDAs and certain supplements to an NDA must contain data to assess the safety and efficacy of the drug for the claimed indications in all relevant pediatric subpopulations and to support dosing and administration for each pediatric subpopulation for which the product is safe and effective. The FDA may grant deferrals for submission of pediatric data or full or partial waivers. The FD&C Act requires that a sponsor who is planning to submit a marketing application for a drug that includes a new active ingredient, new indication, new dosage form, new dosing regimen or new route of administration submit an initial Pediatric Study Plan, or PSP, within 60 days of an end-of-Phase 2 meeting or, if there is no such meeting, as early as practicable before the initiation of the Phase 3 or Phase 2/3 trial. The FDA and the sponsor must reach an agreement on the PSP. A sponsor can submit amendments to an agreed-upon initial PSP at any time if changes to the pediatric plan need to be considered based on data collected from preclinical studies, early phase clinical trials and/or other clinical development programs.

A drug can also obtain pediatric market exclusivity in the U.S. Pediatric exclusivity, if granted, adds six months to existing exclusivity periods and patent terms. This six-month exclusivity, which runs from the end of other exclusivity protection or patent term, may be granted based on the voluntary completion of a pediatric trial or of multiple pediatric trials in accordance with an FDA-issued “Written Request” for such trials, provided that at the time pediatric exclusivity is granted there is not less than nine months of term remaining.

U.S. post-approval requirements for drugs

Drugs manufactured or distributed pursuant to FDA approvals are subject to pervasive and continuing regulation by the FDA, including, among other things, requirements relating to record-keeping, periodic reporting, product sampling and distribution, reporting of adverse experiences with the product, complying with promotion and advertising requirements, which include restrictions on promoting products for unapproved uses or patient populations (known as “off-label use”) and limitations on industry-sponsored scientific and educational activities. Although physicians may prescribe legally available products for off-label uses, manufacturers and individuals

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working on behalf of manufacturers may not market or promote such uses. The FDA and other agencies actively enforce the laws and regulations prohibiting the promotion of off-label uses, and a company that is found to have improperly promoted off-label uses may be subject to significant liability, including investigation by federal and state authorities. Prescription drug promotional materials must be submitted to the FDA in conjunction with their first use or first publication. Further, if there are any modifications to the drug, including changes in indications, labeling or manufacturing processes or facilities, the applicant may be required to submit and obtain FDA approval of a new NDA or NDA supplement, which may require the development of additional data or preclinical studies and clinical trials. The FDA may impose a number of post-approval requirements as a condition of approval of an NDA. For example, the FDA may require post-market testing, including Phase 4 clinical trials, and surveillance to further assess and monitor the product’s safety and effectiveness after commercialization.

In addition, drug manufacturers and their subcontractors involved in the manufacture and distribution of approved drugs, and those supplying products, ingredients, and components of them, are required to register their establishments with the FDA and certain state agencies and are subject to periodic unannounced inspections by the FDA and certain state agencies for compliance with ongoing regulatory requirements, including cGMP, which impose certain procedural and documentation requirements upon us and our contract manufacturers. Manufacturers and other parties involved in the drug supply chain for prescription drug products must also comply with product tracking and tracing requirements and for notifying the FDA of counterfeit, diverted, stolen and intentionally adulterated products or products that are otherwise unfit for distribution in the United States. Failure to comply with statutory and regulatory requirements can subject a manufacturer to possible legal or regulatory action, such as warning letters, suspension of manufacturing, product seizures, injunctions, civil penalties or criminal prosecution. There is also a continuing, annual prescription drug product program user fee.

Later discovery of previously unknown problems with a product, including AEs of unanticipated severity or frequency, or with manufacturing processes, or failure to comply with regulatory requirements, may result in revisions to the approved labeling to add new safety information, requirements for post-market studies or clinical trials to assess new safety risks, or imposition of distribution or other restrictions under a REMS. Other potential consequences include, among other things:

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restrictions on the marketing or manufacturing of the product, complete withdrawal of the product from the market or product recalls;

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safety alerts, Dear Healthcare Provider letters, press releases or other communications containing warnings or other safety information about the product;

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fines, warning letters or untitled letters or holds on post-approval clinical trials;

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refusal of the FDA to approve applications or supplements to approved applications, or suspension or revocation of product approvals;

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product seizure or detention, or refusal to permit the import or export of products;

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injunctions or the imposition of civil or criminal penalties; and

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consent decrees, corporate integrity agreements, debarment or exclusion from federal healthcare programs or mandated modification of promotional materials and labeling and issuance of corrective information.

Marketing exclusivity

Market exclusivity provisions under the FD&C Act can delay the submission or the approval of certain marketing applications. The FD&C Act provides a five-year period of non-patent exclusivity within the United States to the first applicant to obtain approval of an NDA for a new chemical entity. A drug is a new chemical entity if the FDA has not previously approved any other new drug containing the same active moiety, which is the molecule or ion responsible for the action of the drug substance. During the exclusivity period, the FDA may not approve or even accept for review an abbreviated new drug application, or ANDA, or an NDA submitted under Section 505(b)(2), or 505(b)(2) NDA, submitted by another company for another drug based on the same active moiety, regardless of whether the drug is intended for the same indication as the original innovative drug or for another indication. However, such an application may be submitted after four years if it contains a certification of patent invalidity or non-infringement to one of the patents listed with the FDA by the innovator NDA holder.

The FD&C Act alternatively provides three years of marketing exclusivity for an NDA, or supplement to an existing NDA, if new clinical investigations, other than bioavailability studies, that were conducted or sponsored by the applicant are deemed by the FDA to be essential to the approval of the application, for example new indications, dosages or strengths of an existing drug. This three-year exclusivity covers only the modification for which the

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drug received approval on the basis of the new clinical investigations and does not prohibit the FDA from approving ANDAs or 505(b)(2) NDAs for drugs containing the active agent for the original indication or condition of use. Five-year and three-year exclusivity will not delay the submission or approval of a full NDA. However, an applicant submitting a full NDA would be required to conduct or obtain a right of reference to any preclinical studies and adequate and well-controlled clinical trials necessary to demonstrate safety and effectiveness.

Other regulatory matters

From time to time, legislation is drafted, introduced, passed in Congress and signed into law that could significantly change the statutory provisions governing the approval, manufacturing, and marketing of products regulated by the FDA. In addition to new legislation, FDA regulations, guidances, and policies are often revised or reinterpreted by the agency in ways that may significantly affect the manner in which pharmaceutical products are regulated and marketed.

Manufacturing, sales, promotion and other activities of product candidates following product approval, where applicable, or commercialization are also subject to regulation by numerous regulatory authorities in the U.S. in addition to the FDA, which may include the Centers for Medicare & Medicaid Services, or CMS, other divisions of the Department of Health and Human Services, the Department of Justice, the Drug Enforcement Administration, the Consumer Product Safety Commission, the Federal Trade Commission, the Occupational Safety & Health Administration, the Environmental Protection Agency and state and local governments and governmental agencies.

Current and future healthcare reform legislation

In the United States and in some foreign jurisdictions, there have been, and likely will continue to be, a number of legislative and regulatory changes and proposed changes intended to broaden access to healthcare, improve the quality of healthcare, and contain or lower the cost of healthcare. For example, in the United States, the Patient Protection and Affordable Care Act, as amended by the Health Care and Education Reconciliation Act, or ACA, among other things, subjected products to potential competition by lower-cost products, expanded the types of entities eligible for the 340B drug discount program, increased rebates owed by manufacturers under the Medicaid Drug Rebate Program and extended the rebate program to individuals enrolled in Medicaid managed care organizations, established annual fees and taxes on manufacturers of certain branded prescription drugs, and created a Medicare Part D coverage gap discount program for certain Medicare Part D beneficiaries, in which manufacturers must agree to offer 50% (increased effective January 2019 to 70%) point-of-sale discounts off negotiated prices of applicable brand drugs to eligible beneficiaries during their coverage gap period, as a condition for the manufacturer’s outpatient drugs to be covered under Medicare Part D (later replaced altogether by a similar manufacturer-owed discount obligation under the Inflation Reduction Act of 2022).

There have been executive, judicial and congressional challenges to certain aspects of the ACA Act as well as efforts to repeal or replace certain aspects of the ACA. On June 17, 2021, for example, the U.S. Supreme Court dismissed the most recent judicial challenge to the ACA brought by several states without specifically ruling on the constitutionality of the ACA. In addition, President Trump has issued multiple executive orders that have sought to reduce prescription drug costs. Although a number of these and other proposed measures may require authorization through additional legislation to become effective, and the Trump administration may reverse or otherwise change these measures, both the Trump administration and Congress have indicated that they will continue to seek new legislative measures to control drug costs.

Other federal health reform measures have been proposed and adopted in the U.S. since the ACA was enacted. The Budget Control Act of 2011, for example, included aggregate reductions to Medicare payments to providers of up to 2% per fiscal year that will remain in effect through 2031. In addition, the American Taxpayer Relief Act of 2012 was signed into law which, among other things, reduced Medicare payments to several providers, and increased the statute of limitations period for the government to recover overpayments to providers from three to five years.

Furthermore, there has been heightened governmental scrutiny over the manner in which manufacturers set prices for their marketed products, which has resulted in several congressional inquiries and proposed legislation designed to, among other things, bring more transparency to product pricing, review the relationship between pricing and manufacturer patient assistance programs and reform government program reimbursement methodologies for drug products.

In addition, the Inflation Reduction Act of 2022, or the IRA, included several provisions that could impact our business to varying degrees. The IRA, which among other things, allows for Centers for Medicare & Medicaid Services to negotiate prices for certain single-source drugs and biologics reimbursed under Medicare Part B and

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Part D, beginning with select high-cost drugs in 2026. The legislation subjects drug manufacturers to civil monetary penalties and a potential excise tax for offering a price that is not equal to or less than the price negotiated under the law or for taking price increases that exceed inflation. The legislation also requires manufacturers to pay rebates for drugs in Medicare Part D whose price increases exceed inflation. Further, the legislation caps Medicare beneficiaries’ annual out-of-pocket drug expenses at $2,000. The effect of IRA on our business and the healthcare industry in general is not yet known.

Under the One Big Beautiful Bill Act of 2025, or OBBBA, imposed significant reductions in Medicaid funding, additional work requirements for Medicaid recipients, and more frequent reenrollment requirements. These changes are expected to place substantial pressure on state Medicaid budgets, reduce enrollment, and limit covered services, which could decrease utilization of, and reimbursement for, our products, if approved.

We cannot predict the initiatives that may be adopted in the future. The continuing efforts of the government, insurance companies, managed care organizations and other payors of healthcare services to contain or reduce costs of healthcare and/or impose price controls may adversely affect:

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the demand for our product candidates, if we obtain regulatory approval;

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our ability to set a price that we believe is fair for our approved products;

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our ability to generate revenue and achieve or maintain profitability;

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the level of taxes that we are required to pay; and

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the availability of capital.

Any reduction in reimbursement from Medicare or other government programs may result in a similar reduction in payments from private payors, which may adversely affect our future profitability.

Prescription drug pricing in the United States is subject to significant political, legislative, and regulatory scrutiny. In recent years, Congress and federal and state agencies have considered and adopted measures aimed at increasing pricing transparency, reducing drug costs under government programs, reforming reimbursement methodologies, and examining manufacturer patient assistance programs. In 2025, the Trump Administration issued executive actions and supported regulatory initiatives focused on implementing most-favored-nation, or MFN, pricing concepts and expanding direct-to-consumer sales models, and CMS proposed multiple reimbursement models that would incorporate international reference pricing benchmarks into Medicare and Medicaid payment structures. These initiatives, if implemented, could adversely affect the prices that manufacturers are able to obtain for prescription drugs in the United States. Although certain proposals remain subject to rulemaking, legal challenge, or voluntary participation, continued efforts to regulate or constrain drug pricing could materially impact our future revenue, pricing flexibility, and commercial strategy if our product candidates are approved.

Individual states in the United States have also become increasingly active in passing legislation and implementing regulations designed to control pharmaceutical product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing. In addition, regional healthcare authorities and individual hospitals are increasingly using bidding procedures to determine what pharmaceutical products and which suppliers will be included in their prescription drug and other healthcare programs. It is difficult to predict the future legislative landscape in healthcare and the effect on our business, results of operations, financial condition and prospects. However, we expect that additional state and federal healthcare reform measures will be adopted in the future.

Third-party payor coverage and reimbursement

Significant uncertainty exists as to the coverage and reimbursement status of any products for which we may obtain regulatory approval. In the U.S. and markets in other countries, sales of any products for which we may receive regulatory marketing approval for commercial sale will depend, in part, on the availability of coverage and reimbursement from third-party payors. Third-party payors include government healthcare programs (e.g., Medicare, Medicaid), managed care providers, private health insurers, health maintenance organizations and other organizations. These third-party payors decide which medications they will pay for and will establish reimbursement levels. The availability of coverage and extent of reimbursement by governmental and other third-party payors is essential for most patients to be able to afford treatments such as targeted protein degradation therapies.

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In the United States, no uniform policy exists for coverage and reimbursement for products among third-party payors. Therefore, decisions regarding the extent of coverage and amount of reimbursement to be provided can differ significantly from payor to payor. Third-party payors often follow Medicare coverage policy and payment limitations in setting their own reimbursement rates, but also have their own methods and approval process apart from Medicare determinations. Factors payors consider in determining reimbursement are based on whether the product is:

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a covered benefit under its health plan;

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safe, effective and medically necessary;

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appropriate for the specific patient;

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cost-effective; and

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neither experimental nor investigational.

One third-party payor’s decision to cover a particular product or service does not ensure that other payors will also provide coverage for the medical product or service. Third-party payors may limit coverage to specific products on an approved list or formulary, which may not include all FDA-approved products for a particular indication. Also, third-party payors may refuse to include a particular branded product on their formularies or otherwise restrict patient access to a branded drug when a less costly generic equivalent or other alternative is available. Our ability to successfully commercialize our product candidates will depend in part on the extent to which coverage and adequate reimbursement for these products and related treatments will be available from third-party payors.

Moreover, the process for determining whether a payor will provide coverage for a product may be separate from the process for setting the reimbursement rate a payor will pay for the product. A payor’s decision to provide coverage for a product does not imply that an adequate reimbursement rate will be approved. Further, third-party payors are increasingly challenging the price and examining the medical necessity and cost-effectiveness of medical products and services, in addition to their safety and efficacy. In order to secure coverage and reimbursement for any product that might be approved for sale, we may need to conduct expensive pharmacoeconomic studies in order to demonstrate the medical necessity and cost-effectiveness of our products, in addition to the costs required to obtain FDA or comparable regulatory approvals. Additionally, we may also need to provide discounts to purchasers, private health plans or government healthcare programs. Despite our best efforts, our product candidates may not be considered medically necessary or cost-effective. If third-party payors do not consider a product to be cost-effective compared to other available therapies, they may not cover an approved product as a benefit under their plans or, if they do, the level of payment may not be sufficient to allow us to sell our products at a profit. A decision by a third-party payor not to cover a product could reduce physician utilization once the product is approved and have a material adverse effect on sales, our operations and financial condition.

Finally, in some foreign countries, the proposed pricing for a product candidate must be approved before it may be lawfully marketed. The requirements governing product pricing vary widely from country to country. For example, in the European Union, or EU, pricing and reimbursement of pharmaceutical products are regulated at a national level under the individual EU Member States’ social security systems. Some foreign countries provide options to restrict the range of medicinal products for which their national health insurance systems provide reimbursement and can control the prices of medicinal products for human use. To obtain reimbursement or pricing approval, some of these countries may require the completion of clinical trials that compare the cost effectiveness of a particular product candidate to currently available therapies. A country may approve a specific price for the medicinal product or it may instead adopt a system of direct or indirect controls on the profitability of the company placing the medicinal product on the market. There can be no assurance that any country that has price controls or reimbursement limitations for products will allow favorable reimbursement and pricing arrangements for any of our product candidates. Even if approved for reimbursement, historically, product candidates launched in some foreign countries, such as some countries in the EU, do not follow price structures of the U.S. and prices generally tend to be significantly lower.

Other healthcare laws and regulations

Healthcare providers, physicians, and third-party payors will play a primary role in the recommendation and prescription of any products for which we obtain marketing approval. Our business operations and any current or future arrangements with third-party payors may expose us to broadly applicable federal and state fraud and

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abuse laws, as well as other healthcare laws and regulations. These laws may impact, among other things, our proposed sales, marketing, and distribution strategies. In the U.S., these laws include, among others:

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The federal Anti-Kickback Statute, or AKS, which prohibits, among other things, any person or entity from knowingly and willfully offering, soliciting, receiving or paying remuneration (a term interpreted broadly to include anything of value, including, for example, gifts, discounts and credits), directly or indirectly, overtly or covertly, in cash or in kind, to induce or reward, or in return for, either the referral of an individual for, or the purchase, lease, order or recommendation of, or arranging for, an item, good, facility or service for which payment may be made under a federal healthcare program such as Medicare and Medicaid. The AKS has been interpreted to apply to arrangements between manufacturers on one hand and prescribers, purchasers, and formulary managers on the other. A person or entity does not need to have actual knowledge of the statute or specific intent to violate it in order to have committed a violation. Violations can result in significant civil monetary and criminal penalties for each violation, plus up to three times the amount of remuneration, imprisonment, and exclusion from government healthcare programs.

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Additionally, the civil False Claims Act, or FCA, prohibits knowingly presenting or causing the presentation of a false, fictitious or fraudulent claim for payment to the U.S. government. Actions under the FCA may be brought by the Attorney General or as a qui tam action by a private individual in the name of the government. Violations of the FCA can result in very significant monetary penalties, for each false claim and treble the amount of the government’s damages. Manufacturers can be held liable under the FCA even when they do not submit claims directly to government payors if they are deemed to “cause” the submission of false or fraudulent claims. Further, a violation of the AKS can also form the basis for FCA liability.

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The U.S. federal Health Insurance Portability and Accountability Act of 1996, or HIPAA, imposes additional criminal and civil liability for knowingly and willfully executing, or attempting to execute, a scheme to defraud any healthcare benefit program or obtain, by means of false or fraudulent pretenses, representations, or promises, any of the money or property owned by, or under the custody or control of, any healthcare benefit program, regardless of the payor (e.g., public or private); and knowingly and willfully falsifying, concealing or covering up by any trick or device a material fact or making any materially false statement in connection with the delivery of, or payment for, healthcare benefits, items or services. Similar to the AKS, a person or entity does not need to have actual knowledge of the statute or specific intent to violate it in order to have committed a violation.

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HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act of 2009, or HITECH, and its implementing regulations, including the final omnibus rule published on January 25, 2013, imposes, among other things, certain requirements relating to the privacy, security and transmission of individually identifiable health information. Among other things, HITECH makes HIPAA’s privacy and security standards directly applicable to “business associates,” defined as independent contractors or agents of covered entities that create, receive, maintain, transmit, or obtain, protected health information in connection with providing a service for or on behalf of a covered entity. HITECH also increased the civil and criminal penalties that may be imposed against covered entities, business associates and possibly other persons, and gave state attorneys general new authority to file civil actions for damages or injunctions in federal courts to enforce the federal HIPAA laws and seek attorney’s fees and costs associated with pursuing federal civil actions.

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Federal transparency laws, including the federal Physician Payment Sunshine Act created under the ACA, and its implementing regulations, which requires manufacturers of certain drugs, devices, medical supplies, and biologics, among others, to track and disclose payments under Medicare, Medicaid or the Children’s Health Insurance Program (with certain exceptions) and other transfers of value they make to U.S. physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors) and teaching hospitals, as well as ownership and investment interests held by physicians and their immediate family members. Effective January 1, 2022, these reporting obligations were extended to include transfers of value made to certain non-physician providers such as physician assistants and nurse practitioners. This information is subsequently made publicly available in a searchable format on a CMS website.

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Federal government price reporting laws, which require us to calculate and report complex pricing metrics in an accurate and timely manner to government programs.

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Federal consumer protection and unfair competition laws, which broadly regulate marketplace activities and activities that potentially harm consumers.

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Analogous state law equivalents of each of the above U.S. federal laws and similar healthcare laws and regulations in the EU and other jurisdictions, such, such as anti-kickback and false claims laws, which may apply to items or services reimbursed by any third-party payor, including commercial insurers or patients; state and local marketing and/or transparency laws applicable to manufacturers that may be broader in scope than the federal requirements; state laws that require the reporting of information related to drug pricing; state laws that require drug manufacturers to report information related to payments and other transfers of value to physicians and other healthcare providers or marketing expenditures and pricing information; state and local laws that require the licensure and/or registration of pharmaceutical sales representatives; state laws that require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government; and state laws governing the privacy and security of health information and/or other health information in certain circumstances, many of which differ from each other in significant ways and often are not pre-empted by HIPAA, thus complicating compliance efforts. There are ambiguities as to what is required to comply with these state requirements and if we fail to comply with an applicable state law requirement we could be subject to penalties. Finally, there are state and foreign laws governing the privacy and security of health information, many of which differ from each other in significant ways and often are not preempted by HIPAA, thus complicating compliance efforts.

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The scope and enforcement of each of these laws is uncertain and subject to rapid change in the current environment of healthcare reform, especially in light of the lack of applicable precedent and regulations. Federal, state and foreign enforcement bodies have recently increased their scrutiny of interactions between healthcare companies and healthcare providers, which has led to a number of investigations, prosecutions, convictions and settlements in the healthcare industry. It is possible that governmental authorities will conclude that our business practices may not comply with current or future statutes, regulations or case law involving applicable fraud and abuse or other healthcare laws and regulations. If our operations are found to be in violation of any of these laws or any other governmental regulations that may apply to us, we may be subject to significant civil, criminal and administrative penalties, damages, fines, disgorgement, contractual damages, reputational harm, diminished profits and future earnings, individual imprisonment, exclusion from participation in government funded healthcare programs, such as Medicare and Medicaid, and the curtailment or restructuring of our operations, as well as additional reporting obligations and oversight if we become subject to a corporate integrity agreement or similar settlement to resolve allegations of non-compliance with these laws, any of which could adversely affect our ability to operate our business and our financial results. If any of the physicians or other healthcare providers or entities with whom we expect to do business is found to be not in compliance with applicable laws, they may be subject to similar actions, penalties, and sanctions. Ensuring business arrangements comply with applicable healthcare laws, as well as responding to possible investigations by government authorities, can be time- and resource consuming and can divert a company’s attention from the business.

Privacy data protection, and security laws and regulations

We may be subject to Swiss, European, US federal, state, and foreign data protection laws and regulations (i.e., laws and regulations that address privacy and data security) which provide additional privacy restrictions. For example, in the European Economic Area, or EEA, and United Kingdom, or UK, the collection and use of personal data including health information is governed by the provisions of the General Data Protection Regulation, or the EU GDPR, and the UK’s implementation of the same, or the UK GDPR, and collectively the GDPR, as well as national data protection laws in force in relevant EEA Member States and the UK (including the UK Data Protection Act 2018 and the UK Data (Use and Access) Act 2025. The GDPR imposes a broad range of strict requirements on companies subject to the GDPR, such as requirements relating to ensuring a legal basis or condition applies to the processing of personal data, transferring such information outside the EEA/UK, including to the U.S. (see below), expanded disclosures to individuals regarding the processing of their personal data, implementing safeguards to keep personal data secure, having data processing agreements with third parties who process personal data, providing information to individuals regarding data processing activities, responding to individuals’ requests to exercise their rights in respect of their personal data, if required obtaining consent of the individuals to whom the personal data relates, reporting security and privacy breaches involving personal data to the competent national data protection authority and affected individuals, appointing data protection officers, conducting data protection impact assessments, and record-keeping. The GDPR substantially increases the penalties to which we could be subject in the event of any non-compliance, including fines of up to €20,000,000 (£17.5 million for the UK GDPR) or 4% of our corporate group's total annual global revenue from the proceeding year, whichever is greater. The GDPR also confers a private right of action on data subjects and consumer associations to lodge complaints with supervisory authorities, seek judicial remedies, and obtain compensation for

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damages resulting from violations of the GDPR. The GDPR may impose additional responsibility and liability in relation to personal data that we process and we may be required to put in place additional mechanisms to ensure continued compliance with GDPR, which may be onerous and adversely affect our business, financial condition, results of operations and prospects. Compliance with the GDPR is a rigorous and time-intensive process that may increase our cost of doing business or require us to change our business practices, and despite those efforts, there is a risk that we may be subject to fines and penalties, litigation, and reputational harm in connection with our European activities.

The UK’s data protection regime is independent from but aligned to the EU’s data protection regime. Non-compliance with the UK GDPR may result in monetary penalties of up to £17.5 million or 4% of worldwide revenue, whichever is higher.

The GDPR imposes strict rules on the transfer of personal data outside of the EEA/UK to third countries, including the United States in certain circumstances, unless a valid GDPR mechanism (e.g., the European Commission issued Standard Contractual Clauses, or SCCs, and the UK International Data Transfer Addendum/Agreement, or UK IDTA) is put in place, or an international transfer derogation exists under the GDPR. Where relying on the SCCs or UK IDTA for data transfers, we may also be required to carry out transfer impact assessments. Further, the EU and United States have agreed to an adequacy decision for the EU-U.S. Data Privacy Framework, or the "Framework,” which entered into force on July 11, 2023. This Framework provides that the protection of personal data transferred between the EU and the United States is comparable to that offered in the EU. This provides a further avenue to ensuring transfers to the United States are carried out in line with GDPR. There has been an extension to the Framework to cover UK transfers to the United States. The Framework could be challenged like its predecessor frameworks. This complexity and the additional contractual burden increases our overall risk exposure, and there may be further divergence on international transfer safeguards in the future, including with regard to administrative burdens. The international transfer obligations under the EEA and UK data protection regimes will require effort and cost and may result in us needing to make strategic considerations around where EEA/UK personal data is located and which service providers we can utilize for the processing of EEA/UK personal data. Any inability to transfer personal data from the UK and EEA to the U.S (and other third countries) in compliance with data protection laws may adversely affect our operations and our business and financial position. Although the UK is regarded as a third country under the EU’s GDPR, the European Commission or EC issued a decision recognizing the UK as providing adequate protection under the EU GDPR and, therefore, transfers of personal data originating in the EEA to the UK remain unrestricted. The UK government has confirmed that personal data transfers from the UK to the EEA also remain free flowing.

The UK data protection regime is independent from but currently still aligned with the EEA’s data protection regime. However, going forward, there is increasing risk for divergence in application, interpretation and enforcement of the data protection laws as between the UK and EEA, creating additional regulatory uncertainty. For example, the UK Data (Use and Access) Act 2025, now in force, further differentiates the UK and EU data protection regimes. In December 2025, the European Commission adopted a decision determining that the UK continues to provide a level of data protection that is “essentially equivalent” to the EU standards and extended the validity of the UK adequacy decision for six years, through to December 2031. While this renewal reduces immediate adequacy concerns, uncertainty remains regarding how UK data protection laws will evolve in the medium to longer term. The lack of clarity on future UK laws and regulations and their interaction with EU laws and regulations may affect our efforts to maintain a harmonized approach to processing European personal data and expose us to two parallel regimes where the UK GDPR and EU GDPR both apply with differing interpretation and enforcement approaches. This could increase our legal risk, uncertainty, complexity and compliance cost associated with the handling of European personal data, and may require us to adapt our privacy and data security compliance programs to account for legal and regulatory divergence between the UK and EEA. Further, EU Member States have adopted implementing national laws to implement the EU GDPR which may partially deviate from the EU GDPR and the competent authorities in the EU Member States may interpret EU GDPR obligations slightly differently from country to country, so that we do not expect to operate in a uniform legal landscape in the EEA.

In Switzerland, we are also subject to comprehensive data protection requirements including the Swiss Federal Act on Data Protection, or the DPA, which imposes stringent rules on the processing of personal data including health related information.

In the United States, numerous federal and state laws and regulations, including federal health information privacy laws, state data breach notification laws, state health information privacy laws, and federal and state consumer protection laws (e.g., Section 5 of the Federal Trade Commission Act), that govern the collection, use, disclosure and protection of health-related and other personal information could apply to our operations or the

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operations of our collaborators. For example, the California Consumer Privacy Act (CCPA) is a comprehensive law that creates individual privacy rights and protections for California consumers, places increased privacy and security obligations on entities handling personal data of consumers or households, and provides for civil penalties for violations and a private right of action for data breaches. The CCPA requires covered companies to provide certain disclosures to consumers about its data collection, use and sharing practices, and to provide affected California residents with ways to opt-out of certain sales or transfers of personal information.

Further, as of January 1, 2023, the California Privacy Rights Act (CPRA), amended the CCPA and created additional obligations with respect to processing and storing personal information and sensitive personal information. While the CCPA contains an exception for activities that are subject to HIPAA, we cannot yet determine the impact the CCPA and other such future laws, regulations and standards may have on our business

Numerous U.S. states have passed similar consumer privacy laws. Like the CCPA, these laws grant consumers rights in relation to their personal information and impose new obligations on regulated businesses, including, in some instances, broader data security requirements. Such legislation adds additional complexity, variation in requirements, restrictions and potential legal risk, requiring additional investment of resources in compliance programs, impacting our strategies and the availability of previously useful data which may result in increased compliance costs and/or changes in business practices and policies. The existence of comprehensive privacy laws in different states in the country make our compliance obligations more complex and costly and may increase the likelihood that we may be subject to enforcement actions or otherwise incur liability for noncompliance. State laws are changing rapidly and there are discussions in the U.S. Congress of new comprehensive federal data privacy laws to which we could become subject to, if enacted.

Furthermore, other states have proposed or enacted legislation that is focused on more narrow aspects of privacy. In the state of Washington, for example, the My Health My Data Act requires regulated entities to obtain consent to collect health information, grants consumers certain rights, including to request deletion of their information, and provides for robust enforcement mechanisms, including enforcement by the Washington state attorney-general and a private right of action for consumer claims. Additionally, a small number of states have enacted laws that specifically target the collection and use of biometric information.

At the federal level, the FTC has used its authority over “unfair or deceptive acts or practices” to impose stringent requirements on the collection and disclosure of sensitive categories of personal information, including health information. Moreover, the FTC’s expanded interpretation of a “breach” under its Health Breach Notification Rule could impose new disclosure obligations that would apply in the event of a qualifying breach. Regulators and legislators in the U.S. are also increasingly scrutinizing and restricting certain personal data transfers and transactions involving foreign countries. For example, the Department of Justice’s January 8, 2025, rule on “Preventing Access to U.S. Sensitive Personal Data and Government-Related Data by Countries of Concern or Covered Persons, prohibits data brokerage transactions involving certain sensitive personal data categories, including health data, genetic data, and biospecimens, to countries of concern, including China. The regulations also restrict certain investment agreements, employment agreements and vendor agreements involving such data and countries of concern, absent specified cybersecurity controls. Actual or alleged violations of these regulations may be punishable by criminal and/or civil sanctions, and may result in exclusion from participation in federal and state programs.

The uncertainty surrounding the implementation of recent and emerging state privacy and other similar laws, regulations and standards that may be adopted in other jurisdictions exemplifies the vulnerability of our business to the evolving regulatory environment related to personal data and protected health information. Compliance with U.S. and international data protection laws and regulations could require us to take on more onerous obligations in our contracts, restrict our ability to collect, use and disclose data, or in some cases, impact our ability to operate in certain jurisdictions. Failure to comply with these laws and regulations could result in government enforcement actions (which could include civil, criminal and administrative penalties), private litigation, and/or adverse publicity and could negatively affect our operating results and business. Moreover, clinical trial subjects, employees and other individuals about whom we or our potential collaborators obtain personal information, as well as the providers who share this information with us, may limit our ability to collect, use and disclose the information. Claims that we have violated individuals’ privacy rights, failed to comply with data protection laws, or breached our contractual obligations, even if we are not found liable, could be expensive and time-consuming to defend and could result in adverse publicity that could harm our business.

Many jurisdictions outside of Europe where we do business directly or through master resellers today and may seek to expand our business in the future, are also considering and/or have enacted comprehensive data protection legislation. We also continue to see jurisdictions imposing data localization laws. These and similar

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regulations may interfere with our intended business activities, inhibit our ability to expand into those markets, require modifications to our products or services or prohibit us from continuing to offer services in those markets without significant additional costs.

Compliance with other federal and state laws or requirements; changing legal requirements

If any products that we may develop are made available to authorized users of the Federal Supply Schedule of the General Services Administration, additional laws and requirements apply. Products must meet applicable child-resistant packaging requirements under the U.S. Poison Prevention Packaging Act. Manufacturing, labeling, packaging, distribution, sales, promotion and other activities also are potentially subject to federal and state consumer protection and unfair competition laws, among other requirements to we may be subject.

The distribution of pharmaceutical products is subject to additional requirements and regulations, including extensive record-keeping, licensing, storage and security requirements intended to prevent the unauthorized sale of pharmaceutical products.

The failure to comply with any of these laws or regulatory requirements subjects firms to possible legal or regulatory action. Depending on the circumstances, failure to meet applicable regulatory requirements can result in criminal prosecution, fines or other penalties, injunctions, exclusion from federal healthcare programs, requests for recall, seizure of products, total or partial suspension of production, denial or withdrawal of product approvals, relabeling or repackaging, or refusal to allow a firm to enter into supply contracts, including government contracts. Any claim or action against us for violation of these laws, even if we successfully defend against it, could cause us to incur significant legal expenses and divert our management’s attention from the operation of our business. Prohibitions or restrictions on marketing, sales or withdrawal of future products marketed by us could materially affect our business in an adverse way.

Changes in regulations, statutes or the interpretation of existing regulations could impact our business in the future by requiring, for example: (i) changes to our manufacturing arrangements; (ii) additions or modifications to product labeling or packaging; (iii) the recall or discontinuation of our products; or (iv) additional record-keeping requirements. If any such changes were to be imposed, they could adversely affect the operation of our business.

Other U.S. environmental, health and safety laws and regulations

We may be subject to numerous environmental, health and safety laws and regulations, including those governing laboratory procedures and the handling, use, storage, treatment and disposal of hazardous materials and wastes. From time to time and in the future, our operations may involve the use of hazardous and flammable materials, including chemicals and biological materials, and may also produce hazardous waste products. Even if we contract with third parties for the disposal of these materials and waste products, we cannot completely eliminate the risk of contamination or injury resulting from these materials. In the event of contamination or injury resulting from the use or disposal of our hazardous materials, we could be held liable for any resulting damages, and any liability could exceed our resources. We also could incur significant costs associated with civil or criminal fines and penalties for failure to comply with such laws and regulations.

We maintain workers’ compensation insurance to cover us for costs and expenses we may incur due to injuries to our employees, but this insurance may not provide adequate coverage against potential liabilities. However, we do not maintain insurance for environmental liability or toxic tort claims that may be asserted against us.

In addition, we may incur substantial costs in order to comply with current or future environmental, health and safety laws and regulations. Current or future environmental laws and regulations may impair our research, development or production efforts. In addition, failure to comply with these laws and regulations may result in substantial fines, penalties or other sanctions.

Government regulation of drugs outside of the United States

To market any product outside of the U.S., we would need to comply with numerous and varying regulatory requirements of other countries regarding safety and efficacy and governing, among other things, clinical trials, marketing authorization or identification of an alternate regulatory pathway, manufacturing, commercial sales and distribution of our products.

Whether or not we obtain FDA approval of a product, we must obtain the requisite approvals from regulatory authorities in foreign countries prior to the commencement of clinical trials or marketing of the product in those countries. If we fail to comply with applicable foreign regulatory requirements, we may be subject to, among other things, fines, suspension or withdrawal of regulatory approvals, product recalls, seizure of products, operating restrictions and criminal prosecution.

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Non-clinical studies and clinical trials

Similarly to the U.S., the various phases of non-clinical and clinical research in EU, are subject to significant regulatory controls.

Non-clinical studies are performed to demonstrate the safety and non-toxicity of new chemical (or biological) substances. Non-clinical studies, both in vitro and in vivo, must be planned, performed, monitored, recorded, reported and archived in accordance with the GLP principles, which define a set of rules and criteria for a quality system for the organizational process and the conditions for non-clinical studies. These GLP standards reflect the Organization for Economic Co-operation and Development requirements.

In April 2014, the EU adopted the Clinical Trials Regulation (EU) No 536/2014, or the Clinical Trials Regulation, which replaced the Clinical Trials Directive 2001/20/EC on January 31, 2022. The Clinical Trials Regulation, which is directly applicable in all EU Member States (meaning no national implementing legislation in each EU Member State is required), aims to simplify and streamline the approval of clinical trials in the EU, for example by providing for a streamlined application procedure via a single entry point and simplifying reporting procedures for clinical trial sponsors.

Marketing authorizations

In the EU, medicinal products can only be placed on the market after obtaining a marketing authorization, or MA. This process depends, among other things, on the nature of the medicinal product, but the two routes are either the centralized authorization procedure or one of the national authorization procedures.

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Centralized procedure—Under the centralized procedure, following the opinion of the European Medicines Agency’s, or EMA’s, Committee for Medicinal Products for Human Use, or, CHMP, the European Commission issues a single MA valid across the EU as well as the additional states of the EEA (Iceland, Norway and Liechtenstein). The centralized procedure is compulsory for human medicines derived from biotechnology processes, such as genetic engineering, or advanced therapy medicinal products (i.e. gene therapy, somatic cell therapy and tissue engineered products), products that contain a new active substance indicated for the treatment of certain diseases, (i.e. HIV/AIDS, cancer, neurodegenerative disorders, diabetes, autoimmune diseases and other immune dysfunctions and viral diseases), and officially designated orphan medicinal products. For medicines that do not fall within these categories, an applicant has the option of submitting an application for a centralized MA to the EMA, as long as the medicine concerned contains a new active substance not yet authorized in the EU, is a significant therapeutic, scientific or technical innovation, or if its authorization would be in the interest of public health in the EU. Under the centralized procedure the maximum timeframe for the evaluation of a marketing authorization application, or MAA, by the EMA is 210 days, excluding clock stops, when additional written or oral information is to be provided by the applicant in response to questions asked by the Committee for Medicinal Products for Human Use, or CHMP. Clock stops may extend the timeframe of evaluation of an MAA considerably beyond 210 days. Where the CHMP gives a positive opinion, the EMA provides the opinion together with supporting documentation to the European Commission, who makes the final decision to grant an MA, which is issued within 67 days of receipt of the EMA’s recommendation. In exceptional cases, the CHMP might perform an accelerated review of an MAA in no more than 150 days (not including clock stops). Innovative products that target an unmet medical need and are expected to be of major public health interest may be eligible for certain expedited development and review programs, such as the EMA’s PRIME scheme, which provides incentives similar to the Breakthrough Therapy Designation in the U.S. PRIME is a voluntary scheme aimed at enhancing the EMA’s support for the development of medicines that target unmet medical needs. It is based on increased interaction and early dialogue with companies developing promising medicines, to optimize their product development plans and speed up their evaluation to help them reach patients earlier. Product developers that benefit from PRIME designation can expect to be eligible for accelerated assessment, however this is not guaranteed. The benefits of a PRIME designation include the appointment of a CHMP rapporteur before submission of an MAA, early dialogue and scientific advice at key development milestones, and the potential to qualify products for accelerated review earlier in the application process.

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National authorization procedures—There are also two other possible routes to authorize products for therapeutic indications in several EU Member States, which are available for products that fall outside the mandatory scope of the centralized procedure:

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Decentralized procedure—Under the decentralized procedure, an applicant may apply for simultaneous authorization in more than one EU Member State for medicinal products that have not yet been authorized in any EU Member State.

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Mutual recognition procedure—Under the mutual recognition procedure, a medicine is first authorized in one EU Member State, in accordance with the national procedures of that country. Following this, the applicant may seek additional MAs from other EU Member States in a procedure whereby the countries concerned agree to recognize the validity of the original, national MA.

MAs have an initial duration of five years. After these five years, the authorization may be renewed for an unlimited period on the basis of a reevaluation of the risk-benefit balance by the EMA or the relevant national competent authority, as applicable.

Data and market exclusivity

In the EU, upon receiving an MA, innovative medicinal products, sometimes referred to as new active substances (i.e., reference products) generally qualify for eight years of data exclusivity and an additional two years of market exclusivity. If granted, the data exclusivity period prevents generic or biosimilar applicants from relying on the non-clinical and clinical trial data contained in the dossier of the reference product when applying for a generic or biosimilar MA in the EU during a period of eight years from the date on which the reference product was first authorized in the EU. During the additional two-year period of market exclusivity, a generic/biosimilar MAA can be submitted, and the innovator’s data may be referenced, but no generic or biosimilar product can be marketed in the EU until the expiration of the market exclusivity period. The overall ten-year period can be extended to a maximum of eleven years if, during the first eight years of those ten years, the MA holder obtains an MA for one or more new therapeutic indications which, during the scientific evaluation prior to their MA, are held to bring a significant clinical benefit in comparison with existing therapies. However, there is no guarantee that a product will be considered by the EMA or Member State regulatory authorities to be a new active substance, and products may not qualify for data exclusivity. Even if a product gains the prescribed period of data exclusivity, another company may market another version of the product if such company obtained a marketing authorization based on an application with a complete and independent data package of pharmaceutical tests, preclinical tests and clinical trials.

Orphan medicinal products

The criteria for designating an “orphan medicinal product” in the EU are similar in principle to those in the U.S. In the EU, a medicinal product may be designated as orphan if (i) it is intended for the diagnosis, prevention or treatment of a life-threatening or chronically debilitating condition; (ii) either (a) such condition affects no more than five in 10,000 persons in the EU when the application is made, or (b) it is unlikely that the product, without the benefits derived from orphan status, would generate sufficient return in the EU to justify the investment in its development; and (iii) there exists no satisfactory method of diagnosis, prevention or treatment of such condition authorized for marketing in the EU, or if such a method exists, the product will be of a significant benefit to those affected by that condition. The application for orphan designation must be submitted before the MAA. Orphan medicinal products are eligible for financial incentives such as reduction of fees or fee waivers and are, upon grant of an MA, entitled to ten years of market exclusivity for the approved therapeutic indication. During this ten-year orphan market exclusivity period, no MAA shall be accepted in the EU for the same indication in respect of a similar medicinal product to the authorized orphan product. A “similar medicinal product” is defined as a medicinal product containing a similar active substance or substances as contained in an authorized orphan medicinal product, and which is intended for the same therapeutic indication. An orphan medicinal product can also obtain an additional two years of market exclusivity in the EU for pediatric studies. No extension to any supplementary protection certificate can be granted on the basis of pediatric studies for orphan indications. Orphan designation does not convey any advantage in, or shorten the duration of, the regulatory review and approval process.

The ten-year market exclusivity may be reduced to six years if, at the end of the fifth year, it is established that the product no longer meets the criteria for orphan designation, for example, if the product is sufficiently profitable not to justify maintenance of market exclusivity. Additionally, an MA may be granted to a similar medicinal product for the same indication as an authorized orphan product at any time if (i) it is established that a similar medicinal product is safer, more effective or otherwise clinically superior than the authorized orphan product; (ii) the MA holder of the authorized orphan product consents to the second medicinal product authorization; or (iii) the MA holder of the authorized orphan product cannot supply enough orphan medicinal product.

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Pediatric development

In the EU, MAAs for new medicinal products must include the results of trials conducted in the pediatric population, in compliance with a pediatric investigation plan, or PIP, agreed with the EMA’s Pediatric Committee, or PDCO, unless the EMA has granted a product-specific waiver, a class waiver, or a deferral for one or more of the measures included in the PIP. This requirement also applies when a company wants to add a new indication, pharmaceutical form or route of administration for a medicine that is already authorized. The PIP sets out the timing and measures proposed to generate data to support a pediatric indication of the product for which an MA is being sought. The PDCO can grant a deferral of the obligation to implement some or all of the measures of the PIP until there are sufficient data to demonstrate the efficacy and safety of the product in adults. Further, the obligation to provide pediatric clinical trial data can be waived by the PDCO when these data are not needed or appropriate because the product is likely to be ineffective or unsafe in children, the disease or condition for which the product is intended occurs only in adult populations, or when the product does not represent a significant therapeutic benefit over existing treatments for pediatric patients. Products that are granted an MA with the results of the pediatric clinical trials conducted in accordance with the PIP are eligible for a six month extension of the protection under an SPC (provided an application for such extension is made at the same time as filing the SPC application for the product, or at any point up to 2 years before the SPC expires) even where the trial results are negative. This pediatric reward is subject to specific conditions and is not automatically available when data in compliance with the PIP are developed and submitted.

Post-approval requirements

Similar to the United States, both MA holders and manufacturers of medicinal products are subject to comprehensive regulatory oversight by the EMA, the European Commission and/or the competent regulatory authorities of the EU Member States. The holder of an MA must establish and maintain a pharmacovigilance system and appoint an individual qualified person for pharmacovigilance who is responsible for oversight of that system. Key obligations include expedited reporting of suspected serious adverse reactions and submission of periodic safety update reports, or PSURs. All new MAAs must include a risk management plan, or RMP, describing the risk management system that the company will put in place and documenting measures to prevent or minimize the risks associated with the product. The regulatory authorities may also impose specific obligations as a condition of the MA. Such risk-minimization measures or post-authorization obligations may include additional safety monitoring, more frequent submission of PSURs, or the conduct of additional clinical trials or post-authorization safety studies.

The advertising and promotion of medicinal products is also subject to laws concerning promotion of medicinal products, interactions with physicians, misleading and comparative advertising and unfair commercial practices. All advertising and promotional activities for the product must be consistent with the approved summary of product characteristics, and therefore all off-label promotion is prohibited. Direct-to-consumer advertising of prescription medicines is also prohibited in the EU. Although general requirements for advertising and promotion of medicinal products are established under EU Directives, the details are governed by regulations in each EU Member State and can differ from one country to another.

Failure to comply with EU and Member State laws that apply to the conduct of clinical trials, manufacturing approval, authorization of medicinal products and marketing of such products, both before and after grant of the MA, manufacturing of pharmaceutical products, statutory health insurance, bribery and anti-corruption or with other applicable regulatory requirements may result in administrative, civil or criminal penalties. These penalties could include delays or refusal to authorize the conduct of clinical trials, or to grant an MA, product withdrawals and recalls, product seizures, suspension, withdrawal or variation of the MA, total or partial suspension of production, distribution, manufacturing or clinical trials, operating restrictions, injunctions, suspension of licenses, fines and criminal penalties.

The aforementioned EU rules are generally applicable in the European Economic Area, or EEA, which consists of the 27 EU Member States plus Norway, Liechtenstein and Iceland. For other countries outside of the EU, such as countries in Latin America or Asia, the requirements governing the conduct of clinical studies, product licensing, pricing and reimbursement vary from country to country. In all cases, again, the clinical studies are conducted in accordance with GCP and the applicable regulatory requirements and the ethical principles that have their origin in the Declaration of Helsinki.

Should we utilize third-party distributors, compliance with such foreign governmental regulations would generally be the responsibility of such distributors, who may be independent contractors over whom we have limited control.

Reform of the Regulatory Framework in the EU

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The European Commission introduced legislative proposals in April 2023 that, if implemented, will replace the current regulatory framework in the EU for all medicines (including those for rare diseases and for children). In April 2024, the European Parliament adopted its position on the legislative proposals, and in June 2025, the Council of the EU adopted its position. A common position on the text has been agreed upon on December 11, 2025, in the context of subsequent inter-institutional trilogue negotiations. The proposed revisions remain to be adopted, and are not expected to become applicable before 2028.

Brexit and the regulatory framework in the United Kingdom

Following the end of the Brexit transition period on January 1, 2021 and the implementation of the Windsor Framework on January 1, 2025, the United Kingdom, or UK, is not generally subject to EU laws in respect of medicines. The EU laws that have been transposed into UK law through secondary legislation remain applicable in the UK however, new legislation such as the EU Clinical Trials Regulation is not applicable in the UK. As a result of the Northern Ireland protocol, different rules applied in Northern Ireland than in England, Wales, and Scotland, together, Great Britain or GB, for a period following Brexit, which continued to follow the EU regulatory regime. However, on January 1, 2025 a new arrangement called the “Windsor Framework” came into effect and reintegrated Northern Ireland under the regulatory authority of the Medicines and Healthcare products Regulatory Agency, or MHRA, with respect to medicinal products. The Windsor Framework removes EU licensing processes and EU labeling and serialization requirements in relation to Northern Ireland and introduces a UK-wide licensing process for medicines. In particular, the MHRA is now responsible for approving medicinal products placed on the UK market (i.e., Great Britain and Northern Ireland), and the EMA no longer has a role in UK marketing authorizations. A single UK-wide MA will be granted by the MHRA for medicinal products to be sold in the UK, enabling products to be sold in a single pack and under a single authorization throughout the UK. In addition, the new arrangements require, for packs placed on the UK market on or after January 1, 2025, a “UK Only” label, indicating they are not for sale in the EU. However, although separate authorization is now required to market medicinal products in the UK, since January 1, 2024, the MHRA may rely on the International Recognition Procedure, or IRP, when reviewing certain types of MAAs. Pursuant to the IRP, the MHRA will take into account the expertise and decision-making of trusted regulatory partners (e.g., the medicines regulatory authorities in Australia, Canada, Switzerland, Singapore, Japan, the U.S., and the EMA in the EU) when considering an application for a UK marketing authorization. There is no pre-MA orphan designation in the UK. Instead, the MHRA reviews applications for orphan designation in parallel to the corresponding MAA. The criteria are essentially the same, but have been tailored for the market, i.e., the prevalence of the condition in the UK (rather than the EU) must not be more than five in 10,000. Should an orphan designation be granted, the period of market exclusivity will be set from the date of first approval of the product in the UK.

Employees and human capital resources

As of December 31, 2025, we had 150 full-time employees, of which 71 have M.D. or Ph.D. degrees. Within our workforce, 118 employees are engaged in research and development and 32 are engaged in business development, finance, legal, and general management and administration. None of our employees are represented by labor unions or covered by collective bargaining agreements. We consider our relationship with our employees to be good.

Our human capital resources objectives include, as applicable, identifying, recruiting, retaining, incentivizing and integrating our existing and new employees, advisors and consultants. The principal purposes of our equity incentive plans are to attract, retain and reward personnel through the granting of equity-based compensation awards in order to increase shareholder value and the success of our company by motivating such individuals to perform to the best of their abilities and achieve our objectives.

Available Information

Investors and others should note that we announce material information to our investors using our investor relations website (https://ir.monterosatx.com/), SEC filings, press releases, public conference calls and webcasts. We use these channels as well as social media, including LinkedIn and our X (@MonteRosaTx), to communicate with the public about our company, our business, our product candidates and other matters. It is possible that the information we post on social media could be deemed to be material information. Therefore, we encourage investors, the media, and others interested in our company to review the information we post on the social media channels listed on our investor relations website. Information that is contained in and can be accessed through our website or our social media posts are not incorporated into, and does not form a part of, this Annual Report on Form 10-K.

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We file Annual Reports on Form 10-K, Quarterly Reports on Form 10-Q, Current Reports on Form 8-K, proxy statements and other information with the SEC. Our filings with the SEC are available on the SEC’s website at www.sec.gov.

We make available, free of charge, in the Investor Relations section of our website, documents we file with or furnish to the SEC, including our Annual Reports on Form 10-K, Quarterly Reports on Form 10-Q, Current Reports on Form 8-K, including exhibits, proxy and information statements and amendments to those reports. We make this information available as soon as reasonably practicable after we electronically file such materials with, or furnish such information to, the SEC. The other information found on our website is not part of this or any other report we file with, or furnish to, the SEC. Copies of such documents are available in print at no charge to any shareholder who makes a request. Such requests should be made to our corporate secretary at our corporate headquarters, 321 Harrison Avenue, Suite 900, Boston, MA 02118.