Evommune, Inc. (EVMN) Business

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Item 1. Business.

Overview

Evommune is a clinical-stage biotechnology company developing innovative therapies that target key drivers of chronic inflammatory diseases, with initial clinical development programs focusing on chronic spontaneous urticaria (“CSU”), atopic dermatitis (“AD”) and ulcerative colitis (“UC”). Chronic inflammation is a significant healthcare problem in the world, substantially impacting patients’ quality of life and leading to life-threatening conditions. These conditions, if not prevented, ultimately lead to fatal diseases, such as cardiovascular diseases, diabetes and cancer, which contribute to three out of every five deaths worldwide and result in an estimated $90 billion of annual cost to the healthcare system in the United States.

Our mission is to improve patients’ daily lives and prevent the long-term effects of uncontrolled inflammation that are a consequence of the limitations of existing therapies. To achieve this, we are advancing a portfolio of differentiated product candidates that target key drivers of chronic inflammation.

Our management team’s proven drug development expertise and experience in the field of immunology and inflammation, combined with advanced scientific tools, enable us to identify and advance potent, highly selective molecules with distinctive mechanisms of action. By identifying treatment gaps of chronic inflammatory diseases, we strive to transform the treatment landscape, developing therapies that have the potential to offer rapid symptom relief and provide safe, durable resolution of the underlying disease. Among our portfolio of programs, we currently have two product candidates, EVO756 and EVO301, in Phase 2 development. We are initially developing EVO756 for the treatment of CSU and AD, and EVO301 for the treatment of AD and UC. We see broad expansion potential for both programs across additional chronic inflammatory diseases. We also intend to advance additional preclinical programs into clinical development.

Our most advanced clinical-stage product candidate, EVO756, is a potent and highly selective oral small molecule antagonist of MRGPRX2, a receptor predominantly found on mast cells and peripheral sensory neurons. Dysregulated MRGPRX2 activity can play a key role as both a catalyst and perpetuator of disease pathogenesis across a multitude of systemic chronic inflammatory diseases. By targeting MRGPRX2, we believe EVO756 is the only dual mechanism clinical approach that modulates both mast cells and peripheral sensory neurons, representing a new potential therapeutic option to reduce inflammation and provide rapid relief of itch (pruritus). Mast cells are critical regulators of immune response and can be found in most vascularized tissues including skin, lung and the digestive tract. These cells tend to be distributed in close proximity to peripheral sensory neurons, where the activation of the neurons can trigger the inflammatory cascade and mast cells are implicated in further perpetuating neuroinflammation and its related symptoms. We believe MRGPRX2 is the only clinical approach aimed at inhibiting this neuroimmune interaction.

We previously announced the topline results from a Phase 1 proof-of-concept trial in 132 healthy volunteers designed to assess the safety, tolerability, pharmacokinetic (“PK”) properties and pharmacodynamic (“PD”) properties of orally administered EVO756. Comprehensive trial results were presented at the UCARE Global Urticaria Forum meeting in December 2024. EVO756 was observed to be well-tolerated at all doses tested, with no serious adverse events (“SAEs”), and PK results supporting daily dosing. A skin challenge test was also conducted in the multiple ascending dose (“MAD”) portion of the trial in which icatibant, a known MRGPRX2 ligand, representative of a broad class of disease relevant ligands, was administered via intradermal injection to healthy volunteers creating measurable wheals on their skin. EVO756 was observed to robustly decrease the healthy volunteers’ wheals induced by icatibant, evidencing meaningful target engagement at all doses tested. We are currently conducting a Phase 2b trial of EVO756 in CSU and have completed a Phase 2 trial of EVO756 in chronic inducible urticaria (“CIndU” and together with CSU, chronic urticarias or “CU”).

In May 2025, we reported topline results from our U.S. multicenter Phase 2 trial of EVO756 in CIndU that demonstrated clinical activity (including improvement in FricTest score and pruritus numerical rating score (“pruritus-NRS”), as described below) in a patient population with symptomatic dermographism. The trial was designed to generate additional patient data in a population with symptomatic dermographism, which we believe is highly translatable to the CSU patient population due to overlapping disease biology and shared pathophysiology. Third party trials have demonstrated that symptomatic dermographism affects approximately 25% of the CSU patient population; similarly, we believe EVO756’s clinical activity in symptomatic dermographism patients strongly supports the role of MRGPRX2 in neurogenic inflammation, which plays a crucial role in AD.

A total of 30 patients were enrolled in the trial, with 11 patients enrolled in the 300 mg once daily (“QD”) cohort and 19 patients enrolled in the 50 mg twice daily (“BID”) cohort. Rapid clinical activity was observed in both dosing regimens, with some patients demonstrating responses by week one in both FricTest score (a clinician-rated measure of symptomatic dermographism severity ranging from 0 to 4, with higher scores indicating greater severity) and pruritus-NRS. 70% (n=19) of the 27 observed patients demonstrated improvement at just four weeks, with 30% (n=8) of the observed patients achieving a complete response (achieving a FricTest score of zero), of which 50% were immunoglobulin E (“IgE”) high (as defined by a serum IgE level of ≥100 IU/mL). An additional 11% (n=3) achieved a partial response as defined by a ≥2-point decrease in FricTest score and a further 30% (n=8) demonstrated a one-point decrease in FricTest score. The population of subjects observed at four weeks does not include three patients who were unevaluable or lost to follow-up. Observed patients in the 300 mg QD cohort saw an average reduction of 1.4 points in FricTest score after four weeks and observed patients in the 50 mg BID cohort saw an average reduction of 1.5 points. By comparison, in separate, independent trials conducted by third parties, patients treated with 300 mg omalizumab saw a reduction of 1.4 points and patients treated with 300 mg barzolvolimab saw a reduction of 1.6 points in FricTest score after four weeks. EVO756 was observed to be well-tolerated at both dose levels, including the higher 300 mg QD dose. No SAEs were observed and there were no discontinuations due to adverse events (“AEs”).

We initiated a Phase 2b dose-ranging trial in CSU in April 2025 and expect to report initial results in the second quarter of 2026. We also initiated a Phase 2b dose-ranging trial in moderate-to-severe AD patients in August 2025 and expect to report initial results in the second half of 2026. We plan to evaluate EVO756 in additional indications in which mast cell degranulation and neuroinflammation are key drivers of disease, with migraine being our next indication of interest where we plan to initiate a Phase 2b trial in mid-2026.

Our second clinical-stage product candidate, EVO301, is a long-acting fusion protein consisting of an IL-18 binding protein (“BP”) and an anti-serum albumin Fab-associated (“SAFA”) domain. IL-18 is a pro-inflammatory cytokine of the IL-1 family that regulates various immune processes that drive inflammation and is a potent modulator of ongoing inflammation. The IL-18 pathway is believed to play a key role in the severity and progression of several large, highly prevalent chronic inflammatory disease populations with a significant number of uncontrolled patients, including AD and UC. The SAFA domain incorporated into EVO301 utilizes neonatal fragment crystallizable receptor (“FcRn”)-mediated recycling of serum albumin to extend half-life. We believe EVO301’s optimized approach to IL-18 binding and neutralization could enable significant advantages and differentiated clinical outcomes for patients, including with respect to efficacy, tissue distribution, dosing profile and reduced immunogenicity risk. In addition, EVO301’s distinct mechanism and modality complement those of EVO756, providing us with multiple potential avenues to bring innovative therapeutics to the large, underserved and rapidly expanding population of patients suffering from chronic inflammatory diseases.

In February 2026, we announced positive top-line results from a randomized, double-blind, placebo-controlled Phase 2a trial evaluating EVO301 in adult patients with moderate-to-severe AD. The trial met its primary efficacy endpoint at week 12 and achieved highly statistically significant outcomes in adult patients with moderate-to-severe AD. The 70-patient trial was designed to evaluate the safety and efficacy of intravenous dosing of 5 mg/kg on day 1 and day 28 (n=48 active, n=22 placebo) over 12 weeks. The trial met its primary endpoint, demonstrating clinically meaningful activity in AD with statistical significance over placebo achieved at weeks 4, 8 and 12 at p0.01. We believe demonstrating this activity with an IL-18 targeting therapy supports the relevance of this pathway in disease pathophysiology and reinforces that pathways beyond classic Th2 biology can contribute meaningfully to disease activity. Expanding therapeutics to target novel mechanisms like IL 18 could offer benefit for patients who remain uncontrolled on existing therapies and reinforces the urgent need to develop more options across the growing AD population. We plan to rapidly move a subcutaneous formulation of EVO301 into a Phase 2b trial in AD where we believe optimized and more frequent dosing of EVO301 could achieve potential best-in-class Eczema Area and Severity Index (“EASI”) activity.

Beyond AD, we are evaluating a potential Phase 2 trial in moderate-to-severe UC patients. We may also evaluate EVO301 in Crohn’s disease, certain cardiovascular-related inflammatory conditions, and other additional indications, in which dysregulation of the IL-18 pathway contributes to chronic inflammation and tissue damage driving disease pathology. The figure below provides an overview of our current clinical pipeline:

Figure 1: Our Clinical Pipeline

Notes: (1) Other potential indications for EVO756 include asthma, interstitial cystitis, irritable bowel syndrome and pruritus. To date, based on our data from the successful completion of our Phase 1 proof-of-concept trial of EVO756 in healthy volunteers, we believe there is a path to proceed to Phase 2 clinical development for these other indications, similar to our initiation of our Phase 2b trial in AD, subject to standard regulatory requirements. (2) We are currently prioritizing development in other indications ahead of CIndU and may conduct additional CIndU trials in the future.

In addition to our clinical programs, we are advancing a pipeline of preclinical candidates for immunology and inflammation indications and aim to deliver a steady cadence of data for our new programs.

Our Approach to Drug Development and Chronic Inflammation

Collectively, our team members have held leadership roles at over 25 companies and have played key roles in the discovery and development of nearly 30 approved small molecules and biologics, primarily in immunology and inflammation, including Ebglyss (lebrikizumab), Cimzia (certolizumab pegol) and Rezurock (belumosudil). These therapies have significantly impacted patient outcomes, generated billions of dollars in sales and have led to multiple company acquisitions. This experience has informed our approach to drug development and commercialization to become one focused on identifying the areas of highest unmet need in chronic inflammatory diseases, identifying the molecules with the highest probability of improving patient outcomes in those diseases and then advancing our molecules through rigorous and thoughtful development programs.

Our deep knowledge of immunology and inflammation enables us to focus our efforts on key drivers of disease in which a single therapeutic could treat a broad range of indications and address areas of significant unmet need. We prioritize targets with high potential for meaningful patient outcomes and commercial value.

As we discover or in-license product candidates and advance them into the clinic, we design development strategies to rapidly establish proof-of-concept and apply stringent criteria to decide which product candidates should move forward. At every stage, we focus on advancing differentiated candidates that we believe have the highest potential for clinical advancement, guided by regulatory, clinical and commercial considerations.

EVO756, Targeting MRGPRX2 for Chronic Inflammatory Diseases

Mast cells are critical regulators of immune response and can be found in most vascularized tissues including skin, lung and the digestive tract. These cells tend to be distributed in close proximity to peripheral sensory neurons, where the activation of the neurons can trigger the inflammatory cascade and mast cells are implicated in further perpetuating neuroinflammation and its related symptoms. We believe MRGPRX2 is the only clinical approach aimed at inhibiting this neuroimmune interaction. In addition, the cytoplasm of mast cells contains numerous membrane-bound granules that are filled with inflammatory mediators such as histamine and tryptase. When activated under normal conditions, mast cells degranulate, releasing their inflammatory mediators to protect against infections and toxins. They also may play a role in wound healing, angiogenesis (formation of new blood vessels) and initiating adaptive immune responses. However, aberrant activation of MRGPRX2 triggers excessive inflammation, resulting in symptoms such as hives (urticarial wheals), itch, pain, swelling and redness in a multitude of systemic chronic inflammatory diseases across organ systems. We are initially developing EVO756 for the treatment of CSU and AD, but we see broad expansion potential across additional chronic inflammatory diseases as illustrated in the figure below.

Figure 2: EVO756 Proof-of-Concept Roadmap

Notes: (1) Proof-of-concept based on skin challenge test in healthy volunteers.

(2) Proof-of-concept supported by positive clinical data for PACAP (MRGPRX2 ligand) inhibition in migraine prophylaxis (Lundbeck)

EVO756 for the Treatment of Chronic Spontaneous Urticaria

We are progressing the development of EVO756 for CSU, our current lead indication, and have completed an exploratory trial in CIndU. Many patients with CSU are known to also suffer from CIndU. Given the overlapping patient populations and shared underlying biology, we believe aspects of clinical development in CIndU can meaningfully inform that of CSU. In the United States, there are currently an estimated 3,000,000 patients with CSU and 850,000 patients with CIndU. CSU is a chronic inflammatory disease characterized by spontaneous and recurrent hives and angioedema without a known environmental trigger. In contrast, CIndU is triggered by specific physical stimuli such as cold, pressure, friction or heat.

The current landscape of approved and investigational therapeutics for CSU and CIndU lacks a safe, convenient and efficacious treatment option that could be utilized by a broad range of prescribers as a first-line treatment post-antihistamines. While initial treatment for these patients consists of over-the-counter oral antihistamines, it is estimated that greater than half of these patients do not achieve adequate symptom or disease control. There are currently only three available treatments for antihistamine-refractory patients, Xolair (omalizumab), a once monthly subcutaneous IgE mAb, Dupixent (dupilumab), a twice monthly subcutaneous mAb modulating the IL-4 and IL-13 signaling cascade, and Rhapsido (remibrutinib), a twice daily oral Bruton’s tyrosine kinase (BTK) inhibitor approved September 2025, all of which have significant limitations. Xolair has been on-market since 2004 and was approved for use in CSU in 2014; however, its use in CSU has been constrained by safety concerns and limited efficacy, as well as barriers related to monitoring requirements after in-office administration. Dupixent was first approved in 2017 for AD and was subsequently approved for CSU in 2025. Nonetheless, Dupixent has failed in multiple CIndU trials and has failed to show statistically significant improvements in efficacy over the standard of care in omalizumab-refractory or intolerant CSU patients. Early efficacy and itch improvement remains a concern for CSU patients, with approximately 55% to 66% of patients treated with Xolair experiencing itch and hives at 12 weeks and approximately 70% of Xolair-naïve patients treated with Dupixent experiencing itch and hives at 24 weeks. Rhapsido has side effects

on its label including nasopharyngitis, bleeding, headache, nausea and abdominal pain, along with drug interactions recommending against its use with multiple classes of drugs. We believe these limitations play a role in these treatments only being utilized by an estimated 10% of antihistamine-refractory patients. Given there are currently over 3,000,000 patients living with CSU and more than 850,000 patients living with CIndU, we estimate that over 500,000 CU patients who are antihistamine-refractory are untreated and have uncontrolled disease.

We conducted a Phase 1 proof-of-concept randomized, placebo-controlled trial in 132 healthy volunteers designed to assess the safety, tolerability, PK properties and PD properties of orally administered EVO756. Comprehensive trial results were presented at the UCARE Global Urticaria Forum meeting in December 2024. The Phase 1 trial enrolled 55 healthy adults in a single ascending dose (“SAD”) portion and 77 healthy adults in a MAD portion in which participants were treated for 14 days. EVO756 was observed to have an encouraging tolerability profile at all doses tested, including the highest QD dose of 500 mg, with no SAEs observed. A skin challenge test was also conducted in the MAD portion of the trial in which icatibant, representative of a broad class of disease relevant ligands, was administered via intradermal injection to healthy volunteers creating measurable wheals on their skin. EVO756 was observed to robustly decrease the healthy volunteers’ wheals induced by icatibant, evidencing meaningful target engagement at all doses tested. We believe this proof-of-concept portion of the trial supports the potential benefits of EVO756 in CSU.

In May 2025, we reported topline results from our U.S. multicenter Phase 2 trial of EVO756 in CIndU that demonstrated clinical activity (including improvement in FricTest score and pruritus-NRS, as described below) in a patient population with symptomatic dermographism. CIndU is a form of urticaria that has known environmental triggers, including pressure or exposure to cold and has underlying disease pathogenesis similar to CSU. The trial was designed to generate additional patient data in a population with symptomatic dermographism, which we believe will be highly translatable to the CSU patient population given the shared pathologies. Third party trials have demonstrated that symptomatic dermographism affects approximately 25% of the CSU patient population; similarly, we believe EVO756’s clinical activity in symptomatic dermographism patients strongly supports the role of MRGPRX2 in neurogenic inflammation, which plays a crucial role in AD.

A total of 30 patients were enrolled in the trial, with 11 patients enrolled in the 300 mg QD cohort and 19 patients enrolled in the 50 mg BID cohort. Rapid clinical activity was observed in both dosing regimens, with some patients demonstrating responses by week one in both FricTest score (complete response score of zero) and pruritus-NRS (≥2-point decrease). 70% (n=19) of the 27 observed patients demonstrated improvement at just four weeks, with 30% (n=8) of the observed patients achieving a complete response (achieving a FricTest score of zero (a clinician rated measure of symptomatic dermographism severity ranging from 0 to 4, with higher scores indicating greater severity)), of which 50% were IgE high (as defined by a serum IgE level of ≥100 IU/mL). An additional 11% (n=3) achieved a partial response as defined by a ≥2-point decrease in FricTest score and a further 30% (n=8) demonstrated a one-point decrease in FricTest score. The population of subjects observed at four weeks does not include three patients who were unevaluable or lost to follow-up. Observed patients in the 300 mg QD cohort saw an average reduction of 1.4 points in FricTest score after four weeks and observed patients in the 50 mg BID cohort saw an average reduction of 1.5 points. By comparison, in separate, independent trials conducted by third parties, patients treated with 300 mg omalizumab saw a reduction of 1.4 points and patients treated with 300 mg barzolvolimab saw a reduction of 1.6 points in FricTest score after four weeks as shown in Figures 4 and 5 below.

Both the QD and BID regimens were observed to result in rapid and meaningful itch relief. Observed patients in the 300 mg QD cohort experienced an average reduction of 2.4 in pruritus-NRS, while those in the 50 mg BID cohort saw an average reduction of 2.1 points. Importantly, 93% (n=25) of observed patients demonstrated improvement at just four weeks in either FricTest or pruritus-NRS. Further, 75% (n=6) of those who did not achieve a decrease in FricTest score demonstrated a decrease in pruritus-NRS, evidencing the impact of EVO756 on itch at this early time-point, even in the absence of FricTest response. EVO756 was observed to be well-tolerated at both dose levels, including the higher 300 mg QD dose. No SAEs were observed and there were no discontinuations due to AEs. The figure below illustrates the clinical data, including FricTest improvement at four weeks, generated in our Phase 2 CIndU trial of EVO756:

Figure 3: EVO756 FricTest Score Improvements and Other Observed Data

The figures below illustrate the clinical improvements over time for omalizumab and barzolvolimab:

Figure 4: Omalizumab Clinical Activity Improved Over Time

Notes: Direct comparisons cannot be made in the absence of head-to-head trials because of differences in trial design, patient population and other factors.

Figure 5: Barzolvolimab Clinical Activity Improved Over Time

Notes: Direct comparisons cannot be made in the absence of head-to-head trials because of differences in trial design, patient population and other factors.

Examining historical trial data from mast cell targeting therapeutic agents that have been evaluated in CSU and CIndU suggests that CIndU response rate may correlate with clinical response in treating CSU. Our Phase 2 trial of EVO756 in CIndU was designed to generate additional patient data in a population with symptomatic dermographism, which we believe will be highly translatable to the CSU patient population given the shared pathologies. Figure 6 below details selected competitor therapeutic agents that have entered clinical development in CU, highlighting that targeting mast cells potentially indicates translatability from CIndU to CSU:

Figure 6: CIndU Response as a Potential Indicator of Future CSU Profile

Notes: Direct comparisons cannot be made in the absence of head-to-head trials because of differences in trial design, patient population and other factors. Data is presented for information only and does not account for differences in enrollment populations or other cross-trial variabilities.

In CSU, we initiated a Phase 2b dose-ranging trial in approximately 160 moderate-to-severe antihistamine-refractory CSU patients and expect initial data from that trial in the second quarter of 2026. This is a randomized, double-blind, placebo-controlled trial in which participants will receive one of three active dose regimens or placebo. The primary endpoint of the trial is change in a patient’s Urticaria Activity Score over seven days (“UAS7”) at 12 weeks. Beyond the primary endpoint, we are also evaluating other measures of disease, including itch, hive severity and angioedema.

EVO756 for the Treatment of Atopic Dermatitis

Atopic dermatitis, commonly referred to as eczema, is one of the most prevalent chronic inflammatory diseases and is characterized by acute flares of itchy, red, exudative papules and persistently dry, scaly skin. The hallmark feature of AD is intense inflammatory itch, known as pruritus, with episodic flares of rash and underlying chronic inflammation. For most moderate-to-severe AD patients, the disease significantly impacts patients’ quality of life, driven primarily by relentless itch, sleep disruption and visible skin symptoms. The intense itch associated with AD often triggers an itch-scratch cycle, further compromising the epidermal barrier and exacerbating disease. While AD commonly begins in childhood, it is also highly and increasingly prevalent in adults, with about 15% to 20% of children and 1% to 3% of adults impacted, significantly disrupting their quality of life.

Research indicates that mast cells and peripheral sensory neurons play a key role in the pathogenesis of AD. One known driver of AD is the chronic and cyclical release of pro-inflammatory mediators associated with mast cell degranulation. Heightened mast cell activity promotes inflammation and drives itch, while activation of peripheral sensory neurons amplifies the sensation of itch. Third party studies have shown increased mast cell density, elevated MRGPRX2 expression and neuroinflammation correlate with disease severity in lesional AD skin. For example, a third-party study examined the number of mast cells from lesional and non-lesional skin of AD patients and skin of healthy volunteers. The biopsies showed that in AD lesional skin, more mast cells were found as compared to non-lesional skin. In addition, in a third-party preclinical mouse study, AD severity was shown to be specifically associated with MRGPRX2 expression. Internal research conducted by us identified key MRGPRX2 ligands and MRGPRX2 as more abundant in lesional skin. Additionally, our internal research has verified MRGPRX2 expression in sensory neurons and that EVO756 robustly decreased sensory neuron activation when stimulated. Collectively, we believe these findings highlight the MRGPRX2 activation pathway in AD and support the rationale for targeting MRGPRX2 to resolve both skin lesions and itch by modulating mast cells and peripheral sensory neurons.

The current standard of care for first-line treatment of AD are primarily topical corticosteroids and targeted treatments (for example, topical Janus kinase (“JAK”) inhibitor). However, approximately 40% to 50% of AD patients have a moderate-to-severe form of the disease and thus are uncontrolled by topical therapies. For these patients, new systemic agents have emerged as the preferred advanced treatments that target several different inflammatory mediators that contribute to underlying inflammation and flare-ups, including Dupixent (dupilumab), Rinvoq (upadacitinib) and Cibinqo (abrocitinib). Despite the effectiveness of these therapies, some of them are associated with serious risk of life-threatening side effects and carry boxed warnings.

We are developing EVO756 for the treatment of moderate-to-severe AD in adult and pediatric patients whose disease remains uncontrolled with prescription topical therapies. We initiated a Phase 2b dose-ranging trial in moderate-to-severe AD patients in August 2025 and expect to report initial results in the second half of 2026. The primary endpoint is change in EASI score at 12 weeks, and we also plan on assessing Investigator Global Assessment (“IGA”) and pruritus-NRS. In addition, should EVO756 demonstrate a positive treatment effect on itch in the Phase 2b dose-ranging trial, we may subsequently evaluate its potential in other forms of inflammatory itch (pruritus).

Additional Development Opportunities for EVO756

Beyond CSU and AD, there are a number of other systemic chronic inflammatory diseases in which mast cell degranulation and neuroinflammation are implicated, including areas where we believe EVO756 could fulfill significant unmet patient needs. Additional diseases in which we are exploring the potential of MRGPRX2 inhibition include migraine, asthma, interstitial cystitis, irritable bowel syndrome and pruritus. Our next indication of interest is migraine and we plan to initiate a Phase 2b trial in mid-2026. Initiation of a Phase 2 trial in any of these additional indications will be determined based on ongoing trials and corporate resources. To date, based on our data from the successful completion of our Phase 1 proof-of-concept trial of EVO756 in healthy volunteers, we believe there is a path to proceed to Phase 2 clinical development for these other indications, similar to our initiation of our Phase 2b trial in AD, subject to standard regulatory requirements.

EVO301, Our SAFA Binding Protein Targeting IL-18 for Chronic Inflammatory Diseases

Our second clinical-stage product candidate, EVO301, is currently in Phase 2 development for the treatment of moderate-to-severe AD. In June 2024, we secured exclusive global rights to develop and commercialize EVO301 from AprilBio Co. Ltd. (“AprilBio”) (Kosdaq: 397030), a biopharmaceutical company based in South Korea dedicated to developing specialized biologics and antibody drugs, after they progressed EVO301 through a Phase 1 trial.

IL-18 is a pro-inflammatory cytokine of the IL-1 family that not only regulates various immune processes that drive inflammation, but also acts as a potent modulator of ongoing inflammation. The IL-18 pathway is believed to play a role in the severity and progression of several large, highly prevalent chronic inflammatory disease populations with a significant number of uncontrolled patients, including AD and UC.

EVO301 is a long-acting injectable SAFA-IL-18BP fusion protein consisting of a native human IL-18BP domain linked to a human Fab antibody fragment-targeting albumin, designed to neutralize the IL-18 inflammatory pathway. We believe this design, differentiated from mAbs targeting IL-18, potentially confers several advantages including improved activity, decreased immunogenicity and better distribution to sites of inflammation. Based on learnings from biologics targeting other inflammatory targets, we believe these benefits may provide faster onset of action and deliver comparable or better efficacy results to commercially available biologics while potentially offering better tolerability, durability, safety and more convenient dosing.

In a Phase 1 randomized, placebo-controlled SAD trial conducted in 31 healthy volunteers, EVO301 was observed to be well-tolerated at all doses tested, with no SAEs or discontinuations due to AEs. PK observations were favorable and support monthly dosing.

Beyond AD, we are evaluating a potential Phase 2 trial in moderate-to-severe UC patients. We may also evaluate EVO301 in Crohn’s disease, certain cardiovascular-related inflammatory conditions, and additional indications in which dysregulation of the IL-18 pathway may contribute to chronic inflammation and tissue damage driving disease pathology. To date, based on the data from the successful completion of the Phase 1 and Phase 2 trials of EVO301, we believe there is a path to proceed to Phase 2 clinical development for these other indications, subject to standard regulatory requirements.

We believe EVO301’s distinct mechanism and modality complement those of EVO756, providing us with multiple potential avenues to bring innovative therapeutics to the large, underserved and rapidly expanding patient population suffering from chronic inflammatory diseases.

Other Drug Discovery and Development

Beyond our clinical-stage product candidates, we are advancing a suite of discovery-stage programs to broaden and diversify our portfolio. We aim to deliver a steady cadence of clinical data, in line with our vision of addressing chronic inflammatory diseases across multiple pathways and indications.

EVO756: Our MRGPRX2 Antagonist

Overview

Our most advanced clinical-stage product candidate, EVO756, is a potent and highly selective oral small molecule antagonist of MRGPRX2. Dysregulated MRGPRX2 activity is implicated in a range of systemic chronic inflammatory diseases, acting both as a catalyst and perpetuator of disease pathology. The blockade of MRGPRX2 represents an innovative, targeted, dual mechanism approach for the treatment of multiple systemic chronic inflammatory diseases across different organs by inhibiting both mast cell degranulation and neuroinflammation mediated via peripheral sensory neurons.

EVO756 represents a differentiated strategy with the potential to deliver a safe, effective and convenient daily oral treatment. We believe this approach could address significant unmet need in chronic inflammation, align with the preferences of both patients and prescribers, enable broader prescribing beyond specialists and expand the reach of treatment to millions of underserved patients.

Clinical and preclinical data from our team and third parties suggest that blocking MRGPRX2 activation can selectively prevent mast cell degranulation and the release of pro-inflammatory mediators. By selectively inhibiting MRGPRX2, we aim to avoid the safety risks of therapies that deplete mast cells or cause broad immunosuppression.

We are initially developing EVO756 in CSU and AD, two diseases with well-established MRGPRX2 biology and high unmet need, while also planning to expand into additional chronic inflammatory indications.

We conducted a Phase 1 proof-of-concept trial in 132 healthy volunteers designed to assess the safety, tolerability, PK and PD properties of orally administered EVO756. Comprehensive trial results were presented at the UCARE Global Urticaria Forum meeting in December 2024. A skin challenge test was conducted in the MAD portion of the trial in which icatibant, representative of a broad class of disease relevant ligands, was administered via intradermal injection to healthy volunteers creating measurable wheals on their skin. EVO756 was observed to robustly decrease the healthy volunteers’ wheals induced by icatibant, evidencing meaningful target engagement at all doses tested.

We are currently conducting a Phase 2b trial of EVO756 in CSU and have completed a Phase 2 trial of EVO756 in CIndU. In May 2025, we reported topline results from our U.S. multicenter Phase 2 trial of EVO756 in CIndU that demonstrated clinical activity (including improvement in FricTest score and pruritus-NRS, as described below) in a patient population with symptomatic dermographism. Rapid clinical activity was observed in both dosing regimens, with some patients demonstrating responses by week one in both FricTest score (complete response score of zero) and pruritus-NRS (≥2-point decrease). 70% (n=19) of the 27 observed patients demonstrated improvement at just four weeks, with 30% (n=8) of the observed patients (n=8) achieving a complete response (achieving a FricTest score of zero), of which 50% were IgE high. An additional 11% (n=3) achieved a partial response as defined by a ≥2-point decrease in FricTest score and a further 30% (n=8) demonstrated a one-point decrease in FricTest score. The population of subjects observed at four weeks does not include three patients who were unevaluable or lost to follow-up. Both observed dosing levels were observed to result in rapid and meaningful itch relief to patients, with observed patients in the 300 mg QD cohort experiencing an average reduction of 2.4 in pruritus-NRS while observed patients in the 50 mg BID cohort saw an average reduction of 2.1 points. Importantly, 93% (n=25) of observed patients demonstrated improvement at just four weeks in either FricTest or pruritus-NRS. Further, 75% (n=6) of those who did not achieve a decrease in FricTest score demonstrated a decrease in pruritus-NRS, evidencing the impact of EVO756 on itch at this early time-point, even in the absence of FricTest response. EVO756 was observed to be well-tolerated at both dose levels, including the higher 300 mg QD dose. No SAEs were observed and there were no discontinuations due to AEs. We expect to report initial data from the Phase 2b trial of EVO756 in CSU in the second quarter of 2026. We also initiated a Phase 2b dose-ranging trial in AD in August 2025 and expect to report initial results in the second half of 2026.

MRGPRX2 as an Ideal Target for Chronic Inflammatory Disease

MRGPRX2 is highly expressed on mast cells and peripheral sensory neurons and is activated by multiple ligands that are elevated in inflamed tissues, including neuropeptides, host defense peptides, proteases and cytokines. Such ligands have been found to be upregulated in a range of chronic inflammatory diseases including CSU, AD, migraine, asthma, interstitial cystitis and irritable bowel syndrome. Our management team has deep expertise with MRGPRX2, having worked with the target for over a decade, which we believe provides us with powerful insight into the biology, patient needs and treatment landscape in this space.

Mast cells are critical regulators of the immune response and can be found in most vascularized tissues, including skin, lung and the digestive tract. When ligands activate MRGPRX2 on mast cells, they trigger a signaling cascade that induces degranulation, which initiates the release of inflammatory mediators including histamine, chemokines, leukotrienes, prostaglandins, tryptase and chymase. Activation of MRGPRX2 also drives neuroinflammation on peripheral sensory neurons, located in various tissues including skin and lung. Aberrant activation of mast cells and peripheral sensory neurons via the MRGPRX2 receptor can lead to a variety of disease pathologies depending on the affected tissue, resulting in uncontrolled symptoms that are characteristic of many chronic inflammatory diseases such as hives, itch, pain, swelling and redness. Disease pathology is further amplified by the observation that mast cells and peripheral sensory neurons are concurrently activated in certain diseases, such as CSU and AD, which creates upregulated MRGPRX2-dependent feedback loops and intensified symptoms. The following figures illustrate MRGPRX2’s role in mast cell activation and neuroinflammation and as a nexus for mast cell and neuron activation by multiple ligands:

Figure 7: MRGPRX2 in Mast Cell Activation and Neuroinflammation

Figure 8: MRGPRX2, A Nexus for Mast Cell/Neuron Activation by Multiple Ligands

Based on MRGPRX2’s concentrated expression on these two cell types, we believe there is potential for synergistic mast cell and peripheral sensory neuron activation by disease-relevant ligands. We believe MRGPRX2 is the only clinical approach aimed at inhibiting this neuroimmune interaction. We also believe MRGPRX2 antagonism presents a differentiated and compelling safety profile. Existing methods of modulating mast cells include anti-IgE therapies and targeting the receptor tyrosine kinase KIT.

Anti-IgE therapies block mast cell activation but are associated with the risk of anaphylaxis and KIT inhibition, which depletes mast cells, affects many biological processes and has demonstrated a heightened potential for on-target toxicity in clinical trials. Similarly, downstream inhibitors like JAK or Bruton’s tyrosine kinase (“BTK”) reduce inflammation by broadly suppressing immune pathways, leading to potential systemic side effects and safety concerns. In contrast, MRGPRX2 is selectively expressed in mast cells and sensory neurons, which we believe leads to a narrower range of inflammatory outcomes and ultimately lowers the potential for on-target toxicity.

Market Opportunity

We believe EVO756 has the potential to be used for the treatment of a broad spectrum of highly prevalent and debilitating chronic inflammatory diseases in which mast cell and peripheral sensory neuron regulation is central to disease pathogenesis, including cutaneous diseases (such as CU and AD), neurologic conditions (such as migraine), respiratory conditions (such as asthma) and other diseases (such as interstitial cystitis). Standards of care for these diseases, particularly for patients with refractory or moderate-to-severe forms of their disease, are often limited by suboptimal safety or efficacy, as well as barriers related to administration or monitoring, which result in low utilization.

Our initial focus for EVO756 development is CSU and AD, where we see clear paths to create benefits based on high unmet patient need, well-defined clinical endpoints and the potential for both rapid symptom relief and disease-modifying effects through targeted mast cell and peripheral sensory neuron modulation. We also plan to explore additional indications in which mast cell degranulation and neuroinflammation are key drivers of disease, expanding the potential reach of EVO756 across a broad range of chronic inflammatory diseases. The following illustration depicts the broad universe of conditions where we believe targeting MRGPRX2 could potentially provide meaningful clinical benefit:

Figure 9: Targeting MRGPRX2 Creates Broad Opportunity

The prevalence in the United States of certain diseases of interest in which mast cell degranulation and neuroinflammation are believed to play a role is significant, as shown in the table below:

Figure 10: Prevalence of Select Chronic Inflammatory Diseases

Notes: (1) Estimated adult AD prevalence.

Our Solution: EVO756, Our MRGPRX2 Antagonist

We are developing EVO756 as an oral therapy targeting MRGPRX2 to address a broad spectrum of inflammatory indications. We believe EVO756 can be a first-line therapy for CSU and AD and is currently the most advanced program in clinical development targeting MRGPRX2. EVO756’s molecular properties, measured in our in vivo studies, are consistent with Lipinski’s Rule of Five, a set of guidelines used in drug discovery to predict oral bioavailability and avoid off-target effects. Its low molecular weight, low lipophilicity reflected by a favorable cLogP, as well as a high rate of free fraction, make us confident that EVO756 is designed and optimized for oral delivery. We believe EVO756’s carefully designed molecular and PK profile, with high bioavailability and limited off-target potential, differentiates it from other known attempts to mechanistically target MRGPRX2 in chronic inflammatory diseases. The following table depicts select characteristics of EVO756:

Figure 11: Select Characteristics of EVO756

Notes: ADME = Absorption, Distribution, Metabolism, and Excretion; MW = Molecular Weight; PPB = Plasma Protein Binding; DDI = Drug-Drug Interaction.

We have observed that EVO756 exhibits potent activity across a broad and representative panel of inflammatory ligands known to act through MRGPRX2. Because chronic inflammation in individual patients may be driven by varying combinations of disease-associated ligands, we evaluated multiple known ligand classes (as shown in Figure 12 below). Based on preclinical studies and the MAD portion of our Phase 1 proof-of-concept trial, EVO756 was observed to consistently and robustly inhibit degranulation across all tested ligands—both endogenous and exogenous—as shown in Figure 12 below:

Figure 12: EVO756 Is a Highly Potent Oral Small Molecule

Notes: (1) Icatibant used as agonist for PD challenge.

In our completed Phase 1 trial, EVO756 was observed to cause decreases in skin response as measured by changes in icatibant-induced wheals, which we believe confirms target engagement and suggests the potential of EVO756 to block disease relevant ligands in CSU. EVO756 was observed to be well-tolerated at all doses tested, with no SAEs observed, and PK results supporting daily oral dosing.

Chronic Urticaria Background

Urticaria, also known as hives, is a disease characterized by the presence of wheals, itching and angioedema, which is swelling in subcutaneous tissue, often in the lips, face and extremities. This disease is characterized as CU when lasting for a period of more than six weeks. The two forms of CU are CSU and CIndU. CSU is a chronic inflammatory skin disease characterized by spontaneous and recurrent hives and angioedema without a known environmental trigger. In contrast, CIndU is triggered by specific physical stimuli such as pressure, cold, friction or heat. Both are driven by aberrant mast cell activation, leading to the repeated release of histamine and other pro-inflammatory mediators. This activation causes vasodilation, immune cell recruitment, swelling and stimulation of peripheral sensory neurons, resulting in intense, persistent itch. Uncontrolled CU can last months or even years and significantly impact patients through the disruption of daily living and reduction in quality of life.

Currently, in the United States, we estimate that there are more than 3,000,000 patients living with CSU and over 850,000 patients living with CIndU. The current range of existing and potential therapeutics for CU collectively lacks a safe, convenient, efficacious treatment option that could be prescribed by a broad range of prescribers.

Current Treatment Paradigm

Antihistamines are generally the initial treatment for CU due to their availability over-the-counter, low price and benign safety profile. However, approximately 50% of patients treated with antihistamines experience inadequate symptom control. There are only three approved therapeutics available as a therapy for antihistamine-refractory CSU patients: (i) Xolair (omalizumab), a once monthly injectable anti-IgE mAb which contains a black box warning for anaphylaxis, (ii) Dupixent (dupilumab), a twice monthly subcutaneous mAb modulating the IL-4 and IL-13 signaling cascade and (iii) Rhapsido (remibrutinib), a twice daily oral BTK inhibitor.

Approximately two-thirds of the CSU patients treated with Xolair do not experience complete symptom control. In addition, Xolair has safety concerns regarding its black box warning for anaphylaxis and has burdensome monitoring requirements including in-office administration for three consecutive months. We believe these concerns have limited adoption predominantly to allergists and have led to Xolair being significantly underutilized by dermatologists, primary care physicians and pediatricians, with approximately 10% penetration in the antihistamine-refractory CSU market. Overall, we estimate that approximately 450,000 CSU patients in the United States are either untreated or have uncontrolled disease and are not well served by the existing treatment paradigm, as illustrated in the figure below:

Figure 13: CSU Is an Underserved Market with Limited Treatment Options

Notes: (1) In the United States, “Eligible” defined as CSU patients with incomplete response to over-the-counter H1-antihistamines and eligible for targeted therapy; (2) Approximately 50,000 patients currently treated with a biologic.

Dupixent was approved for CSU in April 2025. Despite having shown success in other immunology indications, Dupixent has more limited efficacy in CSU compared with Xolair, with less than a third of Xolair-naïve patients dosed reaching a complete response (as defined by UAS7=0) at week 24 (and notably only a 16% complete response rate at week 12, the common endpoint for competitor CSU trials). Furthermore, Dupixent failed to meet the primary endpoint of ISS7 reduction in a Phase 3 trial in omalizumab-refractory or intolerant patients. Additionally, Dupixent has been associated with conjunctivitis and injection site reactions. Due to these limitations, we estimate there is a significant number of patients who either remain untreated or untreatable with current treatment options. We believe EVO756 may ultimately be a first line treatment option across prescriber types, if approved.

Beyond Xolair and Dupixent, the next most advanced product candidate is Rhapsido, an orally administered BTK inhibitor approved for the treatment of CSU in September 2025. While Rhapsido has been observed in clinical trials to have greater clinical activity than Dupixent, Rhapsido has adverse reactions on its label including nasopharyngitis, bleeding, headache, nausea and abdominal pain, along with drug interactions recommending against its use with multiple classes of drugs. Furthermore, we believe BTK inhibitors as a class have a more concerning safety profile with multiple labeled warnings and precautions. We are also aware of KIT inhibitor programs in development for the treatment of CSU. KIT inhibitors have a proven ability to limit mast cell development and therefore significantly reduce hives for urticaria patients. However, KIT inhibitors also impact the development of a range of other cells, resulting in a variety of side effects, including neutropenia, changes in taste and hair color and spermatogenesis. We believe these challenges could limit KIT inhibitors to a later-line treatment option. The following graphic compares MRGPRX2 to other mechanisms of action being evaluated in CSU:

Figure 14: Potential for EVO756 to Address an Urticaria Market with Significant Therapeutic Opportunity

We believe that MRGPRX2-targeted therapies have the potential to show a superior safety and comparable efficacy profile to Xolair, Dupixent, Rhapsido, and other therapeutic candidates in development, thus having the potential to become the first-line treatment for antihistamine-refractory patients. Nonclinical and clinical data generated internally and by third parties support the potential for MRGPRX2-targeted therapies to emerge with an attractive class profile with efficacy in the range of approved treatments while delivering improved safety, faster symptom relief through direct modulation of peripheral sensory neurons and the convenience of a daily oral. Furthermore, we believe the safety results observed to-date and convenient oral dosing of EVO756 may not only position it to become the backbone therapy for CSU, if approved, but it also has the potential to be used in combination treatment with existing approved biologics, such as Xolair and Dupixent.

Clinical Data

Our Completed Phase 1 Trial

In July 2024, we announced the topline results from a Phase 1 proof-of-concept trial in 132 healthy volunteers designed to assess the safety, tolerability, PK properties and PD properties of orally administered EVO756. Comprehensive trial results were presented at the UCARE Global Urticaria Forum meeting in December 2024. The Phase 1 trial was a SAD and MAD trial in healthy volunteers and was conducted in the United States. The figure below depicts the design of this trial:

Figure 15: Phase 1 Proof-of-Concept Trial Design and Summary

Notes: ECG = electrocardiogram

In the trial, 55 individuals (including placebo) were administered a single dose in the SAD portion and 77 individuals (including placebo) were dosed once or twice daily for 14 days in the MAD portion. In the SAD portion, doses from 1 mg to 500 mg were administered in ascending order across seven cohorts of approximately eight participants each (six active and two placebo). In the MAD cohorts, ascending doses of 10 mg, 30 mg, 100 mg and 240 mg twice daily were administered across four cohorts of 16 subjects each (12 active and four placebo) and a fifth cohort of approximately 16 subjects (12 active and four placebo) were administered 500 mg once daily. A skin challenge test was also conducted in the MAD portion of the trial in which icatibant, representative of a broad class of disease relevant ligands, was administered via intradermal injection to create measurable wheals on their skin.

Safety Results

EVO756 was observed to be well-tolerated at all doses administered in both the SAD and MAD portions of the trial, including up to the 500 mg QD dose. No SAEs were observed and all AEs reported were considered mild or moderate and included headache, dizziness, catheter site pain, diarrhea and lymphadenopathy. There was one discontinuation, which was not considered treatment-related, as the patient withdrew consent prior to completion of treatment. In addition, there were no clinically significant electrocardiogram (“ECG”) or lab abnormalities. The following table summarizes the safety results of this trial:

Figure 16: Safety Results of Phase 1 Trial

PK Results and Trial Dosing

In the MAD portion of the trial, increased dosing from 10 mg twice daily to 240 mg twice daily, and 500 mg once daily, resulted in approximately dose-proportional increases in serum concentrations of EVO756, with about a two-fold accumulation observed from day 1 through day 14. In this trial, serum concentrations of EVO756 were above the IC90for MRGPRX2 inhibition at trough at all dosing levels 30 mg twice daily and higher.

Phase 1 Proof-of-Concept Skin Challenge Test

The Phase 1 trial included a skin challenge test based on work published out of Johns Hopkins University. In a clinical setting, MRGPRX2 ligands, administered intradermally in a skin challenge test, have been shown to produce functional and measurable skin responses (wheals) in healthy individuals and a heightened response in individuals with CU.

We assessed the PD potential of EVO756 in the MAD portion of the trial in which icatibant, whose pharmacology effectively represents typical characteristics of MRGPRX2 ligands, was administered intradermally. Figure 17 below outlines the mechanism and design of this skin challenge test:

Figure 17: Skin Challenge Test: Proof-of-Concept and Target Engagement for Chronic Urticaria

In the skin challenge test, intradermal administration of 10 and 100 µg/mL icatibant-induced wheals consistent with those observed previously in the work performed by Johns Hopkins (Shtessel et al.) resulted in measurable skin responses in a highly controlled setting.

We believe this PD assessment provides proof-of-concept for EVO756 in the treatment of CU as EVO756 was observed to engage MRGPRX2, block the impact of a known MRGPRX2 ligand and robustly reduce the mean size of icatibant-induced wheals (10 µg/mL (7.6 µM) icatibant), as shown in the following chart:

Figure 18: EVO756 Robustly Decreased Icatibant-Induced Wheals

Notes: Error bars represent standard deviation; *p 0.001; **p 0.0001; p-value from LS-means change from baseline in wheal size in a Mixed Model Repeated Measures analysis. Bonferroni adjustment made for multiple comparisons – only comparisons which reached statistical significance of p 0.001 are noted.

At 10 µg/mL of icatibant, which we believe to be the most appropriate comparison for real-world ligand concentrations in humans based on quantitative evaluation of ligand concentrations from biopsies, we observed statistically significant decreases in mean wheal size by EVO756 after two weeks of dosing, as compared to wheal size at baseline after intradermal icatibant injection. Thus, the above results suggest EVO756 may have activity at low dosage levels in what we believe is the most pharmacologically relevant model for a diseased patient. In addition, in our PK research, we have observed high human PK interstitial fluid concentrations (“ISF”), with average ISF compared to plasma PK concentrations ranging from approximately 55–70% over a 24-hour period following a 200 mg dose of EVO756, supporting robust exposure at target site. Further, EVO756 showed dose-dependent response at 100 µg/mL of icatibant, which we believe is a supraphysiological concentration.

Figure 19: PK Modeling of EVO756 Based on Clinical Data Generated to Date

Notes: IC90Primary Mast Cells = 180 ng/mL.

Based on the PK profile generated in this study, we were able to create a model that predicts various once- and twice-daily doses that maintain serum concentrations above the IC90, as illustrated in Figure 19 above. Additionally, mass spectrometry identified MRGPRX2 ligands upregulated in disease tissue, confirming the relevance of ligands used in in vitro mast cell assays and the icatibant skin challenge test.

To further explore the translatability of our PK modeling, we overlayed our modeled human EVO756 drug exposures (skin level-adjusted Ctrough and Cmax, respectively) at the expected Phase 2 dose levels on the concentration plots from our in vitro mast cell degranulation assays. The figure below depicts EVO756’s dose response to 10 µg/mL icatibant in vitro (blue plotted dots) as well as the modeled in vivo tissue concentrations (at both Ctrough (left) and Cmax (right)) at planned Phase 2 dose levels and previously conducted Phase 1 dose levels (grey) where activity has been observed.

Figure 20: EVO756 Target Coverage and Dosing Response

Notes: (1) Mast cell degranulation was determined via CD63 externalization on mast cells by flow cytometry. CD63 externalization was normalized to 100% of max (e.g., icatibant stimulation alone); (2) Ctroughis the modeled drug level in serum at 12 or 24 hours post last BID or QD dose, respectively; (3) Assumes 70% skin distribution and 16% free drug.

Following analysis of our Phase 1 trial results, we initiated our Phase 2 clinical development program and enrolled the first patient in a multi-center CIndU trial in September 2024 and the first patient in a global CSU trial in April 2025, with both trials designed to evaluate the safety and efficacy of EVO756 in CU.

Our Phase 2 Trial in CIndU

In May 2025, we reported topline results from our U.S. multicenter Phase 2 trial of EVO756 in CIndU that demonstrated FricTest score improvement at four weeks, as described below. CIndU is a form of urticaria that has known environmental triggers, including pressure or exposure to cold and has underlying disease pathogenesis similar to CSU. The trial was designed to generate additional patient data in a population with symptomatic dermographism, which we believe will be highly translatable to the CSU patient population, given the shared pathologies. Third party studies have demonstrated that symptomatic dermographism affects approximately 25% of the CSU patient population; similarly, we believe EVO756’s clinical activity in symptomatic dermographism patients strongly supports the role of MRGPRX2 in neurogenic inflammation, which plays a crucial role in AD. Efficacy endpoints included changes from baseline in disease specific provocation thresholds that are used as objective markers to quantify disease severity and response to treatment. EVO756 was administered orally for four weeks with either a once or twice daily dose and was evaluated for safety and efficacy at weekly visits during treatment, with patients serving as their own control. Figure 21 below depicts the trial design of our Phase 2 CIndU trial:

Figure 21: Phase 2 CIndU Trial Design

Notes: SD = symptomatic dermographism; TEAE = Treatment Emergent Adverse Events; BL = Baseline.

A total of 30 patients were enrolled in the Phase 2 trial, with 11 patients assigned to the 300 mg QD cohort and 19 patients to the 50 mg BID cohort. Duration of disease at baseline in the 300 mg QD and 50 mg BID cohorts was 6.3 years and 6.4 years, respectively. A total of 28 patients completed the trial and 27 evaluable patients contributed to the four-week data. Baseline characteristics and patient dispositions for enrolled patients are detailed in Figure 22 below:

Figure 22: Phase 2 CIndU Trial Disposition

Notes: LTFU = Lost-to-Follow-Up

Efficacy Results

To evaluate the efficacy of EVO756, we used a provocation challenge known as FricTest to assess each patient’s threshold for wheal formation. An instrument with four calibrated tines was applied to the patients’ skin to determine the minimum pressure required to elicit a wheal response. 70% (n=19) of the 27 observed patients demonstrated improvement at just four weeks, with 30% (n=8) of the observed patients achieving a complete response (achieving a FricTest score of zero), of which 50% were IgE high. An additional 11% (n=3) achieved a partial response as defined by a ≥2-point decrease in FricTest score and a further 30% (n=8) demonstrated a one-point decrease in FricTest score. The population of subjects observed at four weeks does not include three patients who were unevaluable or lost to follow-up. The following figures summarize observed patient FricTest response at four weeks in the Phase 2 trial:

Figure 23: FricTest Response at Week 4

Notes: (1) Four of the complete responders were IgE high. (2) 75% (N = 6) of those who did not achieve a decrease in FricTest score demonstrated a decrease in pruritus-NRS, evidencing the impact of EVO756 on itch at this early time-point, even in the absence of FricTest response.

Figure 24: FricTest Scores by Subject at Week 4

Observed patients within both cohorts of the Phase 2 trial experienced meaningful reductions in total FricTest score during the duration of the trial, with observed patients in the 300 mg QD cohort experiencing an average reduction in total FricTest score of 1.4 points and observed patients in the 50 mg BID cohort experiencing an average reduction in total FricTest score of 1.5 points. The figure below illustrates total reduction in observed patient FricTest scores over time from week zero to week four in both cohorts of the Phase 2 trial:

Figure 25: Average FricTest Score Over Time by Cohort

Overall, topline results from the Phase 2 CIndU trial of EVO756 included, in both the 300 mg QD and the 50 mg BID cohorts, meaningful and rapid responses in FricTest scores at one week, with three patients achieving a complete response on FricTest at one week. Initial Phase 2 data of mean FricTest reduction from EVO756 in CIndU were similar to previously reported four week data generated by third-party competing agents used for the treatment of CIndU, including the biologics omalizumab (Phase 2 trial, n=37) and barzolvolimab (Phase 2 trial, n=66). In these clinical trials, which had patient populations with comparable baseline levels of disease severity as the EVO756 Phase 2 trial in CIndU, each of omalizumab and barzolvolimab was observed to result in deepening of clinical response beyond week four.

In addition to degree of change in FricTest scores, we also evaluated patients’ change from baseline pruritus-NRS at provocation site, a single-item, patient-reported outcome measure used to assess itch severity. Both the 300 mg QD and the 50 mg BID dose of EVO756 were observed to result in rapid itch relief to patients, with observed patients in the 300 mg QD cohort experiencing an average reduction in pruritus-NRS score of 2.4 points and observed patients in the 50 mg BID cohort experiencing an average reduction of 2.1 points.

Importantly, 93% (n=25) of observed patients demonstrated improvement at just four weeks in either FricTest or pruritus-NRS. Further, 75% (n=6) of those who did not achieve a decrease in the FricTest score demonstrated a decrease in pruritus-NRS, evidencing the impact of EVO756 on itch at this early time-point, even in the absence of FricTest response. The figure below illustrates reduction in provoked itch over time from week zero to week four observed in both cohorts of the Phase 2 trial:

Figure 26: Average Provoked Itch Score Over Time by Cohort

Additionally, both the 300 mg QD and the 50 mg BID dose of EVO756 demonstrated meaningful itch relief to patients with high baseline pruritus-NRS. The table below depicts the pruritus-NRS response at week four in subjects with baseline pruritus-NRS ≥4:

Figure 27: Pruritus-NRS Response at Week 4 in Subjects with Baseline Pruritus-NRS ≥4

Safety Results

EVO756 was observed to be well-tolerated at both doses administered in the Phase 2 trial. No SAEs were observed and there were no discontinuations due to AEs. Figure 28 below shows all AEs that occurred in more than one subject in this trial. The two subjects in the 300 mg QD cohort with AEs of increased ALT and AST had asymptomatic transaminase elevations that were greater than ten times the upper limit of normal at four weeks, which were not present at baseline, week 1 or week 2 and later returned to baseline. Other liver tests, including bilirubin and alkaline phosphatase were within normal limits. Both of these subjects had confounding factors that may have contributed to these elevations. No AEs of ALT or AST elevation were reported in subjects in the 50 mg BID cohort.

Figure 28: Phase 2 CIndU Trial Summary of Treatment Emergent Adverse Events in More than One Subject

Notes: (1) The two subjects in the 300 mg QD cohort with AEs of increased ALT and AST had asymptomatic transaminase elevations that were greater than ten times the upper limit of normal at four weeks, which were not present at baseline, week 1 or week 2 and later returned to baseline. Other liver tests, including bilirubin and alkaline phosphatase were within normal limits. Both of these subjects had confounding factors that may have contributed to these elevations.

In our ongoing Phase 2b clinical trials of EVO756 in CSU and AD, the current protocols include doses ranging up to 150 mg daily.

Clinical Development Plan and Status

Our Ongoing Phase 2b Dose-Ranging Clinical Trial in Chronic Spontaneous Urticaria

In April 2025, we initiated a Phase 2b dose-ranging trial in approximately 160 moderate-to-severe antihistamine-refractory CSU patients in the United States, Europe, Canada and Japan. The global, multi-center, randomized, double-blind, placebo-controlled trial will evaluate the safety, tolerability and efficacy of EVO756 at three doses compared to placebo. Patients will be treated for 12 weeks and evaluated at several pre-specified time points. The primary endpoint of the trial is change in a patient’s UAS7 at 12 weeks. Beyond the primary endpoint, we also intend to evaluate other measures of disease including itch, hive severity and angioedema. The results of the trial are expected to inform dose selection and other trial design considerations for Phase 3 EVO756 development. We anticipate reporting initial data from this trial in the second quarter of 2026. The following figure depicts the trial design of our Phase 2b CSU trial.

Figure 29: Phase 2b CSU Trial Design

Notes: UAS7 = Urticaria Activity Score over 7 days; ISS7 = Itch Severity Score component of UAS7; HSS7 = Hives Severity Score component of UAS7; AAS7 = Angioedema Activity Score; BL = Baseline; Mod-to-Sev = Moderate-to-Severe

Nonclinical Data

We have also been characterizing EVO756 through nonclinical studies on primary pharmacology, safety pharmacology, PK and toxicology. We conducted in vitro primary PD studies and observed the ability of EVO756 to inhibit the activation of MRGPRX2 and confirmed that EVO756 is human-specific and does not inhibit functional orthologue receptors to MRGPRX2 in animal species.

We included characterization of KO mice that lack the murine receptor functional orthologues of the human MRGPRX2 in the toxicology program to document the natural history of complete receptor ablation in target tissues as a proxy for traditional nonclinical on-target safety assessment.

Off-target safety assessment conducted in the good laboratory practice (“GLP”) repeat-dose toxicity studies in rats and dogs for up to 13 weeks identified no adverse histopathology findings and the corresponding No Observed Adverse Effect Levels identified support the current clinical development plan.

EVO756 was not observed to be genotoxic in the bacterial reverse mutation test, in vitro chromosome aberration test or in vivo micronucleus test in rats. EVO756 was not observed to be phototoxic in the 3T3 neutral red uptake phototoxicity test in vitro. Characterization of KO mice conducted to derive potential on-target effects of EVO756 suggested no noteworthy or adverse changes related to genetic alterations resulted from the absence of Mrgpra1 and Mrgprb2 through 26 weeks. Furthermore, no fetal malformations were observed in pregnant Mrgpra1 and Mrgprb2 KO mice in preliminary studies. Additionally, no impact on the central nervous system, cardiovascular or respiratory function was observed, and no fetal malformations were observed in the preliminary embryo-fetal toxicology studies.

EVO756 for the Treatment of Atopic Dermatitis

Atopic Dermatitis Background

Atopic dermatitis, commonly referred to as eczema, is one of the most prevalent chronic inflammatory diseases and is characterized by acute flares of itchy, red exudative papules (raised skin lesions that ooze fluid) and persistently dry, scaly skin. The hallmark of AD is intense inflammatory itch, known as pruritus, and episodic flares of rash and underlying chronic inflammation. For most moderate-to-severe AD patients, the disease significantly impacts patients’ quality of life, driven primarily by relentless itch, sleep disruption and visible skin symptoms. The intense itch associated with AD often triggers an itch-scratch cycle, further compromising the epidermal barrier and exacerbating disease. While AD commonly begins in childhood, it is also highly and increasingly prevalent in adults, with about 15% to 20% of children and 1% to 3% of adults impacted.

Research indicates that mast cells and peripheral sensory neurons play key roles in the pathogenesis of AD. One known driver of AD is the chronic and cyclical release of pro-inflammatory mediators associated with mast cell degranulation. Heightened mast cell activity promotes inflammation and drives itch, while activation of peripheral sensory neurons amplifies the sensation of itch. Third party studies have shown increased mast cell density, elevated MRGPRX2 expression, neuroinflammation and disease severity in lesional AD skin, supporting the rationale for targeting MRGPRX2 to both resolve skin lesions and relieve symptoms. Mast cells are in close proximity and recruited to sensory neurons in inflamed tissue, primarily in response to neuronal release of substance P and other neuropeptides, as well as local production of pro-inflammatory cytokines that enhance mast cell-neuron interactions. We believe that MRGPRX2 is the only target currently being pursued clinically that impacts both mast cells and neuroinflammation, making it uniquely positioned as a potential therapy for AD as illustrated in the figure below:

Figure 30: Rationale for EVO756 in AD

Current Treatment Paradigm

The current standard of care for first-line treatment of AD is primarily topical corticosteroids and targeted treatments (for example, topical JAK inhibitors). However, approximately 40% to 50% of AD patients have a moderate-to-severe form of the disease and thus are uncontrolled by topical therapies. For these patients, new systemic agents have emerged as advanced treatments that systemically target several different inflammatory mediators that contribute to underlying inflammation and flare-ups. Dupixent, an anti-IL-4 receptor alpha that modulates the signaling of IL-4 and IL-13 cytokines, is the preferred biologic for moderate-to-severe AD. The initial dose is two injections followed by one injection every two weeks and is considered to have category-high efficacy with 36% of patients reaching EASI-90 in 16 weeks. While treatment with Dupixent has also been shown to reduce itch (as measured by peak pruritus-NRS) by up to approximately 50%, it typically takes 16 weeks to achieve this level of efficacy and plateaus thereafter. Despite Dupixent’s efficacy, over 60% of AD patients remain uncontrolled and patients may be burdened with potential side effects, including conjunctivitis and injection site reactions, and the burden of twice-monthly injections. Two oral JAK inhibitors, Rinvoq and Cibinqo, have also been approved for the disease and offer improved efficacy with over 40% of patients exceeding EASI-90 at 16 weeks, but are reserved for later lines of treatment due to safety concerns including black box warnings on cardiac events and malignancies. Another biologic, Ebglyss (lebrikizumab), an IL-13 inhibitor, was recently approved by the FDA for the treatment of AD based on clinical results wherein approximately 33% to 43% of patients were observed to achieve IGA 0/1 with ≥2-point improvement from baseline to week 16. Several biologics are in development with differing mechanisms of action including product candidates that target IL-13, OX-40 and IL-18, including our own EVO301. We believe the market for AD therapeutics is in a nascent stage, particularly when compared to the growth observed in the market for psoriasis, which has grown meaningfully since the launch of Enbrel in 2004 as illustrated in the figure below:

Figure 31: Expansion of AD Market Outpacing That of Psoriasis

Notes: “Year 1” for AD represents 2017 (year of Dupixent launch); “Year 1” for psoriasis represents 2004 (year of Enbrel launch in plaque psoriasis). May represent projections and not actual sales.

The following figure provides an illustration of the potential market opportunity for EVO756 in AD in the United States, if approved:

Figure 32: AD Is an Underserved Market Lacking a First Line Oral Option

Given that a significant number of patients with AD remain uncontrolled, we see the need for a therapy with a meaningful efficacy profile, improved safety profile, a fast onset of itch relief and the convenience of daily oral therapy. We believe a treatment option with this product profile would have broad applicability, first-line potential in moderate-to-severe disease and could be utilized by a wider range of prescribers, expanding access. We believe MRGPRX2 is the only target impacting both mast cells and neuroinflammation, two key factors underlying AD.

Clinical Development Plan and Status

Our Ongoing Phase 2b Dose-Ranging Trial in Atopic Dermatitis

Our atopic dermatitis development program is expected to target the treatment of adult and pediatric patients with moderate-to-severe AD, whose disease is not able to be controlled with topical prescription therapies. We initiated a Phase 2b dose-ranging trial in moderate-to-severe AD patients in August 2025 and are currently enrolling patients in the United States and plan to enroll patients in New Zealand. We expect to report initial results in the second half of 2026. The multi-center, randomized, double blind, placebo-controlled trial will evaluate the safety, tolerability and efficacy of EVO756 at three doses compared to placebo. Patients will be treated for 12 weeks and evaluated at several pre-specified time points. The primary endpoint will be percent change in EASI score and we also plan on assessing IGA, pruritus-NRS and safety. The results of the trial are expected to inform dose selection and other trial design considerations for Phase 3 EVO756 development in AD. The following figure depicts the trial design of our Phase 2b dose-ranging trial in AD:

Figure 33: Phase 2b Dose-Ranging Trial Design

Notes: EASI = Eczema Area and Severity Index; vIGA = Validated Investigator Global Assessment; Pruritus-NRS = Pruritus Numerical Rating Scale; BSA = Body Surface Area; BL = Baseline

In addition, if EVO756 demonstrates a positive treatment effect on itch associated with AD in the Phase 2b dose-ranging trial, we may pursue additional indications in which itch is a prominent feature in the future.

EVO756 for the Treatment of Migraine

Migraine Background

Migraine is a neurological disorder characterized by recurrent attacks of intense, often unilateral, throbbing headache lasting four to 72 hours often accompanied by symptoms including nausea, vomiting, and sensitivity to light or sound. It is estimated that migraine affects 40 million people in the United States and more than 10% of the global population. Migraine is the second leading cause of “years lived with a disability” worldwide, disproportionately impacting individuals during peak working years and contributing to an estimated $28 billion in annual United States healthcare costs, excluding broader productivity losses.

More than 10 million Americans are eligible for preventive therapy, yet current treatments are limited to only improving migraine days per month by approximately two days more than placebo. While acute therapies can provide symptomatic relief, they do not reduce underlying disease frequency. Preventive options — including calcitonin gene-related peptide (CGRP)-targeted therapies and neurotoxin approaches — have advanced care; however, approximately 45% of patients fail to achieve a ≥50% reduction in monthly migraine days, and many discontinue due to tolerability, durability, or access challenges. Despite recent innovation, migraine continues to impose significant clinical and

economic burden, underscoring the need for differentiated preventive therapies capable of delivering sustained efficacy with demonstrated safety and convenience.

MRGPRX2 is expressed by both human trigeminal neurons and meningeal mast cells, positioning it as a potential key mediator of neurogenic inflammation in migraine. Activation of trigeminal afferents and meningeal mast cells is central to migraine initiation and propagation, and in vivo preclinical headache models support a pathogenic role for MRGPRX2 signaling in driving migraine-like pain behaviors.

Pituitary Adenylate Cyclase-Activating Polypeptide (“PACAP”), a well-established migraine trigger in humans, is a known ligand of MRGPRX2, directly linking this receptor to a clinically-validated migraine pathway. Clinical trials targeting PACAP have demonstrated efficacy in migraine prophylaxis, further reinforcing the relevance of this biology.

Given that MRGPRX2 can be activated by multiple endogenous and exogenous ligands, antagonism of this receptor represents a broader upstream approach to dampen aberrant trigeminal activation and mast cell–mediated neuroinflammation. We have shown that EVO756 blocks a range of relevant MRGPRX2 ligands, including PACAP, supporting its potential to reduce migraine frequency across a broad patient population, including individuals who do not achieve sufficient benefit with existing preventive therapies.

Clinical Development Plan and Status

Our Planned Phase 2b Trial in Migraine

We plan to initiate a Phase 2 trial in migraine in mid-2026. We expect the trial to be a Phase 2b dose ranging, randomized, double-blind, placebo-controlled trial assessing the efficacy and safety of EVO756 for the prevention of migraine patients.

EVO756 for the Treatment of Other Potential Indications

Overview

We believe EVO756 has the potential to address several additional chronic inflammatory diseases. Building on our ongoing research and nonclinical studies, we are exploring the potential for EVO756 in asthma, interstitial cystitis, irritable bowel syndrome and pruritus (itch) as potential expansion indications due to their large unmet patient needs along with the relevance of mast cells and sensory neurons in these diseases’ pathology.

Background on Other Potential Indications

Asthma

Asthma is a chronic inflammatory disease of the airways characterized by variable airflow obstruction and bronchial hyperresponsiveness to triggers such as allergens, infections or environmental pollutants. It is one of the most common non-communicable respiratory diseases globally and in the United States, affecting both children and adults. The disease typically manifests through episodes of wheezing, coughing, chest tightness and shortness of breath, which may vary in frequency and severity. Asthma imposes a substantial burden on patients and health systems in terms of medical utilization (emergency department visits, hospitalizations), lost productivity and reduced quality of life. Current therapies, such as inhaled corticosteroids, bronchodilators and biologics, do not adequately control symptoms or prevent exacerbations in all patients, leaving a significant unmet need for new treatment modalities.

Interstitial Cystitis

Interstitial cystitis is a chronic condition causing bladder pressure, bladder pain and sometimes pelvic pain. The pain can range from mild discomfort to severe pain. The condition is a part of a spectrum of diseases known as painful bladder syndrome. The symptoms may vary over time, periodically flaring in response to common triggers, such as menstruation, sitting for a long time, stress, exercise and sexual activity. Epidemiological data in the United States suggest interstitial cystitis may affect approximately three to eight million women and one to four million men. Treatment options are limited, frequently palliative, and even if symptoms disappear, may return later. There is a substantial unmet need for therapies that address underlying pathophysiology, relieve pain, reduce urinary symptoms, improve function and offer durable benefit.

Irritable Bowel Syndrome

Irritable bowel syndrome is a common condition characterized by abdominal discomfort associated with altered bowel movement. Recent research has shown that many symptoms of irritable bowel syndrome are related to

hypersensitivity of the nerves found in the wall of the gastrointestinal tract. Prevalence estimates vary depending on diagnostic criteria, but some experts estimate that approximately 10% to 15% of adults in the United States have irritable bowel syndrome, and only about 5% to 7% of them see a provider and receive a diagnosis. This syndrome has a large impact on quality of life, psychological well-being and work productivity. Current treatments include dietary modification, cognitive behavioral therapy, laxatives and anti-diarrheals, which only often provide partial relief, creating an unmet need for novel agents targeting symptoms, visceral hypersensitivity and motility.

Pruritus (Itch)

Pruritus, commonly referred to as itch, is an unpleasant sensory sensation that provokes the desire to scratch. When pruritus persists for more than six weeks, it is defined as chronic pruritus. Pruritus can be painful or irritating and could be localized to one area of the body or spread throughout several areas. It is estimated that pruritus leads to more than seven million ambulatory visits annually in the United States and is among the 50 most prevalent conditions worldwide. Existing therapies, such as hydrocortisone, antihistamines, topical steroids and immunosuppressants, are often only partially effective, underscoring the need for treatments that more directly target itch sensory pathways and underlying immunologic or neuronal drivers.

Ongoing Nonclinical Translational Research

Our ongoing nonclinical translational research efforts are focused on elucidating the role of MRGPRX2 in human disease through a multifaceted approach. These activities include the characterization of MRGPRX2-expressing mast cells and the identification of MRGPRX2 agonists in human patient samples across relevant disease states. In parallel, we are also conducting functional studies in human-derived cell types and tissues to further define the biology of MRGPRX2 signaling. These include in vitro studies using primary human mast cells and neurons, as well as ex vivo studies in disease-relevant human tissues such as trigeminal neurons and meningeal mast cells for migraine and biopsies for other key indications. Lastly, we are utilizing sophisticated computational approaches to provide in silico validation of the critical role for MRGPRX2 in key disease indications.

Additionally, in vivo studies are underway using genetically modified mouse models, including Mrgprb2 knock-out and MRGPRX2 knock-in mice. These studies are complemented by established disease models, such as PACAP-induced migraine, to further assess the therapeutic potential of targeting MRGPRX2. Collectively, these nonclinical investigations are intended to support indication prioritization and inform our clinical development strategy of EVO756 in other potential indications.

We believe that continued interrogation of MRGPRX2’s role across migraine, asthma, interstitial cystitis, irritable bowel syndrome and pruritus will provide critical insights into its role as a key neuronal mediator. These findings will guide our near-term indication expansion efforts and support the initiation of additional clinical trials in the future.

Clinical Development Plan

Initiation of a Phase 2 trial in any of these additional indications will be determined based on ongoing trials and corporate resources. To date, based on our data from the successful completion of our Phase 1 proof-of-concept trial of EVO756 in healthy volunteers, we believe there is a path to proceed to Phase 2 clinical development for these other indications, similar to our initiation of our Phase 2b trial in AD, subject to standard regulatory requirements. We are also currently exploring development of next-generation MRGPRX2 molecules that we believe can be optimized for select indications to bolster our intellectual property portfolio and potentially complement our product candidates to better manage the life cycle management of our development programs.

EVO301: Our SAFA IL-18BP Fusion Protein

Overview

Our second clinical-stage product candidate, EVO301, which is in Phase 2 development for the treatment of atopic dermatitis, is a long-acting biologic designed to neutralize the IL-18 inflammatory pathway, which plays a key role in various immune processes and is thought to be a key driver of immune dysregulation associated with chronic inflammatory diseases. In June 2024, we secured exclusive global rights to develop and commercialize EVO301 from AprilBio, which previously progressed EVO301 through a Phase 1 trial. In that study in healthy volunteers, EVO301 was well-tolerated across all doses evaluated, with no severe AEs observed or discontinuations due to AEs, and demonstrated a favorable PK profile. Importantly, EVO301 was well tolerated with no observed cases of

conjunctivitis, which can be observed with other biologics in AD. We believe EVO301’s differentiated profile may enable it to become a leading therapy for a broad range of chronic inflammatory diseases.

Beyond AD, we are evaluating a potential Phase 2 trial in moderate-to-severe UC patients. We may also evaluate EVO301 in Crohn’s disease and other additional indications in which dysregulation of the IL-18 contributes to chronic inflammation and tissue damage driving disease pathology.

Although we are pursuing AD for both EVO301 and EVO756, we believe these approaches are sufficiently differentiated and complementary to each other given their distinct modalities and potential to be used together. In addition, based on the clinical data generated to-date, we believe each has the potential to transform the immunology and inflammation treatment landscape either as monotherapy or in combination with existing therapies.

IL-18 Mechanism of Action

IL-18, a pro-inflammatory cytokine of the IL-1 family, regulates various immune processes that drive inflammation. It plays an important role in the T-cell-helper type 1 inflammatory response and is a potent modulator of ongoing inflammation. An upregulated IL-18 pathway cyclically activates inflammatory mediators in an aberrant manner, resulting in tissue damage and other inflammatory and sensory disease pathology. We believe that targeting the IL-18 pathway differs from existing treatment options because this pathway impacts both innate and adaptive immune processes, a distinguishing feature that allows for broad applicability across multiple chronic inflammatory diseases. There are several large, heterogeneous chronic inflammatory diseases with significant numbers of uncontrolled patients including AD and inflammatory bowel diseases (“IBD”) in which the IL-18 pathway is believed to play a key role. The following figures illustrate IL-18’s role in both innate and adaptive immune processes, the IL-18BP therapeutic approach, a landscape of diseases that are regulated by the IL-18 pathway and the key role of IL-18 signaling in AD:

Figure 34: IL-18 Drives Various Innate and Adaptive Immune Processes Related to Infection, Inflammation and Autoimmunity

Notes: PAMPs: Pathogen-associated molecular patterns; DAMPs: Damage-associated molecular patterns.

Figure 35: IL-18 Pathways Regulate Many Diseases

Figure 36: IL-18 Signaling in AD

We are aware of one other IL-18 programs in clinical development for chronic inflammatory conditions, which involves a mAb approaches. As a result of its design, we see several potential advantages of the SAFA IL-18BP fusion protein relative to IL-18 mAbs, including tissue penetration and binding affinity. Thus, we believe there is substantial untapped therapeutic opportunity in AD and significant potential for improvement in the treatment landscape with our SAFA IL-18BP fusion protein, EVO301.

Our Solution: EVO301, an IL-18BP Fusion Protein

EVO301 is a long-acting injectable SAFA-IL-18BP fusion protein designed to neutralize aberrantly upregulated IL-18 activity. We believe this approach facilitates more efficient tissue distribution and improved binding affinity and specificity which presents an advantage over existing attempts to antagonize or inhibit the IL-18 pathway, including traditional mAbs. The following graphic depicts the molecular design of EVO301:

Figure 37: EVO301 Molecular Design

Notes: SAFA = Anti-Serum Albumin Fab-Associated.

EVO301 is designed specifically to neutralize upregulated IL-18 activity. Key distinguishing features of EVO301 include:

• selective and high binding affinity of native human IL-18BP and binding to serum albumin, allowing for specific inhibition of IL-18 pro-inflammatory activity and deeper penetration to inflamed tissues;

• smaller molecular weight, enabling improved targeting at the site of inflammation as EVO301 is only a fraction of the molecular weight compared to traditional antibodies;

• extended half-life for the neutralization of IL-18, conveyed by the SAFA, utilizing a body peptide linker which supports FcRn-mediated recycling of serum albumin; and

• lower potential for immunogenicity, as the use of native human IL-18BP, a naturally occurring inhibitor of IL-18, is expected to reduce immunogenicity risk and enhance durability of response.

Further, we believe the distinct mechanism and modality of EVO301 complement those of EVO756, providing us with multiple, potentially synergistic avenues to bring innovative therapeutics to the large, underserved and rapidly expanding population of patients suffering from chronic inflammatory diseases.

Figure 38: Potential for EVO756 and EVO301 Mechanism of Action Synergy in AD

EVO301 for the Treatment of Atopic Dermatitis

Atopic Dermatitis Background

IL-18 acts as a general amplifier of inflammation, capable of driving multiple inflammatory responses, including Th1, Th2, Th17/22 and innate pathways, all of which are highly implicated in AD. Broadly impacting these pathways is crucial for treating conditions with heterogeneous inflammation, where targeting a single pathway may not be optimal. When the IL-18 pathway is upregulated in a chronic, cyclical fashion, it can trigger a cascade of inflammatory mediators that ultimately lead to tissue damage and disease manifestations, including those we see in atopic dermatitis. IL-18 also directly disrupts essential skin barrier functions, positioning it as a pivotal pathogenic factor. Targeting IL-18 offers broader therapeutic utility with a novel approach, simultaneously reducing inflammation and restoring tissue integrity for patients with complex inflammatory conditions.

Current Treatment Paradigm

The current standard of care for first-line treatment of AD is primarily topical corticosteroids and targeted treatments (for example, topical JAK inhibitors). However, approximately 40% to 50% of AD patients have a moderate-to-severe form of the disease and are uncontrolled by topical therapies. For these patients, new systemic agents have emerged as advanced treatments that systemically target several different inflammatory mediators that contribute to underlying inflammation and flare-ups. Dupixent, an anti-IL-4 receptor alpha antagonist that inhibits the signaling of IL-4 and IL-13 cytokines, is currently the preferred biologic for moderate-to-severe AD. The initial dose is two injections followed by one injection every two weeks and is considered to have category-high efficacy with 36% of patients reaching EASI-90 in 16 weeks. While treatment with Dupixent has also been shown to reduce itch (as measured by peak pruritus-NRS) by up to approximately 50%, it typically takes 16 weeks to achieve this level of efficacy and plateaus thereafter. Despite Dupixent’s efficacy, over 60% of AD patients remain uncontrolled and patients may be burdened with potential side effects, including conjunctivitis and injection site reactions, and the burden of twice-monthly injections. Two oral JAK inhibitors, Rinvoq and Cibinqo, have also been approved for the disease and offer improved efficacy with over 40% of patients exceeding EASI-90 at 16 weeks, but are reserved for later lines of treatment due to safety concerns including black box warnings for cardiac events and malignancies. Another biologic, Ebglyss (lebrikizumab), an IL-13 inhibitor, was recently approved by the FDA for the treatment of AD based on clinical results wherein approximately 33% to 43% of patients were observed to achieve IGA 0/1 with ≥2-point improvement from baseline to week 16. Several biologics are in development with differing mechanisms of action including product candidates that target IL-13, OX-40, IL-2R and IL-18, including our own EVO301.

Market Opportunity

We believe the market for AD therapeutics is in a nascent stage, particularly when compared to the growth observed in the market for psoriasis, which has grown meaningfully since the launch of Enbrel in 2004 as illustrated in the figure below:

Figure 39: Expansion of AD Market Outpacing That of Psoriasis

Notes: “Year 1” for AD represents 2017 (year of Dupixent launch); “Year 1” for psoriasis represents 2004 (year of Enbrel launch in plaque psoriasis). May represent projections and not actual sales.

There is a substantial need for broad, safe treatments in AD, where approximately 16 million patients in the United States live with the disease, at least 40% of which are moderate-to-severe patients. Given that a significant number of patients with AD remain uncontrolled, we see the need for a biologic therapy with a competitive efficacy profile targeting a new mechanism of action and improved safety profile. We believe a treatment option with this product profile would have broad applicability, first-line potential in moderate-to-severe disease and could be utilized by a wider range of prescribers, expanding access. We believe IL-18 is the only target impacting broader immunological cascades of Th2, Th1, Th17, Innate Inflammation and IL-22, key factors underlying AD, as shown in the figure below:

Figure 40: IL-18 Impacts Multiple Inflammatory Pathways that Drive AD

Clinical Data

Completed Phase 1 Trial

EVO301 was observed to be well-tolerated at all doses, with no SAEs nor discontinuations due to AEs, in a Phase 1 randomized, placebo-controlled SAD trial in 31 healthy volunteers conducted by our licensor, AprilBio, with five cohorts that consisted of SAD ranging from 0.1 mg/kg up to 10 mg/kg administered intravenously.

The majority of reported AEs were determined to be mild in severity and included headache, nausea and reactions at the infusion site. No discontinuations were attributed to AEs, and there were no SAEs. In addition, there were no clinically significant ECG or lab abnormalities. No measurable impact on PK due to anti-drug antibody formation was observed.

The pharmacokinetic profile of EVO301 supports the potential for monthly dosing. Serum concentrations exceeded the IC90 for more than four weeks after a single administration at dose levels of 0.3 mg/kg or greater.

Completed Phase 2a Trial for Moderate-to-Severe Atopic Dermatitis

We conducted a Phase 2a randomized, double-blind, placebo-controlled, parallel-group trial evaluating EVO301 in 70 adult patients with moderate-to-severe AD dosed on day 1 and day 29. The trial was conducted at sites in Australia and New Zealand and enrolled patients aged ≥18 years with moderate-to-severe AD for at least six months (with EASI score of ≥16, Validated IGA scale ≥3 and BSA of AD of ≥10%). The trial’s primary endpoint was a Bayesian success criterion related to the difference between active and placebo in the percent improvement in baseline in EASI score at week 12. Secondary endpoints include vIGA response, percent change in BSA and change from baseline in pruritus-NRS.

The following figure shows the Phase 2a trial design:

Figure 41: EVO301 Phase 2a Trial Design

Notes: EASI = Eczema Area and Severity Index; vIGA = Validated Investigator Global Assessment; BSA = Body Surface Area.

A total of 70 patients were enrolled in the Phase 2a trial, with 48 patients assigned to the active cohort and 22 patients to the placebo cohort. Baseline EASI in the active and placebo cohorts was 30.0 and 29.8, respectively. A total of 65 patients completed the trial with 45 in the active cohort and 22 in the placebo cohort. There were no treatment related discontinuations in the trial. Baseline characteristics and patient dispositions for enrolled and treated patients are detailed in Figure 42 below:

Figure 42: Phase 2a EVO301 AD Trial Disposition

Notes: 1. Lost to follow-up. 2. Lost to follow-up and subject withdrawal

Efficacy Results

The trial met its primary endpoint, a Bayesian success criterion related to the difference between active and placebo in the percent improvement in baseline in the EASI. While the success criterion required at least 75% of the posterior distribution to be an improvement of at least 8% over placebo, the results of the trial demonstrated 99.8% of

the posterior distribution met that threshold. Furthermore, when analyzed by the more commonly used frequentist method, statistical significance was achieved at weeks 4, 8 and 12 at p0.01.

After just two doses of EVO301 (administered on day 1 and at week 4), efficacy - measured by both % change in EASI and vIGA response - was already comparable to marketed AD biologics. Clinical separation emerged early and responses were durable, with sustained benefit observed 8 weeks after the final dose, as shown in the figures below:

Figure 43: Percent Reduction in EASI at Weeks 4, 8 and 12:

Figure 44: Plotted Curves % Reduction in EASI, by Week:

Approximately 23% of patients treated with EVO301 (vs 0% placebo) achieved vIGA-AD 0/1 (percent of patients achieving a score of 0 or 1 on the vIGA for AD with ≥ 2-point reduction from baseline) at week 12.

Figure 45: vIGA Response at Weeks 4, 8 and 12

After only two administered doses (at day 1 and 28), EVO301 achieved comparable improvement in EASI from baseline to that of other approved biologics targeting alternate mechanisms of action, despite these agents administered under fully optimized dosing regimens.

Figure 46: Placebo-Adjusted Improvement from Baseline in EASI

Note: For illustrative purposes only. Not a head-to-head comparison. Differences exist between trial designs and study characteristics, and caution should be exercised when comparing across trials.

If this activity and safety profile observed to date are sustained or further enhanced in larger trials, we believe EVO301 has the potential to become an attractive first-line option for AD patients who are eligible for systemic therapy, as well as for patients who have experienced an inadequate response to existing therapies. Importantly, by targeting IL-18, EVO301 is designed to address underlying inflammatory drivers of disease more broadly, rather than focusing on a single downstream pathway.

As we advance EVO301 into a Phase 2b subcutaneous dose-ranging trial in moderate-to-severe AD, we will apply the insights from this proof-of-concept trial and leverage the team's extensive past experience optimizing dosing, to design a rigorous and efficient 16-week trial. With higher exposures delivered at an optimized dosing cadence, we

believe there is potential to further increase efficacy beyond the already robust responses observed in our Phase 2a trial.

In addition, EVO301 demonstrated PK and target engagement supportive of a Q4 week dosing regimen, accompanied by corresponding improvements in secondary endpoints and reductions in key Th2-associated biomarkers (CCL-17 (TARC), CCL-22) and non-Th2 associated biomarkers such as IL-22. Collectively, we believe this supports our thesis that IL-18 modulates AD disease pathology more broadly than just Th2 alone. These PK/PD results, combined with the clinical data, support our confidence in both the mechanism and the dosing strategy we plan to take forward.

Safety Results

EVO301 was well tolerated, with no related serious AEs or SAEs reported, no treatment-related discontinuations due to AEs and no meaningful differences in events between the active and placebo groups. There were no clinically significant lab abnormalities and no cases of conjunctivitis were reported.

Figure 47: EVO301 Phase 2a Safety Summary Table and Treatment Emergent Adverse Events in More than 5% of Subjects in Either Arm

Planned Phase 2b Trial for Moderate-to-Severe Atopic Dermatitis

Given the positive data from our Phase 2a trial, we are planning to advance EVO301 into a global Phase 2b trial using a subcutaneous formulation of EVO301, with results expected to support potential future Phase 3 registrational studies for EVO301 in moderate-to-severe AD.

Clinical Development Plan and Status

EVO301 for the Treatment of Inflammatory Bowel Diseases

In the United States, over 2.2 million people live with inflammatory bowel diseases, which include UC and Crohn’s disease. These diseases are characterized by relapsing and remitting inflammation of the gastrointestinal tract, leading to symptoms such as abdominal pain, diarrhea, bleeding and significant impacts on quality of life. Initial treatments often include aminosalicylates, corticosteroids or immunomodulators, yet a substantial portion of the patients require escalation to advanced therapies due to inadequate symptom control or adverse effects. Despite the availability of several advanced therapies including anti-TNF agents, anti-integrins, IL-12/23 inhibitors and JAK inhibitors, the landscape for IBD has no consistent treatment paradigm and continues to be marked by limitations, with up to 50% of patients failing to achieve or maintain meaningful clinical remission. As a result, many IBD patients cycle through multiple therapies without achieving durable disease control, leaving hundreds of thousands of patients in the United States inadequately managed, underscoring the need for new effective mechanisms of action.

Beyond AD, we are evaluating a potential Phase 2 trial in moderate-to-severe UC patients. The results of the trial are expected to inform dose selection and other trial design considerations for further clinical development in IBD. We believe that IL-18 signaling plays a key role in UC, as illustrated in the figure below:

Figure 48: Role of IL-18 in Ulcerative Colitis

Discovery Stage Programs

We are also selectively advancing discovery-stage programs to enable us to consistently deliver data on new product candidates. We are currently evaluating multiple preclinical molecules across various targets for possible nomination as lead development candidates for IND-enabling studies in 2026 and beyond.

We also intend to continue evaluating potential preclinical assets, including through in-licensing or partnerships, that we believe can be optimized for priority indications to broaden our portfolio.

Competition

The biotechnology and biopharmaceutical industries are characterized by rapidly advancing technologies, intense competition and a strong emphasis on proprietary products. While we believe that our technology, the expertise of our management team, clinical capabilities, research and development experience and scientific knowledge provide us with competitive advantages, we face increasing competition from many different sources, including biotechnology and biopharmaceutical companies, academic institutions, governmental agencies and public and private research institutions. Any product candidates that we successfully develop and commercialize will compete with existing therapies and new therapies that may become available in the future.

There are several large biotechnology and biopharmaceutical companies that are currently pursuing the development of products for the treatment of chronic inflammation. Companies that we are aware of that are targeting the treatment of chronic inflammation and related diseases include large companies with revenues and significant financial resources. However, we know of one other company currently in clinical development with an MRGPRX2 antagonist and no other companies currently in clinical development with a serum albumin Fab-associated IL-18BP fusion protein.

Many of our competitors, either alone or with their collaborators, have significantly greater resources, established presence in the market and greater expertise across research and development, manufacturing, preclinical and clinical testing, obtaining regulatory approvals, reimbursement and marketing approved products than we do. These competitors also compete with us in recruiting and retaining qualified scientific, sales, marketing and management personnel, establishing clinical trial sites and patient registration for clinical trials, as well as in acquiring technologies complementary to, or necessary for, our programs. Smaller or early-stage companies may also prove to be significant competitors, particularly through collaborative arrangements with large and established companies. Additional mergers and acquisitions may result in even more resources being concentrated in our competitors.

The commercial potential of our product candidates could be reduced or eliminated if our competitors develop and commercialize products that are safer, more effective, have fewer or less severe side effects, are more convenient or are less expensive. Our competitors also may obtain FDA or regulatory approval from comparable foreign regulatory authorities for their product candidates more rapidly than we may obtain approval for ours, which could result in our competitors establishing a strong market position before we are able to enter the market or make our development more complicated. The key competitive factors affecting the success of our product candidates are likely to be efficacy, safety, cost and convenience.

Intellectual Property

Our owned and exclusively licensed patents and patent applications relate to our compounds for treating certain chronic inflammation indications and include patents and patent applications directed to new compositions of matter and to methods of treating a variety of disorders. As we continue to develop our product candidates, we intend to seek additional patent protection in the United States, EU and in other key commercial markets worldwide.

EVO756

As of December 31, 2025, we exclusively license one patent family that includes one issued U.S. patent, two pending U.S. patent applications and issued and pending foreign counterpart patents and patent applications, relating to compositions of matter and methods of use for our product candidate, EVO756. If we continue to pursue patent protection, and if any patents issue based on our pending applications, we expect such patents to expire in November 2040, without taking into account possible patent term adjustments or extensions.

EVO301

As of December 31, 2025, we exclusively license three patent families that include two issued U.S. patents, two pending U.S. patent applications and issued and pending foreign counterpart patents and patent applications, relating to our product candidate, EVO301. One of these patent families includes U.S. Patent No. 9,879,077, relating to compositions of matter, and U.S. Patent No. 10,618,953, relating to methods of use, both of which are expected to expire in August 2034, absent any patent term extension. The second patent family includes two pending U.S. patent applications that are directed to, among others, compositions of matter and methods of use relating to EVO301. If we continue to pursue patent protection, and if any patents issue based on our pending applications in this patent family, we expect such patents to expire in September 2041 in the United States, absent any patent term adjustment and patent term extension. The third patent family includes one pending PCT application directed to methods of use. If we continue to pursue patent protection, and if any patents issue based on our pending applications in this patent family, we expect such patents to expire in June 2044 in the United States, without taking into account possible patent term adjustments or extensions.

The term of individual patents depends on the legal term for patents in the countries in which they are granted. In most countries, including the United States, the basic patent term is 20 years from the earliest claimed filing date of a non-provisional patent application in the applicable country. In the United States, a patent’s term may, in certain cases, be extended by patent term adjustment, which compensates a patentee for administrative delays by the USPTO in examining and granting a patent, or may be shortened if a patent is terminally disclaimed over a commonly owned patent or a patent naming a common inventor and having an earlier expiration date, or shortened due to an express disclaimer or abandonment. Additionally, the Drug Price Competition and Patent Term Restoration Act of 1984, permits a patent term extension of up to five years beyond the expiration date of a U.S. patent as partial compensation for the length of time the drug is under regulatory review. Patent extensions of up to five years are also available in certain countries under certain circumstances as partial compensation for the regulatory review period in the respective jurisdictions.

For a discussion of the risks associated with our intellectual property, see “Risk Factors—Risks Related to Intellectual Property.”

Strategic Collaborations and License Agreements

Dermira, Inc.

In December 2020, we entered into a License, Development and Commercialization Agreement with Dermira, pursuant to which Dermira granted us an exclusive, worldwide license to develop and commercialize certain compounds, including the compound in development by us known as EVO756 (the “Dermira License Agreement”).

The Dermira License Agreement remains in effect on a product-by-product and a country-by-country basis until the expiration of the royalty term for such product in such country. The Dermira License Agreement may be terminated by either party due to the other party’s uncured material breach or bankruptcy. Additionally, we may terminate the Dermira License Agreement for convenience upon a set number of days’ prior notice.

In consideration for the licenses granted to us under the Dermira License Agreement, we paid to Dermira a $7.5 million upfront license fee. Additionally, in connection with our entry into the Dermira License Agreement, we issued to Dermira 3,227,805 shares of Series A Preferred Stock which was equal to approximately 5% of our fully diluted equity at the time of grant and was calculated by reference to the same per-share purchase price paid by the lead investor in the Series A Preferred Stock financing (as a completed qualified financing).

We are also obligated to pay to Dermira up to $45.0 million in development milestones for the development of EVO756 (or up to $135.0 million for the development of all licensed products), and up to $240.0 million in sales milestones for the development of EVO756 (or up to $720.0 million for the development of all licensed products) as well as tiered royalty payments in mid-single digit to low-tens percentages on worldwide sales of the licensed products.

As of December 31, 2025, we have paid a total of $11.0 million in upfront payments and development milestones under the Dermira License Agreement, which was recognized as research and development expense for the year in which they occurred. No milestones were achieved under the Dermira License Agreement during the year ended December 31, 2024. For the year ended December 31, 2025, we recorded $2.5 million as research and development expense upon achievement of a development milestone under the Dermira License Agreement. Milestones and royalties are contingent upon future events and will be recorded when the milestones are achieved and when payments are due.

Under the Dermira License Agreement, we may sublicense EVO756 to third parties. Dermira has consented to our sublicense of EVO756 to Maruho in Japan and certain Asian countries as described below.

Maruho Co., Ltd.

Maruho Japan Agreement

In September 2023, we entered into a sublicense agreement with Maruho and granted Maruho the exclusive license to develop and commercialize EVO756 in Japan (the “Maruho Japan Agreement”). Under the Maruho Japan Agreement, Maruho is responsible for the development and commercialization of EVO756 in Japan, except that we are required to use commercially reasonable efforts to develop EVO756 in CSU and to include a Japanese cohort in our Phase 1 clinical trial of EVO756.

Under the terms of the Maruho Japan Agreement, we received an upfront payment of $8.0 million in September 2023 and are eligible to receive up to $52.0 million in development, regulatory and commercial milestone payments upon the occurrence of specified events over the term of the agreement. In addition, we are eligible to receive low single digit royalty payments on future sales of EVO756 in Japan, on top of the royalty payments due to Dermira on such sales under the Dermira License Agreement. As of December 31, 2025, we have received a total of $18.0 million under the Maruho Japan Agreement.

The Maruho Japan Agreement remains in effect until the expiration of the royalty term for all licensed products in Japan, which continues until the expiration of all relevant patents and regulatory exclusivities and 10 years from the first commercial sale of the licensed product in Japan, whichever is the latest. The Maruho Japan Agreement may be terminated by either party due to the other party’s uncured material breach or bankruptcy. In addition, we may terminate the agreement if Maruho challenges any licensed patent. Maruho may also terminate the agreement for convenience upon prior written notice to us.

Maruho Greater Asia Agreement

In March 2024, we entered into a separate sublicense agreement with Maruho (the “Maruho Greater Asia Agreement”) and granted Maruho the exclusive license to develop and commercialize EVO756 in China, Taiwan, South Korea and the member states of the Association of Southeast Asian Nations (ASEAN) (the “Territory”). Under the Maruho Greater Asia Agreement, Maruho is responsible for the development and commercialization of EVO756 in the Territory, except that we are required to use commercially reasonable efforts to develop EVO756 in CSU.

Under the terms of the Maruho Greater Asia Agreement, we received an upfront payment of $7.0 million in March 2024 and are eligible to receive up to $54.5 million in development, regulatory and commercial milestone payments upon the occurrence of specified events over the term of the agreement. In addition, we are eligible to receive low single-digit royalty payments on future sales of EVO756 in the Territory, on top of the royalty payments due to Dermira on such sales under the Dermira License Agreement. As of December 31, 2025, we have received a total of $7.0 million under the Maruho Greater Asia Agreement.

The Maruho Greater Asia Agreement remains in effect until the expiration of the royalty term for all licensed products in the Territory, which continues until the expiration of all relevant patents and regulatory exclusivities and 10 years from the first commercial sale of the licensed product in the relevant country in the Territory, whichever is the latest. The Maruho Greater Asia Agreement may be terminated by either party due to the other party’s uncured material breach or bankruptcy. In addition, we may terminate the agreement if Maruho challenges any licensed patent. Maruho may also terminate the agreement for convenience upon prior written notice to us.

AprilBio Co., Ltd.

In June 2024, we entered into a license agreement with AprilBio upon which AprilBio granted us an exclusive worldwide license to develop and commercialize EVO301 (the “AprilBio License Agreement”). Under the AprilBio

License Agreement, we are responsible for the development and commercialization of the licensed product, except that AprilBio was responsible for completing the then ongoing Phase 1 clinical trial. We are required to use commercially reasonable efforts to develop and commercialize the licensed product in certain major market countries and to meet certain specified diligence milestones. In addition, AprilBio also granted us a right of first negotiation to license or acquire rights to other IL-18 products that may be developed by AprilBio if AprilBio completes certain development work for such product within a specified time period.

Under the AprilBio License Agreement, we paid an upfront payment of $15.0 million and are required to pay, upon achievement of specified milestones and the sale of the licensed product, development milestones of up to $82.5 million, sales milestones of up to $377.5 million, and tiered royalty payments in the mid to high-single digit percentage on worldwide sales of the licensed product. In addition, if we sublicense the licensed product, we are required to pay AprilBio a percentage of the sublicense revenue we received, which percentage depends on the timing of the sublicense grant. For the twelve months ended December 31, 2025, we recorded $1.5 million as research and development expense upon achievement of a development milestone under the AprilBio License Agreement. No development milestones were recorded as research and development expenses for the twelve months ended December 31, 2024. No other development or sales milestones have been achieved as of December 31, 2025. As of December 31, 2025, we have paid a total of $16.5 million under the AprilBio License Agreement.

The AprilBio License Agreement remains in effect on a product-by-product and country-by-country basis until the expiration of the royalty term for such product in such country, which continues until the expiration of all relevant patents and regulatory exclusivities and 12 years from the first commercial sale of such product in such country, whichever is the latest. The AprilBio License Agreement may be terminated by either party due to the other party’s uncured material breach or bankruptcy. In addition, AprilBio may terminate the agreement if we challenge any licensed patent or if we cease active development of the licensed product. We may also terminate the agreement for convenience upon prior written notice to AprilBio.

Government Regulation

The FDA and comparable regulatory authorities in state and local jurisdictions and in other countries impose requirements upon companies involved in the clinical development, manufacture, marketing and distribution of drugs, such as those we are developing. These agencies and other federal, state and local entities regulate, among other things, the research and development, testing, manufacture, quality control, safety, effectiveness, labeling, storage, approval, advertising and promotion, distribution, post-approval monitoring and reporting, sampling, export and import and record-keeping associated with all these functions, of our product candidates.

U.S. Government Regulation of Drug Products

In the United States, the FDA regulates drugs under the Federal Food, Drug, and Cosmetic Act (the “FDCA”), and its implementing regulations. The FDA also regulates biological products under the FDCA and the Public Health Service Act. The process of obtaining regulatory approvals and the subsequent compliance with applicable federal, state, local and foreign statutes and regulations require the expenditure of substantial time and financial resources. Failure to comply with the applicable U.S. requirements at any time during the product development process, approval process or after approval, may subject an applicant to a variety of administrative or judicial sanctions, such as the FDA’s refusal to approve pending New Drug Applications (“NDAs”) or Biologics License Applications (“BLAs”), withdrawal of an approval, imposition of a clinical hold, issuance of warning letters, product recalls, product seizures, total or partial suspension of production or distribution, injunctions, fines, refusals of government contracts, restitution, disgorgement or civil or criminal penalties.

The process required by the FDA before a drug may be marketed in the United States generally involves the following:

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Completion of preclinical laboratory tests, animal studies and formulation studies in compliance with the FDA’s GLP regulations;

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

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Approval by an independent institutional review board (“IRB”) at each clinical site before each trial may be initiated;

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Performance of adequate and well-controlled human clinical trials in accordance with GCP requirements to establish the safety and efficacy of the proposed drug product for each indication;

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Submission to the FDA of an NDA or BLA, including payment of application user fees;

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A determination by the FDA within 60 days of its receipt to accept the marketing application for review;

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Satisfactory completion of an FDA advisory committee review, if applicable;

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Satisfactory completion of an FDA inspection of the manufacturing facility or facilities at which the product is produced to assess compliance with current good manufacturing practice (“cGMP”) requirements and to assure that the facilities, methods and controls are adequate to preserve the product’s identity, strength, quality and purity;

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Satisfactory completion of FDA audits of clinical trial sites to assure compliance with GCPs and the integrity of the clinical data; and

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FDA review and approval of the NDA or BLA.

Preclinical Studies

Preclinical studies include laboratory evaluation of product chemistry, toxicity and formulation, as well as in vitro and animal studies to assess potential safety and efficacy. The conduct of preclinical studies is subject to federal regulations and requirements, including good laboratory practice regulations for safety/toxicology studies.

An IND sponsor must submit the results of the preclinical tests, together with manufacturing information, analytical data and any available clinical data or literature and plans for clinical studies, among other things, 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 human clinical trials may begin. Some preclinical testing, such as animal tests of reproductive AEs and carcinogenicity, may continue even after the IND is submitted. An IND automatically becomes effective 30 days after receipt by the FDA, unless before that time the FDA raises concerns or questions related to one or more proposed clinical trials and places the clinical trial on a clinical hold. In such a case, the IND sponsor and the FDA must resolve any outstanding concerns before the clinical trial can begin. As a result, submission of an IND may not result in the FDA allowing clinical trials to initiate.

Clinical Trials

Clinical trials involve the administration of the investigational new drug to human subjects under the supervision of qualified investigators in accordance with GCP requirements, which include the requirement that all research subjects provide their informed consent in writing for their participation in any clinical trial. Clinical trials are conducted under protocols detailing, among other things, the objectives of the trial, the parameters to be used in monitoring safety, and the effectiveness criteria to be evaluated. A protocol for each clinical trial conducted in the United States and any subsequent protocol amendments must be submitted to the FDA as part of the IND. In addition, an IRB representing each institution participating in the clinical trial must review and approve the plan for any clinical trial before it is initiated at that institution. The IRB also must review and approve 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 completion.

Information about certain clinical trials must be submitted within specific timeframes to the Institutes of Health (“NIH”) for public dissemination on their www.clinicaltrials.gov website. Information related to the product, patient population, phase of investigation, trial sites and investigators and other aspects of the clinical trial is made public as part of the registration of the clinical trial. Although sponsors are obligated to disclose the results of their clinical trials after completion, disclosure of the results can be delayed in some cases for up to two years after the date of completion of the trial. Failure to timely register a covered clinical trial or to submit trial results as provided for in the law can give rise to civil monetary penalties and also prevent the non-compliant party from receiving future grant funds from the federal government.

Human clinical trials are typically conducted in three sequential phases, which may overlap or be combined:

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Phase 1: The drug is initially introduced into healthy human subjects or patients with the target disease or condition and tested for safety, dosage tolerance, absorption, metabolism, distribution, excretion and, if possible, to gain an early indication of its effectiveness.

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Phase 2: The drug is administered to a limited patient population to identify possible adverse effects and safety risks, to preliminarily evaluate the efficacy of the product for specific targeted diseases and to determine dosage tolerance and optimal dosage.

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Phase 3: The drug is administered to an expanded patient population, generally at geographically dispersed clinical trial sites, in well-controlled clinical trials to generate enough data to statistically evaluate the efficacy and safety of the product for approval, to establish the overall risk-benefit profile of the product and to provide adequate information for the labeling of the product.

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. In certain instances, the FDA may mandate the performance of Phase 4 clinical trials as a condition of approval on an NDA or BLA.

Progress reports detailing the results of the clinical trials must be submitted at least annually to the FDA and more frequently if SAEs occur. Written IND safety reports must be submitted to the FDA and investigators for serious and unexpected suspected adverse events, findings from other studies or animal or in vitro testing that suggest a significant risk for human subjects 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 submit an IND safety report within 15 calendar days after the sponsor determines that the information qualifies for reporting. The sponsor also must notify the FDA of any unexpected fatal or life-threatening suspected adverse reaction within seven calendar days after the sponsor’s initial receipt of the information.

Phase 1, Phase 2 and Phase 3 trials may not be completed successfully within any specified period, or at all. Furthermore, the FDA or the sponsor may suspend or terminate a clinical trial at any time on various grounds, including a finding that the research subjects are being exposed to an unacceptable health risk. Similarly, an IRB can suspend or terminate approval of a clinical trial at its institution if the clinical trial is not being conducted in accordance with the IRB’s requirements or if the drug has been associated with unexpected serious harm to patients. Additionally, some clinical trials are overseen by an independent group of qualified experts organized by the clinical trial sponsor, known as a data safety monitoring board or committee. This group provides authorization for whether a trial may move forward at designated check points based on access to certain data from the trial.

Concurrent with clinical trials, companies usually complete additional animal studies and also must develop additional information about the chemistry and physical characteristics of the drug as well as finalize a process for manufacturing the product in commercial quantities in accordance with cGMP requirements. The manufacturing process must be capable of consistently producing quality batches of product and, among other things, companies must develop methods for testing the identity, strength, quality and purity of the final product. Additionally, appropriate packaging must be selected and tested and stability studies must be conducted to demonstrate that the drug does not undergo unacceptable deterioration over its shelf life.

NDA or BLA Submission and Marketing Approval

Assuming successful completion of the required clinical testing, the results of the preclinical and clinical studies, 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 or BLA requesting approval to market the product for one or more indications. In most cases, the submission of an application is subject to a substantial user fee.

The FDA conducts a preliminary review of all applications within the first 60 days after submission, before accepting them for filing, to determine whether they are sufficiently complete to permit substantive review. The FDA may request additional information rather than accept an application for filing. In this event, the application must be resubmitted with the additional information. The resubmitted application is also subject to review before the FDA accepts it for filing. Once the submission is accepted for filing, the FDA begins an in-depth substantive review. The FDA reviews an application 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 Prescription Drug User Fee Act (“PDUFA”) guidelines that are currently in effect, the FDA has a goal of ten months from the date of “filing” of a standard NDA or BLA to review and act on the submission and six months from the filing date of an application with priority review. Accordingly, this review process typically takes 12 months and eight months, respectively from the date the application is submitted to the FDA. The FDA does not always meet its PDUFA goal dates for standard or priority review, and the review process is often extended by FDA requests for additional information or clarification. The FDA reviews an NDA or BLA 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 ensure the product’s continued safety, quality and purity.

In addition, under the Pediatric Research Equity Act of 2003, as amended, certain applications or supplements to an approved application must contain data that are adequate to assess the safety and effectiveness 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, on its own initiative or at the request of the applicant, grant deferrals for submission of some or all pediatric data until after approval of the product for use in adults or full or partial waivers from the pediatric data requirements. 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 must submit an initial Pediatric Study Plan (“PSP”), within 60 days of an end-of-Phase 2 meeting or, if there is no such meeting, as early as practicable before initiation of the Phase 3 or Phase 2/3 study. The initial PSP must include an outline of the pediatric study or studies that the sponsor plans to conduct, including study objectives and design, age groups, relevant endpoints and statistical approach or a justification for not including such detailed information, and any request for a deferral of pediatric assessments or a full or partial waiver of the requirement to provide data from pediatric studies along with supporting information. 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 or other clinical development programs.

The FDA may refer an application for a novel drug or a drug that presents difficult questions of safety or efficacy 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.

The FDA also may require the submission of a risk evaluation and mitigation strategy (“REMS”) if it determines that a REMS is necessary to ensure that the benefits of the drug outweigh its risks and to assure the safe use of the drug. A REMS may include one or more elements, including medication guides, physician communication plans, patient package insert or elements to assure safe use, such as restricted distribution methods, patient registries or other risk minimization tools. The FDA determines the requirement for a REMS, as well as the specific REMS provisions, on a case-by-case basis. If the FDA concludes a REMS is needed, the sponsor must submit a proposed REMS. The FDA will not approve the application without a REMS, if required.

Before approving an NDA or BLA, 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 assure consistent production of the product within required specifications. Additionally, before approving an NDA or BLA, the FDA may inspect one or more clinical trial sites to assure compliance with GCP requirements.

After evaluating the application 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 application and may require additional clinical or preclinical testing in order for FDA to reconsider the application. If a Complete Response Letter is issued, the applicant may either resubmit the application within a year, addressing all of the deficiencies identified in the letter, or withdraw the application. Even with submission of this additional information, the FDA ultimately may decide that the application does not satisfy the regulatory 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, 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.

Expedited Development and Priority Review Programs

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.

The FDA has a Fast Track program that is intended to expedite or facilitate the process for reviewing new drugs that meet certain criteria. Specifically, new drugs are eligible for Fast Track designation if they are intended to treat a serious or life-threatening condition and preclinical or clinical data demonstrate the potential to address unmet medical needs for the condition. Fast Track designation applies to both the product and the specific indication for which it is being studied. 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.

Additionally, a drug may be eligible for designation as a breakthrough therapy if the product is intended, alone or in combination with one or more other drugs or biologics, to treat a serious or life-threatening condition and preliminary clinical evidence indicates that the product may demonstrate substantial improvement over currently approved therapies on one or more clinically significant endpoints. The benefits of Breakthrough Therapy designation include the same benefits as Fast Track designation, plus intensive guidance from the FDA to ensure an efficient drug development program. A product may also be eligible for priority review if it treats a serious or life-threatening condition and, if approved, would provide a significant improvement in safety and effectiveness compared to available therapies. The FDA determines at the time that the marketing application is submitted, on a case-by-case basis, whether the proposed drug represents a significant improvement in treatment, prevention or diagnosis of disease when compared with other available therapies. The FDA will attempt to direct additional resources to the evaluation of an application for a new drug designated for priority review in an effort to facilitate the review and to shorten the FDA’s goal for taking action from ten months to six months from the date of filing of a marketing application.

A product may also be eligible for accelerated approval if it treats a serious or life-threatening disease or condition, generally provides a meaningful advantage over available therapies and demonstrates an effect on a surrogate endpoint that is reasonably likely to predict clinical benefit, or on a clinical endpoint that can be measured earlier than irreversible morbidity or mortality (“IMM”), that is reasonably likely to predict an effect on IMM or other clinical benefit. As a condition of accelerated approval, the FDA requires that a sponsor perform adequate and well-controlled post-marketing clinical trials. If the FDA concludes that a drug shown to be effective can be safely used only if distribution or use is restricted, it will require such post-marketing restrictions, as it deems necessary to assure safe use of the product.

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 decide that the time period for FDA review or approval will not be shortened. Fast Track designation, Breakthrough Therapy designation and Priority Review designation do not change the standards for approval, but may expedite the development or review process. Drugs granted accelerated approval also must meet the same statutory standards for safety and effectiveness as those granted traditional approval. Based on current operating plans, we do not intend to pursue any expedited development and priority review programs.

U.S. Marketing Exclusivity

Market exclusivity provisions under the FDCA can delay the submission or the approval of certain follow-on applications. The FDCA provides a five-year period of non-patent marketing exclusivity within the United States to the first applicant to gain 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 accept for review an Abbreviated New Drug Application for a generic version of the drug or a 505(b)(2) NDA for another version of such drug where the applicant does not own or have a legal right of reference to all the data required for approval. However, such a follow-on application may be submitted after four years if it contains a certification of patent invalidity or non-infringement. The FDCA also provides three years of market exclusivity for an NDA, 505(b)(2) 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 period covers only the conditions of use associated with the new clinical investigations and does not prohibit the FDA from approving follow-on applications that do not reference the protected clinical data. 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 all of the preclinical studies and adequate and well-controlled clinical trials necessary to demonstrate safety and effectiveness.

Pediatric exclusivity is another type of regulatory market exclusivity in the United States. Pediatric exclusivity, if granted, adds six months to existing regulatory exclusivity periods or listed patents. This six-month exclusivity may be granted based on the voluntary completion of a pediatric trial in accordance with an FDA-issued “Written Request” for such a trial.

A seven-year period of orphan exclusivity is available for products (i) intended to treat a disease that affects fewer than 200,000 people in the U.S. or (ii) intended to treat a disease that affects more than 200,000 people, but for which there is no reasonable expectation that costs of research and development of the drug for the indication can be recovered by sales of the drug in the United States. A sponsor may request an orphan designation at any time before it submits a marketing application; if the designation is granted and the orphan-designated product is approved, the FDA will not approve another sponsor’s marketing application for the same drug for the same use or indication before the expiration of seven years from the date of such approval, unless the orphan designation is revoked, the approval of the underlying application is revoked or the sponsor is unable to supply sufficient product to meet market demand.

For biologics, the Biologics Price Competition and Innovation Act of 2009 created an abbreviated approval pathway for products that are biosimilar to or interchangeable with an FDA-licensed reference biological product. Biosimilarity, which requires that there be no clinically meaningful differences between the biological product and the reference product in terms of safety, purity and potency, can be shown through analytical studies, animal studies and a clinical study or studies. Interchangeability requires that a product is biosimilar to the reference product and the product must demonstrate that it can be expected to produce the same clinical results as the reference product in any given patient and, for products that are administered multiple times to an individual, the biologic and the reference biologic may be alternated or switched after one has been previously administered without increasing safety risks or risks of diminished efficacy relative to exclusive use of the reference biologic without such alteration or switch. Upon licensure by the FDA, an interchangeable biosimilar may be substituted for the reference product without the intervention of the health care provider who prescribed the reference product. A reference biological product is granted 12 years of data exclusivity from the time of first licensure of the product. In addition, the FDA will not accept an application for a biosimilar or interchangeable product based on the reference biological product until four years after the date of first licensure of the reference product.

Post-Approval Requirements

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 recordkeeping, periodic reporting, product sampling and distribution, advertising and promotion and reporting of adverse experiences with the product. After approval, most changes to the approved product, such as adding new indications or other labeling claims are subject to prior FDA review and approval. There are continuing, annual user fee requirements for any marketed products.

The FDA may impose a number of post-approval requirements as a condition of approval. For example, the FDA may require post-marketing testing, including Phase 4 clinical trials, and surveillance to further assess and monitor the product’s safety and effectiveness after commercialization.

FDA regulations require that products be manufactured in specific facilities (identified in the approved NDA or BLA) and in accordance with cGMP regulations which require, among other things, quality control and quality assurance, the maintenance of records and documentation and the obligation to investigate and correct any deviations from cGMP. In addition, drug manufacturers and other entities involved in the manufacture and distribution of approved drugs are required to register their establishments with the FDA and state agencies and are subject to periodic unannounced inspections by the FDA and these state agencies for compliance with cGMP requirements. Changes to the manufacturing process are strictly regulated and often require prior FDA approval before being implemented. FDA regulations also require investigation and correction of any deviations from cGMP requirements and impose reporting and documentation requirements upon the sponsor and any third-party manufacturers that the sponsor may decide to use. Accordingly, manufacturers must continue to expend time, money and effort in the area of production and quality control to maintain cGMP compliance.

Once approval of a drug is granted, the FDA may withdraw the approval if compliance with regulatory requirements and standards is not maintained or if problems occur after the product reaches the market. 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 mandatory revisions to the approved labeling to add new safety information; imposition of post-market studies or clinical trials to assess new safety risks; or imposition of distribution or other restrictions under a REMS program. Any of these limitations on approval or marketing could restrict the commercial promotion, distribution, prescription or dispensing of products. 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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Fines, warning letters or holds on post-approval clinical trials;

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Refusal of the FDA to approve pending applications or supplements to approved applications or suspension or withdrawal of product approvals;

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Product seizure or detention or refusal to permit the import or export of products; and

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Injunctions or the imposition of civil or criminal penalties.

The FDA strictly regulates marketing, labeling, advertising and promotion of products that are placed on the market. Drugs may be promoted by a manufacturer and any third parties acting on behalf of a manufacturer only for the approved indications and in a manner consistent with the approved label for the product. 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.

Other Healthcare Laws

Healthcare providers, physicians and third-party payors will play a primary role in the recommendation and prescription of drug products for which we obtain marketing approval. Arrangements with third-party payors, healthcare providers and physicians, in connection with the clinical research, sales, marketing and promotion of products, once approved, and related activities, may expose a pharmaceutical manufacturer to broadly applicable fraud and abuse and other healthcare laws and regulations. In the United States, these laws include, without limitation, state and federal anti-kickback, false claims, physician transparency and patient data privacy and security laws and regulations, including but not limited to those described below:

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the Anti-Kickback Statute (“AKS”), which makes it illegal for any person or entity, including a prescription drug manufacturer (or a party acting on its behalf) to knowingly and willfully solicit, receive, offer or pay any remuneration (including any kickback, bribe or rebate), directly or indirectly, overtly or covertly, in cash or in kind, that is intended to induce or reward, referrals including the purchase, recommendation, order or prescription of a particular drug for which payment may be made under a federal healthcare program, such as the Medicare and Medicaid programs. The AKS has been interpreted to apply to arrangements between therapeutic product 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. Further, courts have found that if “one purpose” of remuneration is to induce referrals, the AKS is violated. In addition, the government may assert that a claim including items or services resulting from a violation of the AKS constitutes a false or fraudulent claim for purposes of the federal FCA;

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the federal civil and criminal false claims laws, including the FCA, which can be enforced by private citizens through “qui tam” or “whistleblower” actions, and civil monetary penalty laws, which impose criminal and civil penalties against individuals or entities for, among other things, knowingly presenting, or causing to be presented, claims for payment or approval from Medicare, Medicaid or other federal health care programs that are false or fraudulent; knowingly making or causing a false statement material to a false or fraudulent claim or an obligation to pay or transmit money or property to the federal government; or knowingly concealing or knowingly and improperly avoiding or decreasing such an obligation. Pharmaceutical and other healthcare companies have been, and continue to be, prosecuted under these laws, among other things, for allegedly providing free product to customers with the expectation that the customers would bill federal programs for the product and for causing false claims to be submitted because of the companies’ marketing of the product for unapproved, off-label, and thus generally non-reimbursable, uses. Similar to the AKS, a person or entity does not need to have actual knowledge of these statutes or specific intent to violate them in order to have committed a violation.

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the federal Health Insurance Portability and Accountability Act of 1996 (“HIPAA”), which created additional federal criminal provisions that prohibit 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 (for example, 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 statements in connection with the delivery of, or payment for, healthcare benefits, items or services relating to healthcare matters. Like the AKS, the Patient Protection and Affordable Care Act (the “ACA”) amended the intent standard for certain healthcare fraud provisions under HIPAA such that a person or entity no longer needs 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 (“HITECH”), and their respective implementing regulations, which impose requirements on certain covered healthcare providers, health plans and healthcare clearinghouses as well as their respective business associates and covered subcontractors that perform services for them that involve the creation, use, receipt, maintenance or disclosure of individually identifiable health information, relating to the privacy, security and transmission of individually identifiable health information. HITECH also created four new tiers of civil monetary penalties, amended HIPAA to make civil and criminal penalties directly applicable to business associates and gave state attorneys general new authority to file civil actions for damages or injunctions in federal courts to enforce HIPAA and seek attorneys’ fees and costs associated with pursuing federal civil actions;

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the federal Physician Payments Sunshine Act, created under the ACA, and its implementing regulations, which require manufacturers of drugs, devices, biologics and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program to report annually to the Centers for Medicare and Medicaid Services, under the Open Payments Program, information related to payments or other transfers of value made to physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors), certain other healthcare professionals (such as physician assistants and nurse practitioners) and teaching hospitals, as well as ownership and investment interests held by physicians and their immediate family members; and

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analogous state and foreign laws and regulations, such as state and foreign anti-kickback, false claims, consumer protection and unfair competition laws which may apply to pharmaceutical business practices, including but not limited to, research, distribution, sales and marketing arrangements as well as submitting claims involving healthcare items or services reimbursed by any third-party payor, including commercial insurers; 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 that otherwise restricts payments that may be made to healthcare providers and other potential referral sources; state laws that require drug manufacturers to file reports with states regarding pricing and marketing information, such as the tracking and reporting of gifts, compensations and other remuneration and items of value provided to healthcare professionals and entities; state and local laws requiring the registration of pharmaceutical sales representatives; and state, national and foreign laws governing the privacy and security of health information in certain circumstances, many of which differ from each other in significant ways and may not have the same effect, thus complicating compliance efforts.

Because of the breadth of these laws and the narrowness of the statutory exceptions and regulatory safe harbors available, it is possible that some of a pharmaceutical manufacturer’s business activities could be subject to challenge under one or more of such laws. Efforts to ensure that business arrangements comply with applicable healthcare laws involve substantial costs. It is possible that governmental and enforcement authorities will conclude that a pharmaceutical manufacturer’s business practices do not comply with current or future statutes, regulations or case law interpreting applicable fraud and abuse or other healthcare laws and regulations. If any such actions, which are costly to defend, are instituted against a pharmaceutical manufacturer, and it is not successful in defending itself or asserting its rights, those actions could have a significant impact on its business, including the imposition of significant civil, criminal and administrative penalties, damages, disgorgement, imprisonment, monetary fines, possible exclusion from participation in Medicare, Medicaid and other federal healthcare programs, reporting obligations and oversight if we become subject to integrity and oversight agreements to resolve allegations of non-compliance, contractual damages, reputational harm, diminished profits and future earnings and curtailment of operations, any of which could adversely affect a pharmaceutical manufacturer’s ability to operate its business and the results of operations. In addition, commercialization of any drug product outside the United States will also likely be subject to foreign equivalents of the healthcare laws mentioned above, among other foreign laws.

Current and Future Healthcare Reform Legislation

In both the United States and certain foreign jurisdictions, there have been, and continue to be, a number of legislative and regulatory changes to the health care system. Among policy makers and payors in the United States and elsewhere, there is significant interest in promoting changes in healthcare systems with the stated goals of containing healthcare costs, improving quality and expanding access. In the United States, the pharmaceutical industry has been a particular focus of these efforts and has been significantly affected by major legislative initiatives. In particular, in 2010, the ACA was enacted, which, among other things, increased the minimum Medicaid rebates owed by most manufacturers under the Medicaid Drug Rebate Program, extended the Medicaid Drug Rebate Program to utilization of prescriptions of individuals enrolled in Medicaid managed care organizations, subjected manufacturers to new annual fees and taxes for certain branded prescription drugs and provided incentives to programs that increase the federal government’s comparative effectiveness research.

There have been judicial, administrative, executive and legislative challenges and amendments to certain aspects of the ACA, and we expect there will be additional challenges and amendments to the ACA in the future. For example, on July 4, 2025, the One Big Beautiful Bill Act (the “OBBBA”) was signed into law, which narrowed access to ACA marketplace exchange enrollment and declined to extend the ACA enhanced advanced premium tax credits that expired at the end of 2025, which, among other provisions in the law, are anticipated to reduce the number of Americans with health insurance. The OBBBA also is expected to reduce Medicaid spending and enrollment by implementing work requirements for some beneficiaries, capping state-directed payments, reducing federal funding, and limiting provider taxes used to fund the program. Congress is considering proposed legislation intended to further reduce healthcare costs with alternatives to replace the expired ACA subsidies. It is possible that the ACA will be subject to additional challenges in the future. It is unclear whether the ACA will be overturned, repealed, replaced or further amended. We cannot predict what affect further changes to the ACA would have on our business.

In addition, other legislative changes have been proposed and adopted in the United States since the ACA was enacted. For example, through the process created by the Budget Control Act of 2011, there are automatic reductions of Medicare payments to providers up to 2% per fiscal year, which went into effect in April 2013 and, due to subsequent legislative amendments, will remain in effect until 2032 unless additional Congressional action is taken.

Additionally, there has been heightened governmental scrutiny in the United States of pharmaceutical pricing practices in light of the rising cost of prescription drugs and biologics.

The current administration is pursuing policies to reduce regulations and expenditures across government including at the U.S. Department of Health and Human Services ("HHS"), the FDA, the Centers for Medicare & Medicaid Services ("CMS") and related agencies. These actions, presently directed by executive orders or memoranda from the Office of Management and Budget, may propose policy and personnel changes that create additional uncertainty for our business. For example, the current administration has announced agreements with several pharmaceutical companies that require the drug manufacturers to offer, through a direct to consumer platform, U.S. patients and Medicaid programs prescription drug Most-Favored Nation pricing equal to or lower than those paid in other developed nations, with additional mandates for direct-to-patient discounts and repatriation of foreign revenues. Other recent actions include, for example, (1) directives to reduce agency workforce program cuts, (2) directing HHS and other agencies to lower prescription drug costs through a variety of initiatives, including by improving upon the Medicare Drug Price Negotiation Program and establishing Most-Favored-Nation pricing for pharmaceutical products and (3) as part of the Make America Healthy Again Commission’s Strategy Report released in September 2025, working across government agencies to increase enforcement on direct-to-consumer pharmaceutical advertising. Additionally, the current administration recently called on Congress to enact "The Great Healthcare Plan," to codify and expand Most-Favored Nation pricing, lower government subsidies to private insurance companies, increase healthcare price transparency, expand pharmaceutical drugs available for over-the-counter purchase, and enact restrictions on pharmacy benefit manager payment methodologies, among other things. These actions and policies may significantly reduce U.S. drug prices, potentially impacting manufacturers’ global pricing strategies and profitability, while increasing their operational costs and compliance risks. In June 2024, the U.S. Supreme Court’s Loper Bright decision greatly reduced judicial deference to regulatory agencies, which could increase successful legal challenges to federal regulations affecting our operations. Congress may introduce and ultimately pass health care related legislation that could impact the drug approval process and make changes to the Medicare Drug Price Negotiation Program.

HHS has revoked the Richardson Waiver, which required HHS and its subagencies to provide notice and an opportunity to comment on certain matters relating to agency management or personnel or to public property, loans, grants, benefits or contracts. This could result in modifications to HHS policies in these areas that could adversely affect our business. In addition, the Trump administration has issued an executive order directing agencies to examine all regulations, to repeal regulations that do not comply with statutes or are otherwise burdensome and to consider repealing such regulations without notice and comment, which may result in repeal or modification of regulations without significant advance notice. Congress may introduce and ultimately pass health care related legislation that could, among others, impact the drug approval process, modify the Medicare Drug Price Negotiation Program, expand the orphan drug exclusion under the IRA and reduce Medicaid enrollment and funding.

In addition, individual states in the United States have also increasingly passed legislation and implemented 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.

Legislative and regulatory proposals and enactment of laws, at the foreign federal and state levels, directed at containing or lowering the cost of healthcare, will continue into the future. 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 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 products;

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our ability to obtain coverage and reimbursement approval for a product;

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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.

Regulation Outside the United States

In addition to regulations in the United States, we will be subject to a variety of regulations in other jurisdictions governing, among other things, clinical trials and any commercial sales and distribution of our products. The cost of establishing a regulatory compliance system for numerous varying jurisdictions can be very significant. Although many of the issues discussed above with respect to the United States apply similarly in the context of the EU and in other jurisdictions, the approval process varies between countries and jurisdictions and can involve additional product testing and additional administrative review periods. The time required to obtain approval in other countries and jurisdictions might differ from and be longer than that required to obtain FDA approval. Regulatory approval in one country or jurisdiction does not ensure regulatory approval in another, but a failure or delay in obtaining regulatory approval in one country or jurisdiction may negatively impact the regulatory process in others.

Whether or not we obtain FDA approval for 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. Certain countries outside of the United States have a similar process that requires the submission of a clinical trial application much like the IND prior to the commencement of human clinical trials. In the EU, for example, a clinical trial authorization application (“CTA”), must be submitted for each clinical protocol to each country’s national health authority and an independent ethics committee, much like the FDA and IRB, respectively. Once the CTA is accepted in accordance with a country’s requirements, the clinical trial may proceed.

The requirements and processes governing the conduct of clinical trials vary from country to country. In all cases, the clinical trials are conducted in accordance with GCP, the applicable regulatory requirements and the ethical principles that have their origin in the Declaration of Helsinki.

To obtain regulatory approval of an investigational medicinal product under EU regulatory systems, we must submit a marketing authorization application. The content of the application submitted in the United States is similar to that required in the EU, with the exception of, among other things, country-specific document requirements.

For other countries outside of the EU and the United States, such as countries in Eastern Europe, Latin America or Asia, the requirements governing product development, the conduct of clinical trials, manufacturing, distribution, marketing approval, product licensing, pricing and reimbursement vary from country to country.

Countries that are part of the EU, as well as countries outside of the EU, have their own governing bodies, requirements and processes with respect to the approval of drug products. 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.

Additionally, to the extent that any of our product candidates, once approved, are sold in a foreign country, we may be subject to applicable post-marketing requirements, including safety surveillance, anti-fraud and abuse laws and implementation of corporate compliance programs and reporting of payments or other transfers of value to healthcare professionals.

Authorization Procedures in the EU

In the U.K. and the EEA (the 27 EU member states plus Iceland, Liechtenstein and Norway), medicinal products must be authorized for marketing by using either the centralized authorization procedure or national authorization procedures.

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Centralized procedure—If pursuing marketing authorization of a product candidate for a therapeutic indication under the centralized procedure, following the opining of the EMA’s Committee for Medicinal Products for Human Use (“CHMP”), the European Commission issues a single marketing authorization valid across the EEA. The centralized procedure is compulsory for human medicines derived from biotechnology processes or advanced therapy medicinal products (such as gene therapy, somatic cell therapy and tissue engineered products), products that contain a new active substance indicated for the treatment of certain diseases, such as HIV/AIDS, cancer, neurodegenerative disorders, diabetes, autoimmune diseases and other immune dysfunctions, viral diseases and officially designated orphan medicines. For medicines that do not fall within these categories, an applicant has the option of submitting an application for a centralized marketing authorization to the EMA, as long as the medicine concerned contains a new active substance not yet authorized in the EEA, or is a significant therapeutic, scientific or technical innovation, or if its authorization would be in the interest of public health in the EEA. Under the

centralized procedure, the maximum timeframe for the evaluation of a marketing authorization application (“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 CHMP, and which can add materially to the timeframe. Accelerated assessment might be granted by the CHMP in exceptional cases, when a medicinal product is expected to be of major public health interest, particularly from the point of view of therapeutic innovation. The timeframe for the evaluation of an MAA under the accelerated assessment procedure is 150 days, excluding clock stops.

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

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Decentralized procedure—Using the decentralized procedure, an applicant may apply for simultaneous authorization in more than one EU country of medicinal products that have not yet been authorized in any EU country and that do not fall within the mandatory scope of the centralized procedure.

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Mutual recognition procedure—In 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, additional marketing authorizations can be sought from other EU countries in a procedure whereby the countries concerned recognize the validity of the original, national marketing authorization.

In the EEA, new products for therapeutic indications that are authorized for marketing (that is, reference products) qualify for eight years of data exclusivity and an additional two years of market exclusivity upon marketing authorization. The data exclusivity period prevents generic or biosimilar applicants from relying on the preclinical and clinical trial data contained in the dossier of the reference product when applying for a generic or biosimilar marketing authorization in the EU during a period of eight years from the date on which the reference product was first authorized in the EU. The market exclusivity period prevents a successful generic or biosimilar applicant from commercializing its product in the EU until ten years have elapsed from the initial authorization of the reference product in the EU. The ten-year market exclusivity period can be extended to a maximum of 11 years if, during the first eight years of those ten years, the marketing authorization holder obtains an authorization for one or more new therapeutic indications which, during the scientific evaluation prior to their authorization, are held to bring a significant clinical benefit in comparison with existing therapies.

The criteria for designating an “orphan medicinal product” in the EEA are similar in principle to those in the United States. In the EEA, a medicinal product may be designated as orphan if (1) it is intended for the diagnosis, prevention or treatment of a life-threatening or chronically debilitating condition; (2) either (a) such condition affects no more than five in 10,000 persons in the EU when the application is made or (b) the product, without the benefits derived from orphan status, would not generate sufficient return in the EU to justify investment; and (3) 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 significant benefit to those affected by the condition. Orphan medicinal products are eligible for financial incentives such as reduction of fees or fee waivers and are, upon grant of a marketing authorization, entitled to ten years of market exclusivity for the approved therapeutic indication. During this ten-year orphan market exclusivity period, no marketing authorization application shall be accepted, and no marketing authorization shall be granted for a similar medicinal product for the same indication. An orphan product can also obtain an additional two years of market exclusivity in the EU for pediatric studies.

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, marketing authorization may be granted to a similar product for the same indication at any time if (i) the second applicant can establish that its product, although similar, is safer, more effective or otherwise clinically superior; (ii) the applicant consents to a second orphan medicinal product application; or (iii) the applicant cannot supply enough orphan medicinal product.

As in the United States, the various phases of non-clinical and clinical research in the EU are subject to significant regulatory controls.

The Clinical Trials Directive 2001/20/EC, the Directive 2005/28/EC on GCP and the related national implementing provisions of the individual EU member states govern the system for the approval of clinical trials in the EU. Under this system, an applicant must obtain prior approval from the competent national authority of the EU

member states in which the clinical trial is to be conducted. Furthermore, the applicant may only start a clinical trial at a specific trial site after the competent ethics committee has issued a favorable opinion. The clinical trial application must be accompanied by, among other documents, an investigational medicinal product dossier (the Common Technical Document) with supporting information prescribed by Directive 2001/20/EC, Directive 2005/28/EC and, where relevant, the implementing national provisions of the individual EU member states and further detailed in applicable guidance documents.

In April 2014, the new Clinical Trials Regulation (EU) No 536/2014 or Clinical Trials Regulation, was adopted. It is expected that the Clinical Trials Regulation will apply following confirmation of full functionality of the Clinical Trials Information System, the centralized EU portal and database for clinical trials foreseen by the regulation, through an independent audit. The regulation becomes applicable six months after the European Commission publishes notice of this confirmation. The Clinical Trials Regulation will be directly applicable in all the EU member states, repealing the current Clinical Trials Directive 2001/20/EC. Conduct of all clinical trials performed in the EU will continue to be bound by currently applicable provisions until the Clinical Trials Regulation becomes applicable. The extent to which ongoing clinical trials will be governed by the Clinical Trials Regulation will depend on when the Clinical Trials Regulation becomes applicable and on the duration of the individual clinical trial. If a clinical trial continues for more than three years from the day on which the Clinical Trials Regulation becomes applicable, the Clinical Trials Regulation will at that time begin to apply to the clinical trial. The new Clinical Trials Regulation aims to simplify and streamline the approval of clinical trials in the EU.

The main characteristics of the regulation include (i) a streamlined application procedure via a single-entry point, the “EU portal,” a single set of documents to be prepared and submitted for the application as well as simplified reporting procedures for clinical trial sponsors; and (ii) a harmonized procedure for the assessment of applications for clinical trials, which is divided in two parts. Part I is jointly assessed by the competent authorities of all EU member states in which an application for authorization of a clinical trial has been submitted (member states concerned). Part II is assessed separately by each member state concerned. Strict deadlines have been established for the assessment of clinical trial applications. The role of the relevant ethics committees in the assessment procedure will continue to be governed by the national law of the concerned EU member state. However, overall related timelines will be defined by the Clinical Trials Regulation.

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

Coverage and Reimbursement

Successful commercialization of new drug products depends in part on the extent to which reimbursement for those drug products will be available from government health administration authorities, private health insurers and other organizations. In the United States, government authorities and third-party payors, such as private health insurers and health maintenance organizations, decide which drug products they will pay for and establish reimbursement levels. The availability and extent of reimbursement by governmental and private payors is essential for most patients to be able to afford a drug product. Sales of drug products depend substantially, both domestically and abroad, on the extent to which the costs of drugs products are paid for by health maintenance, managed care, pharmacy benefit and similar healthcare management organizations or reimbursed by government health administration authorities, private health coverage insurers and other third-party payors.

A primary trend in the U.S. healthcare industry and elsewhere is cost containment. Government authorities and third-party payors have attempted to control costs by limiting coverage and the amount of reimbursement for particular drug products. For example, HHS imposes rebates on many Medicare Part B and Medicare Part D products to penalize price increases that outpace inflation on an annual basis. In addition, HHS has been empowered to negotiate the price of certain single-source drugs that have been on the market for at least 7 years and biologics that have been on the market for at least 11 years covered under Medicare as part of the Medicare Drug Price Negotiation Program. Each year up to twenty (20) products will be selected by HHS for the Medicare Drug Price Negotiation Program. Products subject to the Medicare Drug Price Negotiation Program are expected to experience a significant reduction in reimbursement from the Medicare program on a per unit basis.

Third-party payors are increasingly challenging the price, examining the medical necessity and reviewing the cost-effectiveness of medical products, therapies and services, in addition to questioning their safety and efficacy. Obtaining reimbursement for our products may be particularly difficult because of the higher prices often associated

with branded drugs and drugs administered under the supervision of a physician. 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 approvals. Our product candidates may not be considered medically necessary or cost-effective. Obtaining coverage and reimbursement approval of a product from a government or other third-party payor is a time-consuming and costly process that could require us to provide to each payor supporting scientific, clinical and cost-effectiveness data for the use of our product on a payor-by-payor basis, with no assurance that coverage and adequate reimbursement will be obtained. A payor’s decision to provide coverage for a product does not imply that an adequate reimbursement rate will be approved. Further, one payor’s determination to provide coverage for a product does not ensure that other payors will also provide coverage for the product. Adequate third-party reimbursement may not be available to enable us to maintain price levels sufficient to realize an appropriate return on its investment in product development. If reimbursement is not available or is available only at limited levels, we may not be able to successfully commercialize any product candidate that we successfully develop.

In many countries, the prices of drug products are subject to varying price control mechanisms as part of national health systems. In general, the prices of drug products under such systems are substantially lower than in the United States. Other countries allow companies to fix their own prices for drug products but monitor and control company profits. Accordingly, in markets outside the United States, the reimbursement for drug products may be reduced compared with the United States.

In the United States, the principal decisions about reimbursement for new drug products are typically made by CMS, an agency within HHS. CMS decides whether and to what extent a new drug product will be covered and reimbursed under Medicare, and private payors tend to follow CMS to a substantial degree. However, no uniform policy of coverage and reimbursement for drug products exists among third-party payors and coverage and reimbursement levels for drug products can differ significantly from payor to payor. Coverage and reimbursement by a third-party payor may depend upon a number of factors, including the third-party payor’s determination that use of a drug 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.

It is uncertain whether coverage or reimbursement will be available for any product that we commercialize and, if coverage and reimbursement are available, what the level of reimbursement will be. Coverage may also be more limited than the purposes for which the product is approved by the FDA or comparable foreign regulatory authorities. Reimbursement may impact the demand for, or the price of, any product for which we obtain regulatory approval.

These laws and future state and federal healthcare reform measures may be adopted in the future, any of which may result in additional reductions in Medicare and other healthcare funding and otherwise affect the prices we may obtain for any product candidates for which we may obtain regulatory approval or the frequency with which any such product candidate is prescribed or used.

Outside of the United States, the pricing of pharmaceutical products and medical devices is subject to governmental control in many countries. For example, in the EU, pricing and reimbursement schemes vary widely from country to country. Some countries provide that products may be marketed only after a reimbursement price has been agreed. Some countries may require the completion of additional studies that compare the cost effectiveness of a particular therapy to currently available therapies or so-called health technology assessments, in order to obtain reimbursement or pricing approval. Other countries may allow companies to fix their own prices for products but monitor and control product volumes and issue guidance to physicians to limit prescriptions. Efforts to control prices and utilization of pharmaceutical products and medical devices will likely continue as countries attempt to manage healthcare expenditures.

Data Privacy and Security

In the ordinary course of business, we collect, receive, generate, make accessible, protect, secure, dispose, transmit, store, use, disclose, transfer, maintain and otherwise process sensitive information, including personal data.

Accordingly, we are, and may become subject to various foreign, federal, state and local laws, rules, regulations, guidance, industry standards, external and internal privacy and security policies, contractual requirements and other obligations related to data privacy and security.

These data privacy and security obligations are evolving and may impose potentially conflicting obligations. Such obligations may include, without limitation, federal health information privacy laws, state information security and data breach notification laws, state health information privacy laws and federal and state consumer protection laws (for example, the Federal Trade Commission Act). In addition, in the past few years, numerous U.S. states have enacted comprehensive privacy laws, rules and regulations that impose certain obligations on covered businesses (including providing specific disclosures in privacy notices and affording individuals with certain rights concerning their personal data) and similar laws are being considered at the federal level. While certain of these laws do or may exempt some data processed in the context of clinical trials, these developments may further complicate compliance efforts and are examples of the increasingly stringent and evolving regulatory frameworks related to personal data processing, as more fully discussed in the section titled “Risk Factors” included elsewhere in this Form 10-K.

Additionally, as we collect personal data from individuals outside of the United States, through clinical trials or otherwise, we are, and may become subject to foreign data privacy and security laws, such as Australia’s Privacy Act, New Zealand’s Privacy Act, Canada’s Privacy Act, Japan’s Act on the Protection of Personal Information and the European Union’s General Data Protection Regulation. Such foreign data privacy and security laws impose significant and complex compliance obligations on entities that are subject to those laws, as more fully discussed in the section titled “Risk Factors” included elsewhere in this Form 10-K.

Employees and Human Capital Resources

As of December 31, 2025, we had 48 full-time employees, who together hold 19 Ph.D. or M.D. degrees and 29 of whom are engaged in research and development activities. 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 stockholder value and the success of our company by motivating such individuals to perform to the best of their abilities and achieve our objectives.

Facilities

We lease a facility containing 10,665 square feet of laboratory and office space, which is located in Palo Alto, California. The lease expired in July 2025 and has been extended until December 2025. In June 2025, we entered into a new lease agreement for our Palo Alto facility, which will include approximately 32,016 square feet and is expected to commence in March 2026 and expire in June 2031. We also lease offices in New York. We believe that our current facilities are sufficient to meet our current and near-term needs and that, should it be needed, suitable additional space will be available.

Corporate Information

We were incorporated under the laws of the State of Delaware in April 2020 under the name “Evommune, Inc.” Our principal executive office is located at 1841 Page Mill Road, Suite 100, Palo Alto, California 94304. Our telephone number is (925) 247-4481. We completed our initial public offering in November 2025 and our common stock is listed on the New York Stock Exchange under the symbol “EVMN.”

Available Information

Our website address is www.evommune.com and our investor relations website address is https://ir.evommune.com. Our Annual Reports on Form 10-K, Quarterly Reports on Form 10-Q, current reports on Form 8-K and amendments to those reports filed or furnished pursuant to Sections 13(a) and 15(d) of the Exchange Act are available free of charge on our investor relations website as soon as reasonably practicable after we electronically file such material with, or furnish it to, the SEC. The SEC maintains an internet site that contains reports, proxy and information statements and other information. The address of the SEC’s website is www.sec.gov.

Further corporate governance information, including our corporate governance guidelines and board committee charters, is also available on our investor relations website under the heading “Corporate Governance.” The contents of our websites are not intended to be incorporated by reference into this Annual Report on Form 10-K

or in any other report or document we file with the SEC, and any references to our websites are intended to be inactive textual references only.

Evommune, Inc. (EVMN) Business

Overview

Table of Contents

Table of Contents

Figure 1: Our Clinical Pipeline

Our Approach to Drug Development and Chronic Inflammation

EVO756, Targeting MRGPRX2 for Chronic Inflammatory Diseases

Table of Contents

Figure 2: EVO756 Proof-of-Concept Roadmap

Table of Contents

Table of Contents

Figure 3: EVO756 FricTest Score Improvements and Other Observed Data

Figure 4: Omalizumab Clinical Activity Improved Over Time

Table of Contents

Figure 5: Barzolvolimab Clinical Activity Improved Over Time

Figure 6: CIndU Response as a Potential Indicator of Future CSU Profile

Table of Contents

Additional Development Opportunities for EVO756

Table of Contents

EVO301, Our SAFA Binding Protein Targeting IL-18 for Chronic Inflammatory Diseases

Other Drug Discovery and Development

Table of Contents

EVO756: Our MRGPRX2 Antagonist

Overview

MRGPRX2 as an Ideal Target for Chronic Inflammatory Disease

Table of Contents

Figure 7: MRGPRX2 in Mast Cell Activation and Neuroinflammation

Figure 8: MRGPRX2, A Nexus for Mast Cell/Neuron Activation by Multiple Ligands

Table of Contents

Market Opportunity

Figure 9: Targeting MRGPRX2 Creates Broad Opportunity

Table of Contents

Figure 10: Prevalence of Select Chronic Inflammatory Diseases

Our Solution: EVO756, Our MRGPRX2 Antagonist

Figure 11: Select Characteristics of EVO756

Table of Contents

Figure 12: EVO756 Is a Highly Potent Oral Small Molecule

Chronic Urticaria Background

Table of Contents

Current Treatment Paradigm

Figure 13: CSU Is an Underserved Market with Limited Treatment Options

Table of Contents

Figure 14: Potential for EVO756 to Address an Urticaria Market with Significant Therapeutic Opportunity

Clinical Data

Our Completed Phase 1 Trial

Table of Contents

Figure 15: Phase 1 Proof-of-Concept Trial Design and Summary

Notes: ECG = electrocardiogram

Safety Results

Figure 16: Safety Results of Phase 1 Trial

Table of Contents

PK Results and Trial Dosing

Phase 1 Proof-of-Concept Skin Challenge Test

Figure 17: Skin Challenge Test: Proof-of-Concept and Target Engagement for Chronic Urticaria

Table of Contents

Figure 18: EVO756 Robustly Decreased Icatibant-Induced Wheals

Figure 19: PK Modeling of EVO756 Based on Clinical Data Generated to Date

Table of Contents

Figure 20: EVO756 Target Coverage and Dosing Response

Our Phase 2 Trial in CIndU

Table of Contents

Figure 21: Phase 2 CIndU Trial Design

Figure 22: Phase 2 CIndU Trial Disposition

Notes: LTFU = Lost-to-Follow-Up

Efficacy Results

Table of Contents

Figure 23: FricTest Response at Week 4

Figure 24: FricTest Scores by Subject at Week 4

Table of Contents

Figure 25: Average FricTest Score Over Time by Cohort

Table of Contents

Figure 26: Average Provoked Itch Score Over Time by Cohort

Figure 27: Pruritus-NRS Response at Week 4 in Subjects with Baseline Pruritus-NRS ≥4

Safety Results

Table of Contents

Clinical Development Plan and Status

Our Ongoing Phase 2b Dose-Ranging Clinical Trial in Chronic Spontaneous Urticaria

Table of Contents

Figure 29: Phase 2b CSU Trial Design

Nonclinical Data