Tango Therapeutics, Inc. (TNGX) Business

Item 1. Business.

Overview

Tango Therapeutics was founded with a clear mission: to discover the next wave of targeted therapies in oncology by addressing the specific genetic alterations that drive cancer. We leverage our state-of-the-art target and drug discovery platforms to identify novel disease-relevant targets and develop medicines tailored to defined patient populations with high unmet medical need. Our novel small molecules are designed to be selectively active in cancer cells with specific genetic alterations, killing those cancer cells while sparing normal cells. We believe our approach will provide the ability to deliver deep, durable target inhibition with favorable tolerability and safety profiles, thus potentially maximizing clinical benefit.

We are currently focused on clinical development of two MTAP-deleted selective PRMT5 inhibitors: vopimetostat (TNG462) for non-CNS cancers, both as a monotherapy and in combination with RAS inhibitors, and TNG456, our next-generation, brain-penetrant PRMT5 inhibitor, for CNS cancers, including glioblastoma (GBM).

In October 2025, we reported positive data from the ongoing Phase 1/2 clinical trial of vopimetostat monotherapy in patients with MTAP-deleted selective cancers, illustrating clinical activity across multiple cancer types with a favorable safety and tolerability profile. Specifically, the data in second-line MTAP-deleted pancreatic cancer demonstrated a median progression free survival (mPFS) of 7.2 months and 25% objective response rate (ORR), supporting the planned initiation of a 2L pivotal trial in this patient population in 2026. The histology selective cohort, which excludes sarcoma, pancreatic and lung cancer patients, also showed positive data, with a mPFS of 9.1 months and 49% ORR. We are evaluating the development path for the histology selective cohort, as well as for selected indications as stand-alone development opportunities. Lastly, emerging data from the lung cancer cohort are consistent with expectations, and we anticipate providing a safety and efficacy update in 2026.

We are focused on evaluating the combination of vopimetostat with RAS inhibitors, given the overlap in patient populations, robust preclinical data supporting potential strong combination effect in clinical trials, and favorable clinical efficacy, durability, and safety profiles observed with each drug individually. We believe this approach may enable a development path for chemotherapy-free first-line and potentially second-line therapies for MTAP-deleted/RAS-mutated patients with pancreatic and lung cancer. In June 2025, we treated the first patient in our combination clinical trial evaluating vopimetostat with the RAS(ON) multi-selective inhibitor, daraxonrasib, and RAS(ON) G12D-selective inhibitor, zoldonrasib (Revolution Medicines), which enrolled 30 patients as of December 24, 2025. Both combinations have been well-tolerated to date with exposures in the active range for all compounds with encouraging early efficacy data. We anticipate providing a safety and efficacy update from this trial in 2026. Given the differentiated profile of vopimetostat enabling the potential for efficacious and tolerable RAS inhibitor combinations, in March 2026, we entered into a clinical trial collaboration and supply agreement (CTCSA) with Erasca, Inc., or Erasca, to evaluate vopimetostat in combination with Erasca’s pan-RAS molecular glue, ERAS-0015. Under the terms of the agreement, Tango is the sponsor of the trial and Erasca is supplying ERAS-0015 at no cost.

TNG456 is a brain-penetrant PRMT5 inhibitor. In May 2025, the first patient was treated with TNG456 in the dose escalation portion of the Phase 1/2 clinical trial to evaluate the safety, pharmacokinetics, pharmacodynamics and antitumor activity of TNG456 as a monotherapy. The trial is currently enrolling patients with MTAP-deleted solid tumors, with a focus on GBM. We anticipate providing a safety and efficacy update from this trial in 2026.

TNG961 is a novel, potent and selective molecular glue development candidate targeting HBS1L for degradation in solid tumors in FOCAD-deleted/MTAP-deleted cancers. FOCAD deletion occurs in 20-40% of all MTAP-deleted cancers due to the collateral loss with the tumor suppressor gene CDKN2A/B on chromosome 9p21. Cancers with FOCAD loss are dependent on HBS1L for mRNA processing, thus protein synthesis. By degrading HBS1L and disrupting the HBS1L/PELO complex, TNG961 causes tumor regression in FOCAD-deleted preclinical models of multiple histologies. TNG961 is in the IND-enabling phase of development.

TNG260 is a first-in-class CoREST inhibitor. In November 2025, we announced that patients with checkpoint inhibitor resistant STK11 mutant/KRAS wild-type NSCLC receiving clinically active doses of TNG260 plus pembrolizumab had a mPFS of 29 weeks (n=5), more than double the standard of care PFS of ~10 weeks. 80 mg QD of TNG260 was selected for dose expansion, which is ongoing for patients.

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Our Pipeline

We are leveraging the power and productivity of our discovery engine to discover and validate multiple novel targets each year. Our growing pipeline consists of discovery programs for multiple cancer types that currently have limited treatment options, as summarized in Figure 1.

Figure 1. Tango Therapeutics' product pipeline

Our Strategy

We are pioneering novel approaches to the discovery and development of innovative targeted oncology therapies. We leverage the following core strategic components, enabling the pursuit of transformative therapies for patients with cancer:

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Advance the clinical development of vopimetostat as a monotherapy and in combination with other therapies, including RAS inhibitors, in clinical trials to enable multiple registration paths for markets with large addressable patient populations and high unmet need

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Advance the clinical development of TNG456 in the ongoing Phase 1/2 clinical trial, focused on GBM

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Develop the next generation of precision oncology targets to continue to grow our pipeline

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Opportunistically evaluate our pipeline assets and maximize the value through strategic collaborations and licensing deals to bring more medicines to patients, accelerate development timelines and explore combination therapy approaches for our product candidates

BACKGROUND

Unmet need in precision oncology

Many genetic drivers of cancer are well-characterized but remain difficult to target directly, either because their molecular structure resists conventional inhibition (“undruggable” targets) or because the alteration results in loss of the gene’s normal function. As a result, a substantial portion of oncogenic biology remains a largely unaddressed target space. We are applying precision-oncology strategies, including the concept of synthetic lethality, to address the unmet medical need of large patient groups defined by actionable molecular alterations (e.g., specific mutation, deletions, copy-number changes, or immune contextures).

Synthetic lethality as a precision oncology strategy

Synthetic lethal cancer therapies exploit pairs of genes or pathways in which one is inactivated by a tumor-specific alteration and the other is inhibited pharmacologically. While genetic alterations drive the development of cancer, they also

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create unique vulnerabilities that can be targeted therapeutically. Biologically, these vulnerabilities may include an inability of cancer cells to respond to a specific signal, such as DNA damage or cell-cycle arrest, or the inability to remodel chromatin or to maintain cellular homeostasis. A key advantage of the synthetic lethal approach is selectivity: normal cells are not dependent on the same compensatory pathway and are therefore largely unaffected at drug-dose levels that selectively kill alteration-bearing cancer cells, as noted in Figure 2 below. The success of PARP inhibitors in BRCA-mutant breast, ovarian and prostate cancers is the first clinical example of using synthetic lethality to target tumors deficient in DNA-repair mechanism.

Figure 2. In cancer cells, specific molecular alterations create a dependency that allows an inhibitor to target a synthetic-lethal partner gene, causing tumor-cell death. This selective killing only occurs in tumors harboring the defined alteration (e.g. tumor suppressor gene), thereby largely sparing normal tissues offering a wide therapeutic index.

Biomarker driven patient selection

Across our clinical programs, we use molecular biomarkers as the basis for patient selection to enroll those patients most likely to benefit from each new drug candidate. This patient-centric, molecular approach is designed to enable efficient clinical development, increase the probability of success, and deliver the greatest clinical benefit to patients.

OUR CLINICAL STAGE PROGRAMS

PRMT5 inhibitors

PRMT5 has long been a therapeutic target of interest for cancer given its role in regulating proteins involved in multiple essential cellular functions, including RNA splicing, cell cycling, cell death, and metabolic signaling. PRMT5 is a protein arginine methyltransferase that modifies the activity of these proteins, which are critical for growth and viability of both normal and cancer cells. The first generation of PRMT5 inhibitors did not advance in clinical development because they were either SAM-cooperative or SAM-competitive (and not MTA-cooperative), and as a result, they killed rapidly growing normal cells, particularly bone marrow, as effectively as cancer cells. Therefore, on-target, dose-limiting bone marrow toxicity prevented adequate target inhibition in cancer cells. To address this problem, we designed vopimetostat and TNG456 to be MTA-cooperative and thus selectively active (synthetic lethal) in cancer cells that have a homozygous deletion of MTAP, which is not deleted in normal cells.

This synthetic lethal interaction occurs when MTAP is co-deleted as a “passenger” with the frequently-deleted tumor suppressor gene CDKN2A. Synthetic lethality occurs because MTAP-deleted cells accumulate the PRMT5 inhibitory factor MTA. As a result, PRMT5 is partially inhibited in MTAP-deleted cells, making those cells more sensitive than normal cells to further inhibition of PRMT5 activity. Taking advantage of this unique interaction between PRMT5 inhibition and MTAP deletion requires that the inhibitors have a specific binding mechanism called MTA cooperativity. Vopimetostat and TNG456 bind cooperatively with MTA to inhibit PRMT5 function by blocking access to the PRMT5 active site for both protein substrates and the activating PRMT5 co-factor SAM, specifically in tumor cells which are MTAP deleted. This MTA-cooperative binding mechanism allows selective inhibition of PRMT5 in tumor cells that have lost MTAP while being relatively inert in normal cells without MTAP deletion.

MTAP-deletion frequency in multiple solid tumor types

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A partial deletion of chromosome 9p21, driven by loss of the tumor suppressor gene CDKN2A, is the most common homozygous deletion in human cancer. MTAP is adjacent to CDKN2A and is lost along with it in 80-90% of CDKN2A-deleted tumors, thus MTAP is one of the most commonly deleted genes across all cancer types. Based on The Cancer Genome Atlas, SEER, Kantar and other sources, there are at least 15 cancer types where MTAP loss occurs in more than 10% of patients, including approximately 15% of NSCLC, 25% of bladder cancers, 40% of pancreatic cancers, and 45% of GBM. Our development program for vopimetostat is focusing on patients with pancreatic cancer, lung cancer, and histology selective cancers, and we estimate that the annual addressable patient population in the U.S. for these indications totals approximately 60,000 patients. Our development program for TNG456 will focus primarily on patients with GBM, which has an annual addressable U.S. patient population of approximately 7,000 patients.

Strong preclinical data demonstrated with our MTA-cooperative PRMT5 inhibitors in MTAP-deleted cancers

Since PRMT5 is an essential enzyme for all cell types, we designed our PRMT5 inhibitors to be selectively active in cancer cells that have a homozygous deletion of MTAP, which is not deleted in normal cells.

In normal cells with MTAP, MTA is rapidly degraded by MTAP and therefore does not inhibit PRMT5. When MTAP is deleted in cancer cells, intracellular MTA is markedly elevated compared to normal cells (Figures 3 and 4 below) and partially inhibits PRMT5. Our inhibitors preferentially bind PRMT5 in the presence of MTA and “lock” the enzyme into the inactive state which further inhibits PRMT5 and prevents it from methylating target proteins critical for cell survival. As a result, our inhibitors selectively kill MTAP-deleted tumor cells with elevated MTA levels while sparing normal cells.

Figure 3. Schematic of PRMT5 and MTAP functions

Figure 4. Vopimetostat and TNG456 have an MTA-cooperative mechanism of action that is selective for MTAP-deleted cancer cells

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In preclinical studies, our PRMT5 inhibitors drive dose-dependent, on-target, anti-tumor activity including deep and durable regressions in MTAP-null xenograft models regardless of histology. These preclinical results are driven by vopimetostat has 4nM potency and 45X selectivity for MTAP-deleted cancer cells versus normal cells. Additionally, TNG456 demonstrated 20nM potency and 55X MTAP deletion selectivity.

Preclinical and clinical combination data

We plan to develop vopimetostat and TNG456 as monotherapy agents and in combination with other agents. Based on strong preclinical data showing significant in vivo combination benefit, clinical combinations that are currently being executed, planned or are of potential interest for the future with our PRMT5 inhibitors include RAS, CDK4/6, and MAT2A inhibitors and potentially other oncogene-targeted therapies.

The RAS combinations are a key focus due to the overlap in patient populations with MTAP deletion in pancreatic and lung cancer as well as the anticipated postitive safety profile of both therapies. More than 90% of MTAP-deleted pancreatic adenocarcinomas are RAS-mutant and approximately 40% of RAS mutations are G12D. Additionally, approximately 30% of MTAP-deleted lung adenocarcinomas are also RAS-mutant. Additionally, preclinical in vivo studies showed their combination leads to significant tumor reductions, supporting further clinical testing. We have an ongoing clinical collaboration with Revolution Medicines, Inc., or RevMed, and are currently combining vopimetostat with daraxonrasib, a RAS(ON) multi-selective inhibitor, and separately with zoldonrasib, a RAS(ON) G12D-selective inhibitor, in MTAP-deleted, RAS-mutant pancreatic and lung cancer in a Phase 1/2 clinical trial. We anticipate providing a safety and efficacy update from that study in 2026.

Given the our belief that the differentiated profile of vopimetostat could enable the potential for efficacious and tolerable RAS inhibitor combinations, we have entered into a CTCSA with Erasca to evaluate vopimetostat in combination with Erasca’s pan-RAS molecular glue, ERAS-0015. Under the terms of the agreement, Tango is the sponsor of the trial and Erasca is supplying ERAS-0015 at no cost.

Essentially all MTAP-deleted tumors also harbor a CDKN2A deletion, which may sensitize cancers to CDK4/6 inhibition. We have observed the expected efficacy of this combination in preclinical in vivo studies. We have a clinical collaboration agreement with Eli Lilly and Company, or Lilly, that will supply Verzenio® (abemaciclib), a CDK4/6 inhibitor, for use in combination with TNG456 in our ongoing Phase 1/2 clinical trial focused on MTAP-deleted GBM. We anticipate treating patients with that combination upon confirmation of single-agent TNG456 activity in patients with GBM.

Strong synergy has been demonstrated preclinically with sub-therapeutic doses of vopimetostat and MAT2A inhibition, suggesting the combination of vopimetostat with MAT2A inhibitors may be clinically beneficial in MTAP-deleted tumors.

In preparation for potential first-line pivotal studies and to inform future clinical development opportunities, we are also conducting combination studies to assess tolerability with various agents, including pembrolizumab and chemotherapy.

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Clinical trials

Vopimetostat Phase 1/2 monotherapy

The vopimetostat Phase 1/2 clinical trial is evaluating the safety and efficacy of vopimetostat as a monotherapy in patients with MTAP-deleted solid tumors and is focused on pancreatic and lung cancer. The first patient was dosed in July 2023 and we are currently enrolling patients at 250 mg QD.

In October 2025, we reported positive data from the ongoing Phase 1/2 clinical trial of vopimetostat in patients with MTAP-deleted cancers, demonstrating clinical activity across multiple cancer types with a favorable safety and tolerability profile to date. The cutoff date for the analysis was September 1, 2025 and included all evaluable patients at active doses (200 mg QD and above). Based on our observations of other PRMT5 inhibitors, we believe that the objective response rate, or ORR, improves over time in PRMT5 inhibitors. When all evaluable patients as of September 1, 2025, regardless of duration of follow-up, were assessed for response, the ORR was 20%. At greater than 6 months of follow-up as of September 1, 2025, the ORR increased to 27%. The ORR analyses presented were thus derived from patients enrolled more than 6 months before the data cutoff regardless of outcome, to avoid under-reporting response rates. Therefore, the ORRs were calculated in all tumor-evaluable patients enrolled more than 6 months prior to the efficacy analysis. mPFS was calculated in all patients who received a first scan (~8 weeks).

Across all MTAP-deleted tumor types, there were 94 tumor evaluable patients. We observed an ORR 27% and mPFS of 6.4 months in these patients.

Figure 5: Vopimetostat 27% ORR across cancer types

Figure 6: Durable disease control with vopimetostat across cancer types

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In the 29 patients with second line (2L) MTAP-deleted pancreatic cancer, mPFS was 7.2 months. In patients with 2L pancreatic cancer who were tumor evaluable (n=8), the ORR was 25%, more than double that observed in historical chemotherapy studies (~10%), supporting the planned initiation of a 2L pivotal trial in this patient population in 2026.

Figure 7: Vopimetostat mPFS is 7.2 months in 2L pancreatic cancer

In the histology selective cohort with 37 evaluable patients, we observed a 49% ORR and mPFS of 9.1 months. The histology selective cohort excludes pancreatic and lung cancer patients, as those indications were enrolled in separate cohorts and are being developed independently. Sarcoma patients are also excluded from this analysis, as no activity was observed in this indication (ORR 0%), which will not be pursued in future development. We are evaluating the development path for the histology selective cohort, as well as for selected indications as stand-alone development opportunities.

Figure 8: Vopimetostat 49% ORR in histology selective cohort and mPFS of 9.1 months

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As of September 1, 2025, 41 patients with 2L+ lung cancer were enrolled in the Phase 1/2 clinical trial at active doses, 12 of whom were enrolled more than 6 months prior to the analysis. Emerging data from the lung cohort are consistent with expectations, and we anticipate providing a safety and efficacy update in 2026.

Figure 9: Vopimetostat 250mg QD has a potentially best-in-class safety profile

Vopimetostat demonstrated a favorable safety and tolerability profile with no drug-related dose discontinuations and ~8% dose reduction in patients dosed at 250 mg QD as of the data cutoff date of September 1, 2025. These data support our view that vopimetostat has the potential to be a best-in-class molecule and we believe support the initiation of a registrational trial in 2026 to evaluate 2L MTAP-deleted pancreatic cancer as a single agent.

Vopimetostat Phase 1/2 combination with RAS(ON) inhibitors

We are focused on evaluating the combination of vopimetostat with RAS inhibitors, given the overlap in patient populations, robust preclinical data supporting potential strong combination effect in clinical trials, and favorable clinical efficacy, durability, and safety profiles observed with each drug individually. This approach may enable a development path for chemotheraphy-free first-line and potentially second-line therapies for MTAP-deleted/RAS-mutated patients with pancreatic and lung cancer. We have a collaboration with RevMed to support the ongoing Phase 1/2 combination trial.

In June 2025, the first patient was treated in the combination clinical trial that is evaluating vopimetostat with the RAS(ON) multi-selective inhibitor, daraxonrasib, and RAS(ON) G12D-selective inhibitor, zoldonrasib (RevMed). As of December 24, 2025, we had enrolled 30 patients in the trial, and both combinations were well-tolerated to date with exposures

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in the active range for all compounds. Early efficacy data are encouraging. We anticipate providing a safety and efficacy update from this trial in 2026.

TNG456 Phase 1/2

TNG456 is a brain-penetrant PRMT5 inhibitor being evaluated in an ongoing Phase 1/2 trial enrolling patients with MTAP-deleted solid tumors, with a focus on GBM. In May 2025, we began enrolling patients in the TNG456 Phase 1/2 clinical trial, in which we plan to evaluate patients with TNG456 monotherapy as well as in combination with abemaciclib. The trial is currently in dose escalation and we anticipate providing a safety and efficacy update from this trial in 2026.

We plan to initiate the combination with abemaciclib with evidence of single agenda TNG456 activity in GBM.

We believe that the initial pharmacokinetics from the clinical trial support our hypothesis that TNG456 will reach efficacious exposures in the CNS at well-tolerated doses (Fig 10). In contrast, the results of the TNG908 Phase1/2 clinical trial determined that the TNG908 exposure in the brain of was subtherapeutic. TNG908 was discontinued in November 2024 due to insufficient brain exposure for clinical activity in GBM.

Figure 10. TNG908 (actual) and TNG456 (predicted based on clinical PK at 100mg BID) steady-state clinical exposure in plasma and brain

CoREST inhibition to reserve immune evasion

TNG260 is a first-in-class CoREST inhibitor targeting STK11 mutant/KRAS wild type NSCLC, representing ~10% of lung adenocarcinoma annually in the US (~10,000 patients). STK11 loss-of-function mutations suppress the immune microenvironment of lung cancers. As a result, immune checkpoint inhibitors, like anti-PD-1, are not sufficient to overcome the immune evasive environment of STK11-mutant tumors, leading to poor clinical responses in these patients. Inhibition of the CoREST complex by TNG260 has been shown in preclinical studies to lead to changes in expression of immune-related genes that favor a more active immune environment.

In a syngeneic mouse tumor model where STK11 loss drives resistance to immune checkpoint blockade, CoREST inhibition by TNG260 in combination with an anti-PD-1 antibody resulted in complete tumor regressions in five out of eight treated mice. Treatment was stopped on Day 48 and the five of eight mice that were completely tumor-free at that time remained tumor-free for 21 days with no further treatment. Furthermore, when tumor cells were re-implanted in these mice on day 69, they were rejected, compared to a treatment-naïve group of animals where tumors grew as expected. This demonstrated the induction of immune memory in the animals with complete responses to TNG260 with anti-PD-1 antibody (Figure 11).

Figure 11: Pharmacologic proof-of-concept for CoREST inhibition in STK11 mutant MC38 mouse tumors with TNG260 in combination with an anti-PD-1 antibody

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TNG260 Phase 1/2

In the first quarter of 2023, the FDA cleared the TNG260 IND and we announced the first patient in the Phase 1/2 clinical trial was dosed in July 2023. Data from the dose escalation portion of this study provided early clinical proof-of-concept in a pre-specified subgroup of patients with checkpoint inhibitor resistant STK11 mut/KRAS WT lung cancer. In this group (n=5), the mPFS was 29 weeks, more than double the standard of care PFS of ~10 weeks. There was no evidence of activity in STK11 mutant /KRAS mutant lung cancers or other cancer types. The trial is ongoing in the STK11mut/KRAS WT lung cancer cohort.

Manufacturing

Our lead investigational products are small molecule inhibitors that can be readily manufactured without requiring any specialized equipment or processes. We do not own or operate, and currently have no plans to establish, any manufacturing facilities. We rely, and expect to continue to rely, on third-party Contract Development and Manufacturing Organizations, or CDMOs, for the manufacturing, packaging, labeling and distribution of our investigational products for preclinical and clinical testing, as well as for commercial manufacturing if any of our investigational products obtain marketing approval. A team of internal experts oversee activities at our contracted CDMOs with the goal of ensuring our investigational products are being manufactured under current good manufacturing practices, or cGMP. Currently, all manufacturing of the drug substance for our product candidates to be used in our clinical trials is conducted by one manufacturer and manufacturing of the drug product to be used in our clinical trials is conducted by two manufacturers. We believe that the contracted CDMOs have the capacity to support our potential registrational clinical studies, in addition to the first-in-human studies of our product candidates. The operations of one of these CDMOs are located outside the U.S. and the other CDMO conducts its operations for us in a single location in the United States. In addition to the risks related to having only two CDMOs (and only one manufacturer of drug substance), we may also encounter challenges related to supply chain, climate issues, pandemic and geopolitical risks. We plan to further expand and diversify our supply chain by identifying and contracting other CDMOs (beyond the two CDMOs that are currently conducting operations for us) with the capacity and expertise to support the drug substance and drug product for our product candidates and other investigational products in our pipeline and to manufacture commercial supply of our drugs (if those therapies obtain regulatory approval). For additional information and details on the risk related to manufacturing, see “Item 1A. Risk Factors —The third parties upon whom we rely for the supply of the active pharmaceutical ingredients and drug product to be used in our product candidates are our sole sources of supply, and the loss of any of these suppliers could significantly harm our business. ”

Intellectual Property

We strive to protect and enhance the proprietary technology, inventions and improvements that we believe are commercially important to the development of our business and our product candidates, including seeking, maintaining and defending patent rights, whether developed internally or licensed from third parties. We also rely on trade secrets relating to our proprietary target discovery technology platform and on know-how, continuing technological innovation and in-licensing

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opportunities to develop, strengthen and maintain our proprietary position in the field of precision oncology that may be important for the development of our business and product candidates. We additionally may rely on regulatory protection afforded through data exclusivity, market exclusivity and patent term extensions, where available. Patent rights and regulatory protections are key factors that determine the period of market exclusivity for products in our industry. It is during the period of market exclusivity that, we believe, our potential future products have their greatest commercial value.

Our commercial success may depend in part on our ability to: obtain and maintain patent and other proprietary protection for commercially important technology, inventions and know-how related to our business; defend and enforce our patents; preserve the confidentiality of our trade secrets; and operate without infringing the valid enforceable patents and proprietary rights of third parties. Our ability to limit third parties from making, using, selling, offering to sell, or importing our product candidates (and any future products that may be approved for marketing by regulatory authorities) may depend on the extent to which we have rights under valid and enforceable licenses, patents, or trade secrets that cover these activities. In some cases, enforcement of these rights may depend on third-party licensors. With respect to both licensed and company-owned intellectual property, we cannot be sure that patents will be granted with respect to any of our pending patent applications or with respect to any patent applications filed by us in the future, nor can we be sure that any of our existing patents or any patents that may be granted to us in the future will be commercially useful in protecting our commercial products and methods of manufacturing the same and to the extent such patents are commercially useful in protecting our commercial products or methods of manufacturing, such patents may be challenged or invalidated or otherwise become less useful in protecting our commercial products and methods of manufacturing.

Because a significant portion of a pharmaceutical product’s patent protection can elapse during the course of developing and obtaining regulatory approval of the product, certain countries, including the U.S., provide compensatory mechanisms to extend patent terms for pharmaceutical products. Patent expiration dates noted in the following paragraphs refer to statutory expiration dates and do not take into account any potential patent term adjustment or extension that may be available, or any potential disclaimers that may be needed to obtain certain patents that may reduce the term of such patents to correspond to that of earlier-expiring patents. There is no guarantee that any of our product candidates would be eligible for patent term extensions.

PRMT5 inhibitors

We exclusively own eleven patent families covering the composition of matter, methods of use, manufacture, crystalline forms and formulations for TNG908, vopimetostat, TNG456 and other structurally related PRMT5 inhibitors.

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For the first family, four US patents have been granted, and patent applications are pending in the United States, Argentina, Pakistan, Taiwan, Australia, Brazil, Canada, China, Eurasia, Europe, Hong Kong, Israel, India, Japan, Korea, Mexico, Malaysia, New Zealand, Singapore, Thailand, Ukraine and South Africa. Any patents granted in this family would be expected to expire no earlier than 2041.

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For the second family, patent applications are pending in the United States, Australia, Brazil, Canada, China, Eurasia, Europe, Israel, India, Japan, Korea, Mexico, Malaysia, New Zealand, Singapore, Thailand, Ukraine and South Africa. Any patents granted in this family would be expected to expire no earlier than 2042.

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For the third family, patent application are pending in the United States, Taiwan, Australia, Brazil, Canada, China, Eurasia, Europe, Israel, India, Japan, Korea, Mexico, Malaysia, New Zealand, Singapore, Thailand, Ukraine and South Africa. Any patents granted in this family would be expected to expire no earlier than 2043.

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For the fourth family, patent applications are pending in the United States, Australia, Canada, China, Europe, Israel, Japan, Korea, New Zealand, and South Africa. Any patents granted in this family would be expected to expire no earlier than 2043.

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Patent Cooperation Treaty applications are pending in each of the fifth, sixth, seventh, eighth, and ninth patent families. A provisional application is pending in each of the tenth and eleventh family. Any patents granted in any of these families would be expected to expire no earlier than 2045.

Additionally, we exclusively own five patent families covering other PRMT5 inhibitors and their methods of use with expiration dates ranging from 2039 to 2043. Two US patents have been granted in the first family. A US patent application is pending in the second family. Patent applications are pending in United States, Taiwan, Europe and Japan for the third family. Patent applications are pending in the United States, Taiwan, Europe and Japan for the remaining two families.

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CoREST inhibitors

We exclusively own four patent families covering the composition of matter, methods of use, solid forms and methods of manufacturing for our clinical compound TNG260 and other structurally related CoREST inhibitors. For the first family, a United States patent is granted and patent applications are pending in the United States, Taiwan, Australia, Brazil, Canada, China, Eurasia, Europe, Hong Kong, Israel, India, Japan, Korea, Mexico, Malaysia, New Zealand, Singapore, Thailand, Ukraine and South Africa. Any patents granted in this family would be expected to expire no earlier than 2042. For the second family, patent applications are pending in the United States, Brazil, Canada, China, Eurasia, Europe, Hong Kong, Israel, Japan, Korea, Mexico, Malaysia, New Zealand, Singapore, Thailand, Ukraine and South Africa. Any patents in this family, if granted, are expected to expire no earlier than 2043. Patent Cooperation Treaty applications are pending in the third and fourth families and any patents in these families, if granted, are expected to expire no earlier than 2046.

HBS1L degraders

We exclusively own six patent families covering the composition of matter and methods of use for our product candidate TNG961 and other HBS1L inhibitors. Patent Cooperation Treaty applications are pending in each of the six families. Any patents in these families, if granted, are expected to expire no earlier than 2045.

Government Regulation

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

In the United States, the FDA regulates drug products under the Federal Food, Drug, and Cosmetic Act, or FD&C Act, its implementing regulations, and other federal statutes and regulations. Drugs are also subject to other federal, state and local statutes and regulations. If we fail to comply with applicable FDA or other regulatory requirements at any time with respect to product development, clinical testing, approval or any other regulatory requirements relating to product manufacture, processing, handling, storage, quality control, safety, pharmacovigilance, marketing, advertising, promotion, packaging, labeling, export, import, distribution or sale, we may become subject to administrative or judicial sanctions or other legal consequences. These sanctions or consequences could include, among other things, the FDA’s refusal to approve pending or future applications, issuance of clinical holds for ongoing studies or study termination, suspension or revocation of approved applications, FDA Form 483s, warning or untitled letters, product withdrawals or recalls, product seizures, total or partial suspensions of manufacturing or distribution, injunctions, fines, civil penalties or criminal prosecution.

Our product candidates must be approved for therapeutic indications by the FDA before they may be marketed in the United States. For drug product candidates regulated under the FD&C Act, the FDA must approve a New Drug Application, or NDA. The process generally involves the following:

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

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manufacturing in compliance with current Good Manufacturing Practices, or cGMP, of the drug substance and drug product to be used in human clinical trials along with required analytical and stability testing;

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submission to the FDA of an IND, which must become effective before clinical trials may begin and must be updated when certain changes are made;

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approval by an institutional review board, or IRB, or independent ethics committee at each clinical trial site before a clinical trial may be initiated at that site;

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

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preparation and submission of an NDA to the FDA;

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a determination by the FDA within 60 days of its receipt of an NDA to file the application for review;

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

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satisfactory completion of an FDA audit of clinical trial sites that generated the data in support of the NDA;

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payment of an application fee, as applicable, for FDA review of the NDA; and

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FDA review of the NDA, including, where applicable, consideration of the views of any FDA advisory committee, and FDA approval of the NDA prior to any commercial marketing or sale of the drug in the United States.

Preclinical studies and clinical trials for drugs

Before testing any drug in humans, the product candidate must undergo rigorous preclinical testing. Preclinical studies include laboratory evaluations of product chemistry, formulation and stability, as well as in vitro and animal studies to assess safety and in some cases to establish the rationale for therapeutic use. The conduct of preclinical studies is subject to federal and state regulation and requirements, including GLP requirements for certain safety/toxicology studies. The results of the preclinical studies, together with manufacturing information and analytical data, must be submitted to the FDA as part of an IND.

An IND is a request for authorization from the FDA to administer an investigational product to humans and must become effective before clinical trials may begin. An IND includes the general investigational plan and the protocol(s) for clinical studies, the results of animal and in vitro studies assessing the toxicology, pharmacokinetics, pharmacology, and pharmacodynamic characteristics of the product; chemistry, manufacturing, and controls information; and any available human data or literature to support the use of the investigational product. Additional preclinical testing may and often does continue after the IND is submitted. The IND automatically becomes effective 30 days after receipt by the FDA, unless the FDA raises concerns or questions within the 30-day time period, including concerns that human research subjects will be exposed to unreasonable health risks, and imposes a full or partial clinical hold. A clinical hold can also be imposed once a trial has already begun, thereby halting the trial until any safety concerns or deficiencies articulated by FDA are corrected.

The clinical stage of development involves the administration of the product candidate to healthy volunteers or patients under the supervision of qualified investigators, who generally are physicians not employed by or under the trial sponsor’s control, in accordance with GCP requirements, which include the requirement that all research subjects provide their informed consent for their participation in a clinical trial. Clinical trials are conducted under protocols detailing, among other things, the objectives of the clinical trial, dosing procedures, inclusion and exclusion criteria and the parameters and criteria to be used in monitoring safety and evaluating effectiveness. Each protocol, and any subsequent amendments to the protocol, must be submitted to the FDA as part of the IND. Furthermore, each clinical trial must be reviewed and approved by an IRB for each institution at which the clinical trial will be conducted to ensure that the risks to individuals participating in the clinical trials are minimized and are reasonable compared to the anticipated benefits. The IRB also approves the informed consent form that must be provided to each clinical trial subject or his or her legal representative and must oversee the clinical trial until its completion. The FDA, the IRB, or the sponsor may suspend or discontinue a clinical trial at any time on various grounds, including a finding that the subjects are being exposed to an unacceptable health risk.

There also are requirements governing the registration and reporting of ongoing and completed clinical trials to public registries. For example, information about certain clinical trials must be submitted within specific timeframes for publication on www.ClinicalTrials.gov, a clinical trials database maintained by the National Institutes of Health. Sponsors are also obligated to disclose the results of their clinical trials after completion. Disclosure of the results of these trials can be delayed until the new product or new indication being studied has been approved. Competitors and patients may use this publicly available information to gain knowledge regarding the progress of development programs. Failure to timely register a covered clinical study or to submit study results as provided for in the law can give rise to consequences such as public notifications of noncompliance and civil monetary penalties.

A sponsor that wishes to conduct a clinical trial outside of the United States may, but need not, obtain FDA authorization to conduct the clinical trial under an IND. If a foreign clinical trial is not conducted under an IND, the FDA may nevertheless accept the results of the study in support of an NDA if the study was conducted in accordance with GCP

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requirements, and the FDA is able to validate the data through independent analysis and an onsite inspection if deemed necessary.

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

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Phase 1 — Phase 1 clinical trials involve initial introduction of the investigational product in a limited population of healthy human volunteers or patients with the target disease or condition. These studies are typically designed to test the safety, dosage tolerance, absorption, metabolism, distribution, and excretion of the investigational product in humans, and, if possible, to gain early evidence of effectiveness.

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

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Phase 3 — Phase 3 clinical trials typically involve administration of the investigational product to an expanded patient population to further evaluate dosage, to provide statistically significant evidence of clinical efficacy and to further test for safety, generally at multiple geographically dispersed clinical trial sites. These clinical trials are intended to establish the overall risk/benefit profile of the investigational product and to provide an adequate basis for product approval and physician labeling. Generally, two adequate and well-controlled Phase 3 trials are required by the FDA for approval of an NDA.

In 2023, we received FDA clearances of our IND applications for vopimetostat and TNG260 to initiate Phase 1/2 clinical trials for each product candidate. In 2025, we received clearance of our IND application for TNG456 to initiate Phase 1/2 clinical trials for this product candidate.

In March 2022, the FDA released final guidance titled “Expansion Cohorts: Use in First-In-Human Clinical Trials to Expedite Development of Oncology Drugs and Biologics,” which outlines how drug developers can utilize an adaptive trial design commonly referred to as a seamless trial design in early stages of oncology drug development (i.e., the first-in-human clinical trial) to compress the traditional three phases of trials into one continuous trial called an expansion cohort trial. Information to support the design of individual expansion cohorts are included in IND applications and assessed by the FDA. Expansion cohort trials can potentially bring efficiency to drug development and reduce development costs and time.

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

Progress reports detailing the results of clinical trials, among other information related to development under an IND, must be submitted at least annually to the FDA. Written IND safety reports must be submitted to the FDA and investigators within 15 days to report 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 also notify the FDA of any unexpected fatal or life-threatening suspected adverse reaction as soon as possible but in no case later than seven calendar days after the sponsor’s initial receipt of the information.

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

U.S. marketing approval for drugs

Assuming successful completion of the required clinical testing, the results of the preclinical studies and clinical trials, together with detailed information relating to the product’s chemistry, manufacturing, and controls and proposed labeling, among other things, are submitted to the FDA as part of an NDA package requesting approval to market the product for one or more indications. An NDA must contain data supporting the drug’s safety and efficacy for the requested indications and must

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include both negative and ambiguous results of preclinical studies and clinical trials, as well as positive findings. Data may come from company-sponsored clinical trials intended to test the safety and efficacy of the product candidate or from a number of alternative sources, including studies initiated by investigators. To support marketing approval, the data submitted must be sufficient in quality and quantity to establish the safety and efficacy of the investigational drug to the satisfaction of the FDA. The FDA must approve an NDA before a drug may be marketed in the United States.

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

The FDA also may require submission of a Risk Evaluation and Mitigation Strategy, or REMS, if it believes such a strategy is necessary to ensure that the benefits of the drug outweigh its risks. A REMS can include use of risk evaluation and mitigation strategies such as medication guides, physician communication plans, assessment plans, and/or elements to assure safe use, such as restricted distribution methods, patient registries, special monitoring or other risk-minimization tools.

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

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

After evaluating the NDA and all related information, including an 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 indicates that the review cycle of the application is complete and the application is not ready for approval. A Complete Response Letter generally states specific conditions that must be met in order to secure final approval of the NDA. The FDA may require additional clinical or preclinical testing or recommend other actions, such as requests for additional information or clarification, that the applicant might take in order to resubmit the NDA for FDA reconsideration. Even with a submission that includes this additional information, the FDA ultimately may decide that the application does not satisfy the regulatory criteria for approval. If and when those criteria have been met to the FDA’s satisfaction, the FDA will typically issue an approval letter. An approval letter authorizes commercial marketing of the product with specific prescribing information for one or more 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 product’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-approval studies or surveillance programs. Some types of changes to the approved product, such as adding new indications, certain manufacturing changes, and additional labeling claims, are subject to further testing requirements and FDA review and approval of a supplemental application.

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Orphan drug designation and exclusivity

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

If a product that has orphan drug designation subsequently receives the first FDA approval for the disease or condition for which it has such designation, the product is entitled to a seven-year period of marketing exclusivity during which the FDA may not approve any other applications to market the same drug for the same indication, except in limited circumstances, such as a subsequent product’s showing of clinical superiority over the product with orphan exclusivity or where the original applicant cannot produce sufficient quantities of product. Competitors, however, may receive approval of different drugs for the indication for which the orphan product has exclusivity or obtain approval for the same drug for a different indication than that for which the orphan product has exclusivity. Orphan drug exclusivity could block the approval of one of our product candidates for seven years if a competitor obtains approval for the same drug for the same indication before we do, unless we are able to demonstrate that our product candidate is clinically superior. If an orphan designated product receives marketing approval for an indication broader than its designation, it may not be entitled to orphan exclusivity.

The FDA has granted orphan drug designation to vopimetostat for the treatment of soft tissue sarcoma and for the treatment of pancreatic cancer, and to TNG456 for the treatment of malignant glioma.

Expedited development and review programs for drugs

The FDA has 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; the purpose of these programs is to get important new drugs to patients more quickly than standard FDA review timelines typically permit.

A product candidate is eligible for Fast Track designation if it is intended to treat a serious or life-threatening disease or condition and demonstrates the potential to address unmet medical needs for such disease or condition. Fast Track designation applies to the combination of the product candidate 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. Rolling review means that the FDA may review portions of the marketing application before the sponsor submits the complete application. In 2023, the FDA granted Fast Track designation to vopimetostat for previously treated, locally advanced, and unresectable or metastatic MTAP-deleted solid tumors, and to TNG260 in combination with an anti-PD-1 antibody for the treatment of patients with previously treated, advanced (metastatic or locally advanced and not amenable to curative intent therapy) NSCLC with STK-11 mutations. In February 2025, the FDA granted Fast Track designation to TNG456 as a single agent, for the treatment of patients with locally advanced or metastatic solid tumors with MTAP loss, and in combination with abemaciclib, for the treatment of patients with locally advanced or metastatic NSCLC with MTAP loss.

In addition, a product candidate may be eligible for Breakthrough Therapy designation if it is intended to treat a serious or life-threatening disease or condition and preliminary clinical evidence indicates that the drug, alone or in combination with one or more other drugs, may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development. Breakthrough Therapy designation provides all the features of Fast Track designation as well as more intensive FDA interaction and guidance.

Products with Fast Track or Breakthrough Therapy designation may also be eligible for additional FDA programs intended to expedite the review and approval process, including priority review and accelerated approval. Any product submitted to the FDA for approval that has the potential to provide a significant improvement in safety or effectiveness in the treatment, diagnosis or prevention of a serious disease or condition may be eligible for priority review. Under priority review, the FDA’s PDUFA goal date to take action on an NDA is six months from filing, compared to ten months from filing for a standard review. Products are eligible for accelerated approval if they can be shown to have an effect on a surrogate endpoint

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that is reasonably likely to predict clinical benefit, or an effect on a clinical endpoint that can be measured earlier than an effect on irreversible morbidity or mortality, which is reasonably likely to predict an effect on irreversible morbidity or mortality or other clinical benefit, taking into account the severity, rarity, or prevalence of the condition and the availability or lack of alternative treatments.

Accelerated approval is generally contingent on a sponsor’s agreement to conduct, in a diligent manner, adequate and well-controlled post-approval confirmatory studies to verify and describe the product’s clinical benefit and, under the Food and Drug Omnibus Reform Act of 2022, or FDORA, the FDA may require, as appropriate, that such trials be underway prior to approval. Under FDORA, the FDA has increased authority for expedited procedures to withdraw approval of a drug or an indication approved under accelerated approval if, for example, the confirmatory trial fails to verify the predicted clinical benefit 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 the time period for FDA review or approval may not be shortened. Furthermore, these FDA programs do not change the scientific or medical standards for approval or the quality of evidence necessary to support approval, though they may expedite the development or review process.

Pediatric information and pediatric exclusivity

Under the Pediatric Research Equity Act, or PREA, as amended, certain NDAs and NDA supplements must contain data that can be used to assess the safety and efficacy of the product candidate for the claimed indications in all relevant pediatric subpopulations and to support dosing and administration for each pediatric subpopulation for which the product is safe and effective. The FDA may grant deferrals for submission of pediatric data or full or partial waivers. The PREA requires that a sponsor who is planning to submit a marketing application for a product candidate that includes a new active ingredient, new indication, new dosage form, new dosing regimen or new route of administration submit an initial Pediatric Study Plan, or PSP, within 60 days of an end-of-Phase 2 meeting or, if there is no such meeting, as early as practicable before the initiation of the Phase 3 or Phase 2/3 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. The FDA and the sponsor must reach an agreement on the PSP. Unless otherwise required by regulation, PREA does not apply to a drug for an indication for which orphan designation has been granted, except that PREA will apply to an original NDA for a new active ingredient that is orphan-designated if the drug is a molecularly targeted cancer product intended for the treatment of an adult cancer and is directed at a molecular target that FDA determines to be substantially relevant to the growth or progression of a pediatric cancer.

A drug may also obtain pediatric exclusivity in the United States. Pediatric exclusivity, if granted, adds six months to existing regulatory exclusivity periods and, for a drug, to patent terms. This six-month exclusivity may be granted based on the voluntary completion of a pediatric study that adequately responds to an FDA-issued “Written Request” for such a study.

U.S. post-approval requirements for drugs

Drugs manufactured or distributed pursuant to FDA approvals are subject to continuing regulation by the FDA, including, among other things, requirements relating to recordkeeping, periodic reporting, product sampling and distribution, reporting of adverse experiences and promotion and advertising requirements. FDA's advertising and promotion requirements include restrictions on promoting products for unapproved uses or patient populations (known as “off-label use”) and limitations on industry-sponsored scientific and educational activities. Although physicians may prescribe approved products for off-label uses, manufacturers may not market or promote such uses. The FDA and other agencies enforce the laws and regulations prohibiting the promotion of off-label uses, not only by company employees but also by agents of the company or those speaking on the company’s behalf, and a company that is found to have improperly promoted off-label uses may be subject to significant liability, including investigation by federal and state authorities. Failure to comply with these requirements can result in, among other things, adverse publicity, warning letters, corrective advertising and potential civil and criminal penalties, including liabilities under the False Claims Act where products are reimbursed under federal health care programs. Promotional materials for approved drugs must be submitted to the FDA in conjunction with their first use or first publication. Further, for certain modifications to the drug, including changes in indications, labeling or manufacturing processes or facilities, the applicant may be required to submit and obtain prior FDA approval of an NDA supplement, which may require the development of additional data or preclinical studies and clinical trials.

The FDA may impose a number of post-approval requirements as a condition of approval of an NDA. For example, the FDA may require post-market testing, including Phase 4 clinical trials, and surveillance to further assess and monitor the

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product’s safety and effectiveness after commercialization, as well as the manufacturing process for making the drug to confirm continued compliance with cGMP. Manufacturers and certain subcontractors must register their establishments with the FDA and applicable state agencies and are subject to periodic unannounced inspections for compliance with regulatory requirements. Changes to the manufacturing process are strictly regulated and, depending on the nature of the change, may require prior FDA approval before implementation. In addition, manufacturers and other parties involved in the drug supply chain must comply with product tracking and tracing requirements and notify the FDA of counterfeit, diverted, stolen and intentionally adulterated products or products that are otherwise unfit for distribution. Accordingly, manufacturers must continue to expend time, money and effort in the area of production and quality control to maintain compliance with cGMP and other regulatory requirements.

The FDA may withdraw approval of a product 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 adverse events of unanticipated severity or frequency, or with manufacturing processes, or failure to comply with regulatory requirements, may result in revisions to the approved labeling to add new safety information, requirements for post-market studies or clinical trials to assess new safety risks, or imposition of distribution or other restrictions under a REMS. Other potential consequences include, among other things:

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

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

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fines, FDA Form 483s, warning letters, untitled letters or clinical holds on post-approval clinical trials or clinical trials involving related product candidates;

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

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suspension of production or distribution;

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

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injunctions or the imposition of civil or criminal penalties; and

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

Regulation of companion diagnostics

Companion diagnostics provide information that is essential for the safe and effective use of a corresponding drug. A companion diagnostic may be used to help identify patients who are most likely to benefit from a particular drug, identify patients likely to be at increased risk for serious side effects as a result of treatment with a particular drug, or monitor response to treatment with a particular drug for the purpose of adjusting treatment to achieve improved safety or effectiveness. Companion diagnostics are regulated as medical devices by the FDA. In the United States, the FD&C Act, its implementing regulations, and other federal and state statutes and regulations govern, among other things, medical device design and development, preclinical and clinical testing, premarket clearance or approval, registration and listing, manufacturing, labeling, storage, advertising and promotion, sales and distribution, export and import, and post-market surveillance. Unless an exemption or FDA exercise of enforcement discretion applies, diagnostic tests generally require marketing clearance or approval from the FDA prior to commercialization. The two primary types of FDA marketing authorization applicable to a medical device are clearance of a premarket notification, or 510(k), and premarket approval, or PMA. In January 2024, FDA announced its intention to initiate a reclassification process for most in vitro diagnostics, including companion diagnostics. FDA also indicated that it will continue to take a risk-based approach in the initial classification of individual in vitro diagnostics to determine whether a new diagnostic test may be classified into class II through the de novo classification process. In so doing, FDA signaled that it may regulate most future companion diagnostics as class II devices (which is a medical device that poses a medium to high risk to patients and users).

The FDA has issued several guidance documents regarding the co-development of drugs and companion diagnostic tests, including a 2014 final guidance titled “Guidance for Industry: In Vitro Companion Diagnostic Devices”, a 2016 draft guidance titled “Principles for Codevelopment of an In Vitro Companion Diagnostic Device with a Therapeutic Product,” and a 2020 final guidance titled “Developing and Labeling In Vitro Companion Diagnostic Devices for a Specific Group or Class

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of Oncology Therapeutic Products." Once cleared or approved, the companion diagnostic device must comply with applicable post-marketing requirements including the FDA’s quality management system regulation (QMSR), adverse event reporting, recalls and corrections, and product marketing requirements and limitations. Like drug manufacturers, companion diagnostic manufacturers are subject to unannounced FDA inspections at any time during which the FDA will conduct an audit of the product(s) and the company’s facilities for compliance with regulatory requirements.

Other regulatory matters

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

Other healthcare laws

Healthcare providers, physicians, and third-party payors will play a primary role in the recommendation and prescription of any products for which we will seek to obtain marketing approval. Our business operations and any current or future arrangements with third-party payors, healthcare providers and physicians may expose us to certain liabilities and other healthcare laws and regulations that may constrain the business or financial arrangements and relationships through which we develop, market, sell and distribute any drugs for which we obtain marketing approval in the future. 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 federal Anti-Kickback Statute prohibits, among other things, persons and entities from knowingly and willfully soliciting, offering, paying, receiving or providing any remuneration (including any kickback, bribe, or certain rebate), directly or indirectly, overtly or covertly, in cash or in kind, to induce or reward, or in return for, either the referral of an individual for, or the purchase, order or recommendation of, any good or service, for which payment may be made, in whole or in part, under a federal healthcare program such as Medicare and Medicaid. A person or entity need not have actual knowledge of the federal Anti-Kickback Statute or specific intent to violate it in order to have committed a violation. Violations are subject to civil and criminal fines and penalties for each violation, plus up to three times the remuneration involved, imprisonment, and exclusion from government healthcare programs. The Anti-Kickback Statute has been interpreted to apply to arrangements between pharmaceutical manufacturers, on the one hand, and prescribers, purchasers and formulary managers, on the other. In addition, the government may assert that a claim that includes items or services resulting from a violation of the federal Anti-Kickback Statute constitutes a false or fraudulent claim for purposes of the civil False Claims Act.

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The federal civil and criminal false claims and civil monetary penalties laws, including the federal False Claims Act, or FCA, imposes criminal and civil penalties, including through civil whistleblower or qui tam actions, against individuals or entities for knowingly presenting, or causing to be presented, to the federal government, claims for payment that are false or fraudulent or making a false statement to avoid, decrease or conceal an obligation to pay money to the federal government. Manufacturers can be held liable under the FCA even when they do not submit claims directly to government payors if they are deemed to “cause” the submission of false or fraudulent claims. The federal False Claims Act also permits a private individual acting as a “whistleblower” to bring actions on behalf of the federal government alleging violations of the federal False Claims Act and to share in any monetary recovery.

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The federal civil monetary penalties laws impose civil fines for, among other things, the offering or transfer or remuneration to a Medicare or state healthcare program beneficiary, if the person knows or should know it is likely to influence the beneficiary’s selection of a particular provider, practitioner, or supplier of services reimbursable by Medicare or a state health care program, unless an exception applies.

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HIPAA, which imposes criminal and civil liability for knowingly and willfully executing a scheme, or attempting to execute a scheme, to defraud any healthcare benefit program, including private payors, knowingly and willfully embezzling or stealing from a healthcare benefit program, willfully obstructing a criminal investigation of a healthcare offense, or falsifying, concealing or covering up a material fact or making any materially false statements in connection with the delivery of or payment for healthcare benefits, items or services. Similar to the

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federal Anti-Kickback Statute, a person or entity may be found guilty of violating HIPAA without actual knowledge of the statute or specific intent to violate it.

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HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act of 2009, or HITECH, and their respective implementing regulations, impose, among other things, specified requirements on covered entities and their respective business associates relating to the privacy and security of individually identifiable health information, including mandatory contractual terms and required implementation of technical safeguards of such information. HITECH also created new tiers of civil monetary penalties, amended HIPAA to make civil and criminal penalties directly applicable to business associates in some cases, and gave state attorneys general new authority to file civil actions for damages or injunctions in federal courts to enforce the federal HIPAA laws and seek attorneys’ fees and costs associated with pursuing federal civil actions.

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Federal price reporting laws, which require manufacturers to calculate and report complex pricing metrics to government programs, where such reported prices may be used in the calculation of reimbursement and/or discounts on approved products.

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The Physician Payments Sunshine Act, enacted as part of the Patient Protection and Affordable Care Act, as amended by the Health Care and Education Reconciliation Act of 2010, or collectively, the ACA, imposed new annual reporting requirements for certain manufacturers of drugs, devices, biologics, and medical supplies for which payment is available under Medicare, Medicaid, or the Children’s Health Insurance Program, for certain payments and “transfers of value” provided to physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors, as well as certain other non-physician licensed providers 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.

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Analogous state and foreign laws and regulations, including, but not limited to, state anti-kickback and false claims laws, may be broader in scope than the provisions described above and may apply regardless of payor. Some state laws require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines and relevant federal government compliance guidance; require drug manufacturers to report information related to payments and other transfers of value to physicians and other healthcare providers; restrict marketing practices or require disclosure of marketing expenditures and pricing information. State and foreign laws may govern the privacy and security of health information in some circumstances. These data privacy and security laws may differ from each other in significant ways and often are not pre-empted by HIPAA, which may complicate compliance efforts.

The scope and enforcement of each of these laws is uncertain and subject to rapid change in the current environment of healthcare reform, especially in light of the lack of applicable precedent and regulations. Federal and state enforcement bodies have recently increased their scrutiny of interactions between healthcare companies and healthcare providers, which has led to a number of investigations, prosecutions, convictions and settlements in the healthcare industry. It is possible that governmental authorities will conclude that our business practices do not comply with current or future statutes, regulations or case law involving applicable fraud and abuse or other healthcare laws and regulations. If our operations are found to be in violation of any of these laws or any other related governmental regulations that may apply to us, we may be subject to significant civil, criminal and administrative penalties, damages, fines, imprisonment, disgorgement, exclusion from government funded healthcare programs, such as Medicare and Medicaid, reputational harm, additional oversight and reporting obligations if we become subject to a corporate integrity agreement or similar settlement to resolve allegations of non-compliance with these laws and the curtailment or restructuring of our operations.

Insurance Coverage and Reimbursement

In the United States and markets in other countries, patients who are prescribed treatments for their conditions and providers performing the prescribed services generally rely on third-party payors to reimburse all or part of the associated healthcare costs. Thus, even if a product candidate is approved, sales of the product will depend, in part, on the extent to which third-party payors, including government health programs in the United States such as Medicare and Medicaid, commercial health insurers and managed care organizations, provide coverage, and establish adequate reimbursement levels for, the product. In the United States, the principal decisions about reimbursement for new medicines are typically made by CMS. CMS decides whether and to what extent a new medicine will be covered and reimbursed under Medicare and private payors tend to follow CMS to a substantial degree. Coverage and reimbursement for drug products can differ significantly from payor to payor. The process for determining whether a third-party payor will provide coverage for a product may be separate from the process for setting the price or reimbursement rate that the payor will pay for the product once coverage is approved. Third-party payors are increasingly challenging the prices charged, examining the medical necessity, reviewing the cost-effectiveness of medical products and services and imposing controls to manage costs. Third-party payors may limit

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coverage to specific products on an approved list, also known as a formulary, which might not include all of the approved products for a particular indication.

In order to secure coverage and reimbursement for any product that might be approved for sale, a company may need to conduct expensive pharmacoeconomic studies in order to demonstrate the medical necessity and cost-effectiveness of the product, which will require additional expenditure above and beyond the costs required to obtain FDA or other comparable regulatory approvals. Some product candidates may not be considered medically necessary or cost effective. A decision by a third-party payor not to cover a product could reduce physician utilization once the product is approved and have a material adverse effect on sales, our operations and financial condition (when a product candidate is approved for marketing). Levels of coverage and reimbursement for a product can differ significantly from payor to payor.

The containment of healthcare costs has become a priority of federal, state and foreign governments (and other third-party payers), and the prices of pharmaceutical products have been a focus in this effort. Governments have shown significant interest in implementing cost-containment programs, including price controls, restrictions on reimbursement and requirements for substitution of generic products. Adoption of price controls and cost-containment measures, and adoption of more restrictive policies in jurisdictions with existing controls and measures, could further limit a company’s revenue generated from the sale of any approved products. Coverage policies and third-party payor reimbursement rates may change at any time.

In the European Union, or 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 upon. Some countries may require the completion of additional studies that compare the cost-effectiveness of a particular product candidate to currently available therapies or so-called health technology assessments, in order to obtain reimbursement or pricing approval. For example, the EU provides options for its Member States to restrict the range of products for which their national health insurance systems provide reimbursement and to control the prices of medicinal products for human use. EU Member States may approve a specific price for a product or may instead adopt a system of direct or indirect controls on the profitability of the company placing the product on the market. Other EU Member States allow companies to fix their own prices for products, but monitor and control prescription volumes and issue guidance to physicians to limit prescriptions. Recently, many countries in the EU have increased the amount of discounts required on pharmaceuticals and these efforts could continue as countries attempt to manage healthcare expenditures, especially in light of the severe fiscal and debt crises experienced by many countries in the EU. The downward pressure on healthcare costs in general, particularly prescription products, has become intense. As a result, increasingly high barriers are being erected to the entry of new products. Political, economic and regulatory developments may further complicate pricing negotiations, and pricing negotiations may continue after reimbursement has been obtained. Reference pricing used by various EU Member States, and parallel trade, i.e., arbitrage between low-priced and high-priced Member States, can further reduce prices. There can be no assurance that any country that has price controls or reimbursement limitations for pharmaceutical products will allow favorable reimbursement and pricing arrangements for any products, if approved in those countries.

Current and future healthcare reform legislation

In the United States and certain foreign jurisdictions, there have been, and likely will continue to be, a number of legislative and regulatory changes and proposed changes regarding the healthcare system directed at broadening the availability of healthcare, improving the quality of healthcare, and containing or lowering the cost of healthcare. For example, in 2010, the United States Congress enacted the ACA, which, among other things, includes changes to the coverage and payment for products under government health care programs. The ACA includes provisions of importance to our potential product candidates that:

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created an annual, nondeductible fee on any entity that manufactures or imports specified branded prescription drugs and biologic products, apportioned among these entities according to their market share in certain government healthcare programs;

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expanded eligibility criteria for Medicaid, thereby potentially increasing a manufacturer’s Medicaid rebate liability;

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expanded manufacturers’ rebate liability under the Medicaid Drug Rebate Program;

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expanded the types of entities eligible for the 340B drug discount program;

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established the Medicare Part D coverage gap discount program by requiring manufacturers to provide point-of-sale-discounts off the negotiated price of applicable brand drugs to eligible beneficiaries during their coverage gap period as a condition for the manufacturers’ outpatient drugs to be covered under Medicare Part D; and

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created a Patient-Centered Outcomes Research Institute to oversee, identify priorities in, and conduct comparative clinical effectiveness research, along with funding for such research.

Other legislative changes have been proposed and adopted in the United States since the Affordable Care Act was enacted. For example, the Budget Control Act of 2011 and subsequent legislation, among other things, created measures for spending reductions by Congress that include aggregate reductions of Medicare payments to providers of 2% per fiscal year, which remain in effect through 2031. The U.S. American Taxpayer Relief Act of 2012 further reduced Medicare payments to several types of providers and increased the statute of limitations period for the government to recover overpayments to providers from three to five years. On March 11, 2021, President Biden signed the American Rescue Plan Act of 2021 into law, which eliminates the statutory Medicaid drug rebate cap, currently set at 100% of a drug’s average manufacturer price, for single source and innovator multiple source drugs, beginning January 1, 2024. Due to the Statutory Pay-As-You-Go Act of 2010, estimated budget deficit increases resulting from the American Rescue Plan Act of 2021, and subsequent legislation, Medicare payments to providers were further reduced starting in 2025. These laws and regulations may result in additional reductions in Medicare and other healthcare funding and otherwise affect the prices we may obtain for any of our product candidates for which we may obtain regulatory approval or the frequency with which any such product candidate is prescribed or used.

On May 30, 2018, the Right to Try Act was signed into law. The law, among other things, provides a federal framework for certain patients to access certain investigational new drug products that have completed a Phase 1 clinical trial and that are undergoing investigation for FDA approval. Under certain circumstances, eligible patients can seek treatment without enrolling in clinical trials and without obtaining FDA permission under the FDA expanded access program. There is no obligation for a pharmaceutical manufacturer to make its drug products available to eligible patients as a result of the Right to Try Act.

Additionally, there has been increasing legislative and enforcement interest in the United States with respect to drug pricing practices. Specifically, there has been heightened governmental scrutiny over the manner in which manufacturers set prices for their marketed products, which has resulted in several U.S. Congressional inquiries and proposed and enacted federal and state legislation designed to, among other things, bring more transparency to drug pricing, reduce the cost of prescription drugs under Medicare, and review the relationship between pricing and manufacturer patient programs. On December 19, 2025, CMS released two proposed rules that would incorporate most‑favored nation (“MFN”) pricing principles into federal reimbursement for prescription drugs. The first proposal, the Global Benchmark for Efficient Drug Pricing Model (“GLOBE”) for Medicare Part B, would require manufacturers of specified single‑source drugs and sole‑source biologics to pay incremental rebates based on international benchmark prices, with participation triggered for products meeting CMS’s spending and eligibility criteria. The second proposal, the Guarding U.S. Medicare Against Rising Drug Costs (“GUARD”) model for Medicare Part D, would similarly mandate manufacturer rebates for qualifying sole‑source drugs where the Medicare net price exceeds an MFN benchmark derived from international reference pricing methodologies. As proposed, GLOBE would begin a five‑year performance period on October 1, 2026 and GUARD would begin its performance period in 2027. These proposals will likely be subject to legal challenges that could delay their implementation or modify their impact on manufacturer pricing and revenue. Additionally, in November 2025, CMS introduced the GENErating cost Reductions for U.S. Medicaid (“GENEROUS”) Model, a voluntary MFN framework for manufacturers participating in the Medicaid Drug Rebate Program. Although it is voluntary, the GENEROUS Model could also impact the drug pricing landscape for manufacturers.

The Inflation Reduction Act of 2022, or IRA, includes several provisions that may impact our business to varying degrees, including provisions that reduce the out-of-pocket cap for Medicare Part D beneficiaries from $7,050 to $2,000 starting in 2025, thereby effectively eliminating the coverage gap; impose new manufacturer financial liability on certain drugs under Medicare Part D; and allow the U.S. government to negotiate Medicare Part B and Part D price caps for certain high-cost drugs and biologics without generic or biosimilar competition. Specifically, under the IRA, a single-source pharmaceutical product qualifies for selection for participation in the drug price negotiation program if it is (i) a small-molecule drug for which at least seven years have passed since the date of approval from the FDA and there is no generic on the market (as of the date of selection); or (ii) a biologic for which 11 years have passed since the date of FDA licensure and there is no biosimilar on the market (as of the date of selection). Given that any negotiated price does not take effect until approximately two years after selection, small-molecule drug and biologic manufacturers are afforded at least nine years and 13 years, respectively, before they may be obligated to sell their product under Medicare Part B and Part D, as applicable, at CMS-negotiated pricing. The IRA also requires companies to pay rebates to Medicare to the extent that drug pricing increases faster than inflation, and it also further delayed until January 1, 2032 the implementation of the HHS rebate rule that would have limited the fees that pharmacy benefit managers can charge. Further, under the IRA, orphan drugs are exempted from the Medicare drug price negotiation program, but only if they have a single orphan designation and for which the only approved indication is for that disease or condition. Under the One Big Beautiful Bill Act of 2025 ("OBBBA"), this restriction was

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eliminated; and effective for the 2028 initial price applicability year, all orphan drugs, regardless of the number of orphan drug designations or indications, are exempt from the Medicare drug price negotiation program. The implementation of the IRA is currently subject to ongoing litigation challenging the constitutionality of the IRA Medicare drug price negotiation program. Although the effects of the IRA on our business and the healthcare industry in general are not yet known, we are taking into consideration the potential impact of the IRA on our development and commercialization activities.

We expect that additional U.S. federal healthcare reform measures will be adopted in the future, any of which could limit the amounts that the U.S. Federal Government will pay for healthcare drugs and services, which could result in reduced demand for our drug candidates or additional pricing pressures.

Individual states in the United States have also become increasingly active in passing legislation and implementing regulations designed to control pharmaceutical and biological product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain drug access and marketing cost disclosure and transparency measures designed to encourage importation from other countries and bulk purchasing. Legally mandated price controls on payment amounts by third-party payors or other restrictions could harm our business, financial condition, results of operations and prospects. In addition, regional healthcare authorities and individual hospitals are increasingly using bidding procedures to determine what pharmaceutical products and which suppliers will be included in their prescription drug and other healthcare programs. This could reduce the ultimate demand for our drugs (if approved for marketing) or put pressure on our drug pricing, which could negatively affect our business, financial condition, results of operations and prospects.

In addition, at the state level, legislatures have increasingly passed legislation and implemented regulations similar to those under consideration at the federal level, as well as laws designed to control pharmaceutical and biotherapeutic product pricing, including restrictions on pricing or reimbursement at the state government level, limitations on discounts to patients, marketing cost disclosure and transparency measures, restrictions or other limitations on patient assistance, and, in some cases, policies to encourage importation from other countries (subject to federal approval) and bulk purchasing. Certain states are also pursuing cost containment efforts through Prescription Drug Affordability Boards (“PDABs”) and similar entities. While many PDABs have been granted authority to promote drug price transparency and reporting, some states have granted PDABs more expansive authority, including to set Upper Payment Limits (UPLs) on select, high price drugs. The adoption and implementation of UPLs may put downward pressure on drug prices and impact our company’s future revenues.

Outside the United States, ensuring coverage and adequate payment for a product also involves challenges. Pricing of prescription pharmaceuticals is subject to government control in many countries. Pricing negotiations with government authorities can extend well beyond the receipt of regulatory approval for a product and may require a clinical trial that compares the cost-effectiveness of a product to other available therapies. The conduct of such a clinical trial could be expensive and result in delays in commercialization.

Other United States environmental, health and safety laws and regulations

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

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

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

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Government regulation of drugs outside of the United States

To market any product outside of the United States, we would need to comply with numerous and varying regulatory requirements of other countries regarding safety and efficacy and governing, among other things, clinical trials, marketing authorization, manufacturing, commercial sales, promotion and distribution of our potential future products. For instance, in the European Economic Area, or the EEA (comprised of 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 — The centralized procedure provides for the grant of a single marketing authorization by the European Commission that is valid throughout the EEA. Pursuant to Regulation (EC) No. 726/2004, the centralized procedure is compulsory for specific products, including for medicines produced by certain biotechnological processes, products designated as orphan medicinal products, advanced therapy products (gene therapy, somatic cell therapy and tissue engineered products) and products with a new active substance indicated for the treatment of certain diseases, which includes products for the treatment of cancer. For medicines that do not fall within one of the mandatory categories, an applicant still has the option of submitting an application for a centralized marketing authorization to the European Medicines Agency, or EMA, as long as the medicine concerned contains a new active substance not yet authorized in the EU, is a significant therapeutic, scientific or technical innovation, or if its authorization would be in the interest of public health in the EU. If pursuing marketing authorization of a product candidate for a therapeutic indication under the centralized procedure, the EMA’s Committee for Medicinal Products for Human Use, or CHMP, is responsible for conducting an initial assessment of whether a product meets the required quality, safety and efficacy requirements, and whether a product has a positive benefit/risk ratio. Under the centralized procedure the maximum timeframe for the evaluation of a marketing authorization application, or MAA, by the EMA is 210 days, excluding clock stops, when additional written or oral information is to be provided by the applicant in response to questions asked by the CHMP. Clock stops may extend the timeframe of evaluation of a MAA considerably beyond 210 days. Where the CHMP gives a positive opinion, it provides the opinion together with supporting documentation to the European Commission, who make the final decision to grant a marketing authorization, which is issued within 67 days of receipt of the EMA’s recommendation. 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 a MAA under the accelerated assessment procedure is 150 days, excluding clock stops, but it is possible that the CHMP may revert to the standard time limit for the centralized procedure if it determines that the application is no longer appropriate to conduct an accelerated assessment.

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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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Using the decentralized procedure, an applicant may apply for simultaneous authorization in more than one EEA country for a medicinal product that has not yet been authorized in any EEA country and that does not fall within the mandatory scope of the centralized procedure.

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Using the mutual recognition procedure, a medicine is first authorized in one EEA country, in accordance with the national procedures of that country. Following this, additional marketing authorizations can be sought from other EEA countries in a procedure whereby the countries concerned recognize the validity of the original, national marketing authorization.

In both cases, as with the centralized procedure, the competent authorities of the EEA countries assess the risk-benefit balance of the product on the basis of scientific criteria concerning its quality, safety and efficacy before granting the marketing authorization.

Now that the United Kingdom, or UK, has left the EU, the UK is no longer covered by the EU procedures for the grant of marketing authorizations under the centralized EU procedure and a separate marketing authorization is therefore required to market drugs in the UK. However, although a separate marketing authorization is required to market a product in the UK, on January 1, 2024, the Medicines and Healthcare Products Regulatory Agency, or MHRA, put in place a new international recognition framework which means that the MHRA may have regard to decisions on the approval of marketing authorizations made by the EMA and certain other regulators when determining an application for a new UK marketing authorization. As a result of the Northern Ireland protocol, following Brexit, the EMA remained responsible for approving novel medicines for supply in Northern Ireland under the EU centralized procedure, and a separate authorization was required

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to supply the same medicine in Great Britain (England, Wales and Scotland). However, on January 1, 2025, a new arrangement called the "Windsor Framework" came into effect and placed medicinal products supplied to Northern Ireland largely under the regulatory authority of the MHRA. The Windsor Framework removes EU licensing processes and certain EU labeling and serialization requirements for medicines supplied to Northern Ireland and introduces a UK-wide licensing process for medicines. A single United Kingdom-wide marketing authorization will be granted by the MHRA for all novel medicinal products to be sold in the United Kingdom, enabling products to be sold in a single pack and under a single authorization throughout the United Kingdom. In addition, the new arrangements require all medicines placed on the UK market to be labelled “UK only”, indicating they are not for sale in the EU.

In the EU, new products that are authorized for marketing (i.e., 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 referencing the preclinical and clinical trial data contained in the dossier of the innovator 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 innovator product was first authorized in the EU. The additional two-year period of 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 overall ten-year period can be extended to a maximum of eleven 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. Even if a compound is considered to be a new chemical entity so that the innovator gains the prescribed period of data exclusivity, another company may market another version of the product if such company obtained marketing authorization based on a MAA with a complete independent data package of pharmaceutical tests, preclinical tests and clinical trials.

The criteria for designating an “orphan medicinal product” in the EU are similar in principle to those in the United States. In the EU, under Article 3 of Regulation (EC) 141/2000, a medicinal product may be designated as orphan if it meets the following criteria: (i) it is intended for the diagnosis, prevention or treatment of a life-threatening or chronically debilitating condition; and (ii) either (a) such condition affects no more than five in 10,000 persons in the EU when the application is made, or (b) it is unlikely that the product, without the benefits derived from orphan status, would generate sufficient return in the EU to justify the investment needed for its development; and (iii) there exists no satisfactory method of diagnosis, prevention or treatment of such condition, 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, unless certain conditions are met. An orphan product can also obtain an additional two years of market exclusivity in the EU for pediatric studies. Orphan drug designation does not convey any advantage in, or shorten the duration of, the regulatory review and approval process.

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

The system for the approval of clinical trials in the EU is governed by the EU Clinical Trials Regulation 536/2014. Under this system, an applicant must obtain prior approval from the national competent authority, or NCA, 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 study site after the competent ethics committee, or EC, has issued a favorable opinion. The EU Clinical Trials Regulation (which replaced the previous Clinical Trials Directive 2001/20/EC on January 31, 2022) is directly applicable in all Member States (and so does not require national implementing legislation in each Member State) and aims at simplifying and streamlining the approval of clinical studies in the EU. The main characteristics of the Regulation include: a streamlined application procedure via a single-entry point through the Clinical Trials Information System, or CTIS; a single set of documents to be prepared and submitted for the application as well as simplified reporting procedures for clinical trial sponsors; and a harmonized procedure for the assessment of applications for clinical trials, which is divided in two parts (Part I contains scientific and medicinal product documentation and Part II contains the national and patient-level documentation). Part I is assessed by a coordinated review 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”) of a draft report prepared by a reporting Member State. Part II is assessed separately by each Member State concerned. Strict deadlines have also been established for the assessment of clinical trial applications.

All of the aforementioned EU rules are generally applicable in the EEA.

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

Government regulation of data collection outside of the United States

We conduct clinical trials in the EU, and as a result are subject to additional privacy restrictions in relation to those clinical trials. The collection and use of personal health data in the EEA is governed by the General Data Protection Regulation 2016/679, or the EU GDPR, and national implementing laws. Switzerland has passed similar laws, and following the UK’s decision to leave the EU, the UK has enacted legislation which is substantially aligned with the GDPR, by virtue of the EU (Withdrawal) Act 2018, as amended (together with the EU GDPR, the GDPR). The GDPR applies to the processing of personal data by any company established in the EEA or UK and to companies established outside the EEA or UK to the extent they process personal data in connection with the offering of goods or services to data subjects in the EEA or UK, or the monitoring of the behavior of data subjects in the EEA or UK. The GDPR enhances data protection obligations for data controllers of personal data, including strict requirements relating to the processing of sensitive data (such as health data), ensuring there is a legal basis or condition to justify the processing of personal data, stringent requirements relating to the consent of data subjects (where required), expanded disclosures about how personal data is used, enhanced requirements for securing personal data, requirements to conduct privacy impact assessments for “high risk” processing, limitations on retention of personal data, mandatory data breach notification and “privacy by design” requirements, and creates direct obligations on service providers acting as processors. The GDPR also imposes strict rules on the transfer of personal data outside of the EEA or UK to countries that do not ensure an adequate level of protection, like the United States. Failure to comply with the requirements of the GDPR and the related national data protection laws of the EU Member States, the UK, and Norway, Iceland and Liechtenstein, which may deviate slightly from the GDPR, may result in fines of up to 4% of a company’s global revenue for the preceding financial year, or €20,000,000, whichever is greater. Moreover, the GDPR grants data subjects the right to claim material and non-material damages resulting from infringement of the GDPR. Maintaining compliance with the GDPR will continue to require significant time, resources and expense. There has been limited enforcement of the GDPR to date in biopharmaceutical development, so we face uncertainty as to the exact interpretation of the new requirements on any current and future trials and we may be unsuccessful in implementing and maintaining all measures required by data protection authorities or courts in interpretation of the law.

Further, since the UK’s decision to leave the EU, the UK is now regarded as a “third country” for the purposes of transfers of personal data from the EEA. The European Commission has, however, issued an adequacy decision recognizing the UK as providing adequate data protection and, therefore, transfers of personal data originating in the EEA to the UK remain unrestricted. Likewise, the UK government has confirmed that personal data transfers from the UK to the EEA remain free flowing. However, the UK government is planning to reform its data protection law with the Data (Use and Access) Bill, which it introduced to Parliament on 24 October 2024. These potential future changes to UK data protection laws may alter the similarities between the UK and EEA data protection regime and threaten the UK adequacy decision from the European Commission.

Data protection authority activity differs across the EU and UK, with certain authorities applying their own agenda which shows there is uncertainty in the manner in which data protection authorities will seek to enforce compliance with GDPR. For example, it is not clear if the authorities will conduct random audits of companies doing business in the EU, or if the authorities will wait for complaints to be filed by individuals who claim their rights have been violated. Enforcement uncertainty and the costs associated with ensuring GDPR compliance are onerous and may adversely affect our business, financial condition, results of operations and prospects.

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

Competition

We face direct competition from pharmaceutical and biotechnology companies leveraging the principle of synthetic lethality as well as companies developing therapies for the same target pathway and the same indications. Well-established companies that are developing or may develop therapies based on synthetic lethality include AstraZeneca, Amgen, Bristol Myers Squibb (BMS), Gilead, GlaxoSmithKline, Merck KGaA, Pfizer, Lilly and Roche. Smaller and earlier-stage companies

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focused on synthetic lethality include Artios Pharma, BeOne, Exelixis, IDEAYA Biosciences, Repare Therapeutics and Servier Pharmaceuticals.

Our PRMT5 inhibitor program, which includes vopimetostat and TNG456, will face direct competition from companies that have clinical-stage, MTA-cooperative PRMT5 inhibitors that are selective for MTAP-deleted cancers. We are aware that BMS (which acquired Mirati Therapeutics, Inc., or Mirati), Amgen, AstraZeneca, BeOne and Abbisko are in Phase 1/2 clinical trials with MTA-cooperative PRMT5 inhibitor programs, using the same mechanism of action as vopimetostat and TNG456. There may be additional competition from other drug candidates not yet in clinic trials, such as Gilead Sciences and IDEAYA Biosciences. Currently, there are no MTA-cooperative PRMT5 inhibitors that are authorized for marketing by any regulatory authority.

Indirect competition may come from MAT2A inhibitor programs that are uniquely different than the vopimetostat and TNG456 mechanism of action but are synthetic lethal with MTAP-deletions. MAT2A is an enzyme upstream of PRMT5 essential for the metabolism of the PRMT5 co-factor SAM that acts on the same pathway as vopimetostat and TNG456. We are aware that IDEAYA Biosciences, BeOne, Insilico Medicine and Servier Pharmaceuticals have clinical MAT2A inhibitor programs.

We are not aware of any competition from other companies developing a similar mechanism as TNG260, our CoREST inhibitor program. Indirect competition may come from LSD1 inhibitor programs that target a different class of HDAC inhibitors than TNG260. We are aware that Jubilant Therapeutics has an LSD1-HDAC6 clinical program.

We face competition more broadly across the oncology market for safe, efficacious, and reimbursable cancer treatments. The most common methods of treating patients with cancer are surgery, radiation, and drug therapy, including chemotherapy, hormone therapy, biologic therapy (such as monoclonal and bispecific antibodies), immunotherapy, cell-based therapy and targeted therapy, or a combination of any such methods. There are a variety of available drug therapies marketed for cancer. In many cases, these drugs are administered in combination to enhance efficacy. If any of our product candidates are approved, they may compete with these existing drugs and other therapies, and to the extent they are ultimately used in combination with or as an adjunct to these therapies, our product candidates may not be competitive with them. Some of these drugs are branded and subject to patent protection, and others are available on a generic basis. Insurers and other third-party payors may also encourage the use of generic products or specific branded products. As a result, obtaining market acceptance of, and gaining significant share of the market for, any of our product candidates that we successfully introduce to the market may pose challenges. In addition, many companies are developing new oncology therapeutics, and we cannot predict what the standard of care will be as our product candidates progress through clinical development.

Many of our competitors, either alone or with their collaborators, have significantly greater resources, expertise in research and development, manufacturing, preclinical and clinical testing, obtaining regulatory approvals and 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 significant competitors, particularly through collaborative arrangements with large and established companies. Additionally, mergers and acquisitions may result in even more resources being concentrated in our competitors.

Employees and Human Capital Resources

Attracting and retaining qualified and experienced employees in research and development, clinical, manufacturing, regulatory, quality and other positions is crucial to our ability to compete effectively. Competition for these employees is intense in the pharmaceutical industry in which we operate. Our ability to recruit and retain such employees depends on a number of factors, including the growth of our organization, the culture and work environment we have created, our organizational values and goals and our corporate philosophy; talent development and career opportunities; and compensation and benefits.

As of December 31, 2025, we had 137 full-time employees. 97 employees are engaged in research and development and 40 are engaged in business development, finance, legal, and general management and administration. None of our employees are represented by labor unions or covered by collective bargaining agreements.

Talent Acquisition and Employee Development

Our principal talent acquisition goal is to attract, retain, and develop the highest quality talent. As we build our organization beyond drug discovery and drug development, our goals have been extended to include establishing an employee

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base that will allow us to efficiently move our pipeline products through clinical trials, regulatory approvals and into the markets where we can help patients and their families and, simultaneously, to have employees that provide diverse backgrounds and ideas, are trained to operate and act at the highest standards of ethics and integrity, and are dedicated to achieve the highest level of innovation and to advance precision oncology treatments through the use of synthetic lethality. To support our talent acquisition, our human resources programs are designed to develop talent to prepare them for leadership positions in the future; reward employees through competitive benefits programs, including competitive pay, incentive compensation, and an equity program that aligns the incentives of our employees with the interests of our shareholders; enhance our culture through efforts aimed at making the workplace engaging and inclusive; and retain and develop talent that embody our core values.

Diversity

Our employees represent a broad set of backgrounds, perspectives and experiences. We attribute a significant aspect of our early growth and success to the diversity that our employees bring with them to their professional roles. We view our culture, which includes a commitment to diversity, equity and inclusion, as the foundation upon which we are building a leading synthetic lethality business that strives to make advances in oncology care, all with the objective of benefiting patients. We are focused on building a work environment in which employees can express themselves and have a voice in how we operate.

Our commitment to diversity, equity, inclusion, and belonging is an integral part of our corporate culture, embedded within our overall operational framework. We view diversity through a broad lens that encompasses cultural, ethnic, gender, sexual orientation, experiences, world views, and backgrounds, with the goal of fostering a truly inclusive environment. Our recruiting program also aims to ensure that our workforce reflects a wide range of experiences, backgrounds and perspectives. We regularly highlight our employees' diverse backgrounds, experiences, and traditions through in-office events, ensuring that inclusiveness is a daily practice. Our inclusive environment is further supported by multiple forums that encourage employees to share their opinions, including engagement surveys and Tips for Tango (an initiative that was instituted to allow employees to submit suggestions to improve any aspect of our work environment, work processes or culture). Utilizing insights from these activities, we are committed to fostering a workplace where inclusiveness and belonging are foundational.

Further, the Nominating and Corporate Governance Committee charter sets forth specific guidelines that the Committee will use in evaluating future individuals for nomination to the Board of Directors. Among the identified factors the Committee is to consider in nominating a candidate is the diversity of a candidate. The Board recognizes that diversity plays an important role in its functioning and operations.

These and similar programs are important to develop a sense of belonging for all employees and for our Board of Directors.

Employee Engagement

We survey our employees on an annual basis to assess the overall engagement of our workforce, and compare our engagement results against prior year results, as well as a set of benchmark companies in the biotech sector and of similar size (as measured by number of employees). We compare both our internal and comparative results to assess our employee engagement performance during the preceding year and to determine areas of focus going forward. We leverage an engagement task force that consists of employees from each of our functional business areas, with the oversight of a member of the management team, to obtain detailed feedback on the survey results and to generate and implement proposals to improve the employee experience.

We implemented a number of initiatives in response to employee feedback from the 2024 engagement survey, including: (i) completing follow-up focus groups and a targeted survey to better understand associates’ comfort with speaking up and to identify opportunities to strengthen openness and dialogue; (ii) establishing a standardized process to increase transparency around associate departures; and (iii) implementing a clearly defined and equitable promotions process, which was communicated company-wide in October 2025.

In our most recent engagement survey, conducted in 2025, results continued to be generally higher than our benchmark dataset, supporting our view that overall employee engagement remains strong. The survey also highlighted areas of strength, including managers’ demonstrated care for associate well-being, associates’ understanding of how their work contributes to Company goals, and the Company’s commitment to social responsibility, including community support and sustainability.

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As is the case with every survey, we also used the data to identify areas where we want to focus our efforts for improvement, including letting associates know that their feedback is encouraged and will not be viewed negatively. As we did in 2024, we will take these 2025 results and enable actions that will further improve our engagement. We also conduct regular townhall meetings with our employees that are intended to keep our employees updated on important corporate initiatives and to obtain input from employees on these initiatives. We also use periodic employee surveys so we can quickly obtain employee feedback on new programs or policies that are under consideration.