NASDAQ: VSTM

For our clinical-stage pipeline programs, we are evaluating VS-7375, a potential best-in-class oral KRAS G12D (ON/OFF) inhibitor, for the treatment of patients with KRAS G12D mutated cancers, including pancreatic ductal adenocarcinoma (“PDAC”), non-small cell lung cancer (“NSCLC”), colorectal cancer (“CRC”) and other KRAS G12D mutated cancers.

A summary of our commercial and pipeline products is shown below.

Not shown: Two undisclosed assets at discovery phase targeting RAS/MAPK pathway-driven cancers as part of the GenFleet Therapeutics collaboration.​

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The information below summarizes our key achievements in 2025 and the anticipated near-term milestones for our pipeline programs.

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AVMAPKI FAKZYNJA CO-PACK

AVMAPKI FAKZYNJA CO-PACK received accelerated approval by the U.S. Food and Drug Administration (FDA) on May 8, 2025 for the treatment of adults with KRAS-mutated recurrent LGSOC who have received prior systemic therapy, approximately two months in advance of the Prescription Drug User Fee Act (“PDUFA”) action date of June 30, 2025.

The product was commercially available within a week of approval and was subsequently listed as a Category 2A recommendation for KRAS-mutated recurrent LGSOC in the National Comprehensive Cancer Network® (“NCCN®”) Clinical Practice Guidelines in Oncology (“NCCN Guidelines®”).

Potential label and commercial geographic expansion of the combination therapy progressed:

●Additional patient enrollment for RAMP 301 was completed in December 2025 following a pre-planned interim analysis (“IA”) by the Independent Data Monitoring Committee (“IDMC”), which recommended a modest, one-time increase of 29 patients across KRAS mutation status based on the total enrollment achieved in October 2025. We expect to report a topline readout of the primary endpoint in mid-2027.

●The European Commission granted Orphan Drug Designation in July 2025 for avutometinib plus defactinib for the treatment of ovarian cancer based on a positive opinion from the European Medicines Agency Committee for Orphan Medicinal Products.

●Preliminary safety and efficacy data from the Phase 2 RAMP 201J trial in Japan was presented in November 2025 at the International Gynecologic Cancer Society (“IGCS”) 2025 Annual Meeting and we are continuing enrollment of patients into the RAMP 301 study in Japan.

Avutometinib in combination with defactinib

In May 2025, we reported that we selected the recommended Phase 2 dose (“RP2D”) known as “dose level 1” in our RAMP 205 trial, which is evaluating avutometinib plus defactinib and in combination with standard of care chemotherapy (gemcitabine and Nab-paclitaxel) in front-line metastatic PDAC. In the study, dose level 1 demonstrated a confirmed overall response rate (“ORR”) of 83% (10/12) patients. Adverse events across all dose cohorts remained generally consistent with the previously announced safety and tolerability profile, and no new safety signals have emerged.

We completed enrollment of the expansion cohort of a total of 29 patients at RP2D, and we expect to report an update on the safety and efficacy of this expansion cohort in the first half of 2026.

In September 2021, we entered into a clinical collaboration agreement with Amgen, Inc. (“Amgen”) to evaluate avutometinib in combination with Amgen’s KRAS G12C inhibitor LUMAKRAS® (sotorasib) with and without defactinib in a Phase1/2 study entitled RAMP 203 in patients naïve to or previously treated with a KRAS G12C inhibitor. Following evaluation of interim data in December 2025 we announced the discontinuation of RAMP 203 to focus resources on clinical development of VS-7375, reflecting the evolving treatment landscape for KRAS G12C inhibitors and the strategic prioritization of programs with the greatest potential impact for patients living with advanced lung cancer.

VS-7375

In January 2025, we licensed VS-7375 from GenFleet Therapeutics (“GenFleet”) and announced in June 2025 that the first patient had been dosed in the monotherapy portion of VS-7375-101, the U.S. Phase 1/2 clinical trial evaluating VS-7375 in patients with advanced KRAS G12D mutant solid tumors, including PDAC, NSCLC, and CRC.

In July 2025, the FDA granted Fast Track Designation (“FTD”) to VS-7375, for the first-line (“1L”) treatment of patients with KRAS G12D-mutated locally advanced or metastatic PDAC and for the treatment of patients with

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KRAS G12D-mutated locally advanced or metastatic PDAC who have received at least one prior line of standard systemic therapy.

We continue to make progress with the VS-7375-101 trial, which includes both monotherapy and combination dose escalation and dose expansion cohorts, as follows:

●In the monotherapy dose escalation phase, we cleared the 400 mg, 600 mg, and 900 mg daily dose (“QD”) dose levels with no dose-limiting toxicities (“DLTs”) and no major toxicities and dose escalation continues. In October 2025, we reported promising anti-tumor activity was observed in patients with various solid tumors, including metastatic PDAC.

●In a pharmacokinetics (PK) analysis, doses of VS-7375 at 600 mg QD and above, with feeding and anti-emetic prophylaxis, yielded similar exposures to fasted patients in China. The clinical exposures observed correspond with the exposures achieved in preclinical models necessary for maximal anti-tumor efficacy.

●As of the January 30, 2026 data cutoff, VS-7375 demonstrated an encouraging safety profile and was generally well-tolerated across all monotherapy dose levels evaluated to date. Patients (n=23) receiving VS-7375 at either 400 mg QD, 600 mg QD or 900 mg QD with a mean duration of therapy of 1.6 months (0.7-5.6), reported no drug related liver function test abnormalities. There was no drug-related neutropenia or anemia >Grade 2 and rates of nausea, vomiting and diarrhea remained lower than those reported by our partner in China. No DLTs have been reported to date, and the maximum tolerated dose has not been reached.

●We initiated the monotherapy dose expansion cohorts with the 600 mg QD dose and are increasing enrollment across three different cohorts: second line (“2L”) PDAC, second- and third-line (“2L/3L”) NSCLC, and other second line or greater (“2L+”) KRAS G12D mutated solid tumors.

●In our combination cohorts we are enrolling patients into three different cohorts, including 2L+ solid tumors in combination with cetuximab, 1L NSCLC in combination with carboplatin/pemetrexed/pembrolizumab, and 2L PDAC in combination with gemcitabine and Nab-paclitaxel.

●We cleared the 400 mg and 600 mg QD dose of VS-7375 in combination with cetuximab and are evaluating higher doses.

We plan to report an update on early dose-escalation data from the VS-7375-101 trial in first half of 2026.

Following recent feedback from the FDA, we are amending the VS-7375-101 Phase 1/2 protocol and breaking out disease-specific Phase 2 registration-directed trials for KRAS G12D mutated 2L PDAC, 2L/3L NSCLC (monotherapy), and 2L+ CRC in combination with cetuximab.

Our partner, GenFleet, is developing VS-7375 as GFH375 in greater China and to date has generated data in more than 150 patients with PDAC, NSCLC and other solid tumor cancers. GenFleet reported initial positive safety and anti-tumor activity in 2L PDAC (58.3% ORR in 12 patients) and 2L NSCLC (68.8% ORR in 16 patients). GenFleet has an ongoing Phase 1/2b trial of GFH375 in combination with cetuximab or chemotherapy in KRAS G12D-mutated solid tumors in China. The chemotherapy combination will be conducted in 1L PDAC in China. GenFleet is also conducting a Phase 3 trial in China evaluating GFH375 in patients with pretreated KRAS G12D-mutated metastatic pancreatic cancer.

Preclinical Programs

We continue to progress preclinical research programs across our pipeline assets. We also have two undisclosed assets at discovery phase targeting RAS/MAPK pathway-driven cancers as part of the GenFleet Agreement.

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OUR STRATEGY

Our goal is to deliver transformative therapies that meaningfully improve outcomes for patients living with RAS/MAPK pathway-driven cancers. We are developing small molecule therapeutics targeting this pathway and have already successfully demonstrated clinical-to-commercial success in bringing novel RAS/MAPK pathway-targeted therapies from development through FDA approval to commercialization. We are well-positioned to deliver continued commercial success and develop a potential best-in-class treatment for long-term growth.

Precision targeting of RAS/MAPK pathway-driven cancers differentiates our science. Our focus is on novel small molecule drugs developed both as monotherapy and in combination that inhibit critical signaling pathways in cancer promoting cell survival and tumor growth. This includes targeting RAS directly with KRAS G12D inhibition, targeting the pathway downstream with RAF/MEK inhibition, and targeting the parallel pathway that drives resistance with FAK inhibition.

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Our lead FDA-approved combination product, AVMAPKI FAKZYNJA CO-PACK, is indicated for the treatment of patients with KRAS-mutated recurrent LGSOC who have received prior systemic therapy. We have established a commercial presence in the U.S. that is scalable to maximize future oncology development programs and launches.

Our innovative pipeline is anchored by VS-7375, a potential best-in-class KRAS G12D (ON/OFF) inhibitor targeting the most prevalent KRAS mutation in human cancers. We believe VS-7375 addresses a significant opportunity across multiple KRAS G12D-mutated solid tumors with a differentiated profile and best-in-class anti-tumor activity. We see substantial potential to address a significant unmet medical need and establish leadership in this therapeutic area.

Our key priorities are as follows:

●Maximize and sustain commercial momentum leveraging our established engagement with the healthcare provider community and building upon the strong foundation achieved in our initial launch

●Advance VS-7375 through development to produce topline clinical data readouts and drive toward registration-directed studies across KRAS G12D mutated solid tumors, including PDAC, NSCLC, and CRC

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●Rigorously follow patients to achieve data maturity in our Phase 3 confirmatory trial, RAMP 301, which may support label expansion in the U.S. and regulatory submissions outside of the U.S.

●Maintain prudent capital management through key inflection points

●Continue to support our people and culture through this next phase of growth

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AVMAPKI FAKZYNJA CO-PACK FDA Approved for KRAS-mutated recurrent LGSOC

AVMAPKI FAKZYNJA CO-PACK received accelerated approval by the FDA on May 8, 2025, approximately two months in advance of the PDUFA action date of June 30, 2025, for the treatment of adult patients with KRAS-mutated recurrent LGSOC who have received prior systemic therapy. The product was commercially available within a week of approval and was subsequently listed as a Category 2A recommendation in the National Comprehensive Cancer Network® (NCCN®) Clinical Practice Guidelines in Oncology (NCCN Guidelines®). Prior to this approval, there were no FDA-approved treatments specifically for KRAS-mutated recurrent LGSOC.

LGSOC is a rare ovarian cancer that is persistent and starts in the thin layer of tissue around the ovaries (also known as the epithelium). Low-grade means the cancer cells look a lot like normal cells, and serous means the cancer started in the serous membrane, which is part of the epithelium. There are approximately 6,000 to 8,000 women with LGSOC living in the U.S., and 1,000 to 2,000 cases are diagnosed each year. LGSOC is most commonly diagnosed in women between the ages of 20 to 30 and 50 to 60. More than 80% of patients experience a recurrence. The RAS/MAPK pathway is a primary driver of tumor growth and genetic mutations that activate this pathway are found in many cancers. In LGSOC, 70% of patients have a RAS/MAPK pathway-associated mutation. One of these mutations, known as KRAS, is present in approximately 30% of patients with LGSOC.

Cancer is highly dependent on the RAS/MAPK signaling pathway for its growth, and blocking any single node in this pathway is generally insufficient for deep and durable anti-cancer activity as the cancer will compensate by activating other signaling proteins within the RAS pathway or in parallel pathways. AVMAPKI (avutometinib) inhibits MEK kinase activity while also blocking the compensatory reactivation of MEK by upstream RAF. RAF and MEK proteins are regulators of the RAS/RAF/MEK/ERK (MAPK) pathway. Blocking RAF and/or MEK activates FAK, a key mediator of drug resistance. FAKZYNJA (defactinib) is a FAK inhibitor. The avutometinib and defactinib combination was designed to provide a more complete blockade of the signaling that drives the growth and drug resistance of RAS/MAPK pathway-dependent tumors.

Commercial Launch

AVMAPKI plus FAKZYNJA is only commercially available in the U.S. as an oral combination co-pack with the two prescription products, known as “AVMAPKI FAKZYNJA CO-PACK.” The product was available at our designated specialty pharmacies within five days of approval. Our first full seven months of commercial launch in 2025 resulted in the recognition of $30.9 million in net product revenue. Over the past few years, as part of our pre-launch efforts and educational work with our medical science liaisons, and now with the addition of our field sales team, we have generated strong awareness and built a highly experienced and motivated team. We believe our initial launch success has been driven by consistent adoption among both academic centers and community oncologists.    

We defined three key strategic launch imperatives to drive our launch: 1) effectively reach healthcare providers, keeping in consideration that the top 100 commercial healthcare organizations in the U.S. comprise approximately 50% of the sales opportunity; 2) engage and support patients throughout their journey since, as patients progress through other therapies, many will be ready for a new treatment option; and 3) ensure seamless access to support patients and ensure any barriers to reimbursement are removed. Our approach is highly targeted, and we are utilizing a deliberate mix of one-on-one meetings, group discussions, and conference engagements to maximize the impact of every interaction in this rare disease market. We have received a favorable mix of orders between the two specialty pharmacies onboarded in the second quarter of 2025 and the four specialty distributors we added in the third quarter of 2025.

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We believe we are well-positioned for continued growth as we aim to achieve our goal that every KRAS-mutated LGSOC patient should not only receive this treatment but should do so at their first recurrence. 

Accelerated Approval

Verastem initiated a rolling New Drug Application (“NDA”) in May 2024 and aligned with the FDA on plans to complete the NDA submission in October 2024 for adult patients with KRAS-mutated recurrent LGSOC, who received at least one prior systemic therapy. The NDA included safety and efficacy results from 57 patients with KRAS-mutated recurrent LGSOC enrolled in our Phase 2 RAMP 201 clinical trial. In the study, AVMAPKI and FAKZYNJA, in combination, showed a confirmed ORR by blinded independent central review (“BICR”) of 44% (25/57; 95% Confidence Interval (“CI”): 31-58) in patients with a KRAS mutation. The DOR ranged from 3.3 to 31.1 months in the KRAS mutant population. The safety of AVMAPKI and FAKZYNJA, in combination, was evaluated in 57 patients with KRAS-mutated recurrent LGSOC. Possible serious side effects with AVMAPKI FAKZYNJA CO-PACK include ocular disorders, skin toxicities (“rash”), hepatotoxicity, rhabdomyolysis, and fetal harm when administered during pregnancy. The most common side effects, including laboratory changes, of AVMAPKI FAKZYNJA CO-PACK include increased levels of an enzyme in the blood (“CPK”), nausea, fatigue, abnormal liver test (“AST”), and rash. The NDA also includes supportive data from our FRAME Phase 1 trial, the first study conducted with the AVMAPKI and FAKZYNJA combination therapy in recurrent LGSOC.

We completed our submission in October 2024, and the FDA accepted the NDA under the accelerated approval pathway in December 2024. The NDA was granted Priority Review with a PDUFA action date of June 30, 2025.

Prior to NDA acceptance, the FDA granted Breakthrough Therapy Designation (“BTD”) for the combination therapy for patients with recurrent LGSOC after one or more prior lines of therapy, including platinum-based chemotherapy, in May 2021. BTD allows for the expedited development and review of drugs for serious or life-threatening conditions. Avutometinib alone or in combination with defactinib was also granted Orphan Drug Designation by the FDA for the treatment of LGSOC, which recognized this rare cancer as distinct from high-grade serous ovarian cancer (“HGSOC”). These designations, combined with the early approval, underscored the urgency and importance of addressing the unmet treatment needs of women living with LGSOC.

RAMP 201 Clinical Trial

RAMP 201 (ENGOTov60/GOG3052) was a Phase 2 adaptive, two-part multicenter, parallel cohort, randomized, open-label trial to evaluate the efficacy and safety of avutometinib alone and in combination with defactinib in patients with recurrent low-grade serous ovarian cancer. The first part of the study determined the selection of the go forward regimen, which was the combination of avutometinib and defactinib versus avutometinib alone, based on overall response rates. The expansion phases of the trial evaluated the safety and efficacy of the go forward regimen of avutometinib 3.2 mg twice weekly and defactinib 200 mg twice daily.

In October 2024, we announced the primary analysis of the RAMP 201 study with a data cutoff of June 30, 2024, that was presented at the IGCS 2025 Annual Meeting. The study showed a confirmed ORR by BICR of 31% (34/109; 95% CI: 23-41) in all evaluable patients with measurable disease with approximately 12 months of follow up. Among patients with KRAS-mutated LGSOC, the confirmed ORR was 44% (25/57; 95% CI: 31-58), and for patients with KRAS wild-type LGSOC the confirmed ORR was 17% (9/52; 95% CI: 8-30). The median duration of response (“mDOR”) was 31.1 months (95% CI: 14.8-31.1) in all evaluable patients, with 31.1 months (95% CI: 14.8-31.1) in the KRAS mutant population and 9.2 months (95% CI: 5.5-NEi) in the KRAS wild-type population. The median progression-free survival was 12.9 months (95% CI: 10.9-20.2) in all evaluable patients, with 22 months (95% CI: 11.1-36.6) in the KRAS mutant population and 12.8 months (95% CI: 7.4-18.4) in the KRAS wild-type population. The disease control rate (“DCR”) at six or more months was 61% in the total evaluable population, 70% in KRAS mutant population and 50% in KRAS wild-type population. The updated data demonstrated that avutometinib in combination with defactinib was generally well-tolerated, with a 10% discontinuation rate due to adverse events and no new safety signals were identified. The most common treatment-related adverse events (all grades, grade ≥3) for the combination were nausea (67.0%, 2.6%), diarrhea (58.3%, 7.8%), and increased blood creatine phosphokinase levels (60.0%, 24.3%).

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The primary analysis of the RAMP 201 study was published in the Journal of Clinical Oncology in July 2025. The FRAME study was published in Nature in June 2025.

RAMP 301 Phase 3 Confirmatory Clinical Trial

AVMAPKI FAKZYNJA CO-PACK is approved under accelerated approval based on the tumor response rate and duration of response. The FDA requires that we confirm the benefit in a confirmatory trial. In December of 2023, we initiated a global, randomized, confirmatory Phase 3 trial known as RAMP 301 in an international collaboration between The GOG Foundation, Inc. and the European Network of Gynaecological Oncological Trial groups. RAMP 301 is evaluating the combination of avutometinib and defactinib versus standard of care chemotherapy or hormonal therapy for the treatment of patients with recurrent LGSOC with and without a KRAS mutation. RAMP 301 will serve as the confirmatory study required by the FDA for the combination of avutometinib and defactinib for the initial indication of KRAS-mutated recurrent LGSOC, potentially leading to full approval, and has the potential to support an expanded indication regardless of KRAS mutation status. The primary endpoint is progression-free survival by BICR. Secondary endpoints include ORR, DOR, DCR, safety and tolerability, patient-reported outcomes, and overall survival (“OS”). RAMP 301 has enrolled patients in the United States, Australia, Canada, Europe, United Kingdom, and Korea.

The planned enrollment for RAMP 301 of the targeted 270 patients was completed in October 2025, a full quarter earlier than anticipated. Additional patient enrollment was also completed ahead of schedule in December 2025, following a pre-planned IA by the IDMC, which recommended a modest, one-time increase of 29 patients across KRAS mutation status based on the total enrollment achieved in October 2025. We expect to report a topline readout of the primary endpoint in mid-2027.

Post-marketing Accelerated Approval Requirement and Commitments

As a condition of receiving accelerated approval for the AVMAPKI FAKZYNJA CO-PACK, we are required to conduct additional studies to verify the clinical benefit of AVMAPKI FAKZYNJA CO-PACK and address post-marketing commitments as agreed upon with the FDA. We need to complete the ongoing Phase 3 RAMP 301 trial and provide the progression-free survival (“PFS”) and the final overall survival analyses, intended to describe and verify the clinical benefit of avutometinib and defactinib combination in adult patients with recurrent KRAS-mutated LGSOC with central KRAS testing results for all patients. We are also required to complete a pediatric study of avutometinib and defactinib to evaluate preliminary efficacy, and characterize dose, pharmacokinetics (“PK”) pharmacodynamics (“PD”) and preliminary safety in pediatric patients ages 2 to <17 years of age with relapsed or refractory unresectable or metastatic RAS/MAPK pathway-driven pediatric cancers.

In addition, we are also required to:

●assess drug-drug interaction risks when defactinib is taken with CYP3A4 inhibitors through a trial evaluating the effect of a moderate CYP3A4 inhibitor on defactinib PK and identify the appropriate dosing

●evaluate the potential risk of cardiomyopathy in adult patients with recurrent LGSOC receiving the combination of avutometinib and defactinib

●enroll at least 15 evaluable patients with moderate hepatic impairment to evaluate the potential risk of increased serious adverse reactions with avutometinib in combination with defactinib

●assess the effect of severe hepatic impairment on defactinib and its active metabolite to evaluate the potential serious risk of increased serious adverse reactions in patients with severe hepatic impairment

●assess the effect of severe hepatic impairment on avutometinib to evaluate the potential serious risk of increased serious adverse reactions in patients with severe hepatic impairment

●assess the severe renal impairment on avutometinib to evaluate the potential serious risk of increased serious adverse reactions in patients with severe renal impairment

●complete study VS-6063-108, assessing drug interactions between defactinib and BCRP inhibitor, a P-gp Inhibitor, and a moderate CYP2C9 inhibitor

●assess effects of multiple doses of defactinib on single dose pharmacokinetics of substrates of CYP3A4, CYP2C9, P-gp, BCPR, OATP1B1, and OATP1B3 to evaluate the potential serious risks of

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increased serious adverse reactions from elevated levels of CYP3A4, CYP2C9, P-gp, BCPR, OATP1B1, and OATP1B3 substrates, respectively, when they are used concomitantly with defactinib

●assess the effect of defactinib on MATE2-K substrates drugs interaction risks

●conduct an in vitro study to assess whether additional drug interaction studies are needed for defactinib metabolite M4

●conduct an appropriate analytical and clinical validation study to support the development of a diagnostic device that is essential to the safe and effective use of the combination of avutometinib and defactinib in KRAS-mutated, recurrent low-grade serous ovarian cancer

LGSOC Geographic Commercial Expansion

We continue to make progress on potential geographic commercial expansion of the AVMAPKI and FAKZYNJA combination therapy. The European Commission granted Orphan Drug Designation in July 2025 for avutometinib plus defactinib for the treatment of ovarian cancer based on a positive opinion from the European Medicines Agency Committee for Orphan Medicinal Products. Preliminary safety and efficacy data from the Phase 2 RAMP 201J trial in Japan was presented at the IGCS 2025 Annual Meeting in November 2025 and we are continuing enrollment of patients into the RAMP 301 study in Japan. Plans to engage regulatory authorities in these regions are ongoing.

Product Pipeline

Avutometinib in Combination with Defactinib in First-line Advanced Pancreatic Cancer

In 2025, the National Cancer Institute (“NCI”) estimated that pancreatic cancer was the tenth most common cancer diagnosed in the United States and that the disease represented the third leading cause of cancer-related death in the U.S. Pancreatic cancer often has a poor prognosis, even when diagnosed early. Early detection remains a challenge, and survival rates have not improved significantly during the past 40 years. According to the NCI, the five-year survival rate for pancreatic cancer is 13% (2015-2021) and only 3% for those with advanced disease. In 2025, the NCI estimated that more than 67,000 people in the U.S. would be diagnosed with pancreatic cancer and more than 50,000 were estimated to die from this disease.

The treatment options for pancreatic cancer remain primarily limited to combinations of chemotherapy or chemotherapy plus radiation. Immuno-oncology agents have not demonstrated a significant improvement in treatment outcomes for patients with pancreatic cancer. KRAS mutations occur in up to 95% of pancreatic cancer. KRAS mutations confer constitutive activation of the KRAS protein, which activates RAF and MEK downstream supporting proliferation and survival of tumor cells. This provides the rationale for use of avutometinib to block both RAF and MEK to inhibit KRAS signaling in pancreatic cancer. Additionally, it has been previously reported that inhibition of the MAPK pathway with targeted therapies activates FAK as an adaptive resistance mechanism. Furthermore, FAK has been shown to be hyperactivated in human PDAC, and FAK activation has been correlated with high levels of fibroblasts, poor T cell infiltration and poor overall survival in these patients. Thus, there is a strong scientific rationale for combining avutometinib (to inhibit RAF and MEK to block the MAPK pathway) and defactinib (to inhibit FAK to reduce stromal density and adaptive resistance to avutometinib) to the standard of care gemcitabine/Nab-paclitaxel regimen with the objective of increasing response rate and survival. In preclinical models of pancreatic cancer, this combination of avutometinib and FAK inhibition with gemcitabine and paclitaxel has been shown to induce strong tumor regression.

Avutometinib and defactinib in combination with standard of care chemotherapy (gemcitabine and Nab-paclitaxel) are being evaluated in patients with previously untreated advanced PDAC in the RAMP 205 clinical trial. RAMP 205 is a multicenter, open-label, single-arm Phase 1b/2a study designed to evaluate the safety, tolerability and efficacy of the combination at different doses and schedules to determine the recommended RP2D. We received the first “Therapeutic Accelerator Award” from Pancreatic Cancer Network (“PanCAN”) for up to $3.8 million to support the RAMP 205 study.

In May of 2025, we announced an update on the RAMP 205 trial and that we selected our RP2D as DL1. In the update, DL1 demonstrated a confirmed ORR of 83% (10/12) in patients. Adverse events across all dose cohorts

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remained generally consistent with the previously announced safety and tolerability profile, and no new safety signals have emerged. We completed enrollment of 29 patients in an expansion cohort at the RP2D in 2025, and we expect to report an update on the safety and efficacy of this cohort in the first half of 2026.

VS-7375, an Oral KRAS G12D (ON/OFF) Inhibitor

VS-7375 is a potential best-in-class, potent, and selective oral KRAS G12D dual ON/OFF inhibitor. VS-7375 has a differentiated profile compared to other RAS inhibitors. Based on preclinical data, VS-7375 offers dual, potent inhibition of both ON and OFF states of KRAS G12D. We believe this correlates with better in vivo efficacy and durability versus ON-only RAS inhibitors. VS-7375 has demonstrated a high affinity for KRAS G12D with long residence time (18-24 hours) in preclinical models. We believe this correlates with a more rapid and durable suppression of pERK signaling (which controls growth and cell survival) when compared to other ON-only KRAS G12D inhibitors in tumor cell lines. The selective inhibition of VS-7375 to KRAS G12D has shown, in preclinical models, to spare T cell proliferation to maintain a normal healthy immune response, versus a RAS-multi-inhibitor which impairs T cell proliferation at increasing concentrations of drug. The once daily oral dosing of VS-7375 achieves exposures corresponding to maximal tumor regressions across preclinical models for pancreatic, lung and colorectal cancers.

VS-7375 Licensing

VS-7375 is the lead program from the discovery and development collaboration with GenFleet. We exercised the GenFleet Option (defined herein) in January 2025, announced that our IND application for VS-7375 had been approved by the FDA in April 2025, and initiated a Phase 1/2a clinical trial in June 2025.

GenFleet is developing VS-7375 as GFH375 in greater China. GenFleet’s IND for GFH375 was approved in China in June 2024, and the first patient was dosed in a Phase 1/2 study in July 2024. To date, GenFleet has generated data in more than 150 patients with PDAC, NSCLC, and other solid tumor cancers, and reported initial positive safety and anti-tumor activity in 2L PDAC (58.3% ORR in 12 patients) and 2L NSCLC (68.8% ORR in 16 patients).

GenFleet also has an ongoing Phase 1/2b trial of GFH375 in combination with cetuximab or chemotherapy in KRAS G12D-mutated solid tumors in China. The chemotherapy combination will be conducted in 1L PDAC. GenFleet is also conducting a Phase 3 trial in China evaluating GFH375 in patients with pretreated KRAS G12D-mutated metastatic pancreatic cancer.

VS-7375-101 Phase 1/2 Clinical Trial KRAS G12D Solid Tumors

In June 2025, we dosed the first patient in the monotherapy portion of VS-7375-101, the U.S. Phase 1/2 clinical trial evaluating VS-7375 in patients with advanced KRAS G12D mutant solid tumors, including PDAC, NSCLC, CRC and other KRAS G12D mutated solid tumors. We continue to make progress with the VS-7375-101 trial, which includes both monotherapy and combination dose escalation and dose expansion cohorts.

VS-7375-101 Phase 1/2b Monotherapy Dose Escalation and Dose Expansion Phases

In the monotherapy dose escalation phase, we cleared the 400 mg, 600 mg, and 900 mg daily dose levels with no DLTs and no major toxicities. We reported early safety data that showed limited nausea and vomiting through feeding patients and using standard prophylaxis treatments. We also addressed diarrhea quickly with standard oral agents. Promising anti-tumor activity was observed in patients with various solid tumors, including metastatic PDAC.

We initiated dose expansion cohorts with the 600 mg QD dose and are increasing enrollment across three different cohorts: 2L PDAC, 2L/3L NSCLC, and other 2L+ KRAS G12D mutated solid tumors.

We plan to report early data from the VS-7375-101 trial in the first half of 2026.

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VS-7375-101 Phase 1/2b Combination Dose Escalation and Dose Expansion Phases

In our combination cohorts, we are enrolling patients into three different dose escalation cohorts, including 2L+ solid tumors in combination with cetuximab, 1L NSCLC in combination with carboplatin/pemetrexed /pembrolizumab, and 2L PDAC in combination with gemcitabine and Nab-paclitaxel.

We cleared the 400 mg QD dose and 600 mg QD dose of VS-7375 in combination with cetuximab and higher doses are now being evaluated.

In our dose expansion cohorts, we plan to continue to evaluate VS-7375 alone and in combination with cetuximab in 2L+ CRC. We also plan to continue to evaluate VS-7375 with chemotherapy or immunotherapy in 1L NSCLC and move into the 1L PDAC setting in combination with chemotherapy.

VS-7375 Regulatory Pathway

In July 2025, the FDA granted FTD to VS-7375, for 1L treatment of patients with KRAS G12D-mutated locally advanced or metastatic PDAC and for the treatment of patients with KRAS G12D-mutated locally advanced or metastatic PDAC who have received at least one prior line of standard systemic therapy.

Based on recent FDA feedback, we plan to amend the VS-7375-101 Phase 1/2 protocol to breakout disease specific Phase 2 registration-directed trials for KRAS G12D mutated 2L PDAC, 2L/3L NSCLC and 2L+ CRC. Our development focus is on the highest unmet need populations, and we plan to expedite regulatory submissions as quickly as possible.

Market Opportunity in U.S. for PDAC, NSCLC, CRC KRAS G12D Tumors

KRAS G12D represents 26% of all KRAS mutations, making it the most prevalent KRAS mutation in human cancers. The KRAS G12D mutation occurs most commonly in pancreatic (40%), colorectal (15%), non-small cell lung (5%) and other cancers such as endometrial (5%), biliary tract cancer (7-15%) and small bowel cancer (16%). Across the various KRAS G12D-mutated cancers, the KRAS G12D mutation often correlates with worse outcomes. In pancreatic cancer, it is associated with shorter survival and a higher risk of progression. In lung cancer, the KRAS G12D mutation is a significant driver of the disease, especially among non-smokers and is linked to poor responses to standard of care. In colorectal cancer, which is impacting younger populations, the KRAS G12D mutation is often linked to aggressive tumors. Overall, the KRAS G12D mutation appears across many types of cancer and remains an unmet medical need.

According to external sources, market research, and internal analyses and calculations, we estimate the potential addressable market in KRAS G12D-mutated cancers at launch in the U.S. represents a multi-billion dollar opportunity with the ability to treat approximately 40,000 patients annually across either 1L or 2L treatment (with or without combination treatments) in PDAC, NSCLC, CRC and other solid tumors.

Currently, no therapies are approved in the U.S., Europe or Japan, specifically targeting KRAS G12D mutations in cancer.

INTELLECTUAL PROPERTY

We strive to protect the proprietary technology that we believe is important to our business, including seeking and maintaining patents intended to cover our product candidates and compositions, their methods of use and processes for their manufacture, and any other aspects of inventions that are commercially important to the development of our business. We also rely on trade secrets to protect aspects of our business that are not amenable to, or that we do not consider appropriate for, patent protection.

We plan to continue to expand our intellectual property estate by filing patent applications directed to compositions, methods of treatment, and patient selection created or identified from our ongoing development of our product candidates. Our success will depend on our ability to obtain and maintain patent and other proprietary protection for

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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 and enforceable patents and proprietary rights of third parties. We also rely on know-how, continuing technological innovation, and in-licensing opportunities to develop and maintain our proprietary position. We seek to obtain domestic and international patent protection, and endeavor to promptly file patent applications for new commercially valuable inventions.

The patent positions of biopharmaceutical companies like us are generally uncertain and involve complex legal, scientific and factual questions. In addition, the coverage claimed in a patent application can be significantly reduced before the patent is issued, and patent scope can be reinterpreted by the courts after issuance. Moreover, many jurisdictions permit third parties to challenge issued patents in administrative proceedings, which may result in further narrowing or even cancellation of patent claims. We cannot predict whether the patent applications we are currently pursuing will issue as patents in any particular jurisdiction or whether the claims of any issued patents will provide sufficient protection from competitors.

Because patent applications in the U.S. and certain other jurisdictions are maintained in secrecy for 18 months or potentially even longer, and because publication of discoveries in the scientific or patent literature often lags behind actual discoveries, we cannot be certain of the priority of inventions covered by pending patent applications. Moreover, we may have to participate in interference proceedings or derivation proceedings declared by the U.S. Patent and Trademark Office to determine priority of invention.

Patents

As of December 31, 2025, our patent portfolio includes issued and pending patent applications worldwide. These patents and patent applications fall into three categories: (1) the RAF/MEK inhibition program; (2) the FAK inhibition program, and (3) KRAS inhibition program.

RAF/MEK inhibition program (avutometinib)

We have exclusively licensed a patent portfolio of four patent families that are owned or exclusively licensed by Chugai and therefore we have an exclusive option to exclusively license either directly from Chugai or from any party that has an exclusive license from Chugai. The first patent family has claims directed to the composition of matter of avutometinib, and includes granted patents in various jurisdictions, such as the U.S., Australia, Brazil, Canada, China, Europe (validated in several countries), Japan, Korea, Israel, and New Zealand that are expected to expire in February of 2027, without giving effect to any potential patent term extensions and patent term adjustments and assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees. The second patent family has claims directed to methods of making avutometinib and includes granted patents in Europe, Japan, and the U.S. that are expected to expire in September of 2032, without giving effect to any potential patent term extensions and patent term adjustments and assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees. The third patent family has claims directed to a dosing protocol of avutometinib, and includes two granted patents in the United States, that are expected to expire in November of 2038, granted patents in Australia, Europe, Korea, and Taiwan, and pending patent applications in various jurisdictions, such as Brazil, Canada, China, Europe, Hong Kong, Japan, Mexico, and Singapore. Patents that issue in this family will have a statutory expiration date in May of 2038, without giving effect to any potential patent term extensions and patent term adjustments and assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees. The fourth patent family covers a method of using avutometinib in combination with a FAK inhibitor, such as defactinib, for treating a patient, and includes two granted patents in the U.S. and granted patents in Japan, Hong Kong, Macau, Singapore, and Taiwan that are expected to expire in September of 2040, without giving effect to any potential patent term extensions and patent term adjustments and assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees, and pending patent applications in Australia, Brazil, Canada, China, Eurasia, Europe, Hong Kong, Indonesia, Japan, Korea, Mexico, Malaysia, New Zealand, Singapore, and the U.S.

In addition, we own one patent family covering solid forms of avutometinib, which includes two granted patents in the U.S. that are expected to expire in December of 2042, a pending patent application in the U.S., and pending foreign patent applications in various jurisdictions, such as Australia, Canada, China, Europe, Japen, Korea, and

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Singapore, that if issued are expected to expire in May of 2043, without giving effect to any potential patent term extensions and patent term adjustments and assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees. We also own eight patent families and co-own three patent families covering various methods of using a dual RAF/MEK inhibitor for treating a patient. Our eight patent families have claims directed to using a dual RAF/MEK inhibitor in combination with various therapeutic agents, such as a KRAS G12C inhibitors, KRAS G12D inhibitors, and immunotherapeutic agents for treating a patient, and have patent applications pending in various jurisdictions, such as Australia, Canada, China, Europe, and the U.S., that if issued would expire between 2041 and 2043, without giving effect to any potential patent term extensions and patent term adjustments and assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees. Our three co-owned patent families have claims directed to using a dual RAF/MEK inhibitor in combination with other therapeutics and including a pending US provisional application and patent applications pending in various jurisdictions, such as Australia, Canada, China, Europe, and the U.S., that if issued are expected to expire in 2042 to 2045, without giving effect to any potential patent term extensions and patent term adjustments and assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees.

FAK inhibition program (defactinib)

We have exclusively licensed a portfolio of patents owned by Pfizer, which are directed to FAK inhibitor compounds and methods of their use, for example in cancer. One patent family has claims directed to the composition of matter of defactinib, has a patent application pending in the United States, and patents granted in various jurisdictions, such as Australia, Canada, China, Europe (validated in various countries), Israel, Japan, Korea, Singapore, and the United States, that are expected to expire in April of 2028, without giving effect to any potential patent term extensions and patent term adjustments and assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees. For example, US 7,928,109 covers the composition of matter of defactinib specifically, and US 8,247,411 covers the composition of matter of defactinib generically. Also included are issued and pending patent applications having claims directed to methods of treatment and methods of making defactinib. For example, US 8,440,822 and US 10,450,297 cover methods of making defactinib.

In addition to the issued patents exclusively licensed from Pfizer, we own or co-own three patent families with claims directed to defactinib. One patent family is co-owned with Pfizer and has claims directed to compositions (e.g., oral dosage forms) of defactinib and certain methods of use. This family contains granted patents in various jurisdictions, such as Europe (validated in various countries), Australia, Brazil, Hong Kong, Israel, Japan, Korea, Mexico, New Zealand, and South Africa and pending patent applications in the United States, Brazil, China, Europe, Israel, and Japan. The patents and pending patent applications, if issued, are expected to expire in January of 2035, without giving effect to any potential patent term extensions and patent term adjustments and assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees. We own a second patent family with claims directed to methods of using a FAK inhibitor, such as defactinib, in combination with a MEK inhibitor for treating a patient. Patents in this family have been granted in the U.S., Japan, Hong Kong, and Europe, and are expected to expire in February 2035, without giving effect to any potential patent term extensions and patent term adjustments and assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees. We own a third patent family with claims directed to methods of using a FAK inhibitor, such as defactinib, in combination with an immunotherapeutic agent. Patent applications in this family have been granted in the U.S., Europe, Canada, China, Israel, and Mexico, and are expected to expire in June 2036, without giving effect to any potential patent term extensions and patent term adjustments and assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees. Patent applications in this family are also pending the U.S., Australia, Canada, China, Europe, Japan, and Singapore.

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KRAS inhibition program (VS-7375)

We in-licensed a patent portfolio from GenFleet, which includes four patent families directed to KRAS inhibitors. In regard to VS-7375, two patent families have claims directed to the composition of matter of VS-7375. One patent family includes patent applications pending in various jurisdictions, such as the United States, Europe, and Japan, that if issued would expire in August of 2042, without giving effect to any potential patent term extensions and patent term adjustments and assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees. The other patent family includes patent applications pending in various jurisdictions, such as Australia, Brazil, Canada, Europe, Japan, Korea, Mexico, and the U.S., that if issued, are expected to expire in September of 2043, without giving effect to any potential patent term extensions and patent term adjustments and assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees.

The other two patent families are directed to other KRAS inhibitors. One family includes patent applications in the U.S. and Europe, that if issued are expected to expire in April of 2042, without giving effect to any potential patent term extensions and patent term adjustments and assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees. The remaining family includes patent applications in various jurisdictions such as the U.S., Australia, Brazil, Canada, Europe, Japan, and Korea, that if issued are expected to expire in March of 2042, without giving effect to any potential patent term extensions and patent term adjustments and assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees.

Patent Term

The base term of a U.S. patent is 20 years from the filing date of the earliest-filed non-provisional patent application from which the patent claims priority. The term of a U.S. patent can be lengthened by patent term adjustment, which compensates the owner of the patent for administrative delays at the U.S. Patent and Trademark Office. In some cases, the term of a U.S. patent is shortened by terminal disclaimer that reduces its term to that of an earlier-expiring patent.

The term of a U.S. patent may be eligible for patent term extension under the Drug Price Competition and Patent Term Restoration Act of 1984, referred to as the Hatch-Waxman Act, to account for at least some of the time the drug is under development and regulatory review after the patent is granted. With regard to a drug for which FDA approval is the first permitted marketing of the active ingredient, the Hatch-Waxman Act allows for extension of the term of one United States patent that includes at least one claim covering the composition of matter of an FDA-approved drug, an FDA-approved method of treatment using the drug, and/or a method of manufacturing the FDA-approved drug. The extended patent term cannot exceed the shorter of five years beyond the non-extended expiration of the patent or 14 years from the date of the FDA approval of the drug. Some foreign jurisdictions, including Europe and Japan, have analogous patent term extension provisions, which allow for extension of the term of a patent that covers a drug approved by the applicable foreign regulatory agency.

LICENSES AND COMMERCIAL AGREEMENTS

GenFleet Therapeutics Inc.

On August 24, 2023, we entered into a collaboration and option agreement (the “GenFleet Agreement”) with GenFleet pursuant to which GenFleet granted us options to obtain exclusive development and commercialization rights worldwide outside of mainland China, Hong Kong, Macau, and Taiwan (the “Verastem Territory”) for up to three oncology programs targeting RAS pathway driven cancers (the “GenFleet Options”). We may exercise our GenFleet Options on a program-by-program basis. In December 2023, we announced the lead oncology discovery program is VS-7375, a potential best-in-class oral and selective KRAS G12D (ON/OFF) inhibitor.

In January 2025, we exercised our GenFleet Option with respect to VS-7375 and made a $6.0 million payment to GenFleet. In January 2025, we entered into a supply agreement with GenFleet pursuant to which GenFleet agreed to provide us with compound and licensed product for development use for VS-7375.

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We made an upfront payment of $2.0 million to GenFleet in September 2023 and will provide $1.5 million of research support over the first three years of the GenFleet Agreement. In addition, pursuant to the GenFleet Agreement, upon achievement of certain milestones, and upon us exercising its GenFleet Options, GenFleet will be entitled to receive payments of up to $622.0 million, inclusive of (i) up to $154.0 million upon achievement of certain development and commercialization milestones, (ii) up to $450.0 million upon achievement of certain sales milestones, and (iii) up to $18.0 million upon exercise of all three GenFleet Options. We paid GenFleet a $3.0 million milestone payment in the year ended December 31, 2024, upon GenFleet achieving a development milestone. We have also agreed to pay GenFleet royalties on net sales of licensed products in the Verastem Territory ranging from the mid to high single digits.

We may terminate the GenFleet Agreement in its entirety or on a program-by-program basis by providing 90 days’ written notice to GenFleet. Either party may terminate the GenFleet Agreement in its entirety or on a program-by-program and country-by-country basis, with 60 days’ written notice for the other party’s material breach if such party fails to cure the breach. Either party may also terminate the GenFleet Agreement in its entirety upon certain insolvency events involving the other party.

Secura Bio, Inc.

On August 10, 2020, we and Secura signed an Asset Purchase Agreement (the “Secura APA”) and on September 30, 2020, the transaction closed.

Pursuant to the Secura APA, we sold to Secura our exclusive worldwide license for the research, development, commercialization, and manufacture in oncology indications of products containing duvelisib. The sale included certain intellectual property related to duvelisib in oncology indications, certain existing duvelisib inventory, claims and rights under certain contracts pertaining to duvelisib. Pursuant to the Secura APA, Secura assumed all operational and financial responsibility for activities that were part of the duvelisib oncology program, including all commercialization efforts related to duvelisib in the United States and Europe, as well as our ongoing duvelisib clinical trials. Further, Secura assumed all obligations with existing collaboration partners developing and commercializing duvelisib, which include Yakult Honsha Co., Ltd. (“Yakult”), CSPC Pharmaceutical Group Limited (“CSPC”), and Sanofi. Additionally, Secura assumed all royalty payment obligations due under the amended and restated license agreement with Infinity Pharmaceuticals, Inc. (“Infinity”).

Pursuant to the terms of the Secura APA, Secura paid us an up-front payment of $70.0 million, and has agreed to pay us (i) regulatory milestone payments up to $45.0 million, consisting of a payment of $35.0 million upon receipt of regulatory approval of COPIKTRA in the United States for the treatment of peripheral T-cell lymphoma (“PTCL”) and a payment of $10.0 million upon receipt of the first regulatory approval for the commercial sale of COPIKTRA in the European Union for the treatment of PTCL, (ii) sales milestone payments of up to $50.0 million, consisting of $10.0 million when total worldwide net sales of COPIKTRA exceed $100.0 million, $15.0 million when total worldwide net sales of COPIKTRA exceed $200.0 million and $25.0 million when total worldwide net sales of COPIKTRA exceed $300.0 million, (iii) low double-digit royalties on the annual aggregate net sales above $100.0 million in the United States, European Union, and the United Kingdom of Great Britain and Northern Ireland and (iv) 50% of all royalty, milestone and sublicense revenue payments payable to Secura under our existing license agreements with Sanofi, Yakult, and CSPC, and 50% of all royalty, and royalty payments payable to Secura under any license or sublicense agreement entered into by Secura in certain jurisdictions. In the year ended December 31, 2024, Secura achieved $100.0 million of total worldwide net sales of COPIKTRA which triggered a $10.0 million milestone payment to us, which we received in July 2024.

Secura’s royalty obligations remain in effect on a country-by-country basis upon the last to occur (a) 10 years from the first commercial sale of product containing duvelisib in such country or (b) the expiration of all valid patent claims covering products containing duvelisib in such country.

In December 2021, Secura announced it had voluntarily withdrawn COPIKTRA (duvelisib) from the U.S. for treatment of patients with relapsed or refractory follicular lymphoma after at least two prior systemic therapies. On June 30, 2022, the FDA issued a drug safety communication warning that resulted from a clinical trial showing a possible increased risk of death with COPIKTRA compared to another medicine to treat chronic blood cancer called leukemia and lymphoma. The clinical trial also found that COPIKTRA was associated with a higher risk of serious

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side effects, including infections, diarrhea, inflammation of the intestines and lungs, skin reactions, and high liver enzyme levels in the blood. In September 2022, the FDA’s Oncologic Drug Advisory Committee (“ODAC”) voted eight to four against COPIKTRA’s use in patients with relapsed or refractory chronic lymphocytic leukemia/ small lymphocytic lymphoma after at least two prior therapies citing an unfavorable risk/benefit profile. In September 2022, Secura’s sublicensee, Yakult, announced it had withdrawn its NDA for duvelisib in Japan.

Chugai Pharmaceutical Co., Ltd.

On January 7, 2020, we entered into a license agreement with Chugai (the “Chugai Agreement”) whereby Chugai granted us an exclusive worldwide license for the development, commercialization, and manufacture of products containing avutometinib.

Under the terms of the Chugai Agreement, we received an exclusive right to develop and commercialize products containing avutometinib at our own cost and expense. In February 2020, we paid Chugai a non-refundable payment of $3.0 million. We are further obligated to pay Chugai double-digit royalties on net sales of products containing avutometinib, subject to reduction in certain circumstances. Chugai also obtained opt back rights to develop and commercialize avutometinib (a) in the European Union, and (b) in Japan and Taiwan. Chugai has communicated their intention not to exercise their opt back rights for Japan, Taiwan, or the European Union. Chugai and we have made customary representations and warranties and have agreed to certain customary covenants, including confidentiality and indemnification.

Unless earlier terminated, the Chugai Agreement will expire upon the fulfillment of our royalty obligations to Chugai for the sale of any products containing the avutometinib, which royalty obligations expire on a product-by-product and country-by-country basis, upon the last to occur, in each specific country, of (a) expiration of valid licensed patent claims covering such product or (b) 12 years from the first commercial sale of such product in such country.

We may terminate the Chugai Agreement upon 180 days’ written notice. Subject to certain limitations, Chugai may terminate the Chugai Agreement upon written notice if we challenge any patent licensed by Chugai to us under the Chugai Agreement. Either party may terminate the license agreement in its entirety with 120 days’ written notice for the other party’s material breach if such party fails to cure the breach. Either party may also terminate the Chugai Agreement in its entirety upon certain insolvency events involving the other party.

Pfizer Inc.

On July 11, 2012, we entered into a license agreement (the “Pfizer Agreement”) with Pfizer under which Pfizer granted us worldwide, exclusive rights to research, develop, manufacture and commercialize products containing certain of Pfizer’s inhibitors of FAK, including defactinib, for all therapeutic, diagnostic and prophylactic uses in humans. We have the right to grant sublicenses under the foregoing licensed rights, subject to certain restrictions. We are solely responsible, at our own expense, for the clinical development of these products, which is to be conducted in accordance with an agreed upon development plan. We are also responsible for all manufacturing and commercialization activities at our own expense. Pfizer provided us with an initial quantity of clinical supplies of one of the products for an agreed upon price.

Upon entering into the Pfizer Agreement, we made a onetime cash payment to Pfizer in the amount of $1.5 million and issued 16,001 shares of our common stock, adjusted for our Reverse Stock Split (defined herein). In April 2025, we entered into an amendment to the Pfizer Agreement such that a $7.5 million milestone became payable upon FDA approval of AVMAPKI FAKZYNJA CO-PACK on May 8, 2025 (the “First Pfizer Milestone”), and $8.0 million milestone (the “Second Pfizer Milestone”) is payable upon the one-year anniversary of the FDA approval of AVMAPKI FAKZYNJA CO-PACK. We made the First Pfizer Milestone payment in 2025 and expect to make the Second Pfizer Milestone payment in 2026. Pfizer is also eligible to receive up to $2.0 million in developmental milestones and up to an additional $110.0 million based on the successful attainment of regulatory and commercial sales milestones. Pfizer is also eligible to receive high single to mid-double-digit royalties on future net sales of the products. Our royalty obligations with respect to each product in each country begin on the date of first commercial sale of the product in that country, and end on the later of 10 years after the date of first commercial sale of the

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product in that country or the date of expiration or abandonment of the last claim contained in any issued patent or patent application licensed by Pfizer to us that covers the product in that country.

The Pfizer Agreement will remain in effect until the expiration of all our royalty obligations to Pfizer, determined on a product by product and country by country basis. So long as we are not in breach of the Pfizer Agreement, we have the right to terminate the license agreement at will on a product by product and country by country basis, or in its entirety, upon 90 days written notice to Pfizer. Either party has the right to terminate the Pfizer Agreement in connection with an insolvency event involving the other party or a material breach of the Pfizer Agreement by the other party that remains uncured for a specified period of time. If the Pfizer Agreement is terminated by either party for any reason, worldwide rights to the research, development, manufacture and commercialization of the products revert back to Pfizer.

COMPETITION

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

Many of our competitors may have significantly greater financial resources and expertise in research and development, manufacturing, preclinical testing, conducting clinical trials, obtaining regulatory approvals, and marketing approved products than we do. Mergers and acquisitions in the pharmaceutical, biotechnology, and diagnostic industries may result in even more resources being concentrated among a smaller number of our competitors. These competitors also compete with us in recruiting and retaining qualified scientific and management personnel and establishing clinical trial sites and patient registration for clinical trials, as well as in acquiring technologies complementary to, or necessary for, our programs. Smaller or early-stage companies may also prove to be significant competitors, particularly through collaborative arrangements with large and established companies.

The key competitive factors affecting the success of all our product candidates, if approved, are likely to be their efficacy, safety, side effects, convenience, price, the level of generic competition, and the availability of reimbursement from government and other third-party payors.

Our commercial opportunity could be reduced or eliminated if our competitors develop and commercialize products that are safer, more effective, have fewer or less severe side effects, are more convenient, or are less expensive than any products that we may develop. Our competitors also may obtain FDA or other regulatory approval for their products more rapidly than we may obtain approval for ours, which could result in our competitors establishing a strong market position before we are able to enter the market. In addition, our ability to compete may be affected in many cases by insurers or other third-party payors seeking to encourage the use of generic products. There are many generic products currently on the market for the indications that we are pursuing, and additional generic products are expected to become available over the coming years. If our therapeutic product candidates are approved, we expect that they will be priced at a significant premium over competitive generic products.

The most common methods of treating patients with cancer are surgery, radiation, and drug therapy, including chemotherapy, hormone therapy, immunotherapy, and targeted drug therapy. There are a variety of available drug therapies marketed for cancer. In many cases, these drugs are administered in combination to enhance efficacy. To the extent our product candidates are ultimately used in combination with or as an adjunct to existing drug or other therapies, our product candidates will not be competitive with them. Some of the currently approved drug therapies are branded and subject to patent protection, and others are available on a generic basis. Many of these approved drugs are well established therapies and are widely accepted by physicians, patients and third-party payors. In general, although there has been considerable progress over the past few decades in the treatment of cancer and the currently marketed therapies provide benefits to many patients, these therapies all are limited to some extent in their

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efficacy and frequency of adverse events, and none of them are successful in treating all patients. As a result, the level of morbidity and mortality from cancer remains high.

In addition to currently marketed therapies, there are also a number of products in late-stage clinical development to treat cancer. These products in development may provide efficacy, safety, convenience, and other benefits that are not provided by currently marketed therapies. As a result, they may provide significant competition for any of our product candidates for which we obtain market approval.

Several FDA-approved RAF and/or MEK inhibitors are commercially available; however, we are not aware of any products that are specifically approved for KRAS-mutated recurrent LGSOC. Competitors that are currently developing RAF and/or MEK inhibitors are Abbvie, AstraZeneca, Bristol Myers Squibb Company, Erasca, Genentech, Novartis AG, and Pfizer. Other competitors developing KRAS G12D inhibitors and pan-KRAS inhibitors are Astellas Pharma Inc., AstraZeneca, Bayer, BeOne, Boehringer Ingelheim, Chugai, D3 Bio, Eli Lilly, GenFleet, Genentech, Incyte Corporation, Jacobio, Jiangsu Hengrui Pharmaceuticals Company Ltd, Quanta Therapeutics, Ranok Therapeutics, Revolution Medicine, and Tyligand Bioscience; however, we are not aware of any FDA-approved treatments for the KRAS G12D mutation.

MANUFACTURING

We contract with third parties for the manufacture of our product candidates for preclinical studies, clinical trials, and commercial requirements and we intend to continue to do so in the future.

​

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Avutometinib

(AVMAPKI)

We work with one contract manufacturing organization (“CMO”) for the manufacture of avutometinib drug product, two CMOs for the production of avutometinib drug substance, and one CMO for avutometinib drug packaging/labeling.

Defactinib

(FAKZYNJA)

We have one CMO for the manufacture of defactinib drug product, one CMO for the production of defactinib drug substance, and one CMO for defactinib drug packaging/labeling.

VS-7375

We currently are party to a supply agreement with GenFleet pursuant to which we expect to obtain VS-7375 finished product from GenFleet. We are in the process of completing tech transfers with a two domestic CMO to onshore the manufacture of both drug substance and drug product of VS-7375 to the US.

​

We do not own or operate, and currently have no plans to establish, any manufacturing facilities. We have supply agreements in place with these CMOs and we obtain drug substance, drug product and packaging/labeling services from these CMOs on a purchase order basis. We may elect to pursue relationships with other CMOs for manufacturing of drug product, drug substance, and packaging/labeling for later-stage clinical trials, commercialization or for risk management. We have personnel with pharmaceutical development and manufacturing experience who are responsible for the relationships with our CMOs.

​

All of our drug candidates are organic compounds of low molecular weight, generally called small molecules. We select compounds not only on the basis of their potential efficacy and safety, but also for their ease of synthesis and the reasonable cost of their starting materials. We expect to continue to develop drug candidates that can be produced cost-effectively at third-party CMOs.

APPLICABLE LAWS AND GOVERNMENT REGULATION

Government authorities in the U.S., at the federal, state and local level, and in other countries extensively regulate, among other things, the research, development, testing, manufacture, including any manufacturing changes, packaging, storage, recordkeeping, labeling, advertising, promotion, distribution, marketing, post-approval monitoring and reporting, import and export of pharmaceutical products, such as those we are developing.

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U.S. Drug Approval Process

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

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

●completion of preclinical laboratory tests, animal studies, and formulation studies in compliance with the FDA’s good laboratory practice regulations and applicable requirements for the humane use of laboratory animals or other applicable requirements;

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

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

●performance of adequate and well-controlled human clinical trials in accordance with good clinical practices (“GCP”) and other clinical-trial related regulations to establish the safety and efficacy of the proposed drug for each indication;

●submission to the FDA of an NDA and payment of user fees for FDA review of NDA;

●satisfactory completion of an FDA advisory committee review, if applicable;

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

●FDA review and approval of the NDA.

The U.S. Supreme Court’s June 28, 2024 decision in Loper Bright Enterprises v. Raimondo (“Loper”) overturned the longstanding Chevron doctrine under which administrative agencies, including the FDA, were entitled to deference in the interpretation of “ambiguous” federal statutes. The full impact of the Loper decision is not yet known, but it could lead to significant changes in FDA regulation of our business and the pharmaceutical industry.

Preclinical Studies

Before testing any product candidate in humans, the product candidate must undergo rigorous preclinical testing. Preclinical studies include laboratory evaluation of product chemistry and formulation, as well as in vitro and animal studies to assess the potential for adverse events and in some cases to establish a rationale for therapeutic use. The conduct of preclinical studies is subject to federal regulations and requirements. An IND sponsor must submit the results of the preclinical tests, together with manufacturing information, analytical data, any available clinical data or literature and plans for clinical studies, among other things, to the FDA as part of an IND. Some long-term preclinical testing, such as animal tests of reproductive adverse events and carcinogenicity, may continue after the IND is submitted. An IND automatically becomes effective thirty days after receipt by the FDA, unless before that time the FDA raises concerns or questions related to one or more proposed clinical trials and places the trial on clinical hold. In such a case, the IND sponsor and the FDA must resolve any outstanding concerns before the clinical trial can begin. As a result, submission of an IND may not result in the FDA allowing clinical trials to commence.

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Clinical Trials

Clinical trials involve the administration of the investigational new drug to human subjects under the supervision of qualified investigators in accordance with GCP requirements, which include, among other things, the requirement that all research subjects provide their informed consent in writing before their participation in any clinical trial. Clinical trials are conducted under written study protocols detailing, among other things, the objectives of the study, the parameters to be used in monitoring safety and the effectiveness criteria to be evaluated. A protocol for each clinical trial and any subsequent protocol amendments must be submitted to the FDA as part of the IND. In addition, an IRB at each institution participating in the clinical trial must review and approve the plan for any clinical trial before it commences at that institution, and the IRB must conduct continuing review. The IRB must review and approve, among other things, the study protocol and informed consent information to be provided to study subjects. An IRB must operate in compliance with FDA regulations. Information about certain clinical trials must be submitted within specific timeframes to the National Institutes of Health for public dissemination on their ClinicalTrials.gov website.

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

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

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

●Phase 3: The drug is administered to an expanded patient population in adequate and well-controlled clinical trials to generate sufficient data to statistically confirm the efficacy and safety of the product for approval, to establish the overall risk-benefit profile of the product and to provide adequate information for the labeling of the product.

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

Progress reports detailing the results of the clinical trials must be submitted at least annually to the FDA and more frequently if serious adverse events occur. Phase 1, Phase 2 and Phase 3 clinical trials may not be completed successfully within any specified period, or at all. Furthermore, the FDA or the sponsor may suspend or terminate a clinical trial at any time on various grounds, including a finding that the research subjects are being exposed to an unacceptable health risk. Similarly, an IRB can suspend or terminate approval of a clinical trial at its institution if the clinical trial is not being conducted in accordance with the IRB’s requirements or if the drug has been associated with unexpected serious harm to patients.

Marketing Approval

Assuming successful completion of the required clinical testing, the results of the preclinical and clinical studies, together with detailed information relating to the product’s chemistry, manufacture, controls and proposed labeling, among other things, are submitted to the FDA as part of an NDA requesting approval to market the product for one or more indications. Under federal law, the submission of most NDAs is additionally subject to a substantial application user fee, scheduled in 2026 to exceed $4.6 million, and the sponsor of an approved NDA is also subject to annual program fees, based on the number of approved products. These fees are typically adjusted annually. User fee statutory authority expires every five years. The PDUFA was re-authorized for an additional five years in 2022

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until 2027, and negotiations are underway to re-authorize PDUFA for fiscal years 2028 through 2032. Fee waivers are available in certain circumstances, including a waiver of the application fee for an orphan drug application.

The FDA conducts a preliminary review of all NDAs within the first 60 days after submission before accepting them for filing to determine whether they are sufficiently complete to permit substantive review. The FDA may request additional information rather than accept an NDA for filing. In this event, the application must be resubmitted with the additional information. The resubmitted application is also subject to review before the FDA accepts it for filing. Once the submission is accepted for filing, the FDA begins an in-depth substantive review. The FDA has agreed to specified performance goals in the review of NDAs. Under these goals, the FDA has committed to review most such applications for non-priority products within 10 months after accepting the application for filing, and most applications for priority review products, that is, drugs that the FDA determines represent a significant improvement over existing therapy, within six months after accepting the application for filing. The review process may be extended by the FDA for three additional months to consider certain information or clarification regarding information already provided in the submission. The FDA may also refer applications for novel drugs or products that present difficult questions of safety or efficacy to an advisory committee, typically a panel that includes clinicians and other experts, for review, evaluation and a recommendation as to whether the application should be approved. The FDA is not bound by the recommendations of an advisory committee, but it considers such recommendations carefully when making decisions.

Under the Pediatric Research Equity Act of 2003, as amended and reauthorized by the Food and Drug Administration Amendments Act of 2007 (“FDAAA”), an NDA or supplement to an NDA must contain data that are adequate to assess the safety and effectiveness of the drug for the claimed indications in all relevant pediatric subpopulations, and to support dosing and administration for each pediatric subpopulation for which the product is safe and effective. The FDA may, on its own initiative or at the request of the applicant, grant deferrals for submission of some or all pediatric data until after approval of the product for use in adults, or full or partial waivers from the pediatric data requirements. Unless otherwise required by regulation, the pediatric data requirements do not apply to products with orphan drug designation.

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

The testing and approval process requires substantial time, effort and financial resources, and each may take many years to complete. Data obtained from clinical activities are not always conclusive and may be susceptible to varying interpretations, which could delay, limit or prevent regulatory approval. The FDA may not grant approval on a timely basis, or at all. We may encounter difficulties or unanticipated costs in our efforts to develop our product candidates and secure necessary governmental approvals, which could delay or preclude us from marketing our products.

After the FDA’s evaluation of the NDA and inspection of the manufacturing facilities, the FDA may issue an approval letter or a complete response letter. An approval letter authorizes commercial marketing of the drug with specific prescribing information for specific indications. A complete response letter generally outlines the deficiencies in the submission and may require substantial additional testing or information in order for the FDA to reconsider the application. If the FDA issues a complete response letter, the applicant may either resubmit the NDA, addressing all of the deficiencies identified in the letter, or withdraw the application. If and when those deficiencies have been addressed to the FDA’s satisfaction in a resubmission of the NDA, the FDA will issue an approval letter. The FDA has committed to reviewing such resubmissions in two to six months depending on the type of information included. Even with submission of this additional information, the FDA ultimately may decide that the application does not satisfy the regulatory criteria for approval and refuse to approve the NDA.

Even if the FDA approves a product, it may limit the approved indications for use for the product, require that contraindications, warnings or precautions be included in the product labeling, require that post-approval studies, including Phase 4 clinical trials, be conducted to further assess a drug’s safety after approval, require testing and surveillance programs to monitor the product after commercialization, or impose other conditions, including

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distribution restrictions or other risk management mechanisms, 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-market studies or surveillance programs. After approval, some types of changes to the approved product, such as adding new indications, manufacturing changes and additional labeling claims, are subject to further testing requirements and FDA review and approval.

Expedited Development and Review Programs

The FDA has various programs, including fast track designation, breakthrough therapy designation, priority review and accelerated approval, which are designed to expedite or facilitate the process for the development and FDA review of drugs and biologics that are intended for the treatment of serious or life-threatening diseases or conditions and demonstrate the potential to address unmet medical needs. The purpose of these programs is to provide important new drugs and biologics to patients earlier than under standard FDA review procedures.

●Fast Track Designation. To be eligible for a fast track designation, the FDA must determine, based on the request of a sponsor, that the product is intended for the treatment of a serious or life-threatening condition for which there is no effective treatment, and demonstrates the potential to address unmet medical needs for the condition. Under the fast track program, the sponsor of a new drug candidate may request the FDA to designate the product for a specific indication as a fast track product concurrent with or after the filing of the IND for the product candidate. The FDA must determine if the product candidate qualifies for fast track designation within 60 days after receipt of the sponsor’s request.

In addition to other benefits, such as the ability to use surrogate endpoints and have greater interactions with the FDA, the FDA may initiate review of sections of a fast track product’s NDA before the application is complete. This rolling review is available if the applicant provides and the FDA approves a schedule for the submission of the remaining information and the applicant pays applicable user fees. However, the FDA’s time period goal for reviewing a fast track application does not begin until the last section of the NDA is submitted. In addition, the fast track designation may be withdrawn by the FDA if the FDA believes that the designation is no longer supported by data emerging in the clinical trial process.

●Breakthrough Designation. A drug may be designated as a breakthrough therapy if the drug is intended to treat a serious or life-threatening disease or condition and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints. The breakthrough therapy designation provides all the benefits of the fast track program, including the eligibility for rolling review. The FDA may take certain administrative actions with respect to breakthrough therapies, including holding meetings with the sponsor throughout the development process, providing timely advice to the product sponsor regarding development and approval, involving more senior staff in the review process, assigning a cross-disciplinary project lead for the review team and taking other steps to aid sponsors in designing the clinical trials. Although breakthrough designation does not affect the regulatory standards for approval, the frequent interactions with the FDA may facilitate a more efficient development program. In addition, the breakthrough designation may be withdrawn by the FDA if the FDA believes that the drug no longer meets the conditions for qualification.

●Priority Review. Under FDA policies, a product candidate may be eligible for priority review, or review within a six-month time frame, compared to the ten-month time frame for a standard review, from the time a complete application is accepted for filing. Products regulated by the FDA’s Center for Drug Evaluation and Research (“CDER”) are eligible for priority review if they provide a significant improvement compared to marketed products in the treatment, diagnosis or prevention of a disease.

●Accelerated Approval. Under the FDA’s accelerated approval regulations, the FDA may approve a drug for a serious or life-threatening illness that provides meaningful therapeutic benefit to patients over existing treatments based upon a surrogate endpoint that is reasonably likely to predict clinical benefit. In clinical trials, a surrogate endpoint is a measurement of laboratory or clinical signs of a disease or condition that substitutes for a direct measurement of how a patient feels, functions or survives. Surrogate endpoints can often be measured more easily or more rapidly than clinical endpoints. A product candidate approved on

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this basis is subject to rigorous post-marketing compliance requirements, including the completion of one or more Phase 4 or post-approval clinical trials to confirm the effect on the clinical endpoint. Failure to conduct required post-approval studies or confirm a clinical benefit during post-marketing studies, would allow the FDA to withdraw the drug from the market on an expedited basis. The Food and Drug Omnibus Reform Act of 2022 (“FDORA”) signed by President Biden on December 29, 2022 as part of the Consolidated Appropriations Act, 2023 (H.R. 2617) includes numerous reforms to the accelerated approval process for drugs and biologics and enables the FDA to require, as appropriate, that a post-approval study be underway prior to granting accelerated approval. FDORA also expands the expedited withdrawal procedures available to the FDA to allow the agency to use expedited procedures if a sponsor fails to conduct any required post-approval study of the product with due diligence. FDORA also adds the failure of a sponsor of a product approved under accelerated approval to conduct with due diligence any required post-approval study with respect to such product or to submit timely reports with respect to such product to the list of prohibited acts in the FDCA. All promotional materials for drug candidates approved under accelerated regulations are subject to prior review by the FDA.

Orphan Drugs

Under the Orphan Drug Act, the FDA may grant orphan drug designation to drugs intended to treat a rare disease or condition, which is generally defined as a disease or condition that affects fewer than 200,000 individuals in the U.S. 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. The first NDA applicant to receive FDA approval for a particular active ingredient to treat a particular disease with FDA orphan drug designation is entitled to a seven-year exclusive marketing period in the U.S. for that product, for that indication. During the seven-year exclusivity period, the FDA may not approve any other applications to market the same drug for the same orphan indication, except in limited circumstances, such as a showing of clinical superiority to the product with orphan drug exclusivity in that it is shown to be safer, more effective or makes a major contribution to patient care. Orphan drug exclusivity does not prevent the FDA from approving a different drug for the same disease or condition, or the same drug for a different disease or condition. The FDA has historically taken the position that the scope of orphan exclusivity aligns with the approved indication or use of a product, rather than the disease or condition for which the product received orphan designation. However, on September 30, 2021, the U.S. Court of Appeals for the 11th Circuit issued a decision in Catalyst Pharms., Inc. v. Becerra holding that the scope of orphan drug exclusivity must align with the disease or condition for which the product received orphan designation, even if the product’s approval was for a narrower use or indication. It remains to be seen how this decision affects orphan drug exclusivity going forward. Among the other benefits of orphan drug designation are tax credits for certain research and a waiver of the NDA application user fee.

The Hatch Waxman Act

Abbreviated New Drug Applications

In seeking approval for a drug through an NDA, applicants are required to list with the FDA each patent with claims that cover the applicant’s product or a method of using the product. Upon approval of a drug, each of the patents listed in the application for the drug is then published in the FDA’s Approved Drug Products with Therapeutic Equivalence Evaluations, commonly known as the Orange Book. Drugs listed in the Orange Book can, in turn, be cited by potential competitors in support of approval of an abbreviated New Drug Application (“ANDA”). Generally, an ANDA provides for marketing of a drug product that has the same active ingredients in the same strengths, dosage form and route of administration as the listed drug and has been shown to be bioequivalent through in vitro or in vivo testing or otherwise to the listed drug. ANDA applicants are not required to conduct or submit results of preclinical or clinical tests to prove the safety or effectiveness of their drug product, other than the requirement for bioequivalence testing. Drugs approved in this way are commonly referred to as “generic equivalents” to the listed drug and can often be substituted by pharmacists under prescriptions written for the original listed drug.

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The ANDA applicant is required to certify to the FDA concerning any patents listed for the approved product in the FDA’s Orange Book, except for patents covering methods of use for which the ANDA applicant is not seeking approval. Specifically, the applicant must certify with respect to each patent that:

●the required patent information has not been filed;

●the listed patent has expired;

●the listed patent has not expired, but will expire on a particular date and approval is sought after patent expiration; or

●the listed patent is invalid, unenforceable or will not be infringed by the new product.

A certification that the new product will not infringe the already approved product’s listed patents or that such patents are invalid or unenforceable is called a Paragraph IV certification. If the applicant does not challenge the listed patents or indicate that it is not seeking approval of a patented method of use, the ANDA application will not be approved until all the listed patents claiming the referenced product have expired.

If the ANDA applicant has provided a Paragraph IV certification to the FDA, the applicant must also send notice of the Paragraph IV certification to the NDA and patent holders once the ANDA has been accepted for filing by the FDA. The NDA and patent holders may then initiate a patent infringement lawsuit in response to the notice of the Paragraph IV certification. The filing of a patent infringement lawsuit within 45 days after the receipt of a Paragraph IV certification automatically prevents the FDA from approving the ANDA until the earlier of 30 months after the NDA or patent holder’s receipt of the Paragraph IV certification, expiration of the patent, settlement of the lawsuit or a decision in the infringement case that is favorable to the ANDA applicant.

The ANDA also will not be approved until any applicable non-patent exclusivity period, such as exclusivity for obtaining approval of a new chemical entity, for the referenced product has expired. Federal law provides a period of five years following approval of a drug containing no previously approved active moiety during which ANDAs for generic versions of those drugs cannot be submitted unless the submission contains a Paragraph IV challenge to a listed patent, in which case the submission may be made four years following the original product approval. Federal law provides for a period of three years of exclusivity during which the FDA cannot grant effective approval of an ANDA for the conditions of use covered by the exclusivity, but FDA requires as a condition of approval new clinical trials conducted by or for the sponsor. This three-year exclusivity period often protects changes to a previously approved drug product, such as a new dosage form, route of administration, combination or indication. Under the Best Pharmaceuticals for Children Act, federal law also provides that periods of patent and non-patent marketing exclusivity listed in the Orange Book for a drug may be extended by six months if the NDA sponsor conducts pediatric studies identified by the FDA in a written request. For written requests issued by the FDA after September 27, 2007, the date of enactment of the FDAAA, the FDA must grant pediatric exclusivity no later than nine months prior to the date of expiration of patent or non-patent exclusivity in order for the six-month pediatric extension to apply to that exclusivity period.

Combination Therapy

Combination therapy is a treatment modality that involves the use of two or more drugs to be used in combination to treat a disease or condition. If those drugs are combined in one dosage form, such as one pill, that is known as a fixed dose combination product, and it is reviewed pursuant to the FDA’s Combination Rule at 21 CFR 300.50 (“the Rule”). The Rule provides that two or more drugs may be combined in a single dosage form when each component contributes to the claimed effects and the dosage of each component (amount, frequency, duration) is such that the combination is safe and effective for a significant patient population requiring such concurrent therapy as defined in the labeling for the drug.

Not all combination therapy falls under the category of a fixed dose combination. For example, the FDA recognizes that two drugs in separate dosage forms and in separate packaging, that otherwise might be administered as monotherapy for an indication, also may be used in combination for the same indication. In 2013, the FDA issued

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guidance to assist sponsors that were developing the range of combination therapies that fall outside the category of fixed dose combinations. That guidance provides recommendations and advice on such topics as: (1) assessment at the outset whether two or more therapies are appropriate for use in combination; (2) guiding principles for nonclinical and clinical development of the combination; (3) options for regulatory pathways to seek marketing approval of the combination; and (4) post-marketing safety monitoring and reporting obligations. Given the wide range of potential combination therapy variations, the FDA indicated it intends to assess each potential combination on a case-by case basis and encouraged sponsors to engage in early and regular consultation with the relevant review division at the agency throughout the development process for its proposed combination.

Combination Products

The FDA regulates combinations of products that cross FDA centers, such as drug, biologic or medical device components that are physically, chemically or otherwise combined into a single entity, as a combination product. The FDA center with primary jurisdiction for the combination product will take the lead in the premarket review of the product, with the other center consulting or collaborating with the lead center.

The FDA’s Office of Combination Products (“OCP”) determines which center will have primary jurisdiction for the combination product based on the combination product’s “primary mode of action.” A mode of action is the means by which a product achieves an intended therapeutic effect or action. The primary mode of action is the mode of action that provides the most important therapeutic action of the combination product, or the mode of action expected to make the greatest contribution to the overall intended therapeutic effects of the combination product.

Often it is difficult for the OCP to determine with reasonable certainty the most important therapeutic action of the combination product. In those difficult cases, the OCP will consider consistency with other combination products raising similar types of safety and effectiveness questions, or which center has the most expertise to evaluate the most significant safety and effectiveness questions raised by the combination product.

A sponsor may use a voluntary formal process, known as a Request for Designation, when the product classification is unclear or in dispute, to obtain a binding decision as to which center will regulate the combination product. If the sponsor objects to that decision, it may request that the agency reconsider that decision.

Other Regulatory Requirements

Any drug manufactured or distributed by us pursuant to FDA approvals would be subject to extensive and continuing regulation by the FDA, including, among other things, requirements relating to recordkeeping, periodic reporting, product sampling and distribution, advertising and promotion and reporting of adverse experiences with the product. After approval, most changes to the approved product, such as adding new indications or other labeling claims are subject to prior FDA review and approval.

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-marketing testing, including Phase 4 clinical trials, and surveillance to further assess and monitor the product’s safety and effectiveness after commercialization. Regulatory approval of oncology products often requires that patients in clinical trials be followed for long periods to determine the overall survival benefit of the drug.

In addition, drug manufacturers and other entities involved in the manufacture and distribution of approved drugs are required to register their establishments with the FDA and state agencies and are subject to periodic unannounced inspections by the FDA and these state agencies for compliance with cGMP requirements. Changes to the manufacturing process are strictly regulated and often require prior FDA approval before implementation. FDA regulations also require investigation and correction of any deviations from cGMP and impose reporting and documentation requirements upon us and any third-party manufacturers that we may decide to use. Accordingly, manufacturers must continue to expend time, money and effort in the areas of production and quality control to maintain cGMP compliance.

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Once an approval is granted, the FDA may withdraw the approval if compliance with regulatory requirements and standards is not maintained or if problems occur after the product reaches the market. Later discovery of previously unknown problems with a product, including 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, imposition of post-market studies or clinical trials to assess new safety risks or imposition of distribution or other restrictions under a Risk Evaluation and Mitigation Strategy program. Other potential consequences include, among other things:

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

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

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

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

●consent decrees, corporate integrity agreements, injunctions or the imposition of civil or criminal penalties.

The FDA strictly regulates marketing, labeling, advertising and promotion of products that are placed on the market. Drugs may be promoted only for the approved indications and in accordance with the provisions of the approved label. The FDA and other agencies actively enforce the laws and regulations prohibiting the promotion of off-label uses, and a company that is found to have improperly promoted off-label uses may be subject to significant liability. The current administration announced in September 2025 that it intends to prioritize enforcement of pharmaceutical advertising requirements.

Additional Provisions

As part of the sales and marketing process, pharmaceutical companies frequently provide samples of approved drugs to physicians. The Prescription Drug Marketing Act (“PDMA”) imposes requirements and limitations upon the provision of drug samples to physicians, as well as prohibits states from licensing distributors of prescription drugs unless the state licensing program meets certain federal guidelines that include minimum standards for storage, handling and record keeping. In addition, the PDMA sets forth civil and criminal penalties for violations.

Other Healthcare Laws

In the U.S., pharmaceutical manufacturers are subject to numerous other federal, state and local laws designed to, for example, prevent fraud and abuse; prevent the causing of false claims to be submitted to government healthcare programs; promote transparency in interactions with others in the healthcare industry; regulate pricing of drugs; require reporting of drug prices and payment of rebates or offering of discounts to certain government programs and public and private payors; and protect the privacy of individual information. These laws are enforced by various federal and state enforcement authorities, including but not limited to, the U.S. Department of Justice, and individual U.S. Attorney offices within the Department of Justice, the U.S. Department of Health and Human Services (“HHS”), HHS’ various divisions, including but not limited to, the Centers for Medicare & Medicaid Services (“CMS”), and the Office of Inspector General, and state boards of pharmacy.

We may be subject to various federal and state laws pertaining to health care “fraud and abuse,” including anti-kickback laws and false claims laws, for activities related to past and future sales of any products reimbursable by third-party payors such as federal health care programs (including Medicare and Medicaid) or, in some cases, commercial health plans. Anti-kickback laws generally prohibit a pharmaceutical manufacturer from soliciting, offering, receiving, or paying anything of value to generate business, including the purchase, prescription or use of a particular drug. False claims laws generally prohibit anyone from knowingly and willingly presenting, or causing to be presented, any claims for payment for reimbursed drugs or services to third-party payors that are false or fraudulent.

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Laws and regulations have also been enacted by the federal government and various states to regulate the sales and marketing practices of pharmaceutical manufacturers with marketed products. The laws and regulations generally limit financial interactions between manufacturers and health care providers; require manufacturers to adopt certain compliance standards; require disclosure to the government and public of financial interactions; require disclosure of marketing expenditures or pricing information, regulate drug pricing and/or require the registration of pharmaceutical sales representatives. Many of these laws and regulations contain ambiguous requirements or require administrative guidance for implementation. Given the lack of clarity in laws and their implementation, any future activities (if we obtain approval and/or reimbursement from federal healthcare programs for our product candidates) could be subject to challenge.

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

Federal and state consumer protection and unfair competition laws and regulations broadly regulate marketplace activities and that potentially harm consumers and could apply to the activities of pharmaceutical manufacturers.

We may be subject to data privacy and security laws in the various jurisdictions in which we operate, obtain or store personally identifiable information. Numerous U.S. federal and state laws govern the collection, use, disclosure and storage of personal information. Various foreign countries also have, or are developing, laws governing the collection, use, disclosure and storage of personal information. Globally, there has been an increasing focus on privacy and data protection issues that may affect our business.

Efforts to ensure that our activities comply with applicable healthcare laws and regulations will involve substantial costs. Given the breadth of the laws and regulations, limited guidance for certain laws and regulations and evolving government interpretations of the laws and regulations, governmental authorities may possibly conclude that our business practices may not comply with such laws. If our operations are found to be in violation of any of these laws or any other governmental regulations that may apply to us, we may be subject to significant civil, criminal and administrative penalties, damages, fines, exclusion from government funded healthcare programs, such as Medicare and Medicaid, and the curtailment or restructuring of our operations. Further, defending against any such actions can be costly, time-consuming and may require significant personnel resources. Therefore, even if we are successful in defending against any such actions that may be brought against us, our business may be impaired.

Foreign Regulation

In order to market any product outside of the U.S., we would need to comply with numerous and varying regulatory requirements of other countries regarding safety and efficacy and governing, among other things, clinical trials, marketing authorization, commercial sales and distribution of our products. Regardless of our current FDA approval or any future FDA approvals we may obtain for a product, we would need to obtain the necessary approvals by the comparable regulatory authorities of foreign countries before we can commence clinical trials or marketing of the product in those countries. The approval process varies from country to country and can involve additional product testing and additional administrative review periods. The time required to obtain approval in other countries might differ from and be longer than that required to obtain FDA approval. Regulatory approval in one country does not ensure regulatory approval in another, but a failure or delay in obtaining regulatory approval in one country may negatively impact the regulatory process in others.

Pharmaceutical Coverage, Pricing and Reimbursement

Significant uncertainty exists as to the coverage and reimbursement status of new drug products. Sales of our product candidates, if approved, will depend, in part, on the extent to which the costs of the products will be covered by third-party payors, including government health programs such as Medicare and Medicaid, commercial health insurers and managed care organizations. The process for determining whether a payor will provide coverage for a drug product may be separate from the process for setting the price or reimbursement rate that the payor will pay for the drug product once coverage is approved. Third-party payors may limit coverage to specific drug products on an approved list, or formulary, which might not include all of the approved drugs for a particular indication.

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In order to secure coverage and reimbursement for any product that might be approved for sale, we may need to conduct expensive pharmacoeconomic studies in order to demonstrate the medical necessity and cost effectiveness of the product, in addition to the costs required to obtain FDA or other comparable regulatory approvals. We may also need to provide discounts to purchasers, private health plans or government healthcare programs. Our product candidates may not be considered medically necessary or cost effective. Even if covered, third-party payors may seek to control utilization of our products through various mechanisms (e.g., requiring a prescriber to obtain prior authorization from a health plan before the product will be covered by the health plan or establishing patient copays and deductibles that encourage use of other products over our products). A payor’s decision to provide coverage for a drug product does not imply that an adequate reimbursement rate will be approved. Third-party reimbursement may not be sufficient to enable us to maintain price levels high enough to realize an appropriate return on our investment in product development. Additionally, coverage and reimbursement for drug products can differ significantly from payor to payor. One third-party payor’s decision to cover a particular drug product or service does not ensure that other payors will also provide coverage for the drug product or will provide coverage at an adequate reimbursement rate.

Within the U.S., FDA-approved drugs could potentially be covered by various government health benefit programs as well as purchased by government agencies. The participation in such programs or the sale of products to such agencies is subject to regulation. The marketability of any of our approved products may suffer if the government and third-party payors fail to provide adequate coverage and reimbursement.

Medicaid is a joint federal and state program that is administered by the states for low income and disabled beneficiaries. Under the Medicaid Drug Rebate Program, participating manufacturers are required to pay a rebate for each unit of product reimbursed by the state Medicaid programs. The amount of the rebate for each product is set by law and may be subject to an additional discount if certain pricing increases more than inflation. State Medicaid programs and Medicaid managed care plans can seek additional “supplemental” rebates from manufacturers.

Medicare is a federal program that is administered by the federal government that covers individuals aged 65 and over, disabled individuals and certain other eligible individuals. Medicare Part D provides coverage to enrolled Medicare patients for self-administered drugs (i.e., drugs that do not need to be injected or otherwise administered by a physician). Medicare Part D is administered by private prescription drug plans approved by the U.S. government and each drug plan establishes its own Medicare Part D formulary for prescription drug coverage and pricing, which the drug plan may modify from time-to-time. The prescription drug plans negotiate rebates and other discounts with manufacturers and may condition formulary placement on the availability of manufacturer discounts. Manufacturers with marketed brand name drugs may be asked to provide discounts on brand name prescription drugs utilized by Medicare Part D beneficiaries in order for a given prescription drug plan to cover the manufacturer’s drug. Under a new manufacturer discount drug program that became effective January 1, 2025, manufacturers pay 10% of the allowed cost of the drug after a Medicare beneficiary has met the standard deductible until the beneficiary reaches the annual out-of-pocket cap ($2,100) and then 20% of the allowed cost of the drug. Additionally, as the result of recent changes under the Inflation Reduction Act of 2022 (“IRA”), drug utilization under Medicare Part B and Part D may be subject to an additional Medicare discount if the pricing increases more than inflation.

Drug products are subject to discounted pricing when purchased by federal agencies via the Federal Supply Schedule (“FSS”). FSS participation is required for a drug product to be covered and reimbursed by certain federal agencies and for coverage under the Medicaid Drug Rebate Program and Medicare Part B. FSS pricing is negotiated periodically with the Department of Veterans Affairs. FSS pricing is subject to statutory reporting requirements and is negotiated periodically with the Department of Veterans Affairs, including by reference to a manufacturer’s comparable non-federal customer pricing. In addition, prices for drugs purchased by the Veterans Administration (“VA”), Department of Defense (including drugs purchased by military personnel and dependents through the TRICARE retail pharmacy program), Coast Guard, and Public Health Service (“PHS”) through the FSS are subject to a cap on pricing (known as the “federal ceiling price”) and may be subject to an additional discount if pricing increases more than the rate of inflation.

To maintain coverage of drugs under the Medicaid Drug Rebate Program and Medicare Part B, manufacturers are required to participate in and extend discounts to certain purchasers under the PHS pharmaceutical pricing program.

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Purchasers eligible for discounts include hospitals that serve a disproportionate share of financially needy patients, community health clinics and other entities that receive health services grants from the PHS.

The containment of healthcare costs has become a priority for federal, state and foreign governments, and the prices of drugs have been a focus in this effort. Third-party payors are increasingly challenging the prices charged for medical products and services and examining the medical necessity and cost effectiveness of medical products and services, in addition to their safety and efficacy. If these third-party payors do not consider our products to be cost effective compared to other available therapies, they may not cover our products after approval as a benefit under their plans or, if they do, the level of payment may not be sufficient to allow us to sell our products at a profit. Federal and state governments in the U.S. as well as foreign governments have shown significant interest in implementing cost containment programs to limit the growth of government paid healthcare costs, including price controls, restrictions on reimbursement and requirements for substitution of generic products for branded prescription drugs. Adoption of such controls and measures, and tightening of existing controls and measures, could limit payments for pharmaceuticals such as the drug candidates that we are developing and could adversely affect our net revenue and results.

Pricing and reimbursement schemes vary widely from country to country. Some countries provide that drug products may be marketed only after a reimbursement price has been agreed. Some countries may require the completion of additional studies that compare the cost effectiveness of a particular product candidate to currently available therapies. For example, the European Union provides options for its member states to restrict the range of drug products for which their national health insurance systems provide reimbursement and to control the prices of medicinal products for human use. European Union member states may approve a specific price for a drug product or may instead adopt a system of direct or indirect controls on the profitability of the company placing the drug product on the market. Other member states allow companies to fix their own prices for drug products but monitor and control company profits. The downward pressure on healthcare costs in general, particularly prescription drugs, has become very intense. As a result, increasingly high barriers are being erected to the entry of new products. In addition, in some countries, cross border imports from low-priced markets exert competitive pressure that may reduce pricing within a country. There can be no assurance that any country that has price controls or reimbursement limitations for drug products will allow favorable reimbursement and pricing arrangements for any of our products.

The marketability of products for which we may receive regulatory approval for commercial sale may suffer if the government and private third-party payors fail to provide adequate coverage and reimbursement, seek to control utilization, or create pressure to provide price concessions, coverage policies, third-party reimbursement rates and drug pricing regulation may change at any time. Even if favorable coverage and reimbursement status is attained for a product, less favorable coverage policies and reimbursement rates may be implemented in the future.

New Legislation and Regulations

From time to time, legislation is drafted, introduced and passed in the U.S. Congress that could significantly change the statutory provisions governing the testing, approval, manufacturing and marketing of pharmaceutical products. For example, in 2016, Congress enacted and President Obama signed into law the 21st Century Cures Act that amends a number of sections of the FDCA. Additionally, in December 2022, President Biden signed into law the Consolidated Appropriations Act, 2023 (H.R. 2617) that contains important reforms relevant to the FDA, including the FDORA and the Prepare for and Respond to Existing Viruses, Emerging New Threats, and Pandemics Act. In addition to new legislation, FDA regulations and policies are often revised or interpreted by the agency in ways that may significantly affect our business and our products. It is impossible to predict whether further legislative changes will be enacted or whether FDA regulations, guidance, policies or interpretations changed or what the effect of such changes, if any, may be.

Additionally, in the U.S., federal and state governments continue to propose and pass legislation designed to reform delivery of, or payment for, healthcare, which include initiatives to reduce the cost of healthcare generally and drugs specifically. For example, in 2010, Congress enacted the Patient Protection and Affordable Care Act and the Healthcare and Education Reconciliation Act (collectively, “ACA”), which expanded healthcare coverage through Medicaid expansion and the implementation of the individual mandate for health insurance coverage, and included changes to the coverage and reimbursement of drug products under government healthcare programs as well as the imposition of annual fees on manufacturers of branded pharmaceuticals.

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Beyond the ACA, there are ongoing and widespread healthcare reform efforts, a number of which have focused on regulation of prices or payment for drug products. Drug pricing and payment reform has been an ongoing focus. For example, the Inflation Reduction Act ("IRA") of 2022 includes several changes intended to address rising prescription drug prices in Medicare Parts B and D, with varying implementation dates. These changes include caps on Medicare Part D out-of-pocket costs, Medicare Part B and Part D drug price inflation rebates, a new Medicare Part D manufacturer discount drug program (replacing the prior Medicare Part D coverage gap discount program) and a drug price negotiation program for certain high spend Medicare Part B and D drugs (with the first set of negotiated Medicare maximum fair prices going into effect in 2026). The IRA has had a significant impact on the pharmaceutical industry and that impact is anticipated to continue.

Beyond the IRA, changes to Medicaid effective in 2024 eliminated the Medicaid rebate cap and changes to certain Medicare price reporting requirements for drugs beginning in 2026 will likely increase the administrative and compliance burden for manufacturers. In addition, recent legislation expanded the orphan drug exclusion in the IRA Medicare drug price negotiation program.

Under the current presidential administration, there has been significant reform activity focused on drug pricing and reimbursement. For example, President Trump issued an Executive Order in April 2025 with multiple directives aimed at lowering drug prices, including refining the Medicare drug price negotiation program established by the IRA, accelerating competition for high-cost prescription drugs by accelerating approval of generics and biosimilars and facilitating the process for re-classifying prescription drugs as over-the-counter drugs, and increasing drug importation. In May 2025, President Trump issued another Executive Order that directed government agencies and officials to identify most-favored nation pricing targets for prescription drugs (and looked to pharmaceutical manufacturers to make significant progress towards delivering target prices to patients), prevent foreign countries from disproportionately shifting the cost of global pharmaceutical research and development to the U.S., and facilitate direct-to-consumer purchasing programs for pharmaceutical manufacturers to sell their products to patients at the most-favored-nation price. In the wake of the Executive Orders and related executive initiatives, a number of pharmaceutical manufacturers have announced direct-to-consumer offerings with discounted prices and/or reached agreement with the federal government regarding pricing for drugs, including prices for Medicaid drugs and newly launched products. A future website sponsored by the federal government that is anticipated to offer pharmaceutical direct-to-consumer channels has also been announced. Federal agencies are developing new drug pricing pilot programs, such as a Medicaid model that would authorize the federal government to negotiate Medicaid supplemental rebates with participating manufacturers on behalf of state Medicaid programs, in exchange for standardized coverage criteria for participating manufacturer drugs, and proposed Medicare Part B and Part D pilot models that, if finalized as proposed, would replace existing inflation-based Medicare rebates with rebates determined on the basis of international prices, for drugs and patients subject to the model.

Other healthcare reform efforts or actions may affect access to healthcare coverage or the funding of health care benefits, although the full impact of such efforts or actions cannot be predicted. For example, the Congressional Budget Office has estimated that Medicaid provisions in the 2025 budget reconciliation legislation, including restrictions in eligibility and funding for Medicaid, as well as changes to the healthcare marketplace such as the elimination of certain subsidies, will increase the number of uninsured patients.

Individual states in the U.S. have also become increasingly active in passing legislation and implementing regulations designed to control pharmaceutical product pricing, including price and reimbursement constraints, restrictions on copayment assistance by pharmaceutical manufacturers, value-based pricing, marketing cost disclosure and other transparency measures, and, in some cases, measures designed to encourage importation from other countries and bulk purchasing.

Healthcare reform efforts have been and may continue to be subject to scrutiny, legal challenge and subsequent amendment, creating further uncertainty.

Other government actions could have an adverse effect upon, and could prevent, our products’ commercial success. For example, the Trump Administration’s announced tariff on branded or patented drugs may increase the cost of drug products that are imported from abroad or manufactured using products or materials imported from abroad. The timeline for implementation of this tariff has not yet been finalized. As another example, the Budget Control Act of 2011, as amended, resulted in the imposition of reductions in Medicare (but not Medicaid) payments to providers in

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2013 and remains in effect through 2032 unless additional Congressional action is taken. Any significant spending reductions affecting Medicare, Medicaid or other publicly funded or subsidized health programs that may be implemented and/or any significant taxes or fees that may be imposed on us could have an adverse impact on our results of operations.

Healthcare reform initiatives at the federal or state level could affect demand for, or pricing of, our product candidates if approved for sale. We cannot predict the ultimate content, timing or effect of any such reform. There is no assurance that healthcare reform will not adversely affect our future business and financial results.

HUMAN CAPITAL RESOURCES

We believe our employees are among the most important assets to our company and are key to achieving our goals and expectations. Accordingly, we focus significant attention on attracting and retaining talented individuals. To support these objectives, our human resources programs reflect our commitment to our core values (Purposeful, Unwavering, Influential, Insightful and Symbiotic) and are designed to prioritize our employees’ well-being, support their career goals, offer competitive wages and benefits, and enhance our culture through efforts aimed at making the workplace more satisfying, engaging and inclusive.

In order to attract qualified applicants to Verastem and retain such employees, we offer a total rewards package consisting of base salary and cash target bonus, a comprehensive benefit package, and equity compensation for every employee. Bonus opportunity and equity compensation increase as a percentage of total compensation based on level of responsibility. Actual bonus payout is based on our achievement of corporate goals and individual performance. In addition, many of our employees are stockholders of the company through participation in our Employee Stock Purchase Plan, which aligns the interests of our employees with our stockholders by providing stock ownership on a tax-deferred basis. We also provide for employer matching contributions equal to 100% of employee deferral contributions up to a deferral rate of 6% of eligible compensation to our Section 401(k) retirement savings plan.

As of December 31, 2025, we had 102 full time equivalent employees, including a total of 23 employees with M.D. or Ph.D. degrees, and two part-time employees. Of the full time equivalent employees, 56 employees were engaged in research and development activities. We consider the intellectual capital of our employees to be an essential driver of our business and key to our success. None of our employees are represented by a labor union or covered by a collective bargaining agreement. We consider our relationship with our employees to be good.

BUSINESS—EXECUTIVE OFFICERS OF THE REGISTRANT

The following table sets forth the name, age and position of each of our executive officers as of February 27, 2026.

Name

​ ​ ​

Age

​ ​ ​

Position

Executive Officers:

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​

​

​

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Daniel W. Paterson

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64

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President, Chief Executive Officer

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Michael Kauffman

​

62

​

President of Development

​

Daniel Calkins

​

38

​

Chief Financial Officer

​

Daniel W. Paterson, has served as our Chief Executive Officer since August 2023 and as our President since June 2019, in addition to serving as our Chief Operating Officer from December 2014 to July 2023, as our Chief Business Officer from July 2013 to December 2014 and as our Vice President, Head of Corporate Development and Diagnostics from March 2012 until July 2013. Prior to joining us in March 2012, Mr. Paterson was a consultant in 2011. From 2009 through 2010, Mr. Paterson was the Chief Operating Officer of On-Q-ity. Mr. Paterson was the President and Chief Executive Officer of The DNA Repair Company from 2006 until 2009, when it was acquired by On-Q-ity. Previously, he held senior level positions at IMS Health, CareTools, OnCare, and Axion. Mr. Paterson holds a B.A. in Biology from Boston University and attended the Northeastern University Graduate Pharmacology program.

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Michael Kauffman M.D., Ph.D., has served as our President of Development since December 2025 after serving as lead director of our board of directors since June 2016. Michael has been a member of our board of directors since November 2012 and continues to serve on our board of directors. Prior to his role as President of Development, he was the Chief Executive Officer, president and board member of Nereid Therapeutics Inc from November 2023 to November 2025. Prior to this, Dr. Kauffman was the cofounding Chief Executive Officer and acting Chief Medical Officer of Karyopharm Therapeutics Inc., a publicly traded commercial stage biotechnology company, from January 2011 to April 2021 and senior clinical advisor from May 2021 to May 2022. Prior to this, Dr. Kauffman was the Chief Medical Officer of Onyx Pharmaceuticals, Inc., a publicly traded biotechnology company, from November 2009 until December 2010. Dr. Kauffman received an M.D. and Ph.D. in molecular biology and biochemistry from Johns Hopkins University and holds a B.A. in biochemistry from Amherst College. Dr. Kauffman trained in Internal Medicine at Beth Israel Deaconess and rheumatology at Massachusetts General Hospitals, and is board certified in internal medicine.

Daniel Calkins, has served as our Chief Financial Officer since October 2023, prior to which Mr. Calkins served as our Vice President, Finance from September 2022 to October 2023, as our Corporate Controller from March 2020 to September 2022, as our Assistant Controller from May 2019 to March 2020, and as our Associate Director, SEC Reporting and Technical Accounting from December 2018 to May 2019. Prior to joining us in December 2018, Mr. Calkins held various positions of increasing responsibility at CFGI from May 2013 to December 2018. Prior to CFGI, Mr. Calkins began his career at PwC LLP in the assurance practice. Mr. Calkins holds a B.S. in Accounting from Bryant University and M.S. in Accounting from Northeastern University.

OUR CORPORATE INFORMATION

We were incorporated under the laws of the State of Delaware in August 2010. Our principal executive offices are located at 117 Kendrick Street, Suite 500, Needham, Massachusetts 02494 and our telephone number is (781) 292-4200.

ADDITIONAL INFORMATION

We maintain a website at www.verastem.com. We make available, free of charge on our website, our annual reports on Form 10-K, quarterly reports on Form 10-Q, current reports on Form 8-K and all amendments to those reports filed or furnished pursuant to Section 13(a) or 15(d) of the Securities Exchange Act of 1934, as amended (the “Exchange Act”) as soon as reasonably practicable after we electronically file those reports with, or furnish them to, the SEC. We also make available, free of charge on our website, the reports filed with the SEC by our executive officers, directors and 10% stockholders pursuant to Section 16 under the Exchange Act as soon as reasonably practicable after copies of those filings are provided to us by those persons. The information contained on, or that can be accessed through, our website is not a part of or incorporated by reference in this Annual Report on Form 10-K.

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