EX-99.1 2 tm2525447d1_ex99-1.htm EXHIBIT 99.1

Exhibit 99.1

 

Delivering Novel Therapies for RAS/MAPK Pathway Driven Cancers Corporate Presentation | September 2025

 

 

2 Forward - Looking Statements This presentation includes forward - looking statements about, among other things, Verastem Oncology’s (the “Company”) programs and product candidates, strategy, future plans and prospects, including statements relate d to the approval and commercialization of AVMAPKI FAKZYNJA CO - PACK ( avutometinib capsules; defactinib tablets) as a treatment for adult patients with KRAS - mutant recurrent Low - Grade Serous Ovarian Cancer (LGSOC), the expected outcome and benefits of collaborations, including with GenFleet Therapeutics (Shanghai), Inc. ( GenFleet ), including the conduct of a Phase 1/2a study with respect to VS - 7375 , the status of enrollments for and potential of the results of the RAMP 301 Phase 3 trial to confirm the results of the RAMP 201 study specific to KRAS mutant patients and to expand the indication regardless of KRAS mutation status, the structure of our planned and pending clinical trials, the potential cl in ical value of various of the Company's clinical trials, including the RAMP 201J, RAMP 203, RAMP 205 , RAMP 301 and VS - 7375 trials , the timing of commencing and completing trials, including topline data reports, interactions with regulators, the timeline and indications for clinical development, regulatory submissions, the potential for and timing of commercialization of product candidates and potential for additional development programs involving the Company’s l ead compound and the potential market opportunities of, and estimated addressable markets for, our drug candidates. The words "anticipate," "believe," "estimate," "expect," "may," "plan," "target," "potential," "would," "could," "should," "continue," “ca n” and similar expressions are intended to identify forward - looking statements, although not all forward - looking statements cont ain these identifying words. Each forward - looking statement is subject to risks and uncertainties that could cause actual results to diffe r materially from those expressed or implied in such statement. Applicable risks and uncertainties include the risks and uncertainties, among other things, regarding: the success in the dev elo pment and potential commercialization of our product candidates, including avutometinib in combination with other compounds, including defactinib , LUMAKRAS and others; the uncertainties inherent in research and development, such as negative or unexpected results of clin ica l trials, the occurrence or timing of applications for our product candidates that may be filed with regulatory authorities in any jurisdictions; whether and when regulatory authorities in any jurisdictions may approve any such applicati ons that may be filed for our product candidates, and, if approved, whether our product candidates will be commercially successfu l in such jurisdictions; our ability to obtain, maintain and enforce patent and other intellectual property protection for our pro duc t candidates; the scope, timing, and outcome of any legal proceedings; decisions by regulatory authorities regarding trial de sig n, labeling and other matters that could affect the timing, availability or commercial potential of our product candidates; whet her preclinical testing of our product candidates and preliminary or interim data from clinical trials will be predictive of the re sults or success of ongoing or later clinical trials; that the timing, scope and rate of reimbursement for our product candidates is u nce rtain; that the market opportunities of our drug candidates are based on internal and third - party estimates which may prove to b e incorrect; that third - party payors (including government agencies) may not reimburse; that there may be competitive developments affecting our product candidates; that data may not be available when expected; that enrollment of clinical trials may take l on ger than expected, which may delay our development programs, including delays in review by the U.S. Food and Drug Administration (FDA); the risk that our RAMP 301 trial may not confirm the results of the RAMP 201 trial specific to the use of AVMAPKI FAKZYNJA CO - PACK in adult patients with KRAS mutant recurrent LGSOC; the risks associated with preliminary and interim data, which may not be representative of more mature data, including with respect to in terim duration of therapy data; that our product candidates will cause adverse safety events and/or unexpected concerns may arise from additional data or analysis, or result in unmanageable safety profiles as compared to their levels of efficacy; that we may be unable to successfully validate, develo p a nd obtain regulatory approval for companion diagnostic tests for our product candidates that require or would commercially benef it from such tests, or experience significant delays in doing so; that the mature RAMP 201 data and associated discussions with the FDA may not support the scope of a new drug application submission for the avutometinib and defactinib combination in LGSOC including with respect to Kirsten rat sarcoma viral oncogene homolog (KRAS) wild - type (KRAS wt ); that our product candidates may experience manufacturing or supply interruptions or failures; that any of our third - party contract research organizations, c ontract manufacturing organizations, clinical sites, or contractors, among others, who we rely on fail to fully perform; that we face substantial competition, which may result in others developing or commercializing products before or more successfully than w e d o which could result in reduced market share or market potential for our product candidates; that we will be unable to successfully initiate or complete the clinical development and eventual commercialization of our product candidates; that th e d evelopment and commercialization of our product candidates will take longer or cost more than planned, including as a result of conducting additional studies or our decisions regarding execution of such commercialization ; that we may not have sufficient cash to fund our contemplated operations, including certain of our product development prog ram s; that we may not attract and retain high quality personnel; that we or Chugai Pharmaceutical Co., Ltd. may fail to fully perform under the avutometinib license agreement; that our total addressable and target markets for our product candidates might be smaller than we are pres en tly estimating; that we or Secura Bio, Inc. will fail to fully perform under the asset purchase agreement with Secura Bio, Inc., inc luding in relation to milestone payments; that we will not see a return on investment on the payments we have and may continu e t o make pursuant to the collaboration and option agreement with GenFleet , or that GenFleet will fail to fully perform under the agreement; that we may not be able to establish new or expand on existing collaborations o r partnerships, including with respect to in - licensing of our product candidates, on favorable terms, or at all; that we may be unable to obtain adequate financing in the fu ture through product licensing, co - promotional arrangements, public or private equity, debt financing or otherwise; that we will not pursue or submit regulatory filings for our product candidates; that, due to the recent change in presidential administration and the significant reduction in the FDA's workforce and potent ial reductions to the FDA's budget, we may experience a materially impact to the FDA's ability to engage in a variety of activities that may affect our business, including routine regulatory a nd oversight activities; and that our product candidates may not receive regulatory approval, become commercially successful products, or result in new treatment options being offered to patients. Other risks and uncertainties include those identified under the heading “Risk Factors” in the Company’s Annual Report on For m 1 0 - K for the year ended December 31, 2024 , as filed with the Securities and Exchange Commission (SEC) on March 20 , 2025 , and in any subsequent filings with the SEC, which are available at www.sec.gov and www.verastem.com. The forward - looking statements in this presentation speak only as of the original date of this presentation, and we undertake n o obligation to update or revise any of these statements whether as a result of new information, future events or otherwise, except as required by law. Use of Non - GAAP Financial Measures This presentation contains references to our non - GAAP operating expense, a financial measure that is not calculated in accordanc e with generally accepted accounting principles in the US (GAAP). This non - GAAP financial measure excludes certain amounts or expenses from the corresponding financial measures determined in accordance with GAAP. Management believes this non - GAAP informa tion is useful for investors, taken in conjunction with the Company’s GAAP financial statements, because it provides greater transparency and period - over - period comparability with respect to the Company’s operating performance and can enhance in vestors’ ability to identify operating trends in the Company’s business. Management uses this measure, among other factors, to assess and analyze operational results and trends and to make financial and operational decisions. Non - GAAP information is no t prepared under a comprehensive set of accounting rules and should only be used to supplement an understanding of the Company’s operating results as reported under GAAP, not in isolation or as a substitute for, or superior to, financial inform ati on prepared and presented in accordance with GAAP. In addition, this non - GAAP financial measure is unlikely to be comparable wit h non - GAAP information provided by other companies. The determination of the amounts that are excluded from non - GAAP financial mea sures is a matter of management judgment and depends upon, among other factors, the nature of the underlying expense or income amounts. Reconciliations between this non - GAAP financial measure and the most comparable GAAP financial measure are in cluded in the footnotes to the slides in this presentation on which such non - GAAP number appears. Third - Party Sources Certain information contained in this presentation, including industry and market data and other statistical information, rel ate s to or is based on studies, publications, surveys and other data obtained from third - party sources and the Company’s own intern al estimates and research. While the Company believes these third - party sources to be reliable as of the date of this presentation, it has not independently verified, and makes no representation as to the adequacy, fairness, accuracy or completeness of, any information obtained from third - party sources. In addition, all of the market data included in this presentation involves a numb er of assumptions and limitations, and there can be no guarantee as to the accuracy or reliability of such assumptions Disclaimers

 

 

3 3 Commercial Product and Pipeline Positioned to Deliver Long - Term Shareholder Value • Strong early execution of commercial launch • May 2025 approval of AVMAPKI FAKZYNJA CO - PACK, six weeks ahead of PDUFA action date • First - ever FDA - approved treatment specifically f or KRAS - mutated recurrent low - grade serous ovarian cancer (LGSOC) with listing as Category 2A in NCCN Guidelines • Advancing our novel, early - stage pipeline in RAS/MAPK pathway - driven cancers • VS - 7375, an oral KRAS G12D (ON/OFF) inhibitor: initiated Phase 1/2a trial in patients with advanced KRAS G12D mutant solid tumors outside of China; encouraging initial safety and efficacy results from partner in China • Maximizing the synergistic potential of avutometinib plus defactinib combination in other advanced solid tumors • RAMP 205: front - line metastatic pancreatic cancer; DL1 achieved confirmed ORR of 83% (10/12) • RAMP 203: advanced KRAS G12C mutant non - small cell lung cancer; no DLTs were observed in the triplet combination cohort • Existing cash, investments, and anticipated future product sales give us a strong financial position and runway into the second half of 2026 PDUFA: Prescription Drug User Fee Act; KR AS: Kirsten Rat Sarcoma Virus; MAPK: Mitogen - activated P rotein K inases; FDA: Food and Drug Administration; NCCN: National Comprehensive Cancer Network; DL: dose - level: ORR: objective response rate: DLT: dose - limiting toxicity

 

 

4 AVMAPKI FAKZYNJA CO - PACK Commercial Launch is Off to a Strong Start FDA Approved on May 8, 2025, Nearly Two Months Ahead of PDUFA action date RAS/MAPK Pathway Directed MOA • AVMAPKI offers dual inhibition of RAF and MEK • FAKZYNJA mediates drug resistance of activated RAF/MEK • Together, they offer a more complete blockade of the signaling that drives growth and drug resistance in the RAS/MAPK pathway Clinically Meaningful Response Rates and Long Duration of Treatment • 44% ORR, 3.3 to 31.1 months mDOR Manageable Safety Allows for Treatment Until Progression for Most Patients Convenient, Two Orally Dosed Treatments • Novel intermittent dosing schedules Please see the full Prescribing Information for more information Achieved net product revenue of $2.1 million In the first six weeks on the market MOA: Mechanism of Action; RAF: Rapidly Accelerated Fibrosarcoma; MEK, Mitogen - Activated Extracellular Signal - regulated Kinase; mDOR : median Duration of Response

 

 

5 Anticipated Milestones FDA Approved Phase 3 Phase 2 Phase 1 Regimen Trial Name/ Therapeutic Area Asset RAF/MEK Clamp + FAKi RAMP 201, recurrent LGSOC Avutometinib + Defactinib Complete planned enrollment in RAMP 301 by the end of 2025; Report IDMC outcome in Q4 2025 RAF/MEK Clamp + FAKi vs ICT RAMP 301, recurrent LGSOC Avutometinib + Defactinib Expect to report a preliminary update on the Phase 1 monotherapy dose escalation in Q4 2025 KRAS G12D (ON/OFF) inhibitor VS - 7375 - 101, Advanced solid tumors VS - 7375* Expect to complete enrollment in the expansion cohort in Q3 2025 RAF/MEK Clamp + FAKi + gemcitabine, nab - paclitaxel PanCAN Collaboration RAMP 205, 1L mPDAC Avutometinib + Defactinib Report an interim update in Q4 2025 RAF/MEK Clamp ± FAKi + KRAS G12Ci (sotorasib) Amgen Collaboration RAMP 203, advanced KRAS G12C NSCLC Avutometinib “ Defactinib FAKi: focal adhesion kinase inhibitor; ICT: investigator choice of treatment; NSCLC: non - small cell lung cancer; mPDAC : metastatic Pancreatic Ductal Adenocarcinoma; Our Pipeline: Addressing RAS/MAPK - Driven Cancers Not shown: *GenFleet Therapeutics has an ongoing Phase 1/2 clinical trial in China with VS - 7375, known as GFH375 in China. GenFleet retains greater China rights. Verastem has two undisclosed assets at discovery phase targeting the RAS/MAPK - pathway as part of the GenFleet collaboration.

 

 

6 x Reported updated data from the ongoing RAMP 205 trial and s elected dose level 1 cohort for recommended phase 2 dose (RP2D) x Close to completing enrollment in the expansion cohort of 29 patients at the RP2D RAMP 205: Avutometinib + Defactinib + SOC Chemotherapy in 1L mPDAC x Completed enrollment to the KRAS G12C inhibitor, prior - treated stage 1 part B doublet cohort x Completed enrollment in the planned dose level evaluation cohorts for the triplet combination RAMP 203: Avutometinib + Sotorasib ± Defactinib in KRAS G12C in advanced NSCLC Delivering on the Key R&D Milestones Set for 2025 Maximize the synergistic potential of avutometinib + defactinib in other advanced solid tumors x U.S. IND filed and cleared x Dosed first patient in Phase 1/2a trial in U.S. x GenFleet reported updated Phase 1 clinical data from China x Granted FDA Fast Track Designation in 1L and 2L mPDAC VS - 7375, Oral KRAS G12D (ON/OFF) Inhibitor Advance novel, early - stage pipeline R&D: Research and Development. IND: Investigational New Drug

 

 

7 Achieved All Key Milestones in 1H25, On Track To Deliver in 2H25 RAMP 301 Complete planned enrollment in the Phase 3 confirmatory study by the end of 2025. Report IDMC recommendation in Q4 2025. RAMP 201J Report initial data from Phase 2 clinical trial being conducted in Japan in Q4 2025. RAMP 203 Report an interim data update on both doublet and triplet combinations in Q4 2025. RAMP 205 Complete enrollment in the expansion cohort in Q3 2025. PRODUCT LAUNCH • Effectively reach HCPs • Engage with patients • Ensure seamless access VS - 7375 - 101 ​ Expect to report preliminary update on Phase 1 monotherapy dose escalation in Q4 2025. ​ Initiate various dose escalation combination cohorts in Q4 2025. IDMC: Independent Data Monitoring Committee; HCPs: health care professionals

 

 

8 Commercially launched in the U.S. for KRAS - mutated Recurrent LGSOC FDA Approval Date: May 8, 2025

 

 

9 1. AACR Genie v16.1; 2. Cheasley et al., J Pathol 2021; 3. Thomson et al., Gynecol Oncol 2023; 4. Gershenson et al., Gynecol Oncol 2022; 5. Coma et al., AACR 2022 ; 6. Ishii et al., Cancer Res, 2013 ; 7. Lito et al., Cancer Cell, 2014 ; 8. Lubrano et al., AACR 2024 ; 9. Banerji et al., AACR 2020 ; 10. Jones et al., Invest New Drugs 2015; 11. McNamara et al., Gynecol Oncol 2024 ; 12. Banerjee et al., ASCO 2023 Providing More Complete Blockade of the Signaling that Drives Growth and Resistance of RAS/MAPK Pathway - Dependent Tumors ERK: Extracellular Signal - regulated Kinase; FAK: Focal Adhesion Kinase; MEK, Mitogen - Activated Extracellular Signal - regulated Kinase; mTOR: Mammalian Target of Rapamycin; P: Phosphate; PI3K: Phosphatidylinositol 3 - Kinase; RAF: Rapidly Accelerated Fibrosarcoma; RAS: Rat Sarcoma Virus; RhoA: Ras Homolog Family Member A; RTK: Receptor Tyrosine Kinase; YAP: Yes - Associated Protein. • 70% of LGSOC tumors are driven by the RAS/MAPK pathway and about 30% of these have a KRAS mutation 1,2,3,4 • Avutometinib inhibits MEK kinase activity while blocking the compensatory reactivation of MEK by upstream RAF 5,6,7 • Blocking RAF and/or MEK activates FAK, a key mediator of drug resistance 8,9 • Defactinib, a FAK inhibitor, inhibits parallel pathway signaling 10,11,12 • Together, avutometinib plus defactinib offer more complete blockade of the signaling that drives the growth of RAS/MAPK pathway - dependent tumors RAF - MEK Complex Inhibited FAK The Combination of Avutometinib and Defactinib Induces Deeper Inhibition of Tumor Growth

 

 

10 High Unmet Need for an Effective and Tolerable Therapy in Recurrent LGSOC • U.S. incidence / prevalence : 1k - 2k 1 / 6k - 8k 2 • LGSOC affects younger women with bimodal peaks of diagnosis at ages between 20 - 30 and 50 - 60; disproportionately impacts health, fertility, and long - term quality of life 3,4 • 80 - 90% of patients will experience a recurrence 5 • Current standard of care offers low to moderate response rates (6 - 13%) 6,7,8 • Median overall survival (OS) of ~10 years from time of diagnosis 9: KRAS - mutated - ~12 years 10 and KRAS wild - type: ~7 years 10 1. Verastem DOF; 2. US Cancer Statistics. Accessed 2024 ; 3 . Slomovitz Gynecol Oncol 2020; 4. Manning - Geist B et al. Clin Cancer Res 2022;28(20):4456 - 4465; 5. Babaier 2022/p1/para1/ln6,7; 6. Gershenson Gynecol Oncol 2022; 7. Slomovitz Gynecol Oncol 2020; 8. Monk 2020/p3758/table2/footnote - b; 9 Banerjee SN). J Clin Oncol. 41. No 16_suppl (June 1, 2023) 5515 - 5515; 10. Manning - Geist B et al. Clin Cancer Res 2022;28(20):4456 - 4465; Calculated using figures in Gershenson Gynecol Oncol 2022. When you get told that you have a recurrence, the mental load is a lot . You’re thinking, okay, what did I have to do for treatment the first time? Now I have to repeat that . And will there even be something available for me to take for a second, or a third recurrence?

 

 

11 Laser - Focused on Three Strategic Imperatives to Drive a Successful Commercial Launch Effectively reach all healthcare providers Engage and support patients Ensure seamless access Top 100 commercial healthcare organizations contribute ~50% of patient claims 1 Patients likely to have progressed through other therapies, and many will be ready for a new treatment Support the patient to ensure any barriers to reimbursement are removed Surround Sound Support Programs HCPs PATIENTS ACCESS 1 VSTM DOF – Claims L G SOC Proxy

 

 

12 Encouraging Launch Momentum Reinforces Strategic Imperatives to Drive Success Achieved net product revenue of $2.1 million in the first six weeks on the market First patient received product: May 22, 2025 x First - ever approved treatment specifically for people living with KRAS - mutated recurrent LGSOC nearly two months in advance of PDUFA date x Urgent, unmet patient need and significant market opportunity x Experienced and energized field team x Two years of launch preparedness x High physician enthusiasm and engagement x Effective digital surround sound and high website traffic x Extensive payer education

 

 

13 Early Launch Performance Tracking as Expected x Prescriptions coming from a mix of academic and community physicians x Seeing both repeat prescriptions and refills x Payer mix is a combination of commercial and Medicare Effectively reach all healthcare providers Engage and support patients Ensure seamless access x Field team engaged with 93% of top 100 organizations x Medical Science Liaisons held 100+ meetings and hosted >30 educational forums x Branded healthcare professional website is seeing high traffic and downloads of enrollment forms x Branded patient website is seeing high traffic with significant patient brochure downloads x Prelaunch disease education website netted engagement with ~2,500 potential patients x NCCN listing as a Category 2A recommendation for approved indication x Payer coverage has been broad and time to payment fast x Verastem Cares® Program actively supporting patient needs

 

 

14 NCCN Submission for Treatment Guideline Inclusion Under Review for the Entire Population Enrolled in RAMP 201 Study NCCN Category 3 NCCN Category 2b NCCN Category 2a NCCN Category 1 General % Commercial Payer Coverage Binimetinib • Study stopped early due to futility • 16% ORR byBICR • 31% discontinuation rate due to AEs • Supported by MILO study 3 Hormonal therapy (e.g., Anastrozole, Letrozole) & chemotherapy • 6 - 13% ORR 4 • 17 - 30% discontinuation rate due to AEs 4 Trametinib (2 - 4% US utilization rate 1 ) • 26% ORR by INV assessment, no BICR 5 • 36% discontinuation rate due to AEs 5 No category 1 recommendation Examples of Clinical Data in LGSOC and Current NCCN Guideline Category General source: NCCN; McGivney Global Advisory research and analysis; L.E.K. research and analysis. NCCN categories of prefer enc e: Preferred intervention, Other recommended intervention, Useful in certain circumstances. High - level of evidence generally means large randomized controlled Phased 3 trials; Pie charts represent coverage by all major c ommercial players; 1. Data on File; 2. GOG 281 trial Gershenson et al., Lancet 2022; ​ 3. MILO Study Monk et al., J Clin Oncol 2020; 4. Supported by GOG 281 and MILO studies 2,3 ; 5. Supported by GOG 281 2 Current Listing: Avutometinib + Defactinib Combination Therapy • KRAS mt recurrent LGSOC

 

 

15 Continuing Medical Progress in LGSOC

 

 

16 Across Patients With and Without KRAS Mutations in RAMP 201, 82% had a Reduction in Target Lesions while Receiving Avutometinib and Defactinib Source for all data: RAMP 201 data cut off as of June 30, 2024; Responses for 3 patients (KRAS wild type, n=1; KRAS mutant, n =2) were unknown Best Overall Response

 

 

17 *US FDA analysis plan will evaluate PFS independently in KRAS - mt and KRAS wt LGSOC. BICR: blinded independent central review; BID: twice a day; BIW: twice a week; DCR: disease control rate; DoR : duration of response; INV: investigator; KRAS: kirsten rat sarcoma virus; MEKi : MEK inhibitor; mt: mutant; PO: per oral; pts, patients; ORR: objective response rate; OS: overall survival; PD: progressive di sease; PFS: progression - free survival; PROs: patient - reported outcomes; RECIST: response evaluation criteria in solid tumors; wt : wild type. RAMP 301: International Phase 3 Confirmatory Trial of Avutometinib + Defactinib in Recurrent LGSOC on Track for Full Enrollment by YE25 • Entry criteria similar to RAMP 201 patient population, KRAS mt and KRAS wt recurrent LGSOC; prior MEKi and bevacizumab use allowed and post at least one line of platinum chemotherapy • Study sites include the U.S., Canada, UK, Europe, Australia, New Zealand, Japan and South Korea Inclusion Criteria • Recurrent disease after prior platinum therapy • Documented KRAS mutation status • Measurable disease per RECIST v1.1 • Confirmed LGSOC diagnosis • Prior MEKi allowed • Prior bevacizumab allowed RAMP 301 (GOG - 3907/ENGOT - ov81/NCRI): Ongoing Randomized Controlled Trial (RCT) NCT06072781 Pegylated Liposomal Doxorubicin Paclitaxel Letrozole Anastrozole Investigator’s Choice n = 135 Avutometinib 3.2 mg PO BIW Defactinib 200 mg BID 3 weeks on, 1 week off Avutometinib + Defactinib n = 135 May cross over upon BICR - confirmed PD PFS (BICR by RECIST v1.1) Hierarchical Evaluation of PFS*: KRAS mutant LGSOC All recurrent LGSOC KRAS wt LGSOC Primary Endpoint: OS PFS by RECIST v1.1 per INV assessment ORR DoR DCR Safety Pharmacokinetics PROs Secondary Endpoints a a Unless otherwise specified, all tumor response - based endpoints will be analyzed using both BICR and INV assessments 1:1 Randomization n = 270 Stratification Factors: • KRAS mutation status ( wt vs. mt) • Geography (N. America/EU) vs. ROW • Number of prior therapies (1 - 3 vs. 4 or more)

 

 

18 Next Steps in LGSOC Clinical Program Report initial data from the RAMP 201J Phase 2 clinical trial being conducted in Japan in Q4 2025 Complete planned enrollment in RAMP 301 Phase 3 confirmatory study by end of 2025 Continue to advance regulatory pathway in Japan and Europe Announce outcome of IDMC recommendation for RAMP 301 in Q4 2025

 

 

VS - 7375, oral KRAS G12D (ON/OFF) Inhibitor 19

 

 

20 Adapted from Hofmann et al., Cancer Discovery 2022 • The only approved KRAS inhibitors target KRAS G12C, which is largely restricted to NSCLC • KRAS G12D accounts for 26% of all KRAS mutations • KRAS G12D mutations are especially prevalent in pancreatic and colorectal cancers • Targeting KRAS G12D has historically been challenging due to the shallow pocket for drug interaction and lack of a cysteine for covalent binding KRAS G12D is the Most Frequent KRAS Mutation in Human Cancers

 

 

21 *Piro Lito, RAS Initiative Conference 2024; GEF: Guanine nucleotide exchange factor; GAP: GTPase - activating protein; *Zhou et al ., AACR 2024 VS - 7375 is an Oral KRAS G12D (ON/OFF) Inhibitor VS - 7375 IC50 ( nM ) (KRAS G12D binding) KRAS G12D State 2 1 GppNHp - bound (ON/active) 6 1 GDP - bound (OFF/inactive) VS - 7375 is a dual inhibitor of ON (GTP) and OFF (GDP) states of KRAS G12D* Non - covalent inhibitor of KRAS G12D (ON/OFF) with potent anti - tumor efficacy across preclinical models • KRAS - GTP is the active (ON) state, which drives cancer growth • KRAS - GDP is the inactive (OFF) state and represents a KRAS pool that will cycle back to the active ON state • OFF - state selective agents (e.g., approved G12C inhibitors) may give sub - optimal efficacy because they do not target the active ON state • ON - state selective agents (e.g., RMC - 6236) can also drive GTP hydrolysis to the OFF state, which they can no longer bind* • May be ideal to have an inhibitor capable of targeting both the ON and OFF states of KRAS to maintain inhibition around the clock, aiming for maximum efficacy

 

 

22 VS - 7375 (G12D ON/OFF inhibitor) is more efficacious than G12D ON and pan - RAS ON inhibitors in KRAS G12D mutant tumor models KP4 Pancreatic Cancer Model LU0876 NSCLC PDX Model -100 0 100 200 500 1000 1500 2000 R e s p o n s e @ D a y 2 0 ( % c h a n g e f r o m b a s e l i n e ) v e h i c l e R M C - 9 8 0 5 1 0 0 m g / k g Q D V S - 7 3 7 5 5 0 m g / k g B I D 4 SDs R M C - 6 2 3 6 2 5 m g / k g Q D 8 PRs 4 SDs 0 10 20 30 0 500 1000 1500 2000 2500 Days after first dose T u m o r v o l u m e ( m m 3 + / - S E M ) Vehicle VS-7375 50 mg/kg BID RMC-9805 100 mg/kg QD RMC-6236 25 mg/kg QD vehicle RMC-9805 RMC-6236 VS-7375 -100 0 100 200 300 400 500 R e s p o n s e @ D a y 1 4 ( % c h a n g e f r o m b a s e l i n e ) v e h i c l e R M C - 9 8 0 5 1 0 0 m g / k g Q D V S - 7 3 7 5 3 0 m g / k g B I D 7 PRs 1 SD R M C - 6 2 3 6 2 5 m g / k g Q D 1 PR 2 SDs 2 PRs 4 SDs R M C - 9 8 0 5 6 0 m g / k g Q D V S - 7 3 7 5 1 0 0 m g / k g B I D 1 CR 7 PRs Equivalent daily dose Maximal dose 0 10 20 30 0 250 500 750 1000 1250 Days after first dose T u m o r v o l u m e ( m m 3 + / - S E M ) vehicle RMC-9805 RMC-6236 VS-7375 Vehicle VS-7375 30 mg/kg BID po RMC-9805 60 mg/kg QD po RMC-6236 25 mg/kg QD po LS513 Colorectal Cancer Model

 

 

23 GFH375 Demonstrated Encouraging Initial Efficacy in Lung and Pancreatic Cancers Source: GenFleet Therapeutics ASCO 2025 Rapid Oral Presentation June 2, 2025; A First - in - human Phase I/II Study of GFH375, a Highly Selective an d Potent Oral KRAS G12D Inhibitor in Patients in KRAS G12D Mutant Advanced Solid Tumors 52% ORR in PDAC, 100% DCR 42% ORR in NSCLC, 83% DCR • 62 patients were enrolled in the Phase 1 monotherapy portion of the study in China • Oral doses ranging from 100 to 900 mg daily • Patients with advanced KRAS G12D mutant solid tumors • Previously treated with standard therapies C PR confirmed On treatment NSCLC (N=12) 42% (18%, 68%) ORR (90% CI) 83% (56%, 97%) DCR (90% CI) PDAC (N=23) 52% (34%, 70%) ORR (90% CI) 100% (88%, 100%) DCR (90% CI) PR PR PR PR PR SD SD PD SD SD SD PD BOR 1 4 3 4 3 2 1 2 1 2 2 2 PLoT PR PR PR PR PR PR PR PR PR PR PR PR SD SD SD SD SD SD SD SD SD SD SD 4 2 1 3 3 4 2 3 2 1 2 2 2 3 4 2 5 2 2 2 1 3 1 Data cut - off date: 16 May 2025 * Five patients who early dropped out without post - baseline tumor assessment are not included: one PDAC at 600 mg QD due to treatment related AE, one NSCLC at 400 mg QD and three PDAC at 600 mg QD due to patient decision. Efficacy in NSCLC and PDAC Patients at Target Dose Range • 12 NSCLC and 23 PDAC patients treated at 400 mg QD, 600 mg QD or 300 mg BID had tumor response assessed.* ASCO 2025

 

 

24 Duration of Treatment and Tumor Assessment of All Patients Month Data cut - off date: 16 May 2025 All patients received first dose of GFH375 at least 10 weeks prior to data cutoff date. The y - axis tick label is tumor type and number of prior lines of therapies. Abbreviations: NE, not evaluable; PD, progressive disease; PR, p artial response; SD, stable disease. • Median (range) time on treatment: 11.8 weeks (range: 0.1 - 42.1) • Median (range) time to response: 6.2 weeks (range: 6.0 - 24.7) • 36 out of 62 patients are ongoing with treatment Source: GenFleet Therapeutics ASCO 2025 Rapid Oral Presentation June 2, 2025; A First - in - human Phase I/II Study of GFH375, a Highly Selective an d Potent Oral KRAS G12D Inhibitor in Patients in KRAS G12D Mutant Advanced Solid Tumors ASCO 2025

 

 

25 Source: GenFleet Therapeutics WCLC 2025 Mini Oral Presentation September 7. 2025; Efficacy and Safety of GFH375 in Advanced N on - Small Cell Lung Cancer Patients with KRAS G12D Mutation. WCLC 2025 Cut - off date: 01 August 2025. NSCLC at 600 mg QD (n=16) All NSCLC (n=28) 4 (25.0) 12 (42.9) Discontinued n(%) 1 (6.3) 1 (3.6) Adverse event 2 (12.5) 8 (28.6) Progress disease 1 (6.3) 2 (7.1) Patient’s decision 0 1 (3.6) Physician’s decision • 28 NSCLC patients with local tumor testing KRAS G12D+ were treated with GFH375 single agent, including 16 at 600 mg QD. • Majority (60.7%) were never smokers. • Among the 22 patients with baseline PD - L1 TPS data available, none had high expression (TPS ≥ 50%). • 17.9% had baseline brain metastases. • Majority (64.3%) had received at least 2 prior lines of therapies; all received prior platinum - based chemo therapies; 96.4% received prior ICIs. • Most patients were ongoing; the longest follow - up was 55.6 weeks. NSCLC at 600 mg (n=16) All NSCLC (n=28) 60.5 (36 - 74) 61 (36 - 74) Age, median (range), years 8 (50) 13 (46.4) Female, n(%) Smoking status, n(%) 8 (50) ​​ 11 (39.3) Current or former 8 (50) ​ 17 (60.7) ​ Never ECOG PS, n(%) 14 (87.5) 26 (92.9) 1 16 (100) 28 (100) Pathology adenocarcinoma, n(%) 16 (100) 28 (100) Baseline metastasis, n(%) 4 (25.0) 12 (42.9) Bone 1 (6.3) 5 (17.9) Brain 2 (12.5) 3 (10.7) Liver PD - L1 TPS, n(%) ​ 11 (68.8) 22 (78.6) Known 6 (54.5) 2 13 (59.1) 1 < 1% 5 (45.5) 2 9 (40.9) 1 1 - 49% 0 0 ≥ 50% 1.5 (1 - 4) 2 (1 - 4) Prior lines of therapies, median (range) * 16 (100) 27 (96.4) Prior ICI, n(%) 16 (100) 28 (100) Prior platinum, n(%) 16 (100) 25 (89.3) Prior ICI +platinum concurrent, n(%) 1 Percentage denominator is 22. 2 Percentage denominator is 11. * A neoadjuvant and adjuvant therapy would be counted as a line of system therapy if patient relapsed or progressed during treatment or within 6 months of last dose. GFH375: NSCLC Baseline Characteristics & Patient Disposition

 

 

26 Source: GenFleet Therapeutics WCLC 2025 Mini Oral Presentation September 7. 2025; Efficacy and Safety of GFH375 in Advanced N on - Small Cell Lung Cancer Patients with KRAS G12D Mutation. WCLC 2025 600mg QD (N=16) All patients (N=26) 68.8% [41.3%, 89.0%] 57.7% [39.8%, 74.2%] ORR [90% CI] 93.8% [69.8%, 99.8%] 88.5% [72.8%, 96.8%] DCR [90% CI] • ORR is 57.7% in 26 evaluable patients, and 68.8% in 16 patients at 600 mg QD * • Of the 11 patients at 600mg QD with PR, 5 have confirmed and 5 have the potential to confirm the PR • 2 additional patients at 600mg QD with 20 - 30% reduction are still on treatment with potential for response • Among the 5 patients with baseline brain metastases, 2 achieved PR # # • Median (range) time on treatment: 15.1 weeks (range: 4.6 - 55.6) • Median (range) time to response: 6.3 weeks (range: 6.0 - 48.1) C - PR confirmed → - On treatment BM - Brain metastasis at baseline BM BM BM BM BM Data cut - off date: 01 August 2025. All patients received first dose of GFH375 at least 10 weeks prior to data cut - off date. Median follow - up 21.8 weeks (range: 8.3 - 55.6). * One patient (200 mg QD) had no target lesion at baseline but remains stable; one patient (400 mg QD) dropped out early with out post - baseline tumor assessment due to patient’s decision and died 41 days after last dose due to disease progression. # Two patients achieved PR but discontinued before response confirmation. One (400 mg QD) had PD at the 2 nd assessment. The other dropped out due to G4 hepatic function abnormal (recovered after discontinuation). BOR, best overall response; CI, confidence interval; DCR, disease control rate; ORR, objective response rate; PD, progressive di sease; PR, partial response; SD, stable disease; PLoT : number of prior lines of therapies. GFH375: Efficacy in NSCLC

 

 

27 WCLC 2025 GFH375: Safety in All Patients Source: GenFleet Therapeutics WCLC 2025 Mini Oral Presentation September 7. 2025; Efficacy and Safety of GFH375 in Advanced N on - Small Cell Lung Cancer Patients with KRAS G12D Mutation. • 142 patients, including 28 NSCLC, with advanced KRAS G12D mutation were treated with GFH375 single agent. » 93% had baseline ECOG PS = 1. » 75% had received at least ≥ 2 prior lines of therapies. • 97 patients, including 16 NSCLC, were treated at 600 mg QD. • No treatment related death. • 4.2% of patients discontinued treatment due to TRAEs. • 27.5% of patients had grade 3/4 TRAEs. • Overall, GFH375 has manageable safety profile in previously treated advanced cancer patients. • Grade ≥3 TRAEs and SAEs are more frequent in NSCLC patients; however, discontinuation rate appears to be similar. 600 mg QD All dose levels Adverse events, n(%) NSCLC (N=16) All types (N=97) NSCLC 2 (N=28) All types 1 (N=142) TEAEs 16 (100) 96 (99.0) 28 (100) 141 (99.3) All grades 7 (43.8) 41 (42.3) 15 (53.6) 60 (42.3) Grade ≥ 3 3 (18.8) 19 (19.6) 6 (21.4) 27 (19.0) SAE 4 (25.0) 31 (32.0) 10 (35.7) 51 (35.9) Leading to interruption 3 (18.8) 7 ( 7.2) 5 (17.9) 12 ( 8.5) Leading to reduction 1 (6.3) 6 (6.2) 1 (3.6) 9 (6.3) Leading to discontinuation 0 3 (3.1) 0 4 (2.8) Leading to death ​ ​ TRAEs 16 (100) 96 (99.0) 28 (100) 139 (97.9) All grades 6 (37.5) 25 (25.8) ​ 13 (46.4) ​ 39 (27.5) ​ Grade ≥ 3 2 (12.5) 8 (8.2) 4 (14.3) 11 (7.7) SAE 3 (18.8) 19 (19.6) 9 (32.1) 33 (23.2) Leading to interruption 3 (18.8) 7 (7.2) 5 (17.9) 11 (7.7) Leading to reduction 1 ( 6.3) 4 (4.1) 1 ( 3.6) 6 (4.2) Leading to discontinuation 0 0 0 0 Leading to death Data c ut - off date: 17 Jun 2025 The median exposure time to GFH375 in all patients was 9.6 (range: 0.9 - 49.1) week s by the cut - off date. 1 Including all patients treated at all dose levels: 100 mg QD (n=1), 200 mg QD (n=1), 400 mg QD (n=29), 600 mg QD (n=97), 750 m g QD (n=8) , 900 mg QD (n=3), and 300 mg BID (n=3). 2 Including NSCLC patients treated at all dose levels: 100 mg QD (n=1), 200 mg QD (n=1), 400 mg QD (n=7), 600 mg QD (n=16), 7 50 mg QD (n=1) , and 300 mg BID (n=2). SAE, serious adverse event; TEAE, treatment emergent adverse event; TRAE, treatment related adverse event.

 

 

28 WCLC 2025 Source: GenFleet Therapeutics WCLC 2025 Mini Oral Presentation September 7. 2025; Efficacy and Safety of GFH375 in Advanced N on - Small Cell Lung Cancer Patients with KRAS G12D Mutation. GFH375: Safety in All Patients • No new safety signals were observed. • The most frequent TRAEs were gastrointestinal AEs (diarrhea, vomiting, and nausea) and hematological AEs (anemia and neutropenia), mainly grade 1/2 and manageable with supportive medications. • Most frequent G3/4 TRAEs were neutropenia (6.3%) and anemia (4.2%). • Multiple AEs had higher rates in NSCLC patients, potentially due to prior use of ICIs. » 96.4% pts with NSCLC had received ICIs before GFH375 treatment. » The median time of last dose of ICIs to first administration of GFH375 was 2.8 months (range: 1.0 - 40.0); the median time of ICI treatment was 4.3 months (range: 0.7 – 26.5). 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% Most frequent TRAEs (≥10% of all patients) Grade 1 Grade 2 Grade 3 Grade 4 Grade 5 ALT, alanine transaminase; AST, aspartate transferase; TRAE, treatment related adverse event; WBC, white blood cell. Left bar: all patients (N=142) Right bar: NSCLC (N=28)

 

 

29 VS - 7375 - 101 Study Schema, Efficiently Testing KRAS G12D+ Indications with Monotherapy and SOC Combinations Part A: Single Agent Dose Escalation – Any KRAS G12D Solid Tumor Cohort B1: 2L+ PDAC (N=20) Cohort D1: 2L+ CRC Cetuximab (N=20) VS - 7375 + Combinations Part B: Dose Expansion Part C: Combination Dose Escalations Part D: Combination Dose Expansion Dose Level 3: 900 mg QD Dose Level 2: 600 mg QD Dose Level 1: 400 mg QD Dose Level - 1 : 300 mg QD Cohort B2: 2L+ NSCLC (N=20) Cohort B3: 2L+ Solid Tumors (N=20) VS - 7375 Dose Escalation Anticipated dose levels range from 400 - 900 mg QD, with options for reduction if required. + Cohort C1: 2L+ Solid Tumors Cetuximab* Cohort D2: 1L NSCLC Carboplatin/Pemetrexed/ Pembrolizumab (N=20) Select RP2D Select RP2D Cohort C3: 2L+ PDAC Gemcitabine + Nab - Paclitaxel Cohort D3: 2L+ PDAC Gemcitabine/Nab - Paclitaxel (N=20) Select RP2D Select RP2D Cohort C4: 1L PDAC – 75+ yo Gemcitabine Cohort D4: 1L PDAC – 75+ yo Gemcitabine (N=20) Select RP2D Cohort C2: 1L NSCLC Carboplatin/Pemetrexed/Pembrolizum ab The study will evaluate dosing with meals and utilize prophylactic anti - emetics *Anticipated starting dose level for cetuximab combination once the monotherapy clears 600 mg dose level VS - 7375 Monotherapy

 

 

30 • Efficacious starting dose: • 400 mg starting dose supported by monotherapy efficacy/safety in FIH study • Evaluating GI side effect mitigations: • Use prophylactic anti - emetics • Evaluate dosing with and without food • Evaluate additional formulation • Multiple, high - value indication strategy: • Monotherapy expansion cohorts in PDAC & NSCLC • Combination cohorts with cetuximab for CRC, chemotherapy for PDAC, chemo plus I - O for NSCLC • Expand to geographies outside of U.S. Accelerated Development Approach Builds on Preliminary First - in - Human Study Findings Multi - Arm Clinical Study evaluating monotherapy and combinations FDA Engagement Plans • Granted Fast Track Designation for: • First - line in patients with KRAS G12D locally advanced or metastatic PDAC and • Patients with KRAS G12D locally advanced or mPDAC who received at least one prior line of standard systemic therapy in July 2025 • Plan to pursue Breakthrough Therapy Designation • Accelerated clinical development with FDA input

 

 

31 Next Steps in VS - 7375 Clinical Program Expect to report a preliminary update on the Phase 1 monotherapy dose escalation in Q4 2025. ௗ Subject to the results of the Phase 1 monotherapy dose escalation, initiate monotherapy expansion cohorts in PDAC, NSCLC, and other solid tumors. Initiate the dose escalation cohorts in combination with cetuximab, chemotherapy, and chemotherapy with checkpoint - inhibitor for CRC, PDAC, and NSCLC, respectively, in Q4 2025. Subject to the results of the combination dose escalation cohorts with VS - 7375, initiate combination expansion cohorts in CRC, PDAC, and NSCLC.

 

 

Topline Data from RAMP 205: Avutometinib + Defactinib + Standard of Care in First - Line Metastatic Pancreatic Cancer

 

 

33 1 SEER 12; 2 worldometers; 3 Globocan/Japan/factsheet; 4 McIntyre, Cancer Cell, Sept 2023; 5 Yu, Frontiers in Oncology, Jul 2021 Pancreatic Ductal Adenocarcinoma (PDAC) Represents an Area of High Unmet Need 0 5 10 15 20 25 30 35 40 45 50 5-Yr Relative Survival KRAS Mutations Are Present in ~90 - 95% of PDAC 4 High Unmet Need Based on 5 Year Relative Survival of 13.3% Nearly 180,000 Total Incident PDAC Patients 35% 30% 13% 13% 8% KRAS G12D KRAS G12V KRAS G12R Other KRAS mutations KRAS WT ~59,800 1 ~43,200 3 ~77,500 2

 

 

34 DLT: dose - limiting toxicity; RP2D: recommended phase 2 dose; CT: computed tomography; ECOG: European Cooperative Oncology Group; MRI: magnetic resonance imaging RAMP 205: Designed to Identify and Evaluate RP2D in Combination with Chemotherapy for Treatment of Newly Diagnosed mPDAC RAMP 205: Ongoing Phase 1/2 Evaluating Avutometinib + Defactinib with Gemcitabine and Nab - paclitaxel Inclusion Criteria • Histologic or cytologic confirmed mPDAC • Eligible for treatment in the first - line setting (no prior systemic therapy for advanced or metastatic disease) • Measurable by RECIST v1.1 by CT or MRI • ECOG Performance status of ≤1 • Part B only, adequate tissue sample to evaluate KRA mutational status Collaboration with PanCAN , NCT05669482 ​ Part A: Dose Evaluation (3+3 DLT Assessment) RP2D Selection Part B: Dose Expansion (Primary Endpoint: ORR) Avutometinib + Defactinib + Gemcitabine + Nab - paclitaxel Dose Finding Cohorts n=3 - 6 Avutometinib + Defactinib + Gemcitabine + Nab - paclitaxel DLT - Cleared Dose Level Expansion • Patients with PDAC treated at RP2D • Stage 1: 17 patients if ≥7 responders, then • Simon’s 2 - stage design: expand to 29 patients

 

 

35 Updated 05/01/25 Enrolled N=60 Days Chemo Dosing Nab - Paclitaxel Gemcitabine Defactinib Avutometinib Dose Level 12 1 - 8 - 15 125 800 200 2.4 1 12 1 - 8 - 15 100 800 200 3.2 0 12 1 - 8 - 15 100 800 200 2.4 - 1 12 1 - 15 125 800 200 3.2 1a 12 1 - 15 125 1000 200 3.2 2a PART A Enrollment Summary Dose Levels & Administration Schedule (28 - day) Cycle RAMP 205: 12 Patients Enrolled in Each Dose Cohort • Enrolled: (n=60) • Treatment Ongoing: (n=19) • Ended Study: (n=30) • Survival Follow Up: (n=11) Dose level 1 selected as the RP2D

 

 

36 Source: F_TR_WATERFALL.sas Data Cut: 01 AUG 25 Dose Level 1 Demonstrated a Confirmed 83% ORR with Tumor Shrinkage Observed in All Patients Dose Level 1: Response & Disease Control Rate as of August 1, 2025 83.3% ( 10/12) Confirmed ORR, n (%) 10 (83.3) PR, n (%) 2 (16.7) SD, n (%) 0 PD, n (%) 92% (11/12 ) DCR, n (%) ≥ 4 cycles Dose Level 1: Efficacy Evaluable Population (n=12)

 

 

37 Source: Program:F_TX_RS_SWIMMER_DL1.sas Data Cut: 25 APR 25 Encouraging Duration of Treatment Observed to Date for Dose Level 1 Dose Level 1 Duration of Treatment Safety Population (n=12) Historical Gem/Nab PFS 95% CI mPFS Reference Study 4.5 - 5.9 5.5 MPACT N=421 Von Hoff 2013 5.3 - 5.8 5.6 NAPOLI 3 N=387 O’Reilly 2023 Historical Gem/Nab mPFS

 

 

38 Source: Dr. Lim, Siteman Cancer Center 7 Patient with mPDAC Showed Substantial Tumor Shrinkage in Dose Level 1 Before C1 After C2 After C4 After C6 metastasis primary tumor 63 year - old Female

 

 

39 AEs were Generally Manageable, Allowing Patients to Remain on Treatment DL1 Treatment Emergent AE All Grades ≥ 25% / Non - laboratory AEs NAPOLI 3* (N=379) Dose Level 1 (n=12) TEAEs Grade ≥3 n (%) All Grades n (%) Grade ≥3 n (%) All Grades n (%) Preferred term 10 (3) 162 (43) 0 10 (83) Nausea 17 (4) 139 (37) 0 9 (75) Diarrhoea 20 (5) 143 (38) 0 9 (75) Fatigue Not Listed** 119 (31) 0 8 (67) Alopecia 8 (2) 113 (30) 0 8 (67) Constipation Not Listed** 108 (29) 2 (17) 7 (58) Oedema peripheral Not Listed** Not Listed** 0 7 (58) Rash maculo - papular Not Listed** 45 (12) 1 (8) 7 (58) Stomatitis 8 (2) 100 (26) 1 (8) 7 (58) Vomiting Not Listed** 58 (15) 0 6 (50) Dysgeusia Not Listed** Not Listed** 0 6 (50) Hypotension Not Listed** 87 (23) 1 (8) 6 (50) Pyrexia 10 (3) 106 (28) 0 5 (42) Decreased appetite 8 (2) Not Listed** 1 (8) 5 (42) Hypertension 22 (6) 66 (17) 1 (8) 5 (42) Neuropathy peripheral Not Listed** Not Listed** 0 4 (33) Cough Not Listed** Not Listed** 0 4 (33) Dyspepsia 8 (2) 47 (12) 0 4 (33) Dyspnoea Not Listed** Not Listed** 1 (8) 4 (33) Retinopathy Not Listed** Not Listed** 1 (8) 4 (33) Vision blurred Not Listed** Not Listed** 0 3 (25) Abdominal Distension 14 (4) 77 (20) 0 3 (25) Abdominal Pain Not Listed** Not Listed** 0 3 (25) Depression Not Listed** 43 (11) 0 3 (25) Epistaxis 9 (2) Not Listed** 3 (25) 3 (25) Febrile Neutropenia Not Listed** Not Listed** 0 3 (25) Rash • No new or unexpected AEs observed • Most non - laboratory AEs were grade 1 or 2 • AEs were generally manageable, allowing patients to remain on treatment • The rates and severities of most AEs are consistent with the individual rates reported for Gem/Nab and Avutometinib/Defactinib • Nausea, diarrhea, constipation, febrile neutropenia, and anemia may be increased in comparison to those expected with Gem/Nab DL1 Treatment Emergent AE All Grades ≥ 25% / Laboratory - related AEs NAPOLI 3* (N=379) Dose Level (n=12) TEAEs Grade ≥3 n (%) All Grades n (%) Grade ≥3 n (%) All Grades n (%) Preferred term 66 (17) 153 (40) 5 (42) 8 (67) Anaemia 144 (38) 192 (51) 6 (50) 8 (67) Neutropenia*** 11 (3) Not Listed** 2 (17) 7 (58) Hyperbilirubinaemia*** 23 (6) 154 (41) 1 (8) 5 (42) Thrombocytopenia*** 8 (2) 40 (11) 1 (8) 3 (25) Aspartate aminotransferase increased 15 (4) 49 (13) 0 3 (25) Hypokalemia RAMP 205 data source:T_AE_GRADE_PT.sas : Data Cut: 11 APR 25 *Supplement Appendix: (NAPOLI 3). Wainberg et al. The Lancet, Volume 402, Issue 10409, 1272 – 1281 **If “Not Listed” then adverse event is either not reported or did not meet threshold of <10% all grade TEAE or <2% G3 or hig her TEAE. * **'Neutropenia' and 'Neutrophil count decreased' are grouped as 'Neutropenia'. 'Thrombocytopenia' and 'Platelet count decreas ed' are grouped as 'Thrombocytopenia'. ' Hyperbilirubinaemia ' and 'Blood bilirubin increased' are grouped as ' Hyperbilirubinaemia ’’. AE, adverse event;

 

 

40 Next Steps for RAMP 205 Complete enrollment up to 29 patients in RAMP 205 at the RP2D in Q3 2025

 

 

Avutometinib ± Defactinib with Sotorasib (G12Ci) in KRAS G12C mutant NSCLC

 

 

42 Collaboration Verastem & Mariano Barbacid , CNIO (Spain) Addition of FAK inhibitor Augments the Efficacy of Sotorasib + Avutometinib and Reverses Sotorasib Resistance in KRAS G12C NSCLC Preclinical Models AVUTOMETINIB ENHANCES SOTORASIB EFFICACY. ADDITION OF FAK INHIBITOR INDUCES DEEP TUMOR REGRESSIONS IN ALL TREATED MICE ADDITION OF FAKi + AVUTOMETINIB REVERSES SOTORASIB RESISTANCE ADDITION OF AVUTOMETINIB IS INSUFFICIENT TO REVERSE SOTORASIB RESISTANCE -100 0 100 200 300 400 Response at Day 10 R e s p o n s e @ D a y 1 0 ( % c h a n g e f r o m b a s e l i n e ) v e h i c l e 10 PR a v u t o m e t i n i b F A K i s o t o r a s i b s o t o r a s i b + a v u t o m e t i n i b s o t o r a s i b + F A K i s o t o r a s i b + a v u t o m e t i n i b + F A K i 2 SD 1 SD1 SD 8 SD 2 PR 4 SD 3 PR Doses Tested Sotorasib : 30 mg/kg PO QD Avutometinib : 0.3 mg/kg PO QD FAKi : 50 mg/kg PO BID H2122 KRAS G12C NSCLC 0 50 100 150 0 5 10 15 20 25 Days after first sotorasib dose T u m o r v o l u m e ( m m 3 ) Sotorasib + Avutometinib + FAKiSotorasib 0 50 100 150 0 5 10 15 20 25 Days after first sotorasib dose T u m o r v o l u m e ( m m 3 ) Sotorasib + Avutometinib Sotorasib Mouse #1 Mouse #2 Mouse #3 Mouse #4

 

 

43 Collaboration with Amgen, NCT05074810 DRECIST v1.1, response evaluation criteria in solid tumours version 1.1 RAMP 203: Phase 1/2 Trial of Avutometinib + LUMAKRAS TM (Sotorasib) Defactinib in KRAS G12C Advanced NSCLC Inclusion Criteria • Documented KRAS G12C mutation determined using validated test • Treatment with 1 but no more than 3 prior systemic regimens for Stage 3B - C or 4 NSCLC* • May have received adjuvant chemotherapy for earlier - stage disease • Measurable disease per RECIST v1.1 • ECOG performance status ≤ 1 Part A: Dose Evaluation (3+3 DLT Assessment) Avutometinib + Sotorasib Dose Finding Cohort Part B: Dose Expansion (Primary endpoint: ORR) RP2D Selected: 4 mg a vutometinib / 960 mg sotorasib Avutometinib + Sotorasib + Defactinib Dose Finding Cohort Alt - RP2D Selection KRAS G12C inhibitor - naive Progressed on KRAS G12C inhibitor Cohort 1 Patients without Prior KRAS G12C Inhibitor Treatment Stage 1 : ~20 patients Stage 2 : expand to 54 Cohort 2 Patients who Progressed on Prior KRAS G12C Inhibitor Treatment Stage 1 : ~19 patients Stage 2 : expand to 55 Cohort 1 Patients without Prior KRAS G12C Inhibitor Treatment Stage 1 : ~20 patients Stage 2 : expand to 54 Cohort 2 Patients who Progressed on Prior KRAS G12C Inhibitor Treatment Stage 1 : ~19 patients Stage 2 : expand to 55 Enrollment complete *may include patients with or without prior G12C therapy Treatment with RP2D and/or Alt - RP2D Now enrolling Now enrolling Enrollment complete

 

 

44 RAMP 203: No Dose - Limiting Toxicities (DLTs) Were Observed in the First Triplet Combination Cohort in Patients Previously Treated with a G12C Inhibitor Triplet Combination Update: • As of a November 21, 2024, data cutoff, three patients whose cancer previously progressed on a G12C inhibitor have been treated with the triplet combination of sotorasib 960 mg administered daily on a continuous schedule and avutometinib 3.2 mg twice - weekly (BIW) plus defactinib 200 mg twice - daily (BID). Avutometinib and defactinib are administered on a three out of four weeks schedule. ​ • 2 of the 3 patients demonstrated initial tumor reductions of at least 20% at the first scan. As of the data cutoff, all three patients remain on treatment. ​ • Completed enrollment of the planned dose level evaluation cohorts for the triplet combination in Q1 2025. Doublet Combination Update: • As previously reported, the doublet combination of avutometinib with sotorasib has completed enrollment (n=28) in the G12C inhibitor treatment - naïve Stage 1 Part B cohort. ​ • Completed enrollment to the KRAS G 12 C inhibitor, prior - treated Stage 1 Part B doublet cohort in Q 1 2025 . • Patients enrolled in the doublet cohorts continue to be followed for safety and efficacy results (both the prior - treated and treatment - naïve cohorts) .

 

 

45 Next Steps for RAMP 203 Report an interim update on the efficacy and safety results from both the doublet and triplet combinations in Q4 2025

 

 

46 Anticipated Milestones & Financials 46

 

 

47 Execute Successful Commercial Launch in LGSOC, Followed by Meaningful Catalysts to Expand Into Larger, Underserved Patient Populations Anticipated Milestones & Activities in 2H 2025 Program □ Complete planned enrollment in RAMP 301 by end of 2025 □ Announce outcome of IDMC’s sample - size re - estimation recommendation for RAMP 301 in Q4 2025 □ Report initial data from RAMP 201J Phase 2 clinical trial being conducted in Japan with JGOG in Q4 2025 KRAS - mutated Recurrent LGSOC □ Expect to report a preliminary update on the Phase 1 monotherapy dose escalation in Q4 2025. □ Subject to the results of the Phase 1 monotherapy dose escalation, the Company plans to initiate monotherapy expansion cohorts in both advanced PDAC and NSCLC. □ Initiate the dose escalation cohorts in combination with cetuximab, chemotherapy, and chemotherapy with checkpoint - inhibitor for CRC, PDAC, and NSCLC, respectively, in Q4 2025. □ Subject to the results of the Phase 1 dose escalation combinations cohorts with VS - 7375, ௗ the Company ௗ plans to initiate a combination expansion cohort in CRC, PDAC, and NSCLC. ​ □ Complete enrollment in the expansion cohort in Q3 2025 Avutometinib + Defactinib + SOC in First - Line Metastatic Pancreatic Cancer □ Plan to share interim safety and efficacy results from both double and triplet combinations in Q 4 2025 Avutometinib ± Defactinib + Sotorasib: mKRAS G12C NSCLC VS - 7375, oral KRAS G12D (ON/OFF) Inhibitor

 

 

48 *Q2 2025 GAAP operating expenses of $45.90M less Q2 2025 stock - based compensation expense of $3.41M = $42.49M Q1 2025 non - GAAP o perating expenses. **Excludes unexercised warrants (14.1M shares upon exercise) and unexercised pre - funded warrants (9.8M shares upon exercise) . Key Financial Statistics As of and for the quarter ended June 30, 2025 $164.3M Cash, cash equivalents & short - term investments $2.1M Net Product Revenue $45.9M GAAP Operating Expenses $42.5M * Non - GAAP Operating Expenses 61.5M ** Shares Outstanding Oberland Finance Credit Facility • Up to $150M available in a series of notes • $75M principal of notes outstanding • Remaining $75M available at Company’s option upon achievement of pre - defined milestones • $25M tranche upon FDA approval of avutometinib and defactinib for treatment of LGSOC • $50M tranche upon trailing six months revenue of at least $55M • Floating interest rate, subject to a floor and a cap • Interest only payments through January 2031 • No financial covenants

 

 

THANK YOU!

 

 

50 OB: Orange Book Listed Patent AVMAPKI FAKZYNJA CO - PACK Patent Portfolio OB: 7,897,792 Avutometinib COM (expiry 2/9/2027) OB: 11,400,090 – Avutometinib mono dosing - (expiry 10/29/2038) PTE OB: 7,928,109 Defactinib COM US (expiry 4/17/2028) PTA PTE (Aug, 2034) OB: 8,247,411 Defactinib – genus (expiry 4/17/2028) OB: 11,517,573 A+D combo dosing – (expiry 9/11/2040) OB: 11,873,296 Avuto polymorph – (expiry 12/29/2042) PTE (May 2039)

 

 

51 Experienced Senior Management Team Cathy Carew Chief Organizationa l Effectiveness Officer Colleen Mockbee Global Head of Regulatory Affairs and Development Nate Sanburn Chief Business Officer Dan Calkins Chief Financial Officer Matt Ros Chief Operating Officer Mike Crowther Chief Commercial & Strategy Officer Jonathan Pachter, Ph.D. Chief Scientific Officer John Hayslip, M.D. Chief Medical Officer Daniel Paterson President and CEO • Principal – HR Collaborative • Ironwood, ActiveBiotics , Dynogen , Tufts Health Plan • Chief Developmen t Officer & SVP of Regulatory, OncXerna • Head of Global Regulatory, Lilly Oncology • Associate VP, Head of Collaborations & Late Phase BD, Lilly Oncology • National Gene Vector Lab, Indiana Univer sity • Technical Accounting Consultant - CFGI • PwC LLP • CEO, FORE Biotherapeut ics • EVP & CSBO, Epizyme • COO, Sanofi - Genzyme • BMS • CBO, Minerva Biotechnolog ies • Interim US lead and VP of US Marketing, Kite Pharma • Celgene • Head of Cancer Biology – OSI (now Astellas) • Schering - Plough • CMO, I - MAB • Nektar Therapeutics , AbbVie • University of Kentucky’s Markey Cancer Center • CEO, The DNA Repair Co. (now On - Q - ity ) • PharMetrics (now IMS) • Axion Previous experience

 

 

52 Oral Administration of VS - 7375 Inhibits Tumor Growth in a Dose - Dependent Manner in KRAS G12D models AsPC - 1 PDAC Panc 04.03 PDAC GP2D CRC LS513 CRC -100 -50 0 50 100 150 200 250 300 350 R e s p o n s e @ D a y 1 4 ( % c h a n g e f r o m b a s e l i n e ) v e h i c l e V S - 7 3 7 5 1 0 m g / k g V S - 7 3 7 5 3 0 m g / k g V S - 7 3 7 5 1 0 0 m g / k g 6 SDs 1 PR 5 SDs 8 PRs 8 PRs V S - 7 3 7 5 5 m g / k g -100 -50 0 50 100 150 200 250 300 350 R e s p o n s e @ D a y 1 4 ( % c h a n g e f r o m b a s e l i n e ) v e h i c l e V S - 7 3 7 5 1 0 m g / k g V S - 7 3 7 5 3 0 m g / k g V S - 7 3 7 5 1 0 0 m g / k g V S - 7 3 7 5 5 m g / k g 1 SD 4 SDs 5 PRs 3SDs 8 PRs -100 0 100 200 300 500 1000 1500 R e s p o n s e @ D a y 2 1 ( % c h a n g e f r o m b a s e l i n e ) v e h i c l e V S - 7 3 7 5 1 0 m g / k g V S - 7 3 7 5 3 0 m g / k g V S - 7 3 7 5 1 0 0 m g / k g 4 PRs 3 SDs 7 PRs 1 SD Presented at AACR 2024 • 10 mg/kg conferred strong tumor regressions in the most sensitive model (GP2D) • 30 mg/kg conferred strong tumor regressions across all models • 100 mg/kg conferred partial responses (>30% reduction) in >95% of all mice

 

 

53 Dose Levels of 400 and 600 mg QD Achieved Steady State Target Exposures in Almost all Patients Human equivalent to 100 mg/kg in mice (PR in all mice in all models) Human equivalent to 30 mg/kg in mice (Tumor regressions in all models) Human equivalent to 10 mg/kg in mice (Tumor regressions in most sensitive models)

 

 

54 Addition of Cetuximab with VS - 7375 Induces Complete Responses in All Mice in a KRAS G12D Colorectal Cancer Model LS513 Colorectal Cancer Model 0 10 20 30 40 0 500 1000 1500 Tumor growth Days after first dose T u m o r v o l u m e ( m m 3 + / - S E M ) Vehicle GFH375 Cetuximab GFH375 + cetuximab Last dose 0 500 1000 R e s p o n s e @ D a y 3 7 ( % c h a n g e f r o m b a s e l i n e ) v e h i c l e V S - 7 3 7 5 C e t u x i m a b V S - 7 3 7 5 + c e t u x i m a b 1 PR 1 SD 8 CRs -100 Presented at AACR 2025

 

 

55 NR: not reported; IP: intraperitoneal admiration; QD; once per day; QW; once per week; References: GenFleet /Verastem AACR 2024; Hallin et al (Mirati) 2022; RevMed AACR 2023; RevMed AACR 2024; Lilly ENA 2023; Lilly AACR 2024; AstraZeneca (AZ) AACR 2024; Incyte AACR 2024; Quanta AACR 2023; Tyligand AACR 2024; Betta AACR 2024; Zhou et al ( Hengrui ) 2024. The safety and efficacy of VS - 7375 and the other G12D inhibitors has not been established. No conclusions on the clinical safety or efficacy of VS - 7375 or any of the other G12D inhibitors can be drawn at this time. VS - 7375 Shows Potential Best - in - Class Preclinical Properties Relative to Other Known KRAS G12D Inhibitors Hengrui HRS - 4642 Betta BPI - 501836 Tyligand TSN1611 Quanta QTX3046 Incyte INCB161734 AZ AZD0022 Lilly LY3962673 RevMed RMC - 9805 Mirati/BMS MRTX1133 VSTM/ GenFleet VS - 7375 Criteria NR NR 1.2x 0.0003x 1.2x NR 0.016x NR 0.2x 3x ON/OFF selectivity ratio On/Off N N Y Y Y Y Y Y N Y Oral availability in preclinical models Oral NR 0.8 nM NR 30 nM 7 nM NR NR 23 nM NR 0.5 nM AsPC - 1 pERK IC50 Potency NR 2.7 nM NR NR 19 nM NR NR NR NR 0.9 nM Panc 04.03 pERK IC50 Slight regressio n @ 15 mg/kg IV QW NR 10 mg/kg PO BID 100 mg/kg PO BID No regression @ 30 mg/kg PO QD NR 30 mg/kg PO BID 100 mg/kg PO QD 30 mg/kg IP BID 10 mg/kg PO BID GP2D Oral dose for tumor regression Tumor regression NR Regression @ 6 mg/kg IV BIW NR NR Slight regression @ 30 mg/kg PO QD Tumor stasis @ 150 mg/kg PO BID NR NR 30 mg/kg IP BID 10 mg/kg PO BID Panc 04.03 Oral dose for tumor regression NR NR NR NR NR NR NR Y NR Y Efficacy demonstrated in intracranial model BBB