Slide 1: Avutometinib and Defactinib in Recurrent Low-Grade Serous Ovarian Cancer (LGSOC)
Avutometinib and Defactinib in Recurrent Low-Grade Serous Ovarian Cancer (LGSOC) October 17, 2024 Corporate Update Call Amanda, real patient living with recurrent LGSOC Diagnosed at 26 with LGSOC 1
Slide 2: Forward-Looking Statements
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 related to the scope and expecting timing for the completion of
Slide 3: Today's Agenda
Today’s Agenda Opening Remarks Dan Paterson, President & Chief Executive Officer Mature RAMP 201 Data Results John Hayslip, M.D., Chief Medical Officer Changing the Treatment Paradigm Mike Crowther, Chief Commercial & Strategy Officer Closing Remarks Dan Paterson, President & Chief Executive Officer
Slide 4: Opening Remarks
Opening Remarks Dan Paterson, President and CEO 4
Slide 5: Verastem Aims to Deliver First FDA-Approved Treatment Specifically for Recurrent KRAS mutant LGSOC in 2025
Verastem Aims to Deliver First FDA-Approved Treatment Specifically for Recurrent KRAS mutant LGSOC in 2025 Avutometinib + Defactinib Demonstrated Durable Clear Regulatory Path for KRAS Mutant Results Across Various Efficacy Measures in Heavily Pretreated Patients in RAMP 201 • On track to complete t
Slide 6: Primary Analysis of the Phase 2 RAMP 201 Trial Evaluating Avutometinib and Defactinib in Recurrent LGSOC
Defactinib Primary Analysis of the Phase 2 RAMP 201 Trial Evaluating Inhibited FAK Avutometinib and Defactinib in Recurrent LGSOC Avutometinib John Hayslip, M.D., Clamped RAF-MEK Chief Medical Officer Complex 6
Slide 7: High Unmet Need for an Effective & Tolerable Therapy in Recurrent LGSOC
High Unmet Need for an Effective & Tolerable Therapy in Recurrent LGSOC • U.S. Incidence / Prevalence: 1k-2k1 / 6k-8k2 / Worldwide: 80,000 • Affects younger population (20-30s) and disproportionately impacts health, fertility, and long- term quality of life3,4 • 80%+ of patients will experience a re
Slide 8: Avutometinib + Defactinib Aims to Inhibit Multiple Resistance Mechanisms in the RAS/MAPK Pathway
Avutometinib + Defactinib Aims to Inhibit Multiple Resistance Mechanisms in the RAS/MAPK Pathway to Improve Patient Outcomes • 70% of LGSOC tumors are driven by RAS/MAPK pathway-associated mutations1-4 • 30% are KRAS mutant with other mutations including NRAS, BRAF, NF1, and other RAS pathway-associ
Slide 9: RAMP 201: Registration-Directed Phase 2 Trial of Avutometinib ± Defactinib in Recurrent LGSOC
RAMP 201: Registration-Directed Phase 2 Trial of Avutometinib ± Defactinib in Patients with Recurrent LGSOC RAMP 201 (ENGOT-ov60/GOG-3052) Part A ✓ Part B ✓ Part C ✓ Part D ✓ Selection Phase Expansion Phase Expansion Phase Combo Low-dose Avuto Combo Go Forward Regimen Avutometinib + Defactinib Avuto
Slide 10: Avutometinib + Defactinib Demonstrate Durable Results & Low Discontinuation Rates Due to AEs
Avutometinib + Defactinib Demonstrate Durable Results in Efficacy Measures & Low Discontinuation Rates Due to AEs, Regardless of KRAS Status Primary analysis of entire RAMP 201 dataset supports go-forward regimen as optimal dose Avutometinib (3.2 mg BIW) + Defactinib (200 mg BID) Regimen Parts A+B+C
Slide 11: RAMP 201 Enrolled Heavily Pre-treated Patients with a Median of 3 Prior Systemic Regimens
RAMP 201 Enrolled Heavily Pre-treated Patients with a Median of 3 Prior Systemic Regimens • Most patients received prior platinum-based chemotherapy and endocrine therapy • 51% of all patients received prior bevacizumab and about 1 in 5 received prior MEK-only inhibitor therapy Avutometinib + Defact
Slide 12: Mature Data from RAMP 201 Continues to Show Robust Responses
Mature Data from RAMP 201 Continues to Show Robust Responses • Overall: 31% ORR in all evaluable patients • 44% ORR in KRAS mt and 17% ORR in KRAS wt Avutometinib + Defactinib Regimen Response Rate: 3.2 mg BIW + 200 mg BID Parts A, B, and C 3 weeks on / 1 week off All patients KRAS mt KRAS wt N=109
Slide 13: 81% of Patients Achieved a Duration of Response of at Least 6 Months
81% of Patients Achieved a Duration of Response of at Least 6 Months Avutometinib + Defactinib Regimen: Duration of Response 3.7 MONTHS Median time to response (range, 1.7-19.2) 87% DOR for KRAS mt and 63% for KRAS wt at 6 months Avutometinib + Defactinib 3.2 mg BIW + 200 mg BID 3 weeks on / 1 week
Slide 14: 82% of All Patients Had a Reduction in Target Lesions, Regardless of KRAS Status
82% of All Patients Had a Reduction in Target Lesions, Regardless of KRAS Status Avutometinib + Defactinib Regimen: Best Overall Response 120 Best Target Lesion Response Per IRC (% Change From Baseline) 110 Best Overall Confirmed N (%) 50 Response (BICR) Complete Response (KRAS mt) 2 (2) 40 Partial
Slide 15: Receiving Avutometinib and Defactinib Earlier Was Associated with Higher Rates of Response
Receiving Avutometinib and Defactinib Earlier in the Course of Therapy was Associated with Higher Rates of Response Avutometinib + Defactinib Regimen: ORR by Key Subgroups Prior Lines of Therapy Prior Bevacizumab Prior MEKi 1-3 >3 No Yes No Yes 60 50 43% (29%,57%) 37% 40 (25%,50%) 33% (23%,44%) 30 2
Slide 16: Patients Achieved an Overall mPFS of 12.9 Months
Patients Achieved an Overall mPFS of 12.9 Months Avutometinib + Defactinib Regimen: Progression Free Survival (PFS) At 6 Months 79% OVERALL 88% in KRAS mt and 69% in KRAS wt At 12 Months 58% OVERALL 62% in KRAS mt and 53% in KRAS wt PFS, median (95% CI) Total KRAS mt KRAS wt N=109 N=57 N=52 12.9 mos
Slide 17: Low Discontinuation Rate of 10% Due to Adverse Events, No New Safety Signals
Low Discontinuation Rate of 10% Due to Adverse Events, No New Safety Signals Avutometinib + Defactinib Regimen 3.2 mg BIW + 200 mg BID 3 weeks on / 1 week off All patients KRAS mt KRAS wt Patients Treated 115 58 57 Patients on Treatment, n (%) 32 (28) 24 (41) 8 (14) Patients Discontinued Treatment,
Slide 18: Avutometinib Plus Defactinib Continue to Demonstrate a Well-Tolerated Safety Profile
Avutometinib Plus Defactinib Continue to Demonstrate a Well-Tolerated Safety Profile Avutometinib + Defactinib Regimen Severe adverse events are generally uncommon and Treatment-Related Adverse Events 3.2 mg BIW + 200 mg BID (>20% of patients)* 3 weeks on/1 week off typically managed by a treatment
Slide 19: Avutometinib Monotherapy Provided Lower Rate of Response
Avutometinib Monotherapy Provided Lower Rate of Response • Patients enrolled had comparable baseline characteristics as patients randomized to avutometinib plus defactinib regimen • Median of 3 prior lines of therapy, 49% had prior bevacizumab, 26% had prior MEKi • ORR: 17% in all patients, 23% KRAS
Slide 20: Low-Dose Regimen (Part D) Determined to be Suboptimal Based on Pre-Defined Analysis
Low-Dose Regimen (Part D) Determined to be Suboptimal Based on Pre-Defined Analysis Low-dose regimen will not be pursued as a starting dose in the treatment of recurrent LGSOC • Patients enrolled in Part D had comparable baseline characteristics as patients randomized to the avutometinib plus defact
Slide 21: RAMP 301: First Randomized Prospective Study to Fully Characterize KRAS Status
RAMP 301: First Randomized Prospective Study to Fully Characterize KRAS Status of all Enrolled LGSOC Patients RAMP 301: Phase 3 International Confirmatory Trial • Patients enrolling is similar to patient population in RAMP 201, with recurrent KRAS mt and KRAS wt LGSOC; prior MEKi and bevacizumab use
Slide 22: Changing the Treatment Paradigm in Recurrent LGSOC
Changing the Treatment Paradigm in Recurrent LGSOC Mike Crowther Chief Commercial and Strategy Officer 22
Slide 23: 80% of Patients with LGSOC Recur and Often Cycle Through Treatments
80% of Patients with LGSOC Recur and Often Cycle Through Treatments Treatment After Recurrence Pre-Diagnosis Diagnosis Treatment Disproportionally Average delay Driven by NCCN Symptom affects younger up to 3 years4 Guidelines Progression Recurrent women1 &Testing treatments include After subsequent
Slide 24: Current Available Therapies Offer Relatively Poor Response Rates, High Discontinuation Rates
Current Available Therapies Offer Relatively Poor Response Rates, High Discontinuation Rates • These studies started in 2013 and 2014 • In the MILO study no more than 3 lines of prior chemotherapy • Both MILO and GOG studies had low historical use of bevacizumab • No prior MEK was allowed in either
Slide 25: Avutometinib + Defactinib Combo Has the Potential to Address Key Treatment Needs
Avutometinib + Defactinib Combo Has the Potential to Address Key Treatment Needs To date, avutometinib + defactinib combination data in recurrent LGSOC show1: Clinically meaningful response rates Long progression-free survival and and durable benefit in both KRAS duration of treatment mutant and wil
Slide 26: LGSOC Represents a Significant Market Opportunity
LGSOC Represents a Significant Market Opportunity KRAS mutant – Anticipate high market Total Addressable KRAS wild-type Initial Launch penetration in LGSOC Market Opportunity KRAS mt population given: • No FDA approved therapies Estimated Annual Incident Addressable Opportunity1 $300M+ $374M+ for LG
Slide 27: Current Treatments on NCCN Guidelines
Current Treatments on NCCN Guidelines • Plan to submit RAMP 201, inclusive of entire patient population, for publication and NCCN consideration • There are no FDA-approved treatments and no standard sequencing of drugs for recurrent disease NCCN NCCN NCCN NCCN Category 1 Category 2a Category 2b Cate
Slide 28: LGSOC Represents a Significant Market Opportunity
LGSOC Represents a Significant Market Opportunity KRAS mutant – Anticipate high market Total Addressable KRAS wild-type Initial Launch penetration in LGSOC Market Opportunity KRAS mt population given: • No FDA approved therapies Estimated Annual Incident Addressable Opportunity1 $300M+ $374M+ for LG
Slide 29: Efficiently Scaled Launch Model to Deliver Best-in-Class Launch for Recurrent KRAS mutant LGSOC
Efficiently Scaled Launch Model to Deliver Best-in-Class Launch for Recurrent KRAS mutant LGSOC HCO/Key Account Focus Patient Focused • Top 100 commercial HCOs • YTD more than 2,300 patients have contribute 49.4% of patient claims1 registered on disease education website2 HCO/Key • ~400 HCPs manage
Slide 30: Potential to Change Treatment Paradigm and Improve Patient Outcomes
Potential to Change Treat Paradigm and Improve Patient Outcomes 1k-2k incidence with a prevalence of 6k-8k; potential for high market penetration in KRAS mutant at launch enriching overtime with the prevalent patient population Current available therapies offer limited efficacy, relatively high disc
Slide 31: Closing Remarks
Closing Remarks Dan Paterson, President and CEO 31
Slide 32: Verastem Aims to Deliver First FDA-Approved Treatment Specifically for Recurrent KRAS mutant LGSOC in 2025
Verastem Aims to Deliver First FDA-Approved Treatment Specifically for Recurrent KRAS mutant LGSOC in 2025 Avutometinib + Defactinib Demonstrated Durable Clear Regulatory Path for KRAS Mutant Results Across Various Efficacy Measures in Heavily Pretreated Patients in RAMP 201 • On track to complete t
Slide 33: Planned Near-Term LGSOC Commercial Launch, Followed by Meaningful Catalysts
Planned Near-Term LGSOC Commercial Launch, Followed by Meaningful Catalysts to Expand Into Larger, Underserved Patient Populations Program Anticipated Milestones & Activities Avutometinib + Defactinib ❑ Plan to complete rolling NDA in October 2024 in Recurrent Low-grade Serous ❑ Plan to announce mat
Slide 34: Thank you to all the patients, their families, and the site investigators and staff
Thank you to all the patients, their families, and the site investigators and staff that worked on RAMP 201. 34
Slide 35: Q&A
Q&A W YERASTEM ONCOLOGY