Verastem, Inc. · NASDAQ:VSTM
Verastem — Investor Presentation (April 2024)
51 slides from Verastem's investor presentation, Apr 9, 2024
Slide 1: Delivering Novel Therapies in RAS/MAPK Pathway Driven Cancers
Delivering Novel Therapies in RAS/MAPK Pathway Driven Cancers April 2024 Corporate Presentation
Slide 2: Disclaimers
2 Disclaimers Forward - Looking This presentation includes forward - looking statements about Verastem Oncology’s programs and product candidates, strategy, futur e plans and prospects, including statements related to the expected outcome and benefits of collaborations, including with GenFleet Thera
Slide 3: Verastem Oncology: Strong progress in 2023 sets up value-creation opportunities
3 Verastem Oncology Strong progress in 2023 sets up multiple value - creation opportunities » On track to deliver the first approved therapy in LGSOC • Data at ASCO 2023 of avutometinib, a RAF/MEK Clamp in combination with defactinib, a FAK inhibitor, demonstrated robust responses in patients with r
Slide 4: Driving Momentum in 2024: Recap of Recent Key Achievements
4 Avutometinib + Defactinib: Recurrent LGSOC Avutometinib + Defactinib: Metastatic Pancreatic Cancer Avutometinib + KRAS G12C Inhibitors: NSCLC GFH375/VS - 7375: Oral G12D (ON/OFF) Inhibitor Driving Momentum in 2024: Recap of Recent Key Achievements x Received FDA Orphan Drug Designation x Initiated
Slide 5: Clinical Program Designed for Success in LGSOC, Signal Generation
Clinical Program Designed for Success in LGSOC, Signal GenerationRegimenIND-Enabling/Preclinical Phase 1Avutometinib + Defactinib: Recurrent LGSOCRAF/MEKClamp+ FAKiRAF/MEKClamp+ FAKiAvutometinib + KRAS G12C Inhibitors: NSCLCRAF/MEK Clamp+KRAS G12Ci(sotorasib) + FAKiRAF/MEK Clamp+KRAS G12Ci(adagrasib
Slide 6: Avutometinib RAF/MEK Clamp Program Overview
Avutometinib RAF/MEK Clamp Program Overview
Slide 7: Avutometinib is a Differentiated Agent with Potential to Serve as Backbone for Combinations
7 Avutometinib is a Differentiated Agent with the Potential to Serve as the Backbone for Combinations Across RAS Pathway - Driven Cancers • Unique RAF/MEK clamp mechanism of action • Novel intermittent dosing schedule; convenient oral regimen • Orphan Drug Designation for avutometinib alone or in co
Slide 8: Avutometinib is a Unique Small Molecule RAF/MEK Clamp
8 Avutometinib is a Unique Small Molecule RAF/MEK Clamp Contrasting Mechanism of Action vs. MEK - Only Inhibitors Coma et al., AACR 2022; Ishii et al., Cancer Res , 2013; Lito et al., Cancer Cell , 2014 RTK Growth factors Avutometinib RAS RAF MEK ERK Tumor Growth Avutometinib conc. (µmol/L) Avutomet
Slide 9: Avutometinib Inhibits Cell Proliferation Across Multiple RAS/MAPK Pathway Alterations
9 Avutometinib Inhibits Cell Proliferation Across Multiple RAS/MAPK Pathway Alterations and Multiple Solid Tumor Histologies Verastem, unpublished data S W 1 4 6 3 M I A P A C A 2 H 3 5 8 H 1 3 7 3 S W 8 3 7 H 2 1 2 2 H 2 0 3 0 S W 1 5 7 3 H P A C A S P C 1 H P A F I I S N U - C 2 B L S 5 1 3 L S 1
Slide 10: Strong Scientific Rationale for Avutometinib and FAK Inhibitor Combination
10 Strong Scientific Rationale for Avutometinib and FAK Inhibitor Combination Anti - Tumor Efficacy in KRAS Mutant and Wild - Type LGSOC models KRAS mutant LGSOC PDX model RTK RAS RAF MEK ERK YAP Growth factors β α Y397 Integrin FAK Extracellular Matrix SRC RhoA Tumor Growth P AKT avutometinib defac
Slide 11: Optimized Dosing Schedule Defined: Favorable Tolerability Profile
11 Optimized Dosing Schedule Defined: Favorable Tolerability Profile with Novel Intermittent Dosing Regimen Avutometinib monotherapy Daily at MTD N=6 28 - day cycle RP2D Avutometinib monotherapy 4mg twice weekly N=26 28 - day cycle RP2D (Avutometinib 3.2mg twice weekly + defactinib 200mg twice daily
Slide 12: RAS Pathway-Driven Cancers and Rational Avutometinib Combinations
RAS Pathway - Driven Cancers and Rational Avutometinib Combinations
Slide 13: Indications, Regimens and Trials Overview
13 Indication Incidence/ Prevalence Regimen Setting Phase Collaborator RAMP301 LGSOC Avutometinib + defactinib Relapsed Refractory molecularly profiled LGSOC Gynecologic Cancers RAMP201 LGSOC Avutometinib + defactinib Relapsed Refractory molecularly profiled LGSOC Gynecologic Basket* Avutometinib +
Slide 14: Avutometinib Defactinib in Low-Grade Serous Ovarian Cancer
Avutometinib Defactinib in Low - Grade Serous Ovarian Cancer
Slide 15: LGSOC Unmet Need & Opportunity
15 LGSOC Unmet Need & Opportunity • LGSOC is a less common type of ovarian cancer that is often diagnosed in younger women o LGSOC is a unique disease that is distinct from high - grade serous ovarian cancer (HGSOC) in its pathology, protracted clinical course and low response to chemotherapy and th
Slide 16: LGSOC is a Unique RAS Pathway-Driven Cancer with a High Unmet Need
16 LGSOC is a Unique RAS Pathway - Driven Cancer with a High Unmet Need LGSOC is a type of ovarian cancer that disproportionately affects younger women Patients often experience significant pain and suffering from their disease over time A slow growing cancer, that has a median survival of almost 10
Slide 17: Low-Grade and High-Grade Serous Ovarian Cancer Are Different Diseases
17 Low - Grade and High - Grade Serous Ovarian Cancer Are Different Diseases Variable LGSOC HGSOC Nuclear atypia Uniform round to oval with little variation +++ Marked variation Mitotic Index <12 mitoses per 10 hpf >12 mitoses per 10 hpf Chromatin and variation in size of nucleus Little Marked (nucl
Slide 18: Recurrent LGSOC: High Medical Need, No Approved Treatment Options
18 Recurrent LGSOC: High Medical Need No Approved Treatment Options – Limited Benefit from Available Therapies 1 NCCN guidelines v1.2023 No Category 1 recommendations (high - level evidence). Category 2a (lower - level evidence with uniform NCCN consensus) unless otherwise indicated f: There is no s
Slide 19: Recent LGSOC Trials Highlight High Unmet Need
19 Recent LGSOC Trials Highlight High Unmet Need Trial Number of Prior Systemic Therapies Median (range) Prior MEK allowed Prior Bevacizumab Therapy Response Rate ORR Image Assessment Median PFS Months (95% CI) Discontinuation Rate due to AEs GOG 281 1 2 (1 - 10) No * Low % SoC (n=130) 6% 95% CI: (3
Slide 20: FRAME Study: High Rate of Durable Responses with Avutometinib and Defactinib
20 FRAME Study: High Rate of Durable Responses with the Combination of Avutometinib and Defactinib in Recurrent LGSOC (n=26) 28 - day cycles DoR: Duration of Response PFS: Progression free survival NR: Not reached • Overall response rate (ORR) = 42% (11 confirmed PRs/26) o KRAS mutant ORR = 58% (7 c
Slide 21: RAMP 201 Trial Design
21 Avutometinib Mono N=72 (incl Part A + B) Avutometinib + Defactinib N=72 (incl Part A+B) Avutometinib + Defactinib N=32 * Dosing: Avutometinib + Defactinib combo: Avutometinib 3.2 mg PO 2x/wk 21/28 days + Defactinib 200 mg PO BID: 21/28 days; Avutometinib monotherapy: Avutometinib 4.0 mg PO 2x/wk
Slide 22: Updated Data from Part A of RAMP 201
22 “These results demonstrate avutometinib in combination with defactinib can deliver high response rates for patients with recurrent LGSOC with a promising safety profile to date. It is particularly encouraging to see extensive tumor shrinkage in women who have had several treatment lines, includin
Slide 23: Recent LGSOC Trials Show Overall Response Rate >40% with Avutometinib + Defactinib
23 Recent LGSOC Trials with Standard of Care Highlight High Unmet Need: Current Trials with Avutometinib + Defactinib Show Overall Response Rate >40% Trial Median Number of Prior lines of Therapy Prior MEK Allowed Prior Bevacizu mab Therapy Response Rate ORR Image Assessment Median PFS Months (95% C
Slide 24: RAMP Part A: Heavily Pre-Treated Patient Population
24 RAMP 201 Part A: Heavily Pre - Treated Patient Population Prior Platinum - Based Chemotherapy, Endocrine Therapy, Bevacizumab in Most Patients; Prior MEK Inhibitor Therapy was Permitted Avutometinib Monotherapy Avutometinib + Defactinib KRAS mt (n=16) KRAS wt (n=17) Total (n=33) KRAS mt (n=16) KR
Slide 25: RAMP Part A: Evaluable Patient Population
25 RAMP 201 Part A: Evaluable Patient Population * Positive ORR Confirmed by Blinded Independent Central Review (BICR) Support Avutometinib + Defactinib as Go Forward Regimen in LGSOC - Regardless of KRAS Status Avutometinib Avutometinib + Defactinib KRAS mt (n=15) KRAS wt (n=15) Total (n=30) KRAS m
Slide 26: High Disease Control Rate and Tumor Reduction in Recurrent LGSOC
26 Combination of Avutometinib and Defactinib High Disease Control Rate + Tumor Reduction in Recurrent LGSOC Part A (Evaluable for Efficacy *) Confirmed ORR: 45% Confirmed/Unconfirmed ORR: 52% Disease Control Rate (SD+PR): 90% Patients still on study treatment: 45% Minimum follow - up: 12 months RAM
Slide 27: RAMP (Part A) Interim Analysis - Blinded ICR
27 RAMP 201 (Part A) Interim Analysis - Blinded ICR N=29 Combination of Avutometinib and Defactinib Initial Data from RAMP 201 Trial Reinforce Findings from FRAME Trial Reference: Banerjee et al., ESMO Sept 2021 FRAME Investigator Assessment N=26 ASCO 2023 data -80 -60 -40 -20 0 20 B e s t R e s p o
Slide 28: RAMP 201: Safety and Tolerability Profile
28 Avutometinib + Defactinib (n=81) Any Grade Grade ≥3 Nausea, n (%) 50 (61.7) 0 Diarrhea, n (%) 40 (49.4) 3 (3.7) Blood CPK increased, n (%) 39 (48.1) 15 (18.5) Oedema peripheral, n (%) 34 (42.0) 1 (1.2) Vomiting, n (%) 30 (37.0) 0 Vision blurred, n (%) 29 (35.8) 0 Dermatitis acneiform, n (%) 28 (3
Slide 29: RAMP-301: Phase 3 Confirmatory Randomized Trial
29 Phase 3 Confirmatory Trial – Randomized Controlled Trial (RCT) □ RAMP - 301: Avutometinib + Defactinib Recurrent LGSOC KRAS mt+wt Prior platinum chemotherapy Prior MEKi allowed Prior Bev allowed Measurable disease (RECIST 1.1) *A+D Dosing: Avutometinib 3.2 mg PO 2x/ wk 21/28 days + Defactinib 200
Slide 30: RAMP Part A Interim Data Support Meaningful Market Potential
30 RAMP 201 Part A Interim Data Support Meaningful Market Potential for All Recurrent LGSOC Regardless of KRAS Status with Long Duration of Therapy NSCLC KRAS G12C 3 Pancreatic Cancer 3 LGSOC 3 Endometrioid Cancer 3 Metastatic uveal melanoma 3 ~6K patients US 1 ~80K patients WW 1 Patient - months of
Slide 31: Plan to File for Accelerated Approval
31 Plan to File for Accelerated Approval with Mature RAMP 201 and FRAME Study Results • Plan to file for accelerated approval based on the totality of the data from the RAMP 201 and FRAME studies • Report updated topline data from RAMP 201 trial in H1 2024 • Continue site activation (sites currently
Slide 32: Avutometinib with KRAS G12C Inhibitors in Non-Small Cell Lung Cancer
Avutometinib with KRAS G12C Inhibitors in Non - Small Cell Lung Cancer
Slide 33: High Unmet Need in Refractory NSCLC Adenocarcinoma
33 High Unmet Need in Refractory NSCLC Adenocarcinoma Advanced or Metastatic NSCL Cancer Recommend Histologic and Molecular Subtyping 5 Appropriate targeted agent Chemotherapy Docetaxel Gemcitabine Pemetrexed Prior PD - (L)1 No Prior PD - (L)1 PD - (L)1 Chemo PD - (L)1 PD - (L)1 single agent or PD -
Slide 34: Preclinical Synergy of Avutometinib + G12C Inhibitors
34 0 10 20 30 0 500 1000 1500 2000 Tumor growth Days after first dose T u m o r v o l u m e ( m m 3 + / - S E M ) vehicle sotorasib sotorasib + avutometinib sotorasib + avutometinib + FAKi avutometinib trametinib **** **** **** Preclinical Synergy of Avutometinib + G12C Inhibitors in KRAS G12C Model
Slide 35: Avutometinib + FAKi Restores Sotorasib Efficacy in G12Ci-Resistant Models
35 Avutometinib FAKi Restores Anti - Tumor Efficacy of Sotorasib in G12Ci - Resistant KRAS G12C Models Avutometinib is effective against acquired KRAS mutations that occur clinically upon progression on G 1 2C inhibitors Addition of avutometinib + FAKi restores anti - tumor activity after progressio
Slide 36: RAMP 203: Phase 1/2 Trial of Avutometinib + Sotorasib + Defactinib
36 Patients must have a KRAS G12C mutation determined using validated test Treatment with at least 1 but no more than 3 prior systemic regimens, for Stage 3B - C or 4 NSCLC* Patient may have previously received adjuvant chemotherapy for earlier - stage disease Measurable disease according to RECIST
Slide 37: RAMP 203: Objective Responses in KRAS G12C NSCLC
37 RAMP 203: Objective Responses in KRAS G12C NSCLC Sotorasib + Avutometinib Combination *On treatment at time of data cutoff; + Patient with - 38.4% tumor reduction classified as SD due to disease progression prior to confirmatory scan. Reference: Awad et al., EORTC - NCI – AACR Conference Oct 2023
Slide 38: RAMP 204: Phase 1/2 Trial of Avutometinib + Adagrasib
38 RAMP 204: Phase 1/2 Trial of Avutometinib + KRAZATI TM (Adagrasib) in KRAS G12C Advanced NSCLC Patients must have a KRAS G12C mutation determined using validated test Treatment with at least 1 but no more than 3 prior systemic regimens, for Stage 3B - C or 4 NSCLC Patient must have received prior
Slide 39: Avutometinib Combinations in Pancreatic Cancer and Colorectal Cancer
Avutometinib Combinations in Pancreatic Cancer and Colorectal Cancer
Slide 40: Avutometinib + FAKi with Chemotherapy in Pancreatic Cancer Mouse Model
40 Addition of Avutometinib + FAKi to Chemotherapy Induces Tumor Regression and Increases Survival in a KRAS/p53 Pancreatic Cancer Mouse Model x The combination of avutometinib + FAKi induces tumor growth inhibition and increases survival but does not induce tumor regression x Addition of chemo (gem
Slide 41: RAMP 205: Phase 1/2 Trial in Front Line Metastatic Pancreatic Cancer
41 RAMP 205: Phase 1/2 Trial of Avutometinib/Defactinib + GEMZAR TM (Gemcitabine)/ABRAXANE TM (Nab - paclitaxel) in Front Line Metastatic Pancreatic Cancer Patients with confirmed metastatic pancreatic ductal adenocarcinoma Eligible for treatment in the first - line setting with standard gemcitabine
Slide 42: Avutometinib with anti-EGFR mAb Induces Tumor Regression in Colorectal Model
42 Combination of Avutometinib with anti - EGFR mAb Induces Tumor Regression in a KRAS mt Colorectal PDX Model • Avutometinib + anti - EGFR (panitumumab) induces tumor regression in a KRAS mutant CRC patient - derived xenograft model • G12Ci + anti - EGFR (sotorasib + panitumumab and adagrasib + cet
Slide 43: Discovery Efforts
Discovery Efforts
Slide 44: Discovery and Development Collaboration with GenFleet
44 Discovery and Development Collaboration with GenFleet Strengthens Pipeline Targeting RAS Pathway - Driven Cancers • Increases the breadth of Verastem’s oncology pipeline with strategically - aligned RAS pathway focus o Exclusive options for Verastem to exclusively license up to 3 programs with de
Slide 45: Rationale for Inhibitor of KRAS G12D (ON/OFF)
45 Rationale for Designing a Potent and Selective Orally Bioavailable Inhibitor of KRAS G12D (ON/OFF) for the Treatment of Patients with KRAS G12D Cancers Hofmann et al., Cancer Discovery 2022 KRAS G12D (ON/OFF) inhibitor KRAS G12D is the most frequent KRAS mutation in human cancer Ideal to inhibit
Slide 46: GFH375 (VS-7375) is an Oral KRAS G12D (ON/OFF) Inhibitor
46 GFH375 (VS - 7375) is an Oral KRAS G12D (ON/OFF) Inhibitor • GFH375 (VS - 7375) is a potent and selective orally bioavailable inhibitor of KRAS G12D (ON/OFF) with potent anti - tumor efficacy demonstrated across preclinical models • Dual inhibitor of ON (GTP) and OFF (GDP) states of KRAS G12D • O
Slide 47: Financials
Financials
Slide 48: Key Financial Statistics
48 Key Financial Statistics Cash, cash equivalents & investments $137.1M GAAP Operating Expenses $31.1M Non - GAAP Operating Expenses* $29.5M Shares Outstanding 25.3M** As of and for the quarter ended December 31, 2023 • Oxford Finance LLC Credit Facility • Up to $150M available in a series of term
Slide 49: Avutometinib Patent Exclusivity
49 Avutometinib Patent Exclusivity Composition of Matter Method of Making Sept 2032 Dosing Protocol May 2038 Combination w/ Defactinib Dec 2042 Feb 2027 + 5 yrs (PTE) = 2032 Sept 2040 Solid Form PTE 2041 - 2042 if issued Methods or Treating; Combinations
Slide 50: Experienced Senior Management Team
50 Experienced Senior Management Team Dan Calkins Chief Financial Officer Mike Crowther Chief Commercial and Business Strategy Officer Technical Accounting Consultant - CFGI PwC LLP CBO, Minerva Biotechnologies Interim US lead and VP of US Marketing, Kite Pharma Celgene Daniel Paterson President and
Slide 51: Verastem Oncology
W VERASTEM ONCOLOGY