Verastem, Inc. · NASDAQ:VSTM
Verastem — Investor Presentation (June 2023)
63 slides from Verastem's investor presentation, Jun 8, 2023
Slide 1: Corporate Presentation June 2023
Corporate Presentation June 2023
Slide 2: Disclaimers
2 Disclaimers This presentation includes forward - looking statements about, among other things, Verastem Oncology’s programs and product candid ates, including anticipated regulatory submissions, approvals, performance and potential benefits of Verastem Oncology’s product candidates, as well as Ver
Slide 3: Verastem Oncology Well Positioned to Capitalize on Growth Opportunities
3 We are a biopharmaceutical company committed to developing and commercializing new medicines for patients battling cancer Verastem Oncology Well Positioned to Capitalize on Growth Opportunities Avutometinib (VS - 6766; RAF/MEK clamp) and defactinib (FAK inhibitor) are clinically active against RAS
Slide 4: Key VSTM Achievements & Anticipated Milestones
4 Key VSTM Achievements & Anticipated Milestones LGSOC NSCLC 1H2022 RAMP 201 Selection Phase Complete; Initiated enrollment of Expansion Phase RAMP 202 Complete enrollment of Selection Phase 2H2022 Additional Indications Initiate combo study of avutometinib + cetuximab in KRAS mt CRC * RAMP 201 Sele
Slide 5: Avutometinib is a Differentiated Agent with Potential to Serve as Backbone for Combinations
5 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 • Breakthrough Therapy Designation for combination of avu
Slide 6: Strong Scientific Rationale for Avutometinib and FAK Inhibitor Combination
6 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 defact
Slide 7: LGSOC Unmet Need & Opportunity
7 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 thu
Slide 8: RAMP 201 Trial Design
8 Avutometinib Mono N=72 (incl Part A + B) Avutometinib + Defactinib N=72 (incl Part A+B) Avutometinib + Defactinib *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 21/28 d
Slide 9: RAMP ASCO 2023 Update
RAMP 201 ASCO 2023 Update
Slide 10: Updated Data from Part A of RAMP
10 Updated Data from Part A of RAMP 201 “These results demonstrate avutometinib in combination with defactinib can deliver high response rates for patients with recu rre nt LGSOC with a promising safety profile to date. It is particularly encouraging to see extensive tumor shrinkage in women who hav
Slide 11: Recent LGSOC Trials with Standard of Care Highlight High Unmet Need
11 Recent LGSOC Trials with Standard of Care Highlight High Unmet Need in Recurrent LGSOC Trial Median Number of Prior lines of Therapy Prior MEK Allowed Prior Bevaciz umab Therapy Response Rate ORR Image Assessment Median PFS Months (95% CI) Discontinuation Rate Due to AEs GOG 281 1 2 (1 - 10) No *
Slide 12: Current Trials with Combination of Avutometinib and Defactinib
12 Current Trials with Combination of Avutometinib and Defactinib Consistent Overall Response Rate of ~45% Trial Median Number of Prior lines of Therapy Prior MEK Allowed Prior Bevaciz umab Therapy Response Rate ORR Image Assessment Median PFS Months (95% CI) Discontinuation Rate Due to AEs FRAME 1
Slide 13: RAMP (Part A) Interim Analysis - Blinded ICR
13 RAMP 201 (Part A) Interim Analysis - Blinded ICR N=29 Go Forward Regimen: 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=24 F R A 1 0 1 0 0 7 F R A 1 0 1 0 1
Slide 14: RAMP 201: Safety and Tolerability Profile
14 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 15: Plan to File for Accelerated Approval
15 Plan to File for Accelerated Approval based on Completed RAMP 201 and FRAME Study Results • Target enrollment for primary analysis (n=72) in combination has been achieved • Plan to file for accelerated approval based on the totality of the data from the RAMP 201 and FRAME studies • Continued enro
Slide 16: Comprehensive Approach to Establish More Complete Blockade of RAS Pathway
16 Comprehensive approach to establish more complete blockade of RAS pathway & resistance pathways Indication Incidence/ Prevalence Regimen Setting Gynecologic Cancers LGSOC Avutometinib + defactinib Relapsed Refractory molecularly profiled LGSOC Gynecologic Basket* Avutometinib + defactinib Recurre
Slide 17: Broad Development Opportunities Across RAS/MAPK Pathway-Driven Cancers
17 Broad Development Opportunities Across Multiple RAS/MAPK Pathway - Driven Cancers Avutometinib High Priority Registration Indication Registration - Directed Trial Initiated in 4Q20 LGSOC 1,2 (RAMP 201) - Target enrollment reached Key Signal Finding Avutometinib + G12Ci in KRAS G12C NSCLC 2 (RAMP
Slide 18: Robust Clinical Program: Avutometinib in Multiple Combinations
18 INDICATION REGIMEN STUDY NAME PRECLINICAL PHASE 1 PHASE 2 PHASE 3 CLINICAL COLLABORATION WITH LGSOC 1 Avutometinib + defactinib RAMP 201 R/R LGSOC Avutometinib + defactinib IST - FRAME Gynecological Cancers (RAS Pathway - driven) 2 Avutometinib + defactinib IST Mesonephric 2 Avutometinib + defact
Slide 19: Key Financial Statistics
19 Key Financial Statistics Cash, cash equivalents & investments $111.2M GAAP Operating Expenses $15.7M Non - GAAP Operating Expenses* $17.8M Shares Outstanding 16.7M** As of and for the quarter ended March 31, 2023 • Oxford Finance LLC Credit Facility • Up to $150M available in a series of term loa
Slide 20: Avutometinib RAF/MEK Clamp Program Overview
Avutometinib RAF/MEK Clamp Program Overview
Slide 21: Avutometinib is a Unique Small Molecule RAF/MEK Clamp
21 Avutometinib is a Unique Small Molecule RAF/MEK Clamp Avutometinib (RAF/MEK Clamp) Mirdametinib (MEKi) Avutometinib inhibits MEK, BRAF & CRAF by trapping these molecules in inactive complexes MEK inhibitors paradoxically induce MEK phosphorylation (pMEK) by relieving ERK - dependent feedback inhi
Slide 22: Avutometinib Induces Inactive Complexes of MEK with ARAF, BRAF & CRAF
22 Avutometinib is a Unique RAF/MEK Clamp which Induces Inactive Complexes of MEK with ARAF, BRAF & CRAF Contrasting mechanism of action vs. trametinib Deborah Morrison unpublished RTK RAS RAF MEK ERK Tumor Growth Growth factors + Avutometinib Improved ERK blockade Feedback reactivation is blocked;
Slide 23: Avutometinib Inhibits Cell Proliferation Across RAS/MAPK Pathway Alterations
23 Avutometinib Inhibits Cell Proliferation Across Multiple RAS/MAPK Pathway Alterations and Multiple Solid Tumor Histologies Reference: Pachter RAS - Targeted Drug Development Summit 2022; 3D proliferation assay 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
Slide 24: Optimized Dosing Schedule Defined
24 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 25: Avutometinib Patent Exclusivity
25 Avutometinib Patent Exclusivity Composition of Matter Method of Making Sept 2032 Dosing Protocol May 2038 Combination w/ Defactinib 2041 - 2042 if issued Feb 2027 + 5 yrs (PTE) = 2032 Sept 2040 Methods of Treating PTE 2041 - 2042 if issued Combinations
Slide 26: Avutometinib Defactinib in Low-Grade Serous Ovarian Cancer
Avutometinib Defactinib in Low - Grade Serous Ovarian Cancer
Slide 27: LGSOC is a Unique RAS Pathway-Driven Cancer with a High Unmet Need
27 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 28: Low-Grade and High-Grade Serous Ovarian Cancer Are Different Diseases
28 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 29: Recurrent LGSOC: High Medical Need, No Approved Treatment Options
29 Recurrent LGSOC: High Medical Need No Approved Treatment Options – Limited Benefit from Available Therapies References: 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: T
Slide 30: Recent LGSOC Trials Highlight High Unmet Need
30 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 31: FRAME Study: Solid Foundation for Avutometinib with Defactinib in Recurrent LGSOC
31 FRAME Study: Solid Foundation for the Development of Avutometinib in Combination with Defactinib in Recurrent LGSOC (n=24) Reference: Banerjee et al., ESMO Sept 2021 Data cut off April 2021 MEKi: MEK inhibitor Bev: Bevacizumab PFS: Progression free survival NR: Not reached • Overall response rate
Slide 32: RAMP 201 Trial Design
32 Avutometinib Mono N=72 (incl Part A + B) Avutometinib + Defactinib N=72 (incl Part A+B) Avutometinib + Defactinib *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 21/28
Slide 33: RAMP ASCO 2023 Update
RAMP 201 ASCO 2023 Update
Slide 34: Updated Data from Part A of RAMP
34 Updated Data from Part A of RAMP 201 “These results demonstrate avutometinib in combination with defactinib can deliver high response rates for patients with recu rre nt LGSOC with a promising safety profile to date. It is particularly encouraging to see extensive tumor shrinkage in women who hav
Slide 35: Recent LGSOC Trials with Standard of Care Highlight High Unmet Need
35 Recent LGSOC Trials with Standard of Care Highlight High Unmet Need in Recurrent LGSOC Trial Median Number of Prior lines of Therapy Prior MEK Allowed Prior Bevaciz umab Therapy Response Rate ORR Image Assessment Median PFS Months (95% CI) Discontinuation Rate Due to AEs GOG 281 1 2 (1 - 10) No *
Slide 36: Current Trials with Combination of Avutometinib and Defactinib
36 Current Trials with Combination of Avutometinib and Defactinib Consistent Overall Response Rate of ~45% Trial Median Number of Prior lines of Therapy Prior MEK Allowed Prior Bevaciz umab Therapy Response Rate ORR Image Assessment Median PFS Months (95% CI) Discontinuation Rate Due to AEs FRAME 1
Slide 37: RAMP Part A: Heavily Pre-Treated Patient Population
37 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 38: RAMP Part A: Evaluable Patient Population
38 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 39: Go Forward Regimen: Combination of Avutometinib and Defactinib
39 Go Forward Regimen: 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
Slide 40: RAMP (Part A) Interim Analysis - Blinded ICR
40 RAMP 201 (Part A) Interim Analysis - Blinded ICR N=29 Go Forward Regimen: 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=24 F R A 1 0 1 0 0 7 F R A 1 0 1 0 1
Slide 41: RAMP 201: Safety and Tolerability Profile
41 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 42: Plan to File for Accelerated Approval
42 Plan to File for Accelerated Approval based on Completed RAMP 201 and FRAME Study Results • Target enrollment for primary analysis (n=72) in combination has been achieved • Plan to file for accelerated approval based on the totality of the data from the RAMP 201 and FRAME studies • Continued enro
Slide 43: RAMP Part A Interim Data Support Meaningful Market Potential
43 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 44: RAS Pathway-Driven Cancers and Rational Avutometinib Combinations
RAS Pathway - Driven Cancers and Rational Avutometinib Combinations
Slide 45: High Unmet Needs in Additional RAS/MAPK Pathway-Driven Cancers
45 High Unmet Needs in Additional RAS/MAPK Pathway - Driven Cancers NSCLC Incidence 3,5 : 114K Colorectal Incidence 5 : 148K Pancreatic Incidence 5 : 58K Uterine Endometrioid Incidence 4,5 : 59K Melanoma Incidence 5 : 108K Multiple Myeloma Incidence 5 : 32K Melanoma Incidence 5 : 108K Colorectal Inc
Slide 46: Vertical Blockade: Avutometinib as Backbone of Therapy
46 Vertical Blockade: Establishing Avutometinib as the Backbone of Therapy for RAS/MAPK Pathway - Driven Tumors ▪ Current Challenges • Blocking any single target in the pathway is insufficient for maximum depth and duration of anti - tumor efficacy • e.g. SHP2i, KRAS - G12Ci, KRAS - G12Di, RAFi, MEK
Slide 47: Parallel Pathway Inhibition: Avutometinib as Backbone of Therapy
47 Parallel Pathway Inhibition: Establishing Avutometinib as the Backbone of Therapy for RAS/MAPK Pathway - Driven Tumors ▪ Current Challenges • Blocking RAS pathway can be circumvented through parallel pathways • e.g. PI3K/AKT/mTOR, FAK, RhoA, YAP • Combinations of MEKi + AKTi have shown poor toler
Slide 48: Preclinical Synergy of Avutometinib in Combination with Promising Agents
48 Preclinical Synergy of Avutometinib in Combination with Promising Agents for Clinical Investigation H 2 1 2 2 S W 8 3 7 H 1 3 7 3 S W 1 5 7 3 H 3 5 8 H 2 0 3 0 M I A P A C A 2 0 10 20 30 40 50 VS-6766 + AMG 510 C o m b i n e d S y n e r g y S c o r e NSCLC Panc Synergy Antagonism Indication CRC A
Slide 49: Avutometinib Combinations in Non-Small Cell Lung Cancer
Avutometinib Combinations in Non - Small Cell Lung Cancer
Slide 50: High Unmet Need in Refractory KRAS & BRAF mt NSCLC
50 High Unmet Need in Refractory KRAS & BRAF mt 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 singl
Slide 51: Preclinical Synergy of Avutometinib + G12C Inhibitors in KRAS G12C Models
51 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 52: Acquired Resistance Mechanisms to KRAS G12Ci Support Combination with Avutometinib
52 Acquired Resistance Mechanisms to KRAS G12Ci Treatment in Patients Further Support Combination of KRAS G12Ci with Avutometinib Summary of Putative Mechanisms of Acquired Resistance to Adagrasib Treatment • Mechanisms of acquired resistance to KRAS G12Ci adagrasib treatment in patients recently re
Slide 53: RAMP 203: Phase 1/2 Trial of Avutometinib + Sotorasib
53 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 54: RAMP 204: Phase 1/2 Trial of Avutometinib + Adagrasib
54 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 55: RAMP 202: Trial of Avutometinib + Defactinib in BRAF mt NSCLC
55 RAMP 202: Phase 2 Trial of Avutometinib + Defactinib in BRAF mt NSCLC References: 1 Avutometinib 3.2 mg PO 2x/wk (21/28 days) + Defactinib 200 mg PO BID (21/28 days) Patients with Advanced NSCLC 1 - 2 prior regimens 1 prior platinum - containing chemo Prior CPI unless contraindicated Measurable d
Slide 56: Additional Avutometinib Combinations for Pancreatic, Colorectal and Melanoma
Additional Avutometinib Combinations for Pancreatic, Colorectal and Melanoma
Slide 57: Preclinical Synergy of Avutometinib/FAK Inhibition + Chemotherapy in Pancreatic Model
57 Preclinical Synergy of Avutometinib/FAK Inhibition + Chemotherapy 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 (gemcitabine + paclitaxel) to avut
Slide 58: RAMP 205: Trial in Front Line Metastatic Pancreatic Cancer
58 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 59: Avutometinib with anti-EGFR mAb Induces Tumor Regression in KRAS mt Colorectal Model
59 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 60: Avutometinib + FAK Inhibition with Checkpoint Inhibitor in Melanoma Model
60 Combination of Avutometinib + FAK Inhibition with Checkpoint Inhibitor Induces Tumor Regression in an IO - resistant BRAF V600E melanoma model • Avutometinib + IO (anti - PD - 1 + anti - CTLA - 4) induces tumor regression in an IO - resistant syngeneic BRAF V600E melanoma model (YUMM 1.7) • FAK i
Slide 61: Avutometinib Development in Multiple Combinations with Potential Early Read-Outs in 2H 2023
61 Avutometinib Development in Multiple Combinations Across RAS Pathway - Driven Tumors with Potential Early Read - Outs in 2H 2023 Indication Study KRAS G12C NSCLC RAMP 203: Avutometinib/Sotorasib combo KRAS G12C NSCLC RAMP 204: Avutometinib/Adagrasib combo Pancreatic RAMP 205: Avutometinib/Gem/Abr
Slide 62: Experienced Senior Management Team
62 Experienced Senior Management Team Brian Stuglik Chief Executive Officer Cathy Carew Chief Organizational Effectiveness Officer Louis Denis, M.D. Chief Medical Officer Principal – HR Collaborative Ironwood, ActiveBiotics, Dynogen, Tufts Health Plan CMO, Asana BioSciences Boehringer - Ingelheim, P
Slide 63: Verastem Oncology
W VERASTEM ONCOLOGY