Verastem, Inc. · NASDAQ:VSTM
Verastem — Investor Presentation (September 2023)
65 slides from Verastem's investor presentation, Sep 12, 2023
Slide 1: Corporate Presentation September 2023
Corporate Presentation September 2023
Slide 2: Disclaimers
2 Disclaimers This presentation includes forward-looking statements about, among other things, Verastem Oncology’s programs and product candidates, including anticipated regulatory submissions, approvals, performance and potential benefits of Verastem Oncology’s product candidates, as well as Verast
Slide 3: 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 p
Slide 4: Key VSTM Achievements & Anticipated Milestones
4 Key VSTM Achievements & Anticipated Milestones LGSOC NSCLC 1H2023 3Q2023 Additional Indications RAMP 201 Complete target enrollment of Expansion Phase Initiate combo study of avutometinib + pembrolizumab in BRAF mt melanoma * *Investigator-sponsored research **RAMP 201 update expected to be provid
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 avuto
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 defactinib
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 thus
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 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 2
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 recurrent LGSOC with a promising safety profile to date. It is particularly encouraging to see extensive tumor shrinkage in women who have
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 2811 2 (1-10) No * Lo
Slide 12: Current Trials with Avutometinib and Defactinib: Consistent ORR of ~45%
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 FRAME1 3
Slide 13: RAMP (Part A) Interim Analysis and FRAME Findings
13 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=24 FRA101007 FRA101014 FRA101042 FRA101012 FRA103003 FRA
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 • The Company pl
Slide 16: Forward Plan: Confirmatory Randomized Controlled Trial RAMP-301
16 Forward Plan: Confirmatory Trial – Randomized Controlled Trial (RCT) ❖RAMP-301: Prospective Randomized Controlled Trial Confidential. © Verastem Inc. 2023 Recurrent LGSOC KRAS mt+wt Prior platinum chemotherapy Prior MEKi allowed Prior Bev allowed Measurable disease (RECIST 1.1) • A+D
Slide 17: Comprehensive Approach to Blockade of RAS Pathway & Resistance Pathways
17 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 18: Discovery and Development Collaboration with GenFleet
18 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 option for Verastem to license up to 3 programs with development and com
Slide 19: Broad Development Opportunities Across RAS/MAPK Pathway-Driven Cancers
19 Broad Development Opportunities Across Multiple RAS/MAPK Pathway-Driven Cancers R Avutometinib egistration-Directed Clinical Trials Signal Finding Clinical Trials RAS Pathway Dependent Cancers Biomarker Selection Rational Combination s High Priority Registration Indication Registration-Directed T
Slide 20: Robust Clinical Program: Avutometinib in Multiple Combinations
20 INDICATION REGIMEN STUDY NAME PRECLINICAL PHASE 1 PHASE 2 PHASE 3 CLINICAL COLLABORATION WITH LGSOC1 Avutometinib + defactinib RAMP 201 R/R LGSOC Avutometinib + defactinib IST-FRAME Gynecological Cancers (RAS Pathway-driven) Avutometinib + defactinib IST Mesonephric2 Avutometinib + defactinib IST
Slide 21: Key Financial Statistics
21 Key Financial Statistics Cash, cash equivalents & investments $183.1M GAAP Operating Expenses $20.3M Non-GAAP Operating Expenses* $18.9M Shares Outstanding 25.2M** As of and for the quarter ended June 30, 2023 • Oxford Finance LLC Credit Facility • Up to $150M available in a series of term loans
Slide 22: Avutometinib RAF/MEK Clamp Program Overview
Avutometinib RAF/MEK Clamp Program Overview
Slide 23: Avutometinib is a Unique Small Molecule RAF/MEK Clamp
23 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 in
Slide 24: Avutometinib Induces Inactive Complexes of MEK with ARAF, BRAF & CRAF
24 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 25: Avutometinib Inhibits Cell Proliferation Across RAS/MAPK Pathway Alterations
25 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 SW1463 MIAPACA2 H358 H1373 SW837 H2122 H2030 SW1573 HPAC ASPC1 HPAFII SNU-C2B LS513 LS 18
Slide 26: Optimized Dosing Schedule Defined
26 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) N=
Slide 27: Avutometinib Patent Exclusivity
27 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 28: Avutometinib + Defactinib in Low-Grade Serous Ovarian Cancer
Avutometinib Defactinib in Low-Grade Serous Ovarian Cancer
Slide 29: LGSOC is a Unique RAS Pathway-Driven Cancer with High Unmet Need
29 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 y
Slide 30: Low-Grade and High-Grade Serous Ovarian Cancer Are Different Diseases
30 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 (nuclear
Slide 31: Recurrent LGSOC: High Medical Need, No Approved Treatment Options
31 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: There
Slide 32: Recent LGSOC Trials Highlight High Unmet Need
32 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 2811 2 (1-10) No * Low % SoC (n=130) 6% 95% CI: (3%,
Slide 33: FRAME Study Foundation for Avutometinib plus Defactinib
33 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 34: RAMP 201 Trial Design
34 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 35: RAMP ASCO 2023 Update
RAMP 201 ASCO 2023 Update
Slide 36: Updated Data from Part A of RAMP
36 Updated Data from Part A of RAMP 201 “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
Slide 37: Recent LGSOC Trials with Standard of Care Highlight High Unmet Need
37 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 2811 2 (1-10) No * Lo
Slide 38: Current Trials with Avutometinib and Defactinib: Consistent ORR of ~45%
38 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 FRAME1 3
Slide 39: RAMP Part A: Heavily Pre-Treated Patient Population
39 RAMP 201 Part A: Heavily Pre-Treated Patient Population Prior Platinum-Based Chemotherapy, Endocrine Therapy, Bevacizumab in Most Patients; Prior MEK InhibitorTherapy was Permitted Avutometinib Monotherapy Avutometinib + Defactinib KRAS mt (n=16) KRAS wt (n=17) Total (n=33) KRAS mt (n=16) KRAS wt
Slide 40: RAMP Part A: Evaluable Patient Population
40 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 mt
Slide 41: High Disease Control Rate and Tumor Reduction in Recurrent LGSOC
41 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 RAMP
Slide 42: RAMP (Part A) Interim Analysis and FRAME Findings
42 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=24 FRA101007 FRA101014 FRA101042 FRA101012 FRA103003 FRA
Slide 43: RAMP 201: Safety and Tolerability Profile
43 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 44: Plan to File for Accelerated Approval
44 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 • The Company pl
Slide 45: Interim Data Support Meaningful Market Potential for Recurrent LGSOC
45 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 G12C3 Pancreatic Cancer3 LGSOC3 Endometrioid Cancer3 Metastatic uveal melanoma3 ~6K patients US1 ~80K patients WW1 Patient-months of Therapy
Slide 46: RAS Pathway-Driven Cancers and Rational Avutometinib Combinations
RAS Pathway-Driven Cancers and Rational Avutometinib Combinations
Slide 47: High Unmet Needs in Additional RAS/MAPK Pathway-Driven Cancers
47 High Unmet Needs in Additional RAS/MAPK Pathway-Driven Cancers NSCLC Incidence3,5: 114K Colorectal Incidence5 : 148K Pancreatic Incidence5 : 58K Uterine Endometrioid Incidence4,5: 59K Melanoma Incidence5 : 108K Multiple Myeloma Incidence5 : 32K Melanoma Incidence5 : 108K Colorectal Incidence7 : 1
Slide 48: Vertical Blockade: Avutometinib as Backbone of Therapy
48 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, MEKi, ERKi
Slide 49: Parallel Pathway Inhibition: Avutometinib as Backbone of Therapy
49 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 tolerab
Slide 50: Preclinical Synergy of Avutometinib with Promising Agents
50 Preclinical Synergy of Avutometinib in Combination with Promising Agents for Clinical Investigation H2122 SW837 H1373 SW1573 H358 H2030 MIAPACA2 0 10 20 30 40 50 VS-6766 + AMG 510 Combined Synergy Score NSCLC Panc Synergy Antagonism Indication CRC Avutometinib + G12Ci (sotorasib) H2122 SW837 SW15
Slide 51: Avutometinib Combinations in Non-Small Cell Lung Cancer
Avutometinib Combinations in Non-Small Cell Lung Cancer
Slide 52: High Unmet Need in Refractory KRAS & BRAF mt NSCLC
52 High Unmet Need in Refractory KRAS & BRAF mt NSCLC Adenocarcinoma Advanced or Metastatic NSCL Cancer Recommend Histologic and Molecular Subtyping5 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 a
Slide 53: Preclinical Synergy of Avutometinib + G12C Inhibitors in KRAS G12C Models
53 0 10 20 30 0 500 1000 1500 2000 Tumor growth Days after first dose Tumor volume (mm 3 +/- SEM) vehicle sotorasib sotorasib + avutometinib sotorasib + avutometinib + FAKi avutometinib trametinib **** **** **** Preclinical Synergy of Avutometinib + G12C Inhibitors in KRAS G12C Models Synergy of avu
Slide 54: Acquired Resistance Mechanisms to KRAS G12Ci Support Combination with Avutometinib
54 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 55: RAMP 203: Avutometinib + Sotorasib in KRAS G12C NSCLC
55 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 REC
Slide 56: RAMP 204: Avutometinib + Adagrasib in KRAS G12C NSCLC
56 RAMP 204: Phase 1/2 Trial of Avutometinib + KRAZATITM (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 pr
Slide 57: RAMP 202: Avutometinib + Defactinib in BRAF mt NSCLC
57 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 Measura
Slide 58: Additional Avutometinib Combinations for Pancreatic, Colorectal and Melanoma
Additional Avutometinib Combinations for Pancreatic, Colorectal and Melanoma
Slide 59: Preclinical Synergy of Avutometinib/FAK Inhibition + Chemotherapy in Pancreatic Model
59 Preclinical Synergy of Avutometinib/FAK Inhibition + Chemotherapy in a KRAS/p53 pancreatic cancer mouse model ✓ The combination of avutometinib + FAKi induces tumor growth inhibition and increases survival but does not induce tumor regression ✓ Addition of chemo (gemcitabine + paclitaxel) to avut
Slide 60: RAMP 205: Trial in Front Line Metastatic Pancreatic Cancer
60 RAMP 205: Phase 1/2 Trial of Avutometinib/Defactinib + GEMZARTM (Gemcitabine)/ABRAXANETM (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 a
Slide 61: Avutometinib with anti-EGFR mAb in KRAS mt Colorectal Model
61 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 + cetuximab)
Slide 62: Avutometinib + FAK Inhibition with Checkpoint Inhibitor in Melanoma Model
62 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 inhibition de
Slide 63: Avutometinib Development in Multiple Combinations with Potential Early Read-Outs in 2H 2023
63 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/Abraxan
Slide 64: Experienced Senior Management Team
64 Experienced Senior Management Team 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, Pfizer Daniel Paterson President
Slide 65: Verastem Oncology
\W VERASTEM ONCOLOGY