Verastem, Inc. · NASDAQ:VSTM
Verastem — Corporate Update (January 2023)
29 slides from Verastem's corporate update, Jan 24, 2023
Slide 1: LGSOC Program Update January 24, 2023
LGSOC Program Update January 24, 2023
Slide 2: Today's Speakers
2 Today’s Speakers Brian Stuglik Chief Executive Officer, Verastem Oncology Kathleen Moore, MD Assistant Professor at University of Oklahoma Health Sciences Center, Gynecologic Oncologist at University of Oklahoma Health Stephenson Cancer Center and Investigator on RAMP 201 trial Louis Denis, MD Chi
Slide 3: Safe Harbor Statement
3 Safe Harbor Statement 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, that
Slide 4: Brian Stuglik
Brian Stuglik
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 in recurrent low - gra
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: Kathleen Moore, MD
Kathleen Moore, MD
Slide 8: LGSOC is a Unique RAS Pathway-Driven Cancer with a High Unmet Need
8 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 9: Low-Grade and High-Grade Serous Ovarian Cancer Are Different Diseases
9 Low - Grade and High - Grade Serous Ovarian Cancer Are Different Diseases Variable LGSOC (Grade 1) HGSOC (Grade 2/3) Nuclear atypia Uniform round to oval with little variation +++ Marked variation Mitotic Index <12 mitosis per 10 hpf >12 mitoses per 10 hpf Chromatin and variation in size of nucleu
Slide 10: Recurrent LGSOC: High Medical Need, No Approved Treatment Options
10 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 11: Recent LGSOC Trials Highlight High Unmet Need
11 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 3 (1 - 10) No * Low % SoC 6% INV 7.2 (5.6 - 9.9
Slide 12: FRAME Study: Foundation for Avutometinib plus Defactinib in Recurrent LGSOC
12 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 -70 -60 -50 -40 -30 -20 -10 0 10 20 Response by RECIST Time (cycles) R e s p o n s e ( % c h a n g e f r o m b a s e l i n e ) FRA101001 - KRAS G12V FRA101002 - KRAS G12A FRA101009 - KRAS G12D FRA101012 - KRAS WT FRA101007 - KRAS WT FRA101014
Slide 13: Louis Denis, MD
Louis Denis, MD
Slide 14: RAMP 201 Registration-Directed Phase 2 Trial Design
14 Avutometinib Mono N=72 (incl Part A + B) Avutometinib + Defactinib N=72 (incl Part A+B) Avutometinib + Defactinib *Dosing: Defactinib + VS - 6766 combo: Defactinib 200mg PO BID: 21/28 days + VS - 6766 3.2mg PO 2x/ wk 21/28 days; VS - 6766 monotherapy: VS6766 4.0 mg PO 2x/ wk 21/28 days **Expansio
Slide 15: RAMP 201 Trial Design and Part A Selection Phase
15 Avutometinib + Defactinib *Dosing: Defactinib + VS - 6766 combo: Defactinib 200mg PO BID: 21/28 days + VS - 6766 3.2mg PO 2x/ wk 21/28 days; VS - 6766 monotherapy: VS6766 4.0 mg PO 2x/ wk 21/28 days **Expansion Phase – final sample size to be adjusted based on adaptive design KRAS mt (n=16) KRAS
Slide 16: RAMP Part A: Heavily Pre-Treated Patient Population
16 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 17: RAMP Part A: Evaluable Patient Population and ORR
17 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
Slide 18: Go Forward Regimen: Avutometinib and Defactinib Best Response
18 K R A S - W T K R A S - M U K R A S - W T K R A S - W T K R A S - W T K R A S - M U K R A S - M U K R A S - W T K R A S - W T K R A S - M U K R A S - M U K R A S - M U K R A S - M U K R A S - M U K R A S - W T K R A S - W T K R A S - W T K R A S - W T K R A S - M U K R A S - M U K R A S - M U K R
Slide 19: RAMP Part A Interim Analysis Reinforces FRAME Findings
19 Progressive disease with 118% increase 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 Assessme
Slide 20: Treatment-Related Adverse Events
20 Any Grade (%) Grade ≥ 3 (%) Avutometinib Monotherapy Avutometinib + Defactinib Avutometinib Monotherapy Avutometinib + Defactinib KRAS mt (n=26) % KRAS wt (n=38) % Total (n=64) % KRAS mt (n=22) % KRAS wt (n=35) % Total (n=57) % KRAS mt (n=26) % KRAS wt (n=38) % Total (n=64) % KRAS mt (n=22) % KRA
Slide 21: Positive Interim Data Supports Combination for Continued Development
21 Positive Interim Data Supports Selection of Combination of Avutometinib + Defactinib for Continued Development in Recurrent LGSOC – Regardless of KRAS Status Planned Interim Analysis of RAMP - 201 (ENGOTov60/GOG3052) trial • Registration - directed Phase 2 trial of avutometinib +/ - defactinib in
Slide 22: Dan Paterson
Dan Paterson
Slide 23: RAMP Part A Results and FDA Feedback Establish Path to Accelerated Filing
23 RAMP 201 Part A Results and FDA Feedback Establish Path to Accelerated Filing • 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 enrollment in RA
Slide 24: Meaningful Market Potential for All Recurrent LGSOC
24 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 25: RAMP Part A Update Advancing Path to Accelerated Filing
25 RAMP 201 Part A Update Advancing Path to Accelerated Filing • LGSOC is a unique RAS pathway - driven cancer with an unacceptably high unmet need • The unique RAF/MEK clamp mechanism of action and novel intermittent dosing schedule of avutometinib make it an attractive combination partner in RAS p
Slide 26: Q&A
Q&A
Slide 27: Verastem Oncology
W VERASTEM ONCOLOGY
Slide 28: Efficacy and Tolerability of Avutometinib and Defactinib in LGSOC
28 Efficacy and Tolerability of Avutometinib and Defactinib in LGSOC A Head - to - Head Study Has Not Been Performed 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 AE
Slide 29: Avutometinib Development in Multiple Combinations Across RAS Pathway-Driven Tumors
29 Avutometinib Development in Multiple Combinations Across RAS Pathway - Driven Tumors with Potential Early Read - Outs in 2H 2023 Study Study Population RAMP 203: Sotorasib combo KRAS G12C NSCLC RAMP 204: Adagrasib combo KRAS G12C NSCLC RAMP 205: Gem/Abraxane/ Defactinib combo Pancreatic Everolimu