Verastem, Inc. · NASDAQ:VSTM
Verastem — Investor Presentation (June 2022)
55 slides from Verastem's investor presentation, Jun 6, 2022
Slide 1: Corporate Presentation June 2022
Corporate Presentation June 2022
Slide 2: Safe Harbor Statement
2 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 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 VS - 6766 (RAF/MEKi) and defactinib (FAKi) are clinically active against RAS mutant cancers 30% of all h
Slide 4: Key VSTM Milestones 2021-2022
4 Key VSTM Milestones 2021 - 2022 LGSOC NSCLC 1H2021 2H2021 1Q2022 RAMP - 201 Amended to Include KRAS wt patients in Selection Phase RAMP - 201 Target enrollment of Selection Phase Complete Initiated enrollment of Expansion Phase RAMP - 202 Complete enrollment of Selection Phase Updated data from FR
Slide 5: RAF/MEK Clamp Program Overview
VS - 6766 RAF/MEK Clamp Program Overview
Slide 6: VS-6766 is a differentiated, potentially best-in-class asset
6 VS - 6766 is a differentiated, potentially best - in - class asset applicable across multiple patient populations • Unique dual RAF/MEK targeting mechanism of action • Novel intermittent dosing schedule; convenient oral regimen • Breakthrough Therapy Designation in recurrent low - grade serous ova
Slide 7: High Priority Lead Indications with Multiple Growth Opportunities
7 High Priority Lead Indications with Multiple Growth Opportunities VS - 6766 High Priority Registration Indications Registration - Directed Trials Initiated in 4Q20 LGSOC 1,2 (RAMP 201) KRAS G12V mt NSCLC 1,2 (RAMP 202) Key Signal Finding VS - 6766 + G12Ci KRAS G12C mt NSCLC 2 (RAMP 203 - sot
Slide 8: Robust Clinical Program Targeting the RAS Pathway
8 INDICATION REGIMEN STUDY NAME PRECLINICAL PHASE 1 PHASE 2 PHASE 3 CLINICAL COLLABORATION WITH LGSOC 1,2 VS - 6766 +/ - defactinib RAMP 201 R/R LGSOC 4 VS - 6766 + defactinib FRAME R/R endometrioid cancer (KRAS mt) 4 VS - 6766 + defactinib FRAME Gynecological cancers (RAS Pathway - driven) 4 VS - 6
Slide 9: VS-6766 is a unique RAF/MEK Clamp
9 VS - 6766 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 + VS - 6766 Improved ERK blockade Feedback reactivation is blocked; Sustain
Slide 10: VS-6766 inhibits cell proliferation across multiple MAPK pathway alterations
10 VS - 6766 inhibits cell proliferation across multiple MAPK pathway alterations and multiple solid tumor indications SW1463 MIAPACA2 H358 H1373 SW837 H2122 H2030 SW1573 HPAC ASPC1 HPAFII SNU-C2B LS513 LS 180 SKLU1 A427 SNU-C2A H441 SW403 SK-CO-1 SW620 PANC0327 H2291 SNG-M SW480 H2444 CAPAN2 CFPAC1
Slide 11: Vertical Blockade: backbone of therapy for RAS pathway-driven tumors
11 Vertical Blockade: Establishing VS - 6766 as the backbone of therapy for RAS 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, RAFi, MEKi, ERKi • Vertical bl
Slide 12: Parallel Pathway Inhibition: backbone of therapy
12 Parallel Pathway Inhibition: Establishing VS - 6766 as the backbone of therapy for RAS 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 tolerability
Slide 13: +/- Defactinib in Low-Grade Serous Ovarian Cancer
VS - 6766 +/ - Defactinib in Low - Grade Serous Ovarian Cancer
Slide 14: Favorable Tolerability Profile with Novel Intermittent Dosing Regimen
14 Favorable Tolerability Profile with Novel Intermittent Dosing Regimen VS - 6766 monotherapy Daily at MTD N=6 28 - day cycle RP2D VS - 6766 monotherapy 4mg twice weekly N=26 28 - day cycle RP2D (VS - 6766 3.2mg twice weekly + defactinib 200mg twice daily) N=38 21 days of 28 - day cycle Treatment R
Slide 15: Favorable Tolerability Profile at Recommended Phase 2 Dose
15 Favorable Tolerability Profile at Recommended Phase 2 dose for VS - 6766 plus defactinib combination regimen Treatment Related Adverse Events Details* (≥10% patients in cohort 3.2mg 6766 and Def 200mg ) VS - 6766 4mg Twice Weekly (4 wks of every 4 wks) 1 n=22 VS - 6766 3.2mg Twice Weekly Def 200m
Slide 16: 70% of LGSOC tumors driven by mutations in the RAS pathway
16 70% of LGSOC tumors driven by mutations in the RAS pathway 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 years, so
Slide 17: LGSOC: Limited Treatment Options with High Unmet Need
17 LGSOC: Limited Treatment Options with High Unmet Need References: 1 NCCN guidelines v1.2022 2 No standard sequencing of drugs for recurrence disease Low - Grade Ovarian Cancer – Treatment Algorithm 1 Observe only Carbo - Pt + Paclitaxel + hormonal (2b) OR Chemo + Beva for Stage II - IV (2a) OR Ho
Slide 18: VS-6766 with Defactinib Shows Promising ORR with Durability in Refractory LGSOC
18 VS - 6766 in Combination with Defactinib Shows Promising ORR with Durability in Refractory LGSOC with Expanded Number of Patients (n=24) Reference: Banerjee et al., ESMO Sept 2021 Data cut off April 2021 PFS: Progression free survival NR: Not reached • Overall response rate (ORR) = 46% (11 confir
Slide 19: RAMP 201 Registration-directed Phase 2 Trial in Recurrent LGSOC
19 RAMP 201 Registration - directed Phase 2 Trial of VS - 6766 +/ - Defactinib in Recurrent LGSOC - KRAS Mutant (mt) and Wild Type (wt): adaptive design modified based on interim analysis findings *Dosing: Defactinib + VS - 6766 combo: Defactinib 200mg PO BID: 21/28 days + VS - 6766 3.2mg PO 2x/wk 2
Slide 20: RAMP 201 Selection Phase: Interim Analysis Findings - June 2022
20 RAMP - 201Selection Phase: Interim Analysis Findings - June 2022 • All four cohorts from Selection Phase will be enrolled for Expansion Phase (add ~ 20 patients/cohort) • Fully enroll all four Expansion Phase cohorts in 2H 2022 • Select go - forward treatment regimen, timing driven by data maturi
Slide 21: LGSOC market opportunity larger or comparable to other KRAS opportunities
21 LGSOC market opportunity larger or comparable to other high unmet need KRAS opportunities NSCLC KRAS G12C 3 Pancreatic 3 LGSOC 3 Endometrioid 3 Metastatic uveal melanoma 3 ~6K patients US 1 ~80K patients WW 1 Patient - months of Therapy Per Year 2 (across all 2L+ patients) 1 References : Monk, Ra
Slide 22: +/- Defactinib in NSCLC
VS - 6766 +/ - Defactinib in NSCLC
Slide 23: High Unmet Need in Refractory mt NSCLC
23 High Unmet Need in Refractory 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 single ag
Slide 24: VS-6766 Inhibits CRAF - Key Driver of KRAS G12V mt NSCLC
24 VS - 6766 Inhibits CRAF - The key driver of KRAS G12V mt NSCLC References: Ishii et al. Cancer Res (2013), Blasco, R. B. et al. Cancer Cell (2011), Lito, P. et al. Cancer Cell (2014), Sanclemente, M. et al. Cancer Cell (2018) A Precision Approach to KRAS G12V Driven NSCLC CRAF, but not BRAF, abla
Slide 25: VS-6766 +/- FAKi induces tumor regression in KRAS G12V NSCLC model
25 VS - 6766 +/ - FAKi induces significant tumor regression in KRAS G12V mt NSCLC in vivo model, with clear differentiation from trametinib Doses Tested Trametinib: 0.1 mg/kg QD (5 days/week) VS - 6766: 0.1 mg/kg QD (5 days/week) FAKi: 50 mg/kg BID (5 days/week) KRAS G12V mutant; Tp53 KO NSCLC • VS
Slide 26: Case Study: Response in a patient with KRAS G12V mutant NSCLC
26 Case Study: Response to VS - 6766 + defactinib in a patient with KRAS G12V mutant NSCLC Reference: Krebs et al. AACR 2021 May 2019: Diagnosed with NSCLC June 2019 - Sept 2019: Treated with first line Carboplatin + Pemetrexed + Pembrolizumab Oct 2019: Progression, palliative RT to right hip Nov 20
Slide 27: Strong Signal Identified in KRAS G12V NSCLC
27 Strong Signal Identified in KRAS G12V NSCLC Preclinical evidence suggests combination with Defactinib may improve efficacy in KRAS G12V mt NSCLC Activity of VS - 6766 as a single agent and in combo with Defactinib in KRAS G12V mt NSCLC VS - 6766 ± Defactinib Has Shown a 57% ORR in KRAS G12V m
Slide 28: RAMP 202: Registration-directed Phase 2 Trial in advanced NSCLC
28 RAMP 202: Registration - directed Phase 2 Trial of VS - 6766 +/ - Defactinib in advanced NSCLC Primary Cohort: KRAS G12V mt NSCLC References: 1 Defactinib 200 mg PO BID (21/28 days) + VS - 6766 3.2 mg PO 2x/wk (21/28 days) 2 VS - 6766 4.0 mg PO 2x/wk (21/28 days) Advanced NSCLC 1 - 2 prior re
Slide 29: RAMP 202: Additional Cohorts in KRAS non-G12V and BRAF mt NSCLC
29 RAMP 202: Additional Cohorts of VS - 6766 + Defactinib in KRAS non - G12V mt & BRAF mt NSCLC References: 1 Defactinib 200 mg PO BID (21/28 days) + VS - 6766 3.2 mg PO 2x/wk (21/28 days) Advanced NSCLC 1 - 2 prior regimens 1 prior platinum - containing chemo; Prior CPI unless contraindicat
Slide 30: Preclinical synergy of VS-6766 + G12C inhibitors
30 Preclinical synergy of VS - 6766 + G12C inhibitors in KRAS G12C mt models Synergy of VS - 6766 + G12C inhibitors across G12C mutant NSCLC, CRC & Pancreatic cancer cell lines Doses Tested Trametinib: 0.3 mg/kg QD VS - 6766: 0.3 mg/kg QD FAKi: 50 mg/kg BID Sotorasib: 30 mg/kg QD Response @ Day 10 V
Slide 31: Acquired resistance mechanisms to KRAS G12Ci support combination
31 Acquired resistance mechanisms to KRAS G12Ci treatment in patients further support combination of KRAS G12Ci with VS - 6766 Summary of Putative Mechanisms of Acquired Resistance to Adagrasib Treatment • Mechanisms of acquired resistance to KRAS G12Ci adagrasib treatment in patients recently repor
Slide 32: RAMP 203: Phase 1/2 Trial of VS-6766 + sotorasib
32 Patients must have known G12C KRAS 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
Slide 33: Future Opportunities: VS-6766 as Backbone of RAS Therapy
Future Opportunities: VS - 6766 as Backbone of RAS Therapy
Slide 34: High Unmet Needs in RAS/RAF/MEK/ERK-Driven Cancers
34 High Unmet Needs in RAS/RAF/MEK/ERK - Driven Cancers NSCLC Incidence 3,5 : 194K 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 Incidence 7 : 1
Slide 35: Vertical Blockade: Preclinical synergy with promising agents
35 Vertical Blockade: Preclinical synergy 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 H2122 H1373 MIAPACA2 H358 SW1573 HPAC ASPC1 A4
Slide 36: Parallel Pathway Inhibition: Preclinical synergy
36 Parallel Pathway Inhibition: Preclinical synergy in combination with promising agents for clinical investigation Reference: Coma et al., RAS - Targeted Drug Discovery, Feb 2021 H2122 MIAPACA2 H1373 H358 SW1573 A427 HPAC ASPC1 HPAFII SKLU1 CFPAC1 CAPAN2 H2291 PANC0327 H441 H2444 -20 -10 0 10 20 30
Slide 37: VS-6766 with anti-EGFR mAb induces regression in KRAS mt colorectal PDX model
37 Combination of VS - 6766 with anti - EGFR mAb induces tumor regression in a KRAS mt Colorectal PDX model • VS - 6766 + anti - EGFR (panitumumab) induces tumor regression in a KRAS G12V mt CRC patient - derived xenograft model • G12Ci + anti - EGFR (sotorasib + panitumumab and adagrasib + cetuxima
Slide 38: Clinical Program Targeting the RAS Pathway in Additional Indications
38 Clinical Program Targeting the RAS Pathway in Additional Indications 1 Investigator - sponsored trial 2 In preparation/planning INDICATION REGIMEN STUDY NAME PRECLINICAL PHASE 1 PHASE 2 PHASE 3 R/R pancreatic cancer 1 VS - 6766 + defactinib FRAME Metastatic uveal melanoma 1 VS - 6766 + defactinib
Slide 39: Corporate
Corporate
Slide 40: Key Financial Statistics
40 Key Financial Statistics Cash, cash equivalents & investments $106M Non - GAAP Operating Expenses $18M Shares Outstanding 186M As of and for the quarter ended March 31, 2022 Oxford Finance LLC Credit Facility Loan Tranches Event A $25M At closing B $15M COPIKTRA PTCL approval in U.S. or $50M equi
Slide 41: Backup Slides
Backup Slides
Slide 42: Verastem Oncology Strategic Transformation
42 Verastem Oncology Strategic Transformation Q1 2021: LGSOC study updated to include KRAS wild type patients Q4 2020: Initiated registration - directed ph. 2 study in LGSOC Initiated registration - directed ph. 2 study in NSCLC Q3 2020: Divested global rights to Copiktra to Secura Bio Q1 2020: In -
Slide 43: KRAS G12V and G12D Represent ~50% of KRAS Mutations
43 KRAS G12V and G12D Represent ~50% of KRAS Mutations across Human Cancers 21.40% G12V 25.30% G12D 5.10% G12A 13.30% G12C 2.70% Q61H 32.20% Others Pancreatic Adenocarcinoma 1 G12D G12V G12R Q61H Q61R G12A G12C 0 10 20 30 Pancreatic Cancer KRAS Mutation % of patients Uterine Endometrioid Carcinoma 1
Slide 44: VS-6766 and FAK inhibitor combination leads to more robust efficacy in vivo
44 VS - 6766 and FAK inhibitor combination leads to more robust anti - tumor efficacy in vivo KRAS mt Ovarian TOV - 21G in vivo Model 1 KRAS mt NSCLC H358 in vivo Model 2 0 5 10 15 0 100 200 300 400 500 Tumor growth VS-4718 + CH5126766 Days on treatment Tumor volume (mm 3 +/- SEM) Vehicle Trametinib
Slide 45: Overcoming Key Resistance Mechanisms to MEK Inhibitors
45 Overcoming Key Resistance Mechanisms to MEK Inhibitors • MEK inhibition induces compensatory activation of pFAK preclinically and clinically Pre dose Post VS-6766 Post combination 0 50 100 150 p-FAK H-Score o Trametinib induced ↑ pFAK (Y397) preclinically in KRAS mt NSCLC cell lines o Also observ
Slide 46: Pharmacokinetic Profiles of VS-6766 + Defactinib
46 Pharmacokinetic Profiles of VS - 6766 + Defactinib in Combination Similar to that seen in Single Agent Studies Cohort Dose (mg) N Subject AUC 0 - 24h (h*ng/mL) C max (ng/mL) 1 3.2 (with 200mg VS) 3 Mean 6179 354 CV% 32.1 30.4 2a 4 (with 200mg VS) 5 Mean 5353 289 CV% 15.8 16.0 2b 3.2 (with 400mg V
Slide 47: NSCLC Responses with VS-6766 + Defactinib Combination
47 0 10 20 30 40 50 60 70 FRA101017 FRA102005 FRA101043 FRA101040 FRA101034 FRA101018 FRA102016 FRA101026 FRA101020 FRA101036 FRA102004 FRA101010 FRA102008 FRA102006 FRA102007 FRA101041 FRA102017 FRA102002 FRA102009 FRA101031 Time on Treatment (weeks) Unconfirmed PR Partial response Stable disease P
Slide 48: Target exposure covered by twice weekly dosing of 4 mg
48 Target exposure for preclinical tumor regression is covered by twice weekly dosing of 4 mg VS - 6766 3 wks on/1 wk off Modeling of PK for 4 mg VS - 6766 2 /wk, 3 wks on/ 1 wk off, based on 4 mg single dose PK data (study NO 21895 ) Relationship to average exposure for tumor regression in KRAS
Slide 49: Status: Combination of VS-6766 with Everolimus
49 Status: Combination of VS - 6766 with Everolimus (mTOR inhibitor) • Synergy of VS - 6766 + everolimus observed broadly across cancer cell lines with various KRAS mutation variants • A well - tolerated RP2D for VS - 6766 + everolimus has been established with intermittent dosing of both agents (tw
Slide 50: VS-6766 monotherapy has shown clinical activity in several cancer indications
50 VS - 6766 monotherapy has shown clinical activity in several cancer indications, including NSCLC Best Response Guo et al., Lancet Oncology 2020
Slide 51: VS-6766 upregulates MHC Class I antigens on tumor cells
51 VS - 6766 upregulates MHC Class I antigens on tumor cells: a mechanism for potentiation of I/O efficacy Cell Line Tumor type RAS/RAF mutation status A549 Lung KRASmt G12S TOV21g Ovarian KRASmt G13C SKMEL5 Melanoma BRAFmt V600E IGR - 1 Melanoma BRAFmt V600E WM115 Melanoma BRAFmt V600E A549 TOV21g
Slide 52: VS-6766 enhances tumor growth inhibition with anti-PD-1
52 VS - 6766 enhances tumor growth inhibition when combined with anti - PD - 1 in the CT26 KRAS (G12D) syngeneic model Reference: Pachter, RAS - Targeted Drug Development, Sept 2020 -100 0 100 200 300 400 Response at Day 13 % Change in Tumor Volume Vehicle VS-6766 anti-PD-1 VS-6766 + anti-PD-1 20 40
Slide 53: Strong Patent Protection
53 Strong Patent Protection • COM for VS - 6766 to 2027 & defactinib to 2028, Hatch Waxman should extend to 2032 • VS - 6766 intermittent dosing regimen until 2038 if granted • FAK/MEK combination to 2035 • VS - 6766/defactinib combination until 2040 if granted • Method of manufacture for VS - 6766
Slide 54: Experienced Senior Management Team
54 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 - Inge
Slide 55: Verastem Oncology
\W VERASTEM ONCOLOGY