Verastem, Inc. · NASDAQ:VSTM
Verastem — Investor Presentation (January 2022)
53 slides from Verastem's investor presentation, Jan 11, 2022
Slide 1: Corporate Presentation January 2022
Corporate Presentation January 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: 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 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 Corporate 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 da
Slide 5: RAF/MEK Inhibitor Program Overview
VS - 6766 RAF/MEK Inhibitor Program Overview
Slide 6: VS-6766 is a differentiated, best-in-class asset
6 VS - 6766 is a differentiated, best - in - class asset potentially applicable across multiple patient populations • Unique dual RAF/MEK targeting mechanism of action • Best - in - class safety & tolerability profile relative to marketed MEK inhibitors, with potential for combinability with agents
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) Signal Finding VS - 6766 + G12Ci KRAS G12C mt NSCLC 2 (RAMP 203 - sotoras
Slide 8: Robust Pipeline Targeting the RAS Pathway
8 Robust Pipeline Targeting the RAS Pathway and Multiple Growth Opportunities RAMP 201 study = NCT04625270 RAMP 202 study = NCT04620330 RAMP 203 study = NCT05074810 FRAME study = NCT03875820 1 Registration - directed trial *Pre - clinical studies ongoing in multiple KRAS mutant tumors FDA Breakthrou
Slide 9: VS-6766 is a Unique Small Molecule RAF/MEK Clamp
9 VS - 6766 is a Unique Small Molecule RAF/MEK Clamp VS - 6766 (RAF/MEKi) Mirdametinib (MEKi) VS - 6766 inhibits both MEK & RAF kinase activities by trapping them in inactive complexes MEK inhibitors paradoxically induce MEK phosphorylation (pMEK) by relieving ERK - dependent feedback inhibition
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: Establishing VS-6766 as the backbone of therapy
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: Establishing VS-6766 as the 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: VS-6766 +/- 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 for combination
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: VS-6766 with Defactinib Shows Promising ORR with Durability in Refractory LGSOC
16 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 17: LGSOC: Limited Treatment Options with High Unmet Need
17 LGSOC: Limited Treatment Options with High Unmet Need References: 1 NCCN guidelines Low - Grade Ovarian Cancer – Treatment Algorithm 1 Observe only Pt Chemo Combo: Carbo - Pt + Paclitaxel (preferred) + Beva for Stage II - IV (incl maintenance Beva) OR Hormonal Tx (2B) Pt - Chemo combo +/ - Beva
Slide 18: 70% of LGSOC tumors driven by mutations in the RAS pathway
18 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 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) *Dosing: Defactinib + VS - 6766 combo: Defactinib 200mg PO BID: 21/28 days + VS - 6766 3.2mg PO 2x/wk 21/28 days; VS - 6766 monothera py: VS6766 4.0 mg PO 2x/wk 21/
Slide 20: LGSOC market opportunity larger or comparable to other KRAS opportunities
20 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 21: VS-6766 +/- Defactinib in NSCLC
VS - 6766 +/ - Defactinib in NSCLC
Slide 22: High Unmet Need in Refractory KRAS mt NSCLC
22 High Unmet Need in Refractory KRAS mt NSCLC Adenocarcinoma 0 5 10 15 G12C G12V G12D G12A G13C G12S G13D % of Patients KRAS Mutation Advanced or Metastatic NSCL Cancer Recommend Histologic and Molecular Subtyping 5 Appropriate targeted agent Chemotherapy Docetaxel Gemcitabine Pemetrexed Prio
Slide 23: VS-6766 Inhibits CRAF - The key driver of KRAS G12V mt NSCLC
23 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 24: VS-6766 +/- FAKi induces tumor regression in KRAS G12V mt NSCLC in vivo
24 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 25: Case Study: Response to VS-6766 + defactinib in KRAS G12V mutant NSCLC
25 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 26: Strong Signal Identified in KRAS G12V NSCLC
26 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 a Confirmed 57% ORR in KRAS G1
Slide 27: RAMP 202: Registration-directed Phase 2 Trial in KRAS Mutant NSCLC
27 RAMP 202: Registration - directed Phase 2 Trial of VS - 6766+/ - Defactinib in KRAS Mutant (mt), G12V Enriched Advanced 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) This Registration - directed Phase 2
Slide 28: Preclinical synergy of VS-6766 + G12C inhibitors in KRAS G12C models
28 Preclinical synergy of VS - 6766 + G12C inhibitors in KRAS G12C mt models Synergy of VS - 6766 + G12C inhibitor AMG 510 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 AMG 510: 30 mg/kg QD -100 0 100 200
Slide 29: Acquired resistance mechanisms to KRAS G12Ci support combination with VS-6766
29 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 30: RAMP 203: Phase 1/2 Trial of VS-6766 + sotorasib in KRAS G12C NSCLC
30 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 31: Future Opportunities: VS-6766 as Backbone of RAS Therapy
Future Opportunities: VS - 6766 as Backbone of RAS Therapy
Slide 32: Vertical Blockade: Preclinical synergy with several promising targets
32 Vertical Blockade: Preclinical synergy in combination with several promising targets 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 A427 HPAFII SKLU1 PA
Slide 33: Parallel Pathway Inhibition: Two synergistic combinations already in clinic
33 Parallel Pathway Inhibition: Two synergistic combinations already progressed to clinical stage Reference: Coma et al., RAS - Targeted Drug Discovery, Feb 2021 SW1573 H1373 H358 MIAPACA2 H2122 A427 SKLU1 HPAFII ASPC1 HPAC H2291 H2444 CAPAN2 H441 PANC0327 CFPAC1 -40 -20 0 20 40 VS-6766 + M2698 Comb
Slide 34: Corporate
Corporate
Slide 35: Key Financial Statistics
35 Key Financial Statistics Cash, cash equivalents & investments $103.4M Shares fully diluted 196.9M Insider ownership (outstanding / vested) 8.1% / 5.1% As of September 30, 2021 * The 2018 Notes have an initial conversion rate of 139.5771 shares of Common Stock per $1,000 which translates to an ini
Slide 36: Backup Slides
Backup Slides
Slide 37: Verastem Oncology Strategic Transformation
37 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 38: High Unmet Needs in RAS/RAF/MEK/ERK-Driven Cancers
38 High Unmet Needs in RAS/RAF/MEK/ERK - Driven Cancers NSCLC Incidence 3,5 : 194K Colorectal Incidence 5 : 105K Pancreatic Incidence 5 : 58K Uterine Endometrioid Incidence 4,5 : 59K Melanoma Incidence 5 : 108K Multiple Myeloma Incidence 5 : 32K Melanoma Incidence 5 : 108K Ovarian Incidence 5 : 22K
Slide 39: KRAS G12V and G12D Represent ~50% of KRAS Mutations
39 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 40: VS-6766 and FAK inhibitor combination leads to more robust anti-tumor efficacy
40 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 41: Overcoming Key Resistance Mechanisms to MEK Inhibitors
41 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 42: Pharmacokinetic Profiles of VS-6766 + Defactinib in Combination
42 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 43: NSCLC Responses with VS-6766 + Defactinib Combination
43 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 44: Target exposure for preclinical tumor regression covered by twice weekly dosing
44 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 45: Status: Combination of VS-6766 with Everolimus
45 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 46: VS-6766 with anti-EGFR mAb induces tumor regression in KRAS mt colorectal PDX model
46 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 47: VS-6766 monotherapy has shown clinical activity in several cancer indications
47 VS - 6766 monotherapy has shown clinical activity in several cancer indications, including NSCLC Best Response Guo et al., Lancet Oncology 2020
Slide 48: VS-6766 upregulates MHC Class I antigens on tumor cells
48 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 49: VS-6766 enhances tumor growth inhibition combined with anti-PD-1
49 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 50: LGSOC Market Opportunity – Reference Calculations
50 LGSOC Market Opportunity – Reference Calculations NSCLC KRAS G12C 3 Pancreatic 3 LGSOC 1 Endometrioid 3 Metastatic uveal melanoma 3 Patient - months of Therapy Per Year (across all 2L+ patients) 2 Average months on Therapy (per patient) 2 Number of Patients (2L+) 2 - 10,000 20,000 30,000 40,000 1
Slide 51: Strong Patent Protection
51 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 52: Experienced Senior Management Team
52 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 53: Verastem Oncology
\W VERASTEM ONCOLOGY