Verastem, Inc. · NASDAQ:VSTM
Verastem — Investor Presentation (January 2022)
53 slides from Verastem's investor presentation, January 2022
Slide 1: Corporate Presentation
Corporate Presentation January 2022
Slide 2: Safe Harbor Statement
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 are s
Slide 3: Well Positioned to Capitalize on Growth Opportunities
Verastem Oncology Well Positioned to Capitalize on Growth Opportunities New lead clinical program VS-6766 (RAF/MEKi) and defactinib (FAKi) are clinically active against has best-in-class potential RAS mutant cancers FDA Breakthrough Therapy Designation in LGSOC; Supported We are a Rapid development
Slide 4: Key VSTM Milestones 2021-2022
Key VSTM Milestones 2021-2022 1H2021 2H2021 1Q2022 2Q2022 2H2022 Retired Corporate Outstanding Debt RAMP-201 RAMP-201 Top-Line Amended to Include Data from Selection KRAS wt patients in Updated data RAMP-201 Target Phase Selection Phase from FRAME enrollment of RAMP-201 Complete LGSOC cohort Selecti
Slide 5: VS-6766 RAF/MEK Inhibitor Program Overview
VS-6766 RAF/MEK Inhibitor Program Overview
Slide 6: VS-6766 is a differentiated, best-in-class asset
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 from multipl
Slide 7: High Priority Lead Indications with Multiple Growth Opportunities
High Priority Lead Indications with Multiple Growth Opportunities High Priority Registration Indications Signal Finding Registration-Directed Trials Initiated in 4Q20 VS-6766 + G12Ci KRAS G12C mt NSCLC2 (RAMP 203-sotorasib) & (RAMP 204-adagrasib) LGSOC1,2 (RAMP 201) Pancreatic1,2 (10 pt cohort
Slide 8: Robust Pipeline Targeting the RAS Pathway
Robust Pipeline Targeting the RAS Pathway and Multiple Growth Opportunities LGSOC VS-6766 +/- defactinib FDA Breakthrough Therapy Designation for VS-6766 + defactinib KRAS G12V NSCLC VS-6766 +/- defactinib KRAS mt NSCLC | VS-6766 + everolimus (mTORi) RAMP 203 KRAS G12C NSCLC VS-6766 + LUMAKRASTM Cli
Slide 9: VS-6766 is a Unique Small Molecule RAF/MEK Clamp
VS-6766 is a Unique Small Molecule RAF/MEK Clamp 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 of RAF By inhibiting RAF phosphorylation of ME
Slide 10: VS-6766 inhibits cell proliferation across multiple MAPK pathway alterations
VS-6766 inhibits cell proliferation across multiple MAPK pathway alterations and multiple solid tumor indications Other NRAS Other KRAS G12C KRAS G12D KRAS G12V KRAS mt BRAF mt mt mt 10 VS-6766 IC50 (µM) 1 0.1 0.01 SNG-M HPAC SNU-C2B SNU-C2A GAK AN3 CA RKO MIAPACA2 H358 ASPC1 LS 180 A427 H441 SK-CO-
Slide 11: Vertical Blockade: Establishing VS-6766 as the backbone of therapy
Vertical Blockade: Establishing VS-6766 as the backbone of therapy for RAS pathway-driven tumors Growth factors Current Challenges RTK • Blocking any single target in the pathway is insufficient for maximum depth and EGFRi duration of anti-tumor efficacy FGFRi • e.g., SHP2i, KRAS-G12Ci, RAFi, MEKi
Slide 12: Parallel Pathway Inhibition: Establishing VS-6766 as the backbone of therapy
Parallel Pathway Inhibition: Establishing VS-6766 as the backbone of therapy for RAS pathway-driven tumors Growth factors Extracellular Matrix Current Challenges RTK Integrin • Blocking Ras pathway can be circumvented through EGFRi α parallel pathways β FGFRi • e.g., PI3K/AKT/mTOR, FAK, RhoA,YAP F
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
Favorable Tolerability Profile with Novel Intermittent Dosing Regimen Summary of Adverse Events Grade ≥ 3 Occurring in ≥ 5% of patients VS-6766 monotherapy RP2D RP2D Daily at MTD VS-6766 monotherapy (VS-6766 3.2mg twice weekly + N=6 4mg twice weekly defactinib 200mg twice daily) 28-day cycle N=26 N=
Slide 15: Favorable Tolerability Profile at Recommended Phase 2 dose
Favorable Tolerability Profile at Recommended Phase 2 dose for VS-6766 plus defactinib combination regimen VS-6766 3.2mg Twice VS-6766 4mg Weekly Summary of FRAME Safety Profile Treatment Related Adverse Twice Weekly Def 200mg BID Events Details* (4 wks of (3 wks of Most Adverse Events (AE) were G
Slide 16: VS-6766 with Defactinib Shows Promising ORR with Durability in Refractory LGSOC
VS-6766 in Combination with Defactinib Shows Promising ORR with Durability in Refractory LGSOC with Expanded Number of Patients (n=24) Response by RECIST Best response by RECIST KRAS D57-T58ins 20 KRAS D33E, I24N Undocumented Undocumented Undocumented Undocumented 10 Continuing on treatment KRAS G12
Slide 17: LGSOC: Limited Treatment Options with High Unmet Need
LGSOC: Limited Treatment Options with High Unmet Need Low-Grade Ovarian Cancer – Treatment Algorithm1 Stage IA-IB Stage IC Stage II-IV Median PFS Response Rate Discontinuation Therapy Months (95% ORR Rate due to AEs Pt Chemo Combo: CI) Carbo-Pt + Paclitaxel (preferred) Standard of Observe only + Bev
Slide 18: 70% of LGSOC tumors driven by mutations in the RAS pathway
70% of LGSOC tumors driven by mutations in the RAS pathway ~30% of LGSOC Patients Have KRAS mt LGSOC is a type of ovarian cancer that disproportionately ~70% of LGSOC Shows RAS Pathway-Associated mts affects younger women 1,000 to 2,000 patients in the U.S. and 15,000 to 30,000 worldwide diagnosed w
Slide 19: RAMP 201: Registration-directed Phase 2 Trial in Recurrent LGSOC
RAMP 201: Registration-directed Phase 2 Trial of VS-6766+/- Defactinib in Recurrent LGSOC - KRAS Mutant (mt) and Wild Type (wt) Now enrolling expansion phase Selection Phase* Expansion Phase** Defactinib+VS-6766 KRAS-mt (n=16) Recurrent LGSOC Primary Endpoint: Expand each cohort to ~36 patients
Slide 20: LGSOC market opportunity larger or comparable to other KRAS opportunities
LGSOC market opportunity larger or comparable to other high unmet need KRAS opportunities Prevalence Patient-months of Therapy Per Year2 (across all 2L+ patients) ~6K - 50,000 100,000 150,000 patients US1 NSCLC KRAS G12C3 Pancreatic3 LGSOC3 ~4k ~2k Endometrioid3 wild KRAS type mutation Metastatic uv
Slide 21: VS-6766 +/- Defactinib in NSCLC
VS-6766 +/- Defactinib in NSCLC
Slide 22: High Unmet Need in Refractory KRAS mt NSCLC Adenocarcinoma
High Unmet Need in Refractory KRAS mt NSCLC Adenocarcinoma Advanced or Metastatic NSCL Cancer NSCLC Adenocarcinoma3 Recommend Histologic and Molecular Subtyping5 15 EGFR/ALK/ROS1/BRAF Non-targeted Non-Targeted US Annual Incidence1,2: 92K /KRAS-G12C (targeted) PD-(L)1 ≥ 1% PD-(L)1 < 1% WW Annual Inci
Slide 23: VS-6766 Inhibits CRAF - The key driver of KRAS G12V mt NSCLC
VS-6766 Inhibits CRAF - The key driver of KRAS G12V mt NSCLC A Precision Approach to KRAS G12V Driven NSCLC CRAF Drives KRAS G12V mt NSCLC1 CRAF KO Shows Strong KRAS G12V Efficacy CRAF BRAF PI3K +83% OS MEK/ERK AKT/mTOR BRAF KO Has No Effect Tumor Growth KRAS G12V signals mainly through RAF/MEK i
Slide 24: VS-6766 +/- FAKi induces tumor regression in KRAS G12V mt NSCLC in vivo model
VS-6766 +/- FAKi induces significant tumor regression in KRAS G12V mt NSCLC in vivo model, with clear differentiation from trametinib KRAS G12V mutant;Tp53 KO NSCLC 80 Doses Tested Tumor volume fold change 60 Trametinib: 0.1 mg/kg QD (5 days/week) VS-6766: 0.1 mg/kg QD (5 days/week) 40 FAKi: 50 mg/k
Slide 25: Case Study: Response to VS-6766 + defactinib in KRAS G12V NSCLC
Case Study: Response to VS-6766 + defactinib in a patient with KRAS G12V mutant NSCLC VS-6766 + Defactinib 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 2019 – present: On t
Slide 26: Strong Signal Identified in KRAS G12V NSCLC
Strong Signal Identified in KRAS G12V NSCLC VS-6766 ± Defactinib Has a Confirmed 57% ORR in KRAS G12V mt NSCLC in Integrated Analysis Best Response by RECIST in KRAS G12V mt NSCLC Time on Treatment for KRAS G12V mt NSCLC 10 NSCLC (57% ORR; N=7) Weeks on treatment + 0 Mono 216 (% change from baseline
Slide 27: RAMP 202: Registration-directed Phase 2 Trial in KRAS G12V NSCLC
RAMP 202: Registration-directed Phase 2 Trial of VS-6766+/- Defactinib in KRAS Mutant (mt), G12V Enriched Advanced NSCLC Selection Phase Expansion Phase Advanced NSCLC Defactinib+VS-67661 1-2 prior regimens KRAS mt G12V 1 prior platinum- N=16 containing chemo; KRAS Mutant – G12V Prior CPI un
Slide 28: Preclinical synergy of VS-6766 + G12C inhibitors in KRAS G12C mt models
Preclinical synergy of VS-6766 + G12C inhibitors in KRAS G12C mt models Synergy of VS-6766 + G12C inhibitor AMG 510 across VS-6766 & FAKi potentiate AMG 510 efficacy in KRAS G12C mutant G12C mutant NSCLC, CRC & Pancreatic cancer cell lines NSCLC in vivo; Tumor regression in all mice with triple comb
Slide 29: Acquired resistance mechanisms to KRAS G12Ci treatment
Acquired resistance mechanisms to KRAS G12Ci treatment in patients further support combination of KRAS G12Ci with VS-6766 Summary of Putative Mechanisms of Acquired • Mechanisms of acquired resistance to KRAS G12Ci Resistance to Adagrasib Treatment adagrasib treatment in patients recently reported1,
Slide 30: RAMP 203: Phase 1/2 Trial of VS-6766 + LUMAKRAS in KRAS G12C NSCLC
RAMP 203: Phase 1/2 Trial of VS-6766 + LUMAKRASTM (sotorasib) in KRAS G12C-mutated advanced NSCLC Patients must have Part A: Dose Evaluation Part B: Dose Expansion at RP2D known G12C KRAS (3+3 DLT Assessment) (Primary endpoint ORR) mutation determined using validated test Cohort 1 Treatment with
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 in combination with promising targets
Vertical Blockade: Preclinical synergy in combination with several promising targets VS-6766 + pan-HERi (Afatinib) VS-6766 + SHP2i (RMC-4550) VS-6766 + SOS1i (BI-3406) VS-6766 + Afatinib VS-6766 + BI-3406 80% (4/5) 100% (5/5) 100% (6/6) 100% (5/5) 60% (3/5) 83% (5/6) 40 40 Combined Synergy Score Com
Slide 33: Parallel Pathway Inhibition: Two synergistic combinations in clinic
Parallel Pathway Inhibition: Two synergistic combinations already progressed to clinical stage VS-6766 + p70S6K/AKTi (M2698) VS-6766 + mTORi (Everolimus) VS-6766 + M2698 80% (4/5) 80% (4/5) 66% (4/6) 40 Combined Synergy Score 20 0 -20 -40 HPAFII H1373 H358 H2122 A427 H2291 H2444 H441 SW1573 SKLU1 AS
Slide 34: Corporate
Corporate
Slide 35: Key Financial Statistics
Key Financial Statistics As of September 30, 2021 Cash, cash equivalents & investments $103.4M Shares fully diluted 196.9M Insider ownership (outstanding / vested) 8.1% / 5.1% * The 2018 Notes have an initial conversion rate of 139.5771 shares of Common Stock per $1,000 which translates to an initia
Slide 36: Backup Slides
Backup Slides
Slide 37: Verastem Oncology Strategic Transformation
Verastem Oncology Strategic Transformation Q1 2020: In-licensed global rights to VS-6766, best-in-class RAF/MEK inhibitor, from Chugai PIPE financing based on data for new clinical program Q3 2020: Divested global rights to Copiktra to Secura Bio Q4 2020: Initiated registration-directed ph. 2 study
Slide 38: High Unmet Needs in RAS/RAF/MEK/ERK-Driven Cancers
High Unmet Needs in RAS/RAF/MEK/ERK-Driven Cancers KRAS-mutant NSCLC 31% Pancreatic Uterine 21% Colorectal Ovarian 45% 5% Incidence3,5: Incidence5: Endometrioid Incidence5: Incidence5: Cancers1 194K 58K 98% Incidence4,5: 59K 105K 22K NRAS-mutant Melanoma 28% Multiple Myeloma 20% Incidence5: Incidenc
Slide 39: KRAS G12V and G12D Represent ~50% of KRAS Mutations
KRAS G12V and G12D Represent ~50% of KRAS Mutations across Human Cancers Pancreatic Adenocarcinoma1 30 % frequency in a total of 780 cancer patients with KRAS mutations1 Annual Incidence3: 58K % of patients 20 10 21.40% G12V 0 25.30% G12D G12D G12V G12R Q61H Q61R G12A G12C 5.10% G12A 13.30% G12C KRA
Slide 40: VS-6766 and FAK inhibitor combination leads to more robust anti-tumor efficacy
VS-6766 and FAK inhibitor combination leads to more robust anti-tumor efficacy in vivo KRASmt Ovarian TOV-21G in vivo Model1 KRASmt NSCLC H358 in vivo Model2 500 Tumor growth Vehicle 600 400 Vehicle (mm3 +/- SEM) Tumor volume Trametinib 0.3 mg/kg QD Tumor volume 300 (mm3 +/- SEM) 400 Trametinib 1.5
Slide 41: Overcoming Key Resistance Mechanisms to MEK Inhibitors
Overcoming Key Resistance Mechanisms to MEK Inhibitors p-FAK • MEK inhibition induces 150 compensatory activation of pFAK preclinically and clinically o Trametinib induced ↑ pFAK (Y397) 100 preclinically in KRAS mt NSCLC cell lines H-Score o Also observed in patients 50 • VS-6766 induced ↑ pFAK (Y39
Slide 42: Pharmacokinetic Profiles of VS-6766 + Defactinib in Combination
Pharmacokinetic Profiles of VS-6766 + Defactinib in Combination Similar to that seen in Single Agent Studies VS-6766 Defactinib Dose AUC0-24h Cmax AUClast Cmax Cohort N Subject Cohort Dose (mg) N Subject (mg) (h*ng/mL) (ng/mL) (h*ng/mL) (ng/mL) 3.2 Mean 6179 354 Mean 2071 273 1 3 200 (with 200mg VS)
Slide 43: NSCLC Responses with VS-6766 + Defactinib Combination
NSCLC Responses with VS-6766 + Defactinib Combination (n=20) Confirmed responses in 2/2 patients with KRAS G12V mt NSCLC Tumor reduction in 4/6 patients with KRAS G12C mt NSCLC Best response by RECIST in KRAS mt NSCLC Time on Treatment * G12V G12D G12C G12D G12C G12D G12D G12D G12D G12C G12C G12D G1
Slide 44: Target exposure for preclinical tumor regression covered by twice weekly dosing
Target exposure for preclinical tumor regression is covered by twice weekly dosing of 4 mg VS-6766 3 wks on/1 wk off Cav for tumor regression from KRAS G12V mt NSCLC GEMM model 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 NO21895) Relationship
Slide 45: Status: Combination of VS-6766 with Everolimus
Status: Combination of VS-6766 with Everolimus (mTOR inhibitor) • Synergy of VS-6766 + everolimus observed broadly VS-6766 + Everolimus 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
Slide 46: VS-6766 with anti-EGFR mAb induces tumor regression in KRAS mt Colorectal PDX model
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 Vehicle • G12Ci + anti-EGFR (sotorasib + panitumumab and adagrasib + cetuximab) have
Slide 47: VS-6766 monotherapy has shown clinical activity in several cancer indications
VS-6766 monotherapy has shown clinical activity in several cancer indications, including NSCLC Best Response 47 Guo et al., Lancet Oncology 2020
Slide 48: VS-6766 upregulates MHC Class I antigens on tumor cells
VS-6766 upregulates MHC Class I antigens on tumor cells: a mechanism for potentiation of I/O efficacy B2M HLA-A 6 8 DMSO DMSO Relative mRNA Levels Relative mRNA Levels VS-6766 VS-6766 6 4 4 2 RAS/RAF mutation Cell Line Tumor type 2 status 0 A549 TOV21g SKMEL5 IGR1 WM115 0 A549 TOV21g SKMEL5 IGR1 WM1
Slide 49: VS-6766 enhances tumor growth inhibition with anti-PD-1 in CT26 model
VS-6766 enhances tumor growth inhibition when combined with anti-PD-1 in the CT26 KRAS (G12D) syngeneic model Tumor growth Survival 1200 100 Vehicle 1000 80 VS-6766 0.5 mg/kg QD x 28 days anti-PD-1 3 mg/kg 2xW x 4 doses Percent survival 800 Tumor volume (mm3 +/- SEM) 60 VS-6766 + anti-PD-1 600 400 4
Slide 50: LGSOC Market Opportunity – Reference Calculations
LGSOC Market Opportunity – Reference Calculations Number of Patients (2L+)2 Average months on Patient-months of Therapy Therapy (per patient)2 Per Year (across all 2L+ patients)2 - 10,000 20,000 30,000 40,000 - 5.00 10.00 15.00 - 50,000 100,000 150,000 NSCLC KRAS G12C3 Pancreatic3 LGSOC1 Endometrioi
Slide 51: Strong Patent Protection
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 to 2032 • O
Slide 52: Experienced Senior Management Team
Experienced Senior Management Team Brian Stuglik Daniel Paterson Rob Gagnon President and Chief Operating Chief Business and Chief Executive Officer Officer Financial Officer Global VP & Chief Marketing CEO – The DNA Repair Co. (now CFO – Harvard Bioscience, Clean Officer – Lilly Oncology On-Q
Slide 53: THANK YOU
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