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FORM
CURRENT REPORT
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Item 7.01. Other Events
On September 16, 2020, Verastem, Inc. (the “Company”) issued a press release and posted a presentation, which the Company will be presenting at the Second Annual RAS-Targeted Drug Development Summit on September 16, 2020 (the “Presentation”), announcing updated clinical data from the low-grade serous ovarian cancer cohort of the ongoing investigator-initiated Phase 1/2 FRAME study. Copies of the press release and the Presentation are furnished hereto as Exhibits 99.1 and 99.2.
On September 16, 2020, the Company also posted its corporate presentation, a copy of which is furnished hereto as Exhibit 99.3.
Item 9.01. Financial Statements and Exhibits
| Exhibit No. |
Description | |
| 99.1 | Press Release, dated September 16, 2020 | |
| 99.2 | Presentation for Second Annual RAS-Targeted Drug Development Summit | |
| 99.3 | Corporate Presentation, dated September 16, 2020 | |
| 104 | Cover Page Interactive Data File (formatted in Inline XBRL and contained in Exhibit 101) |
SIGNATURE
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
| VERASTEM, INC. | ||
| Date: September 16, 2020 | By: | /s/ Brian M. Stuglik |
| Brian M. Stuglik | ||
| Chief Executive Officer | ||
Exhibit 99.1
Verastem Oncology Announces Presentation of Updated Phase 1/2 FRAME Study Data at the 2nd Annual RAS-Targeted Drug Development Summit
Preliminary Data on VS-6766 and Defactinib Combination Continues to Show Encouraging Response Rates, Durability and a Favorable Safety Profile in KRAS Mutant Low-Grade Serous Ovarian Cancer in Investigator-Initiated Trial
New Preclinical Data Demonstrating Synergy and Tumor Regression with G12C Inhibitors in Combination with VS-6766 and FAK Inhibitor In Vitro and In Vivo Also Presented
Management to Host Investor Conference Call Today at 8:00 AM ET
BOSTON, MA – September 16, 2020 – Verastem, Inc. (Nasdaq:VSTM) (also known as Verastem Oncology), a biopharmaceutical company committed to advancing new medicines for patients battling cancer, today announced updated results from the ongoing investigator-initiated Phase 1/2 FRAME study evaluating VS-6766, its RAF/MEK inhibitor, in combination with defactinib, its FAK inhibitor, which demonstrated robust response rates, duration of response and a favorable safety profile in patients with low-grade serous ovarian cancer (LGSOC). These data will be presented in a virtual oral presentation today by Dr. Udai Banerji from The Institute of Cancer Research and The Royal Marsden at the 2nd Annual RAS-Targeted Drug Development Summit.
“Existing treatments for patients with LGSOC are limited by either 10-25% response rates and/or increased toxicities, leading to high discontinuation rates. The FRAME data being presented today continue to demonstrate that RAF/MEK inhibition combined with FAK inhibition is well tolerated with a 56% overall response rate (ORR) in patients with KRAS-G12 mutant LGSOC and a 41% ORR in the overall LGSOC population. These data are still actively maturing with more than half of the patients still on treatment as of the data cutoff date, and responses in this patient population tend to deepen over time,” said Dan Paterson, President and Chief Operating Officer of Verastem Oncology. “The response rates from this expanded data set are highly encouraging, consistent with the prior positive data from this study, and continue to speak to the significant potential of the VS-6766/defactinib combination for patients battling LGSOC.”
Verastem recently met with the Food and Drug Administration (FDA), and the FDA is supportive of the Company’s adaptive study design for the planned Phase 2 registration-directed trials evaluating VS-6766 and defactinib in patients with recurrent LGSOC. Verastem expects to commence registration-directed clinical trials in both recurrent LGSOC and KRAS mutant non-small cell lung cancer by the end of 2020. Assuming a positive outcome from these registration-directed trials, Verastem expects to submit New Drug Applications to the FDA requesting accelerated approval for the VS-6766/defactinib combination in both LGSOC and KRAS mutant NSCLC.
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Updated Phase 1/2 FRAME Study Results in Patients with LGSOC
Among the patients with LGSOC (n=17), the overall response rate (ORR) was 41% (7 of 17 patients), all partial responses (PRs). Among the patients with KRAS-G12 mutant LGSOC (n=9), the ORR was 56% (5 of 9 patients). Of the seven patients who responded, five had received one or more prior MEK inhibitors. In patients with KRAS mutant LGSOC receiving the recommended Phase 2 dosing (RP2D) regimen, the ORR was 50% (3 of 6 patients). The LGSOC cohort of the FRAME study remains ongoing, with 53% (9 of 17 patients) still on study as of the data cutoff date of August 17, 2020, with three patients on treatment for two years or more.
The most common Grade ≥3 treatment-related adverse events (TEAEs) observed for the recommended Phase 2 dosing regimen were rash (4%) and elevated creatine kinase (4%). No patients discontinued from the FRAME study due to TEAEs.
The novel, intermittent, combination dosing schedule used in the FRAME study continues to show encouraging clinical activity in patients with KRAS mutant LGSOC, including in patients who had previously progressed following treatment with a MEK inhibitor.
“These updated safety and efficacy results in both KRAS mutant LGSOC as well as the overall LGSOC population are highly encouraging. Of particular note in this early look at the data, is the strong, 50% response rate, durability, and tumor reduction seen in patients with KRAS mutant LGSOC receiving the recommended Phase 2 dosing (RP2D) regimen, which is the regimen we will be taking into our upcoming registration-directed study,” said Brian Stuglik, Chief Executive Officer of Verastem Oncology. “With nine out of 11 patients at RP2D active in the study and responses still developing, we look forward to continued data outputs from this study and we remain on track to commence Phase 2 registration-directed trials in both LGSOC and KRAS mutant NSCLC by the end of this year.”
Preclinical Results from Studies Investigating VS-6766 and Defactinib in Combination with G12C Inhibitors
KRAS-G12C inhibitors may benefit from novel combination approaches to enhance their inhibition of the ERK signaling pathway. In the preclinical results that will be presented today at the meeting, VS-6766 showed synergy with KRAS-G12C inhibitors in reducing cancer cell viability across a panel of KRAS-G12C mutant NSCLC and colorectal cancer (CRC) cell lines. This enhanced cellular anti-cancer activity of the combination correlated with deeper and more durable inhibition of ERK pathway signaling relative to G12C inhibition alone. In KRAS-G12C mutant NSCLC models in mice, the RAF/MEK dual inhibitor VS-6766 was more effective than trametinib when compared at equal dose level both alone and in combination with a G12C inhibitor. In the KRAS-G12C NSCLC models tested, the combination of G12C inhibitor with VS-6766 and FAK inhibitor induced tumor regressions of ≥30% in all mice.
“The anti-tumor effects of VS-6766 were generally comparable to those of KRAS-G12C inhibitors in KRAS-G12C NSCLC models in mice and were stronger than the effects of trametinib at a comparable dose,” said Jonathan Pachter, Ph.D., Chief Scientific Officer of Verastem Oncology. “The tumor regressions observed with the triple combination of VS-6766, FAK inhibitor and G12C inhibitor were particularly striking. These data support clinical evaluation of VS-6766 and defactinib with G12C inhibitors in patients with KRAS-G12C mutant tumors.”
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About the Phase 1/2 FRAME Study
The FRAME study is an open-label, investigator-initiated study that is designed to assess safety, dose response and preliminary efficacy of the VS-6766/defactinib combination in patients with KRAS mutant solid tumors, including LGSOC, non-small cell lung cancer (NSCLC) and colorectal cancer (CRC). The FRAME study is being led by Dr. Banerji and is being conducted in the United Kingdom. In this study, VS-6766 was administered using a twice-weekly dose escalation schedule and was administered three out of every four weeks. Defactinib was administered using a twice-daily dose escalation schedule, also three out of every four weeks. Dose levels were assessed in three cohorts: cohort 1 (VS-6766 3.2mg, defactinib 200mg); cohort 2a (VS-6766 4mg, defactinib 200mg); and cohort 2b (VS-6766 3.2mg, defactinib 400mg). The recommended Phase 2 dose was determined to be VS-6766 3.2mg, defactinib 200mg. The FRAME study is now expanding to include new cohorts in pancreatic cancer, KRAS mutant endometrial cancer and KRAS-G12V mutant NSCLC.
Details for the RAS-Targeted Drug Development Summit oral presentation are as follows:
Title: Clinical Combinations: Dual RAF-MEK Inhibitor & FAK for Treatment of KRAS Mutant Cancers With a Focus on Low Grade Ovarian Cancer
Lead author: Udai Banerji, The Institute of Cancer Research and The Royal Marsden
Date and Time: Wednesday, September 16, 2020; 3:35 p.m. ET (12:35 p.m. PT)
Title: Synergistic Combinations with the Dual RAF/MEK Inhibitor VS-6766 to Overcome Resistance Mechanisms
Lead author: Jonathan Pachter, Verastem Oncology
Date and Time: Wednesday, September 16, 2020; 12:10 p.m. ET (9:10 a.m. PT)
Conference Call and Webcast Information
The Verastem Oncology management team will host a conference call and webcast on Wednesday, September 16, 2020, at 8:00 AM ET to discuss the updated Phase 1/2 FRAME study data. The call can be accessed by dialing (877) 341-5660 (US and Canada) or (315) 625-3226 (international), five minutes prior to the start of the call and providing the passcode 5278200.
The live, listen-only webcast of the conference call can be accessed by visiting the investors section of the Company's website at www.verastem.com. A replay of the webcast will be archived on the Company's website for 90 days following the call.
About VS-6766
VS-6766 (formerly known as CH5126766, CKI27 and RO5126766) is a unique inhibitor of the RAF/MEK signaling pathway. In contrast to other MEK inhibitors in development, VS-6766 blocks both MEK kinase activity and the ability of RAF to phosphorylate MEK. This unique mechanism allows VS-6766 to block MEK signaling without the compensatory activation of MEK that appears to limit the efficacy of other inhibitors.
About Defactinib
Defactinib (VS-6063) is an oral small molecule inhibitor of FAK and PYK2 that is currently being evaluated as a potential combination therapy for various solid tumors. The Company has received Orphan Drug designation for defactinib in ovarian cancer and mesothelioma in the US, EU and Australia. Preclinical research by Verastem Oncology scientists and collaborators at world-renowned research institutions has described the effect of FAK inhibition to enhance immune response by decreasing immuno-suppressive cells, increasing cytotoxic T cells, and reducing stromal density, which allows tumor-killing immune cells to enter the tumor.1,2
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About the VS-6766/Defactinib Combination
RAS mutant tumors are present in ~30% of all human cancers, have historically presented a difficult treatment challenge and are often associated with significantly worse prognosis. Challenges associated with identifying new treatment options for these types of cancers include resistance to single agents, identifying tolerable combination regimens with MEK inhibitors and new RAS inhibitors in development addressing only a minority of all RAS mutated cancers.
The combination of VS-6766 and defactinib has been found to be clinically active in patients with KRAS mt tumors. In an ongoing investigator-initiated Phase 1/2 FRAME study, the combination of VS-6766 and defactinib is being evaluated in patients with LGSOC, KRASmt NSCLC and colorectal cancer (CRC). Updated data from this study presented at the 2nd Annual RAS-Targeted Drug Development Summit in September 2020 demonstrated a 56% overall response rate and long duration of therapy among patients with KRAS-G12 mt LGSOC. Based on an observation of higher response rates seen in NSCLC patients with KRAS-G12V mutations in the study, Verastem will also be further exploring the role of VS-6766 and defactinib in KRAS-G12V NSCLC. The FRAME study was expanded in August 2020 to include new cohorts in pancreatic cancer, KRASmt endometrial cancer and KRAS-G12V NSCLC.
About Verastem Oncology
Verastem Oncology (Nasdaq: VSTM) is a development-stage biopharmaceutical company committed to the development and commercialization of new medicines to improve the lives of patients diagnosed with cancer. Our pipeline is focused on novel small molecule drugs that inhibit critical signaling pathways in cancer that promote cancer cell survival and tumor growth, including RAF/MEK inhibition and focal adhesion kinase (FAK) inhibition. For more information, please visit www.verastem.com.
Forward-Looking Statements Notice
This press release includes forward-looking statements about Verastem Oncology’s strategy, future plans and prospects, including statements related to the potential clinical value of the RAF/MEK/FAK combination and the timing of commencing a registration-directed trial for the RAF/MEK/FAK combination. The words "anticipate," "believe," "estimate," "expect," "intend," "may," "plan," "predict," "project," "target," "potential," "will," "would," "could," "should," "continue," “can,” “promising” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Each forward-looking statement is subject to risks and uncertainties that could cause actual results to differ materially from those expressed or implied in such statement.
Applicable risks and uncertainties include the risks and uncertainties, among other things, regarding: the success in the development and potential commercialization of our product candidates, including defactinib in combination with VS-6766; the occurrence of adverse safety events and/or unexpected concerns that may arise from additional data or analysis or result in unmanageable safety profiles as compared to their levels of efficacy; our ability to obtain, maintain and enforce patent and other intellectual property protection for our product candidates; the scope, timing, and outcome of any legal proceedings; decisions by regulatory authorities regarding labeling and other matters that could affect the availability or commercial potential of our product candidates; whether preclinical testing of our product candidates and preliminary or interim data from clinical trials will be predictive of the results or success of ongoing or later clinical trials; that the timing, scope and rate of reimbursement for our product candidates is uncertain; that third-party payors (including government agencies) may not reimburse; that there may be competitive developments affecting our product candidates; that data may not be available when expected; that enrollment of clinical trials may take longer than expected; that our product candidates will experience manufacturing or supply interruptions or failures; that we will be unable to successfully initiate or complete the clinical development and eventual commercialization of our product candidates; that the development and commercialization of our product candidates will take longer or cost more than planned; that we or Chugai Pharmaceutical Co., Ltd. will fail to fully perform under the VS-6766 license agreement; that we may not have sufficient cash to fund our contemplated operations; that we may be unable to make additional draws under our debt facility or obtain adequate financing in the future through product licensing, co-promotional arrangements, public or private equity, debt financing or otherwise; that we will be unable to execute on our partnering strategies for defactinib in combination with VS-6766; that we will not pursue or submit regulatory filings for our product candidates; and that our product candidates will not receive regulatory approval, become commercially successful products, or result in new treatment options being offered to patients.
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Other risks and uncertainties include those identified under the heading “Risk Factors” in the Company’s Annual Report on Form 10-K for the year ended December 31, 2019 as filed with the Securities and Exchange Commission (SEC) on March 11, 2020 and in any subsequent filings with the SEC. The forward-looking statements contained in this press release reflect Verastem Oncology’s views as of the date hereof, and the Company does not assume and specifically disclaims any obligation to update any forward-looking statements whether as a result of new information, future events or otherwise, except as required by law.
References
1 Chénard-Poirier, M. et al. Results from the biomarker-driven basket trial of RO5126766 (CH5127566), a potent RAF/MEK inhibitor, in RAS- or RAF-mutated malignancies including multiple myeloma. Journal of Clinical Oncology 2017: 35. 10.1200/JCO.2017.35.15_suppl.2506.
2 https://clinicaltrials.gov, NCT03875820
Contacts
Investors:
John Doyle
Vice President, Investor Relations & Finance
+1 781-469-1546
jdoyle@verastem.com
Media:
Lisa Buffington
Corporate Communications
+1 781-292-4205
lbuffington@verastem.com
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Exhibit 99.2
1 CONFIDENTIAL. Do Not Distribute. © Verastem Inc. 2018 CONFIDENTIAL. Do Not Distribute. © Verastem Inc. 2018 Synergistic Combinations with the Dual RAF/MEK Inhibitor VS - 6766 to Overcome Resistance Mechanisms Jonathan Pachter, PhD, Chief Scientific Officer – Verastem Oncology RAS - Targeted Drug Development, Sept 16, 2020
2 CONFIDENTIAL. Do Not Distribute. © Verastem Inc. 2018 2 Disclosures ▪ I am an employee of Verastem Oncology ▪ I will be discussing investigational/off - label uses of VS - 6766 (RAF/MEK inhibitor) and defactinib (focal adhesion kinase inhibitor)
3 CONFIDENTIAL. Do Not Distribute. © Verastem Inc. 2018 3 ▪ BRAF & MEK inhibitors can block Growth Factor - stimulated ERK signaling, but Cell Attachment can also stimulate ERK signaling through a FAK - dependent pathway (Slack - Davis, JCB 162 :281, 2003) ▪ GPCR - mediated activation of RhoA and YAP pathways through FAK (Feng, Cancer Cell, 2019) may also confer cancer cell proliferation and survival bypassing the ERK pathway ▪ Signaling through a RhoA - FAK axis is required for maintenance of KRAS - dependent lung adenocarcinomas (Konstantinou, Cancer Discovery 3 :444, 2013) ▪ BRAF inhibition generates a drug - tolerant microenvironment for melanoma cells which can be abolished by FAK inhibition (Hirata, Cancer Cell 27 :574, 2015) RTK RAS RAF MEK ERK RhoA Growth factors PAK1 b a Y397 Integrin FAK ECM SRC RAC GPCR G q YAP RhoA Proliferation/Survival/Migration PLC Ca 2+ /DAG PKC ERK P More Complete Shutdown of RAS Pathway - Driven Tumor Growth Requires Addressing Multiple Resistance Mechanisms
4 CONFIDENTIAL. Do Not Distribute. © Verastem Inc. 2018 RTK RAS RAF MEK ERK RhoA Growth factors β α Y397 Integrin FAK ECM SRC YAP Proliferation/Survival/Migration P • BRAF inhibition induces compensatory activation of pFAK 1 • MEK inhibition induces compensatory activation of pFAK preclinically and clinically 2 • Trametinib induced ↑ pFAK (Y397) preclinically in KRAS mt NSCLC cell lines • Also observed in patients • VS - 6766 induced ↑ pFAK (Y397) as a potential resistance mechanism in the majority of patients • Combination with defactinib reduced this compensatory pFAK signal • Upon MEK blockade, ERK feeds back to activate RAF kinase = Feedback Reactivation References: 1 Chen, Mol Cancer Res 2018; 2 Banerji, BTOG Dublin, Jan 23, 2019 More Complete Shutdown of RAS Pathway - Driven Tumor Growth Requires Addressing Multiple Resistance Mechanisms
5 CONFIDENTIAL. Do Not Distribute. © Verastem Inc. 2018 RTK RAS RAF MEK ERK RhoA Growth factors β α Y397 Integrin FAK ECM SRC YAP Proliferation/Survival/Migration P • In patients with KRAS mt tumors • VS - 6766 induced ↑ pFAK (Y397) as a potential resistance mechanism in the majority of patients • Combination of VS - 6766 with defactinib reduced this compensatory pFAK signal VS - 6766 Defactinib More Complete Shutdown of RAS Pathway - Driven Tumor Growth Requires Addressing Multiple Resistance Mechanisms pFAK (Y397) U. Banerji, AACR 2020
6 CONFIDENTIAL. Do Not Distribute. © Verastem Inc. 2018 6 ▪ VS - 6766 inhibits both MEK & RAF kinase activities ▪ Most MEK inhibitors paradoxically induce MEK phosphorylation (pMEK) by relieving ERK - dependent feedback inhibition of RAF ▪ By inhibiting RAF phosphorylation of MEK, VS - 6766 has advantage of not inducing pMEK ▪ VS - 6766 inhibits ERK signaling more completely; may confer enhanced therapeutic activity VS - 6766 is a Unique Small Molecule RAF/MEK Dual Inhibitor Reference: Ishii et al., Cancer Res , 2013; Lito et al., Cancer Cell, 2014; Blasco, R. B. et al. Cancer Cell (2011); Sanclemente, M. et al. Cancer Cell (2018) RAS RAF MEK ERK Proliferation & Survival
7 CONFIDENTIAL. Do Not Distribute. © Verastem Inc. 2018 7 Defactinib (VS - 6063) – Selective FAK Inhibitor p F A K ( Y 3 9 7 ; H S c o r e ) D a y 1 D a y 1 0 0 50 100 150 Pre - treatment Post - treatment pFAK (Y397; H - Score) * 03 - 315 OVARIAN CANCER: TUMOR BIOPSIES MESOTHELIOMA: TUMOR BIOPSIES FAK EC 50 = 15 nM Defactinib Defactinib µM % C e l l u l a r A u t o p h o s p h o r y l a t i o n 0.0001 0.001 0.01 0.1 1 10 0 25 50 75 100 Dosage : Oral, 400mg BID • Studied in 500+ patients with good safety profile observed to date • DLT not reached • Early signs of clinical efficacy • Well established safety profile as a single agent and in combination: • RAF/ MEKi , PD - 1i, Chemotherapy
8 CONFIDENTIAL. Do Not Distribute. © Verastem Inc. 2018 8 Combination of defactinib with VS - 6766 or trametinib shows synergy in KRAS mt and BRAF mt cell lines
9 CONFIDENTIAL. Do Not Distribute. © Verastem Inc. 2018 9 VS - 6766 and FAK inhibitor combination leads to more robust anti - tumor efficacy in vivo Ovarian cancer model (TOV - 21g KRAS(G13C) mutant) NSCLC cancer model (H2122 KRAS(G12C) mutant) J. Paradis, AACR 2020 0 5 10 15 0 200 400 600 Tumor growth Days on treatment T u m o r v o l u m e ( m m 3 + / - S E M ) Vehicle FAKi 50 mg/kg BID VS-6766 0.3 mg/kg QD VS-6766 + FAKi Trametinib 0.3 mg/kg QD 0 5 10 15 0 100 200 300 400 500 Tumor growth VS-4718 + CH5126766 Days on treatment T u m o r v o l u m e ( m m 3 + / - S E M ) Vehicle Trametinib 1.5 mg/kg QD FAKi 50 mg/kg BID VS-6766 1.5 mg/kg QD VS-6766 + FAKi FAKi + MEKicombination iscytotoxic in vivo CTL MEKi FAKi Combo *** *** *** Trametinib + VS-4718 is more ecient than one alone. Each inhbitor iscytostatic , thecombination iscytotoxic In vitro Trametinib + VS-4718 induced more apoptosis in vitro than each one alone Vehicle Trametinib 1 mg/kg QD FAKi 50 mg/kg BID Trametinib + FAKi Uveal melanoma model (92.1 GNAQ mutant)
10 CONFIDENTIAL. Do Not Distribute. © Verastem Inc. 2018 10 • 9 pts with KRAS - G12 mutations • ORR = 56% (5/9); data still maturing • 4/5 PRs in pts who had previous MEKi • 2 pts on treatment for 2.5 yrs Cut - off August 17, 2020 VS - 6766 in Combination with Defactinib Shows Robust ORR with Durability in Patients with Refractory KRAS Mutant Low Grade Serous Ovarian Cancer 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 FRA101015 FRA101035 FRA102010 FRA101033 FRA101019 FRA101014 FRA101009 FRA101001 FRA101002 Time on Treatment (months) * * G12A G12V G12D G12D G12D G12D G12D G12V Time on Treatment * G12D Previous MEK inhibitor treatment Continuing on treatment * Approaching PR # Time to response Partial Response Stable Disease # 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 -70 -60 -50 -40 -30 -20 -10 0 10 20 Response by RECIST Time (months) 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 FRA101014 - KRAS G12D FRA101015 - KRAS G12V FRA101019 - KRAS G12D FRA102010 - KRAS G12D FRA101033 - KRAS G12D FRA101035 - KRAS G12D Continuing on treatment Udai Banerji, RAS - Targeted Drug Development, 2020 9/16/20, 3:35 pm ET
11 CONFIDENTIAL. Do Not Distribute. © Verastem Inc. 2018 Preclinical evidence suggests combination with Defactinib may improve efficacy in KRAS G12V Activity of VS - 6766 as a single agent and in combo with Defactinib in KRAS G12V 1 additional confirmed PR in KRAS G12V mutant patient as of Mar - 2020 VS - 6766 ± Defactinib Has a Confirmed 57% ORR in KRAS G12V NSCLC in Integrated Analysis Strong Signal Identified in KRAS G12V NSCLC to Be Further Validated Source: 1 Martinez - Garcia, M. et al. Clin. Cancer Res . (2012); 2 Banerji, AACR VM 1, April 27, 2020, CT143 *On Treatment Best Response by RECIST in KRAS G12V NSCLC Time on Treatment for KRAS G12V NSCLC 0% 0% - 8% - 38% - 38% - 61% - 68% -80% -70% -60% -50% -40% -30% -20% -10% 0% 10% Mono Mono Mono Combo Mono Combo Mono Best Response (% Change from Baseline) All Confirmed Responses NSCLC (57% ORR; N=7) Mono = VS - 6766 Monotherapy 1 Combo = VS - 6766 + Defactinib 2 * * March 2020 ** 7 17 18 18 18 58 0 5 10 15 20 25 30 35 40 45 50 55 60 Mono Mono Combo Mono Combo Mono Mono Weeks on Treatment 215 214 * *
12 CONFIDENTIAL. Do Not Distribute. © Verastem Inc. 2018 12 KRAS - G12C mutant tumor models differ in their sensitivity to G12C inhibitors MRTX849 100 mg/kg QD Hallin et al., Cancer Discovery 2020
13 CONFIDENTIAL. Do Not Distribute. © Verastem Inc. 2018 13 G12C inhibitors do not maintain sustained inhibition of pMEK & pERK Densitometry of p - ERK normalized to GAPDH for blots; results represent an average of pERK across 8 cell lines Source: Ryan, M. B. et al. Clin. Cancer Res . (2020) • Sustained inhibition of pMEK & pERK may be essential for durable response in KRAS - G12C mutant NSCLC & colorectal cancer • KRAS - G12C inhibitors as monotherapy transiently inhibit pMEK & pERK in vitro • VS - 6766 yields more complete blockade of pMEK & pERK than other MEKi in preclinical models • Tested hypothesis that VS - 6766 combination with G12C inhibitors should yield deeper & durable inhibition of ERK pathway signaling with corresponding synergy in KRAS - G12C tumor cell lines ARS - 1620 at 1 µM
14 CONFIDENTIAL. Do Not Distribute. © Verastem Inc. 2018 14 G12C inhibition is synergistic with VS - 6766 in KRAS G12C mutant NSCLC & CRC cell lines H2122: AMG 510 + VS - 6766 (RAF/ MEKi ) H2122: MRTX849 + VS - 6766 (RAF/ MEKi ) Synergy Score (Loewe model) Cell line Indication Sensitivity to G12C inhibitors VS - 6766 + AMG 510 VS - 6766 + MRTX849 H2122 NSCLC Moderately sensitive 43.9 46.9 H358 NSCLC Sensitive 14.5 11.9 H2030 NSCLC Moderately sensitive 12.1 ND H1373 NSCLC Sensitive 9.3 9.6 SW1573 NSCLC Insensitive 5 ND SW837 CRC Sensitive 14.9 ND SW1463 CRC Moderately sensitive 11.5 ND
15 CONFIDENTIAL. Do Not Distribute. © Verastem Inc. 2018 15 G12C inhibition is synergistic with VS - 6766 & defactinib in KRAS G12C mutant NSCLC & CRC cell lines AMG 510 + VS - 6766 AMG 510 + Defactinib SW837 (KRAS G12C CRC) AMG 510 + VS - 6766 AMG 510 + Defactinib Loewe Synergy Score H2122 (KRAS G12C NSCLC) AMG 510 + VS - 6766 AMG 510 + Defactinib MRTX849+ VS - 6766 MRTX849 + Defactinib H358 (KRAS G12C NSCLC)
16 CONFIDENTIAL. Do Not Distribute. © Verastem Inc. 2018 16 Addition of VS - 6766 to AMG 510 increases depth & duration of inhibition of p - ERK relative to AMG 510 across a panel of KRAS - G12C mt NSCLC cell lines p - ERK Actin AMG 510 - + - + - + - + VS - 6766 - - + + - - + + H2122 Moderately sensitive SW1573 Insensitive p - ERK Actin AMG 510 - + - + - + - + VS - 6766 - - + + - - + + H1373 Sensitive H358 Sensitive p - ERK Actin AMG 510 - + - + - + - + VS - 6766 - - + + - - + + p - ERK Actin AMG 510 - + - + - + - + VS - 6766 - - + + - - + + Total ERK Total ERK Total ERK Total ERK 4h 48h 0 20 40 60 80 100 H358 p-ERK % p - E R K ( r e l a t i v e t o D M S O ) AMG 510 VS-6766 AMG 510 + VS-6766 Vehicle 4h 48h 0 20 40 60 80 100 H1373 p-ERK % p - E R K ( r e l a t i v e t o D M S O ) AMG 510 VS-6766 AMG 510 + VS-6766 Vehicle 4h 48h 0 20 40 60 80 100 H2122 p-ERK % p - E R K ( r e l a t i v e t o D M S O ) AMG 510 VS-6766 AMG 510 + VS-6766 Vehicle 4h 48h 0 20 40 60 80 100 SW1573 p-ERK % p - E R K ( r e l a t i v e t o D M S O ) AMG 510 VS-6766 AMG 510 + VS-6766 Vehicle 4h 48h 4h 48h 4h 48h 4h 48h 4h 48h 0 20 40 60 80 100 H2122 p-p90RSK % p - p 9 0 R S K ( r e l a t i v e t o D M S O ) AMG 510 100 nM VS-6766 100 nM AMG 510 + VS-6766 Vehicle
17 CONFIDENTIAL. Do Not Distribute. © Verastem Inc. 2018 17 Addition of VS - 6766 to AMG 510 increases depth & duration of inhibition of MEK/ERK signaling relative to AMG 510 across a panel of KRAS - G12C mt NSCLC cell lines Concentrations Tested VS - 6766: 100 nM AMG 510: 100 nM H2122 Moderately sensitive p - MEK1/2 p - ERK p - p90RSK Actin AMG 510 - + - + - + - + VS - 6766 - - + + - - + + 4h 48h H358 Sensitive p - MEK1/2 p - ERK p - p90RSK Actin AMG 510 - + - + - + - + VS - 6766 - - + + - - + + 4h 48h SW1573 Insensitive p - MEK1/2 p - ERK p - p90RSK Actin AMG 510 - + - + - + - + VS - 6766 - - + + - - + + 4h 48h ▪ In G12C cell lines sensitive to AMG 510 (e.g. H358), addition of VS - 6766 to AMG 510 increases duration of inhibition of the MEK/ERK/RSK pathway ▪ In G12C cell lines less sensitive to AMG 510 (e.g. H2122), addition of VS - 6766 to AMG 510 increases inhibition of the MEK/ERK/RSK pathway at both early and late time points p90RSK S6 GSK3 PP - 1
18 CONFIDENTIAL. Do Not Distribute. © Verastem Inc. 2018 18 ▪ VS - 6766 is more effective than trametinib at equal dose ▪ VS - 6766 or FAKi each potentiate the efficacy of AMG 510 ▪ Triple combination of AMG 510 + VS - 6766 + FAKi yields tumor regression in all mice 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 VS - 6766 & FAKi potentiate AMG 510 efficacy in KRAS G12C mutant NSCLC in vivo Tumor regression in all mice with triple combination H2122 KRAS G12C mutant NSCLC -100 0 100 200 300 400 Response at Day 10 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 ) Vehicle VS-6766 0.3mg/kg QD AMG 510 30mg/kg QD VS-6766 + AMG 510 VS-4718 50mg/kg BID VS-6766 + VS-4718 AMG 510 + VS-4718 VS-6766 + AMG 510 + VS-4718 Trametinib 0.3mg/kg QD Trametinib + AMG 510 V e h i c l e T r a m e t i n i b 10 PR V S - 6 7 6 6 F A K i A M G 5 1 0 A M G 5 1 0 + T r a m e t i n i b A M G 5 1 0 + V S - 6 7 6 6 A M G 5 1 0 + F A K i V S - 6 7 6 6 + F A K i A M G 5 1 0 + V S - 6 7 6 6 + F A K i -30 20 1 SD 2 SD 1 SD 1 SD 1 SD 1 PR 8 SD 2 PR 4 SD 3 PR 2 SD 4 PR Response @ Day 10 0 5 10 15 0 200 400 600 Tumor growth Days after first dose T u m o r v o l u m e ( m m 3 + / - S E M ) Vehicle AMG 510 AMG 510 + FAKi AMG 510 + VS-6766 AMG 510 + VS-6766 + FAKi VS-6766
19 CONFIDENTIAL. Do Not Distribute. © Verastem Inc. 2018 19 -100 0 100 200 300 400 Waterfall at Day 21 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 ) Vehicle VS-6766 0.3mg/kg QD AMG 510 10mg/kg QD VS-6766 + AMG 510 VS-4718 50mg/kg BID VS-6766 + VS-4718 AMG 510 + VS-4718 VS-6766 + AMG 510 + VS-4718 Trametinib 0.3mg/kg QD Trametinib + AMG 510 V e h i c l e T r a m e t i n i b 10 PR V S - 6 7 6 6 F A K i A M G 5 1 0 A M G 5 1 0 + T r a m e t i n i b A M G 5 1 0 + V S - 6 7 6 6 A M G 5 1 0 + F A K i V S - 6 7 6 6 + F A K i A M G 5 1 0 + V S - 6 7 6 6 + F A K i 5 SD 6 SD 1 SD 9 PR 4 SD 6 PR 6 SD 3 PR 7 SD SD: Stable disease PR: Partial response VS - 6766 & FAKi potentiate AMG 510 efficacy in KRAS G12C mutant NSCLC in vivo Tumor regression in all mice with triple combination H358 KRAS G12C mutant NSCLC Response @ Day 21 ▪ VS - 6766 is more effective than trametinib at equal dose ▪ VS - 6766 or FAKi each potentiate the efficacy of AMG 510 ▪ Triple combination of AMG 510 + VS - 6766 + FAKi yields tumor regression in all mice Doses Tested Trametinib: 0.3 mg/kg QD VS - 6766: 0.3 mg/kg QD FAKi : 50 mg/kg BID AMG 510: 10 mg/kg QD 0 5 10 15 20 25 0 200 400 600 800 Tumor growth Days after first dose T u m o r v o l u m e ( m m 3 + / - S E M ) Vehicle AMG510 AMG510 + FAKi AMG510 + VS-6766 AMG510 + VS-6766 + FAKi VS-6766
20 CONFIDENTIAL. Do Not Distribute. © Verastem Inc. 2018 20 Role of VS - 6766 in Immuno - Oncology: VS - 6766 upregulates antigen presentation machinery (MHC - I) including b 2 microglobulin Cell Line Tumor type RAS/RAF mutation status A549 Lung KRAS mt G12S TOV21g Ovarian KRAS mt G13C SKMEL5 Melanoma BRAF mt V600E IGR - 1 Melanoma BRAF mt V600E WM115 Melanoma BRAF mt V600E A549 TOV21g SKMEL5 IGR1 WM115 0 2 4 6 B2M R e l a t i v e m R N A L e v e l s DMSO VS-6766 KRAS mt BRAF mt A549 TOV21g SKMEL5 IGR1 WM115 0 2 4 6 8 HLA-A R e l a t i v e m R N A L e v e l s DMSO VS-6766 KRAS mt BRAF mt A549 TOV21g SKMEL5 IGR1 WM115 0 2 4 6 TAP-1 R e l a t i v e m R N A L e v e l s DMSO VS-6766 KRAS mt BRAF mt A549 TOV21g SKMEL5 IGR1 WM115 0.0 0.5 1.0 1.5 2.0 2.5 TAP-2 R e l a t i v e m R N A L e v e l s DMSO VS-6766 KRAS mt BRAF mt VS - 6766 1 µM (except SKMEL5 and IGR - 1, 300 nM )
21 CONFIDENTIAL. Do Not Distribute. © Verastem Inc. 2018 21 VS - 6766 enhances tumor growth inhibition when combined with anti - PD - 1 in the CT26 KRAS (G12D) syngeneic model -100 0 100 200 300 400 Response at Day 13 % C h a n g e i n T u m o r V o l u m e Vehicle VS-6766 anti-PD-1 VS-6766 + anti-PD-1 20 40 60 80 100 0 20 40 60 80 100 Survival Time P e r c e n t s u r v i v a l VS-6766 + anti-PD-1 anti-PD-1 3 mg/kg 2xW x 4 doses VS-6766 0.5 mg/kg QD x 28 days Vehicle Day 11, Last dose anti - PD - 1 Day 28, Last dose VS - 6766 0 10 20 30 40 50 60 70 80 90 100 0 20 40 60 80 100 Survival Days after first dose P e r c e n t s u r v i v a l VS-6766 + anti-PD-1 anti-PD-1 3 mg/kg 2xW x 4 doses VS-6766 0.5 mg/kg QD x 28 days Vehicle 0 2 4 6 8 101214161820222426 0 200 400 600 800 1000 1200 Tumor growth Days after first dose T u m o r v o l u m e ( m m 3 + / - S E M ) Vehicle VS-6766 0.5 mg/kg QD anti-PD-1 3 mg/kg 2xW VS-6766 + anti-PD-1
22 CONFIDENTIAL. Do Not Distribute. © Verastem Inc. 2018 22 Combination of VS - 6766 + anti - PD - 1 induces long - lasting immune memory in the CT26 colorectal cancer model Tumor re - challenge: Tumor - free mice show durable immune memory Tumor - free mice show increase in effector memory T cells Effector Memory CD4 cells - Spleen - Naive VS-6766/PD1 0 20 40 60 C D 3 + C D 4 + C D 4 4 + C D 6 2 L + c e l l s % i n l i v e C D 4 5 + C D 3 + C D 4 + c e l l s ** Effector Memory CD8 cells - Spleen - Naive VS-6766/PD1 0 5 10 15 20 25 C D 3 + C D 8 + C D 4 4 + C D 6 2 L + c e l l s % i n l i v e C D 4 5 + C D 3 + C D 8 + c e l l s ** 0 5 10 15 20 25 30 0 1000 2000 3000 Naive mice (n=5) Days after cell linoculation T u m o r v o l u m e ( m m 3 ) 0 5 10 15 20 25 30 0 1000 2000 3000 Tumor-free mice previously treated with VS-6766 + anti-PD-1 (n=3) Days after cell linoculation T u m o r v o l u m e ( m m 3 )
23 CONFIDENTIAL. Do Not Distribute. © Verastem Inc. 2018 23 VS - 6766 Combinations to Overcome Resistance Mechanisms: Conclusions ▪ Combination of dual RAF/MEK inhibitor VS - 6766 + FAKi may yield more complete RAS pathway shutdown o Synergy in cellular models with tumor regression in vivo o Clinical activity in KRAS mt ovarian cancer & KRAS G12V mt NSCLC patients ▪ Combination of RAF/MEK inhibitor VS - 6766 is synergistic with KRAS - G12C inhibitors across G12C mt NSCLC & CRC cell lines o Strong & durable inhibition of pERK pathway signaling o Tumor regressions in KRAS G12C mt NSCLC models in vivo o In KRAS G12C NSCLC models, triple combination of G12Ci + VS - 6766 + FAKi yields PRs in all mice ▪ Combination of RAF/MEK inhibitor with anti - PD - 1 yields enhanced efficacy & immune memory in vivo o VS - 6766 increases MHC - I expression across KRAS & BRAF mt cell lines
24 CONFIDENTIAL. Do Not Distribute. © Verastem Inc. 2018 24 VS - 6766 Combinations: Next Steps ▪ Registration - directed phase II study of VS - 6766 + defactinib vs. VS - 6766 monotherapy in Low Grade Serous Ovarian Cancer ▪ Registration - directed phase II study of VS - 6766 + defactinib vs. VS - 6766 monotherapy in KRAS - G12V mt NSCLC ▪ Potential for a combination study of VS - 6766 ц defactinib with a G12C inhibitor in patients with KRAS - G12C mt NSCLC and/or CRC
25 CONFIDENTIAL. Do Not Distribute. © Verastem Inc. 2018 Acknowledgments Verastem Oncology ▪ Silvia Coma ▪ David Weaver Emory University ▪ C. Ronald Funk ▪ Edmund Waller Thanks for your attention! Acknowledgments Verastem Oncology ▪ Silvia Coma ▪ Sanjib Chowdhury ▪ Winnie Tam Royal Marsden Hospital ▪ Udai Banerji Thanks for your attention! UCSD ▪ J. Silvio Gutkind
Exhibit 99.3
Updated Results from the Phase 1/2 FRAME Study in Low - Grade Serous Ovarian Cancer September 16, 2020 NASDAQ: VSTM
2 On Today’s Call John Doyle, Vice President, Investor Relations and Finance Dan Paterson, Chief Operating Officer Rachel Grisham, MD, Medical Oncologist, Memorial Sloan Kettering Cancer Cente r ; Brian Stuglik, Chief Executive Officer Rob Gagnon, Chief Financial Officer Prepared Remarks Jonathan Pachter, PhD, Chief Scientific Officer Joining for Q&A Session
3 This presentation includes forward - looking statements about, among other things, Verastem Oncology’s products and product candidates, including anticipated regulatory submissions, approvals, performance and potential benefits of Verastem Oncology products and product candidates, that are subject to substantial risks and uncertainties that could cause actual results to differ materially from those expressed or implied by such statements. Applicable risks and uncertainties include the risks and uncertainties, among other things, regarding: the satisfaction of closing conditions with respect to the sale of the COPIKTRA assets to Secura Bio; the ability of Secura Bio to achieve the clinical and sales milestones necessary to result in additional consideration payable to Verastem. Additional information regarding these factors can be found in Verastem Oncology’s Annual Report on Form 10 - K for the fiscal year ended December 31, 2019 and in any subsequent filings with the SEC, including in the sections thereof captioned “Risk Factors” and “Forward - Looking Information and Factors that May Affect Future Results,” as well as in our subsequent reports on Form 8 - K, all of which are filed with the U.S. Securities and Exchange Commission (SEC) and available at www.sec.gov and www.verastem.com. The forward - looking statements in this presentation speak only as of the original date of this presentation, and we undertake no obligation to update or revise any of these statements. Safe Harbor Statement
Updated Phase 1/2 FRAME Study Data in Low - Grade Serous Ovarian Cancer Dan Paterson President and Chief Operating Officer
5 PHASE 1 / 1B PHASE 2 PHASE 3 MARKET RASm/RAFm gynecological cancers 1,2 VS - 6766 monotherapy FRAME study in LGSOC 1,3 VS - 6766 + defactinib FRAME study in KRASm endometrial cancer 1,3 VS - 6766 + defactinib Registration - directed study in LGSOC VS - 6766 + defactinib RAF/MEK Inhibitor VS - 6766 in Gynecological Malignancies 1 Investigator - sponsored trial 2 Chénard - Poirier, M. et al. Results from the biomarker - driven basket trial of RO5126766 (CH5127566), a potent RAF/MEK inhibitor, in RAS - or RAF - mutated malignancies including multiple myeloma. Journal of Clinical Oncology 2017: 35 3 NCT03875820 Registration - directed study to commence by the end of 2020
6 Favorable Tolerability Profile for Novel Intermittent Dosing Regimen of VS - 6766 plus Defactinib Daily at MTD N=6 28 - day cycle 4mg twice weekly N=26 28 - day cycle RP2D (VS - 6766 3.2mg twice weekly + defactinib 200mg twice daily) N=26 21 days of 28 - day cycle Adverse Event Grade ≥3 Grade ≥3 Grade ≥3 Rash related 3 (50%) 5 (19%) 1 (4%) CK elevation 1 (17%) 2 (8%) 1 (4%) Blurred vision - - - Peripheral edema - - - Diarrhea - 1 (4%) - Mucositis - 1 (4%) - Fatigue - 1 (4%) - Nausea - - - 1 Chenard - Poirier, et al . ASCO 2017.
7 VS - 6766 in Combination with Defactinib Shows Robust ORR with Durability in Refractory LGSOC with Expanded Number of Patients (n=17) 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 -70 -60 -50 -40 -30 -20 -10 0 10 20 Response by RECIST Time (months) 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 - KRAS G12D FRA101015 - KRAS - G12V FRA101019 - KRAS G12D FRA101024 - KRAS WT FRA101025 - KRAS WT FRA102010 - KRAS G12D FRA101028 - Undocumented FRA101032 - KRAS D33E, I24N FRA101033 - KRAS G12D FRA101035 - KRAS G12D FRA101037 - KRAS WT FRA101038 - KRAS WT Continuing on treatment 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 FRA101015 FRA101012 FRA101038 FRA101037 FRA101035 FRA101007 FRA102010 FRA101033 FRA101032 FRA101028 FRA101024 FRA101025 FRA101019 FRA101014 FRA101009 FRA101001 FRA101002 Time on Treatment (months) * * * * * # * * * # * G12A G12V G12D G12D G12D WT WT Undocumented D33E, I24N G12D G12D WT G12D WT WT WT G12V Time on Treatment Previous MEK inhibitor treatment Continuing on treatment * Approaching PR # Time to response Partial Response Stable Disease • KRAS - G12 mutations ORR = 56% (5/9); data still maturing • Current ORR = 41% (7/17); data still maturing • 5/7 PRs in pts who had previous MEKi 1 • 9/17 (53%) still on study 2 • 3 pts on treatment for ~2 yrs or more 1 Patients came off prior MEKi treatment primarily for progression 2 Data cutoff date August 17, 2020
8 VS - 6766 in Combination with Defactinib Shows Robust ORR with Durability in Refractory LGSOC at Phase 2 Dose Level • ORR in KRAS mt = 50% (3/6); data still maturing • Current overall ORR = 45% (5/11); data still maturing • 9/11 (82%) still on study at RP2D 1 • 2 pts on treatment for 2.5 yrs 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 FRA101038 FRA101037 FRA101035 FRA102010 FRA101033 FRA101032 FRA101028 FRA101024 FRA101025 FRA101001 FRA101002 Time on Treatment (months) * * * * * # * * * # * G12A G12V WT WT Undocumented D33E, I24N G12D G12D G12D WT WT Time on Treatment Previous MEK inhibitor treatment Continuing on treatment * Approaching PR # Time to response Partial Response Stable Disease 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 -70 -60 -50 -40 -30 -20 -10 0 10 20 Response by RECIST Time (months) 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 FRA101024 - KRAS WT FRA101025 - KRAS WT FRA102010 - KRAS G12D FRA101028 - Undocumented FRA101032 - KRAS D33E, I24N FRA101033- KRAS G12D FRA101035 - KRAS G12D FRA101037 - KRAS WT FRA101038 - KRAS WT Continuing on treatment All patients on RP2D: 3.2 mg VS - 6766 (2x/wk) + 200 mg Defactinib (BID) q3/4 wks 1 Data cutoff date August 17, 2020
9 KRAS Mutated (mt) and Wild Type (wt), Phase 2, Recurrent LGSOC Adaptive Design for Potential Accelerated Approval * Selection Phase – KRAS mt only ** Expansion Phase – final sample size to be adjusted based on adaptive design FDA Was Supportive of Development Strategy and Adaptive Design This Registration - directed Phase 2 Study is Expected to Commence by Year End 2020 Recurrent LGSOC Measurable disease (RECIST 1.1) Prior MEKi allowed Approximately 32 subjects Primary Endpoint ORR Hierarchical evaluation of: 1) In KRAS mt subjects 2) All subjects (KRASmt & wt) Defactinib+VS - 6766 Defactinib 200 mg PO BID 21/28 days + VS - 6766 3.2 mg PO 2x/wk 21/28 days VS - 6766 Mono VS - 6766 4.0 mg PO 2x/wk 21/28 days Selected Regimen based on ORR Additional 20 - 30 subjects with KRAS mt Additional 36 - 56 subjects with KRAS wt Total Range of Subjects: 88 - 118 Selection Phase* Expansion Phase**
Low - Grade Serous Ovarian Cancer Treatment Landscape and Clinical Perspective Rachel Grisham, MD Memorial Sloan Kettering Cancer Center
11 What is Low - Grade Serous Ovarian Cancer (LGSOC)? 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 patients remain in treatment for a long time Source: Monk, Randall, Grisham, The Evolving Landscape of Chemotherapy in Newly Diagnosed Advanced Epithelial Ovarian Cancer, Am Soc Cli n Oncol Educ Book; 2019; Slomovitz, Gourley, Carey, Malpica, Shih, Huntsman, Fader., Grisham et al, Low - Grade serous ovarian cancer: State of the Science; Gynecol Oncol; 202 0. Grisham, Iyer, Low - Grade Serous Ovarian Cancer: Current Treatment Paradigms and Future Directions; Curr Treat Options Oncology; 2018. Most prior research has focused on high grade serous ovarian cancer (HGSOC). However, LGSOC is clinically, histologically and molecularly unique from HGSOC with limited treatments available 1,000 to 2,000 patients in the U.S. and 15,000 to 30,000 worldwide diagnosed with LGSOC each year
12 Treatment Landscape and Clinical Perspective Rachel Grisham, MD Memorial Sloan Kettering Cancer Center Bio: Dr. Grisham is a medical oncologist with clinical expertise in the diagnosis and treatment of women with gynecologic malignan ci es including ovarian, uterine, and cervical cancers as well as other less common tumors. Her clinical research focuses on develo pin g novel treatments and improving treatment strategies for women with gynecologic malignancies. She has a particular interest in th e use of targeted therapies for the treatment of recurrent ovarian cancer. She has developed, and serves as the principal investiga tor for, ongoing clinical trials in this area. Dr. Grisham earned her M.D. degree from Duke University School of Medicine. She comple ted her residency at Massachusetts General Hospital and subsequently held fellowships at Weill Cornell Medical College and Memorial S loa n Kettering Cancer Center.
Low - Grade Serous Ovarian Cancer Market Opportunity Brian Stuglik Chief Executive Officer
14 KRASm , 32% Wild - Type , 68% Incidence 10 Yr Prevalence Worldwide ~15,000 – 30,000 ~80,000 US ~1,000 – 2,000 ~6,000 32% of LGSOC Patient Have KRAS Mutations LGSOC: Key Drivers Are KRAS/NRAS/BRAF Mutations *Based on LGSOC representing 5 - 10% of epithelial ovarian cancer Wild - type KRAS includes NRAS and BRAF mutations, among others
15 31 - 35% discontinuation rate with MEK inhibitors due to AEs No discontinuations in the FRAME study due to AEs 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 Trametinib Fulvestrant Recurrence Taxane or gemcitabine, or doxorubicine, or topotecan +/ - Beva Trametinib Fulvestrant LGSOC: Limited Treatment Options With High Unmet Need 1 NCCN guidelines 2 Gershenson, et al. ESMO 2019. 3 Farley, et al. Lancet Oncology, 2013. 4 Grisham, Monk, Banerjee, et al. IGCS 2019. Pt - Sensitive Pt - Resistance Limited Response Rates for Available Treatments: 0% 5% 10% 15% 20% 25% 30% Stage IC Stage II - IV Stage IA - IB <10% 2 14% 2 15% 3 26% 2 24% 4
16 Commence Phase 2 registration - directed trial by the end of 2020 Report updated data from FRAME LGSOC cohort in mid - 2021 Validating Clinical Data in LGSOC VS - 6766 ± Defactinib Represents Best in Class Market Opportunity in LGSOC 1 AACR Project Genie, cBioportal KRAS mutations account for 32% 1 of LGSOC cases No FDA - approved therapy; limited treatment options Unmet medical need creates large market opportunity ~6,000 patients living with the disease; ultra - orphan opportunity FRAME study: 56% ORR in KRAS - G12m LGSOC and 41% ORR in overall LGSOC represents best - in - class opportunity FDA supportive of development strategy and registration trial design Key Takeaways Next Steps
Other Program Updates Brian Stuglik Chief Executive Officer
18 NSCLC Clinical Strategy: KRAS Mutant (mt), Enriched G12V, Phase 2, Recurrent NSCLC for Potential Accelerated Approval 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 Study is Expected to Commence by Year End 2020 Recurrent NSCLC 1 - 2 prior regimens 1 prior platinum - containing chemo; Prior CPI unless contraindicated Measurable disease (RECIST 1.1) Appropriate approved therapy for other relevant mutations No prior MEKi, no prior KRAS - specific targeted therapy No untreated CNS metastases ECOG OS 0 - 1 Defactinib+VS - 6766 1 KRAS mt G12V N=16 VS - 6766 2 KRAS mt G12V N=16 KRAS Mutant – G12V Selected Regimen based on ORR Selection Phase Expansion Phase Defactinib+VS - 6766 1 KRAS mt non - G12V N=25, maximum KRAS Mutant – non - G12V Exploratory mutation - specific cohort analyses for ORR Final G12V sample size to be discussed with FDA Non - G12V Cohorts TBD based on results of exploratory analysis
19 Continuing to Move VS - 6766 Forward Aggressively With Additional Opportunities Go - forward strategy is to focus primarily on KRAS G12V patients in NSCLC given clinical signals to - date KRAS G12V cohort added to ongoing FRAME study Completing Phase 1 investigating VS - 6766 in combination with everolimus; plan to advance to Phase 2 in KRASm non - G12V NSCLC Reported new preclinical data demonstrating strong synergy and tumor regression with G12C inhibitors in combination with VS - 6766 and FAK inhibitor in vitro and in vivo NSCLC Expanded FRAME study to include pancreatic and KRASm endometrial patient cohorts to provide early efficacy signals Uveal melanoma IST expected to commence by the end of 2020 VS - 6766 enhances efficacy of anti - PD - 1 in preclinical models Other Tumor Areas
20 PRECLINICAL PHASE 1 / 1B PHASE 2 PHASE 3 MARKET Combinations FRAME study in NSCLC 1 with defactinib FRAME study in CRC 1 with defactinib FRAME study in KRAS - G12V NSCLC 1 with defactinib FRAME study in pancreatic 1 with defactinib Registration - directed study in recurrent KRASm NSCLC with defactinib Uveal melanoma 1 with defactinib KRASm lung 1 VS - 6766 + everolimus DEFACTINIB (FAK inhibition) In combination with PD - 1 inhibitors R/R pancreatic ductal adenocarcinoma 1 Defactinib + pembrolizumab + gemcitabine NSCLC, pancreatic, mesothelioma 1 Defactinib + pembrolizumab Other High Priority Lead Indications with Multiple Growth Opportunities 1 Investigator - sponsored study VS - 6766 (RAF/MEK inhibition ) Registration - directed study to commence by the end of 2020 To commence by the end of 2020
Corporate Rob Gagnon Chief Financial Officer
22 Selling COPIKTRA ® (duvelisib) Rights to Secura Bio Secura Bio to Assume All Operational and Financial Responsibilities, Including Existing Royalty Obligations Beginning in 2021 Annual OPEX Expected to be ~$50 Million New Verastem Headcount of ~50 Provides Cash Runway Through at Least 2024 Total Deal Value Up to $311 Million, Plus Royalties
23 Key Financial Statistics * On April 23, 2019, we entered into a 4th Amendment to our existing Agreement with Hercules Capital, Inc. whereas we may borro w up to an aggregate amount of $75.0 million, of which $35.0 million was outstanding as of the date of amendment and 6/30/2020. ** The 2018 Notes have an initial conversion rate of 139.5771 shares of Common Stock per $1,000 which translates to an initial conversion price of $7.16 per share of Common Stock. Cash, cash equivalents & short - term investments as of 6/30/2020 $160.8M Proforma cash (as of June 30, 2020) of $230 million Inclusive of $70 million received upfront at closing $230M Shares fully diluted as of 6/30/2020 188.2M Hercules Term Loan Facility as of 6/30/2020 $35.0M* 5.00% Convertible Senior Notes Due 2048 (2018 Notes) as of 6/30/2020 $28.3M** Insider ownership (outstanding / vested) as of 6/30/2020 8.3% / 4.3%
24 Monetize COPIKTRA; extend cash runway through at least 2024 Reduce OPEX for 2021 Close Secura Bio transaction in 3Q 2020 Regulatory path forward in LGSOC and KRAS mutant NSCLC during the 3Q 2020 Expand Phase 1/2 FRAME study to include new cohorts in pancreatic cancer, KRASm endometrial cancer and KRAS - G12V NSCLC Present updated data from the LGSOC cohort of the Phase 1/2 FRAME study in Sept 2020 Present preclinical findings in combination w/G12C inhibitors in Sept 2020 Commence registration - directed trial in recurrent LGSOC by year end 2020 Commence registration - directed trial in recurrent KRASm NSCLC by year end 2020 Key Upcoming Milestones for Remainder of 2020 Corporate VS - 6766 & Defactinib
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