FAK INHIBITOR VS-6063

NON-CONFIDENTIAL SUMMARY

NOVEMBER 2014

Confidential Page Verastem, Inc. Confidential

Verastem: Company Summary

• Verastem (VSTM) is a small publically traded Biotech company based in Boston, MA –~40 employees

• Founded in 2010 by Bob Weinberg (MIT) & Eric Lander (Broad Institute)

• Focused on development of small molecule anticancer drugs that target Cancer Stem Cells (CSCs)

• Clinical programs: –Lead program: VS-6063 is a selective inhibitor of FAK & PYK2 protein kinases • Multiple phase 1 & 2 clinical trials in various solid tumor indications –VS-4718 is a structurally distinct backup FAK inhibitor (Phase 1) –VS-5584 is a selective dual PI3K/mTOR kinase inhibitor (Phase 1)

Page 2 Verastem, Inc. Confidential November 12, 2014 Clinical Development of VS-6063

Phase 1 Phase 2 Registration-Directed

VS-6063

Mesothelioma COMMAND – Switch maintenance following front-line therapy

Mesothelioma Window of opportunity

Mesothelioma With VS-5584 in relapsed

Lung KRASmt NSCLC

Ovarian In combo with paclitaxel

Ovarian Window of opportunity

Breast Neo-adjuvant in combination with paclitaxel Ongoing

Planned

Page 3 Novel Drugs Targeting Cancer Stem Cells Verastem Team Executive Management Robert Forrester Joanna Horobin, M.B., Ch.B. President/CEO, BOD Chief Medical Officer CEO/CFO, CombinatoRx/COLY President/CEO, Syndax MeesPierson, Barclays, UBS 10 marketed drugs (Taxotere®, Camptosar®) Breakthrough designation for Entinostat Christoph Westphal, M.D., Ph.D. Jonathan Pachter, Ph.D. Executive Chairman of BOD, Cofounder VP, Head of Research Cofounder/CEO: MNTA, ALNY, XLRN, SIRT, VSTM Head of Cancer Biology, OSI (now Astellas) Cofounder: Alnara (now Lilly), OvaScience (OVAS) Schering-Plough (now Merck) Jack Green Daniel Paterson Chief Financial Officer Chief Business Officer CFO, Genzyme Transgenics Corporation (GTC) CEO: The DNA Repair Co. (now On-Q-ity) PharMetrics (now IMS), Axion Board of Directors Timothy Barberich Henri Termeer Alison Lawton Former CEO/Chair Sepracor (SEPR) Lead Director Former Genzyme (now Sanofi) Former CEO/Chair Genzyme Paul Friedman, M.D. Louise Phanstiel Former President/CEO Incyte (INCY) BOD: Cedars Sinai, MYGN Michael Kauffman, M.D., Ph.D. Stephen Sherwin, M.D. CEO Karyopharm (KPTI), former CMO Onyx BOD: BIIB; NBIX, RIGL

Page 4 Novel Drugs Targeting Cancer Stem Cells November 12, 2014 Scientific Advisory Board

Robert Weinberg, Ph.D. Whitehead Institute/MIT Co-founder & Chairman of SAB Peter Elliott, Ph.D. Phil Sharp, Ph.D. Former SVP/Head – R & D, SIRT (now GSK) MIT – 1993 Nobel Prize in Medicine Millennium (co-developed Velcade®) Cofounder: Biogen, Alnylam; Sirtris SAB Eric Lander, Ph.D. Chris Walsh, Ph.D. Broad Institute/MIT/HMS Harvard Medical School Pioneer of Human Genome Project Cofounder: Genzyme, Vicuron; Sirtris SAB

Richard Sackler, M.D. Joseph (Yossi) Schlessinger, Ph.D. Chairman – Purdue Pharma Yale Medical School Cofounder: Sugen (Pfizer), Plexxikon (Daiichi-Sankyo) Translational Research José Baselga, M.D., Ph.D. Max Wicha, M.D. Physician in Chief; MSKCC Director – University of Michigan Senior Medical Advisor Comprehensive Cancer Center

George Daley, M.D., Ph.D. Eric Winer, M.D. Director – Stem Cell Program Director – Breast Oncology Center Harvard Medical School/HHMI Dana Farber Cancer Institute/HMS

Page 5 Novel Drugs Targeting Cancer Stem Cells November 12, 2014 Verastem Objectives for CRUK Combinations Alliance

• Combine VS-6063 with novel agents

• Some current combination interests with VS-6063 –Immune Checkpoint Antibodies • Proprietary preclinical rationale can be supplied under confidentiality –Cdk4/6 inhibitors • NF2/Merlin is often lost along with INK4a (p16/ARF) • Rationale to target NF2 loss with VS-6063 & p16 loss with cdk4/6 inhibitor

• Open to additional novel combos with scientific rationale

Page 6 Verastem, Inc. Confidential November 12, 2014 FAK as a Cancer Target

Page 7 Verastem, Inc. Confidential November 12, 2014 FAK as an Anti-Cancer Target

• FAK (Focal Adhesion Kinase) is activated in response to Integrin and Growth Factor receptor stimulation • FAK activation triggers signaling pathways essential for tumor cell proliferation, survival, migration, invasion, angiogenesis and resistance to chemo- & radiation therapy • FAK inhibition blocks both primary tumor growth & metastasis

Extracellular Matrix cMETr

GPCr

Focal adhesion contacts Anti-apoptosis/ Angiogenesis Cell adhesion Anti-anoikis (survival) Drug resistance Motility Inplantation/Invasion

Brunton VG & Frame MC. Curr Opin Pharmacol. 2008;8:427 Schlaepfer DD et al. Biochim Biophys Acta. 2004;1692:77

Page 8 Verastem, Inc. Confidential November 12, 2014 FAK is Highly Expressed in Advanced Stages of Cancer Tissue Normal Benign Pre-Invasive Invasive Metastatic Reference

Breast - +++ ++++ Lancet 342:1024, 1993. +/- +++ ++++ Cancer Res 55: 2752, 1995. + +++ +++ Clin Cancer Res 6: 2417, 2000. +/- +/+++ J Gastroenterol 8: 613, 2002. Colon - + ++++ +++++ Lancet 342:1024, 1993. + - +++ +++ +++ Cancer Res 55: 2752,1995. + +++ Ann Surg Oncol 4: 264, 1997. + +++ +++ Clin Cancer Res 6: 2417, 2000. + +++ ++ Clin Cancer Res 7: 3106, 2001. +/- ++/+++ J Gastroenterol 8: 613, 2002.

Thyroid + + +/+++ ++++ Ann Surg Oncol 3: 100, 1996. Prostate +/- + + +++ Int J Cancer 68: 164, 1996. ++ +++ +++ +++ +++ Prostate 53: 124, 2002.

Head-Neck -/++ +++ +/++++ Head Neck 20: 634, 1998. Liver - +++ Clin Cancer Res 10: 2812, 2004 + +++++ Br J Cancer 85: 228, 2001. +/- ++/+++ J Gastroenterol 8: 613, 2002. Stomach +/- ++/+++ J Gastroenterol 8: 613, 2002.

Ovary + ++++ Cancer 86: 1551, 1999. Glioma - - + - +++++ Pediatr Neurosurg 33: 49, 2000. - - + ++ J Cell Sci 113: 421, 2000. - ++ ++ ++ Cancer Res 61: 5688, 2001. + +++ Cancer Res 62: 2699, 2002.

Page 9 Verastem, Inc. Confidential High pFAK Correlates with Poor Prognosis in Ovarian Cancer

• High tumor FAK and pFAK expression correlate with poor survival (Sood et al., J Clin Invest 2010)

Page 10 Verastem, Inc. Confidential November 12, 2014 VS-6063 Selective FAK/PYK2 Inhibitor

FAK EC50 = 15 nM

PYK2 EC50 = 95 nM VS-6063 • Lead FAK/PYK2 Inhibitor • Oral compound with good safety profile & initial signs of activity in Phase 1 • USAN name: defactinib • Orphan designation in US and EU for mesothelioma

Page 11 Verastem, Inc. Confidential November 12, 2014 VS-6063 (Defactinib) Highlights

• Good safety profile across several clinical trials

• Early signs of clinical activity

• Multi-national registration-directed Mesothelioma study in progress –Mesothelioma study targets maintenance setting where there are no existing options for patients –Orphan drug designation for Mesothelioma in US and EU

• VS-6063 can be combined with SoC chemotherapy (weekly paclitaxel)

• Most advanced FAK inhibitor in the clinic

Page 12 Verastem, Inc. Confidential November 12, 2014 VS-6063 Development Rationale 1. Verastem research identified one potential patient selection/enrichment marker –Tumors lacking Merlin (product of NF2 tumor suppressor gene) especially sensitive to FAK inhibitors (Shapiro Sci Trans Med 2014) • Merlin loss especially prevalent (~50%) in mesothelioma 2. FAK inhibitors found to effectively target cancer stem cells (CSCs) across broad range of cancer types – Standard of care (SoC) anticancer agents typically target bulk tumor, but fail to target cancer stem cells which drive tumor recurrence and metastasis – VS-6063 can potentially be used to target CSCs in combination with SoC agents for more durable clinical response 3. VS-6063 can be combined with chemotherapy – Phase 1 paclitaxel combo in ovarian cancer • No impact on paclitaxel pharmacokinetics in patients • Generally well tolerated with no dose limiting toxicities or exacerbation of paclitaxel related toxicities

Page 13 Verastem, Inc. Confidential November 12, 2014 Mesothelioma Rationale:

Loss of Merlin tumor suppressor may predict greater sensitivity to FAK inhibitor VS-6063

Page 14 Verastem, Inc. Confidential November 12, 2014 Low Merlin Expression Increases Sensitivity to VS-6063 in Mesothelioma Models In Vitro and In Vivo Mesothelioma Cell Line Panel

Merlin High

Merlin Low VS-6063 inhibits Merlin- negative mesothelioma tumor growth in the lungs of treated mice

Approximately 50% of mesothelioma tumors have low Merlin

Merlin Actin

Page 15 Novel Drugs Targeting Cancer Stem Cells FAK Inhibitor VS-6063 Preferentially Targets Cancer Stem Cells (CSCs)

Page 16 Verastem, Inc. Confidential November 12, 2014 What is a Cancer Stem Cell (CSC)?

• Tumors are heterogeneous in composition –Bulk tumor (may be effectively targeted by chemotherapy) –Cancer stem cells • Resistant to chemotherapy • Enriched by chemotherapy (clinically and preclinically)

• Cancer Stem Cells –Resistant to standard of care therapy –Functionally defined by their tumor-initiating capability –Mediate cancer recurrence & metastasis –May be identified by specific markers (e.g. ALDH; CD133; SOX2)

• Combinations are important to target both cancer stem cells (VS-6063) & bulk tumor for a more durable clinical response

Page 17 Verastem, Inc. Confidential November 12, 2014 Targeting Cancer Stem Cells for a Durable Clinical Response

Current cancer Problem: treatments

Initial tumor Tumor reduction but Recurring tumor CSCs survive

CSC drugs + current cancer treatments Solution:

Durable clinical response

Initial tumor Tumor reduction and elimination of CSCs

Page 18 Verastem, Inc. Confidential November 12, 2014 Clinical Evidence: Cancer Stem Cells & Poor Prognosis in Breast Cancer

No residual axillary node metastasis

Residual axillary metastasis • N = 115 patients with No ALDH1-positive cells confirmed lymph node metastases at diagnosis Residual axillary metastasis With ALDH1-positive cells • Standard neoadjuvant chemotherapy: AC x 4 followed by weekly PTX x 12

• ALDH1 assessed by IHC

• ** p<0.001

• Presence of ALDH1-positive CSCs in residual disease in axillary nodes after neoadjuvant chemo & surgery associated with poor prognosis

Sakakibara et al, Cancer 2012

Page 19 Verastem, Inc. Confidential November 12, 2014 FAK is Critical for Cancer Stem Cells

FAK • Targeted deletion of FAK reduces tumor initiating capability Luo et al, Cancer Res (2009) 69:466

Integrins

T VS-6063

FAK T VS-4718 • FAK is a critical pathway for cancer stem p130Cas cells and disease progression Shibue et al, Cancer Discovery (2012) 2:706

FAK FAK

D2A1 cells D2A1 cells D2A1 cells Cell mobility Proliferation Tumor initiation Elimination of CSCs Page 20 Verastem, Inc. Confidential November 12, 2014

Figure 3. FAK inhibitor VS-6063 inhibits CSCs across multiple CSC assays (A) VS-6063 inhibits Aldefluor+ CSCs. TNBC cell lines SUM159 and Hs578T were treated with VS-6063 in

Figurematrigel 3 (MG). FAK for 4 inhibitor days. Cells VS -6063 were inhibitsextracted CSCs from across MG and multiple percentage CSC of Aldefluor+ cells (blue) determined by assays (A) VS-6063 inhibits Aldefluor++ Aldefluor assay to measure ALDH cells CSCs. TNBC cell lines SUM159 and FigureFigure 33H.. (CSCs). s FAK578T FAK inhibitor inhibitor were Overall treated VS VS --6063 cell6063 viability with VS (-red6063) was in inhibitsinhibits CSCs CSCsmeasured across across multiple multiple by CellTiter CSC CSC -Glo (Promega) assaysassays (A(Amatrigel)) VSVS--60636063 inhi inhi (MG)bbitsits Aldefluor+ Aldefluor+ for 4 days. Cells were CSCs.CSCs. TNBCTNBCextractedluminescence. cell cell lines lines from SSUMUM 159159 MG( B and and) and TNBC percentage cell line of HHss578T578T were wereCal120 treated treated w with withas VStreated VS--60636063 in inwith VS-6063 in MG VS-6063 Preferentially Targets CSCs in TNBC Cell Lines: matrigel (MG)Aldefluor+ for 4 days. cells Cells ( wereblue ) determined by matrigel (MG)for for 4 4 days. days. Cells Cells were were extracted+ from Multiple in vitro CSC assays extractedextracted Aldefluor from from MG MG and and assay percentage percentage to measure of of ALDH cells Aldefluor+ cells (blue) determined by o Aldefluor+ Matrigel cells (blue ) and determined 10+ 00 by cells/ml plated in Aldefluor-Positive CSCs 2 Tumorsphere Formation Aldefluor assay(CSCs). to measure Overall ALDH + cell cells viability (red) was Aldefluor assayprimary to measure tumorsphere ALDH cells formation assay. Figure 3. FAK inhibitor(CSCs).(CSCs). VS- 6063 Overall Overallmeasured cell cell viability viability by ( (redred CellTiter)) was was -Glo (Promega) inhibits CSCs across multiplemeasured CSC Tumorspheres by CellTiter-Glo (Promega) formed were Non-CSCs measured luminescence. by CellTiter-Glo (Promega)(B) TNBC cell line assays (A) VS-6063 inhibluminescence.itsluminescence. Aldefluor+ ((BB)) TNBCTNBC cell cell line line CSCs. TNBC cell lines SUM159 andenumerat ed after 7 days. Primary Cal120Cal120 w wasasCal120 treatedtreated withwith was VSVS treated--60636063 inin MGMG with VS-6063 in MG Hs578T were treated withfor VS 4- 6063 days. intumor Cells spheres were extracted were from dissociated with CSCs for 4 days.for Cells 4 days. were extracted Cells from were extracted from matrigel (MG) for 4 days.Matrigel Cells were andtrypsin 1000 cells/ml and 1000 plated in cells/ml replated in extracted from MG and percentageMatrigel andMatrigel of 1000 cells/ml and 10plated00 in cells/ml plated in Aldefluor+ cells (blue) determinedprimaryprimary tumorsphere tumorsphere bysecondary formation formation tumorsphere assay. assay. formation Aldefluor assay to measureTumorspheresTumorspheres ALDH+ cellsprimary formed formed tumorsphere were were formation assay. CSCs: Hoechst Dye Exclusion (CSCs). Overall cell viabilityenumeratenumerat (red) wasededTumorspheresassay. after after 7 7 Secondary days. days. Primary Primary tumorspheres formed were were measured by CellTiter-Glotumortumor (Promega)spheresspheresenumerated were were dissociated dissociated after with with 5 days. (C) SUM159 Control VS-6063 luminescence. (B) TNBCtrypsin cell and lineenumerat 1000 cells/mled replated after in 7 days. Primary trypsin andcells 1000 were cells/ml treated replated with in VS-6063 at the Cal120 was treated with VSsecondarysecondary-6063 in MG tumor tumorsphere tumorspherespheres formation formation were dissociated with CSCs CSCs for 4 days. Cells were extracted from assay.assay. Secondary Secondarytrypsinconcentrations tumorspheres tumorspheres and 1000 shown were were cells/ml (0, 0.3, replated 1, or in 3 Matrigel and 1000 cells/mlenumerated plated in after 5 days. (C) SUM159 primary tumorsphere formationenumerated assay.µM) after for 5 days. 2 days (C) S andUM159 percent of SP cells cells were secondary treated with VS-6063 tumorsphere at the formation Tumorspheres formedcells were were determined treated with VS by-6063 FACS. at the enumerated after 7 days.concentrationsconcentrations Primaryassay. shown shown Secondary (0, (0, 0.3, 0.3, 1, 1, or or 3tumorspheres 3 were tumorspheres were dissociatedµM)µM) forfor 2 with2 days days and and percent percent of of SP SP cells cells trypsin and 1000 cells/mldetermineddetermined replated enumerated in by by FACS.FACS. after 5 days. (C) SUM159 Page 21 Verastem, Inc. Confidential secondary tumorsphere formationcells were treated with VS-6063 at the assay. Secondary tumorspheres were enumerated after 5 days. (C) SUM159concentrations shown (0, 0.3, 1, or 3 cells were treated with VS-6063 at theµM) for 2 days and percent of SP cells concentrations shown (0, 0.3, 1, or 3 µM) for 2 days and percent of SP cellsdetermined by FACS. determined by FACS.

VS-6063 Reduces CSCs & Tumor-Initiating Capability In TNBC Xenograft Tumor Model in Contrast to Paclitaxel

• Mice bearing MDA-MB-231 tumors were treated with 50 mg/kg VS-6063 po BID or vehicle control for 25 days and CSC endpoints were assessed • Tumor initiating capability in 2o mice was decreased by VS-6063, but increased by paclitaxel treatment

Page 22 Novel Drugs Targeting Cancer Stem Cells November 12, 2014 VS-6063 maintains stable disease in a Breast Cancer xenograft model after neoadjuvant chemotherapy

Page 23 Verastem, Inc. Confidential November 12, 2014 Summary of Key VS-6063 Clinical Experience and Ongoing Trials

Page 24 Verastem, Inc. Confidential November 12, 2014 Phase 1 Single Agent Dose Escalation

Page 25 Verastem, Inc. Confidential November 12, 2014 Completed Phase 1 Study in Subjects with Advanced Solid Tumors (n=46)

• Patient Population: –Subjects with histologically or cytologically confirmed diagnosis of a non-hematologic malignancy that is unresponsive to currently available therapies

• Primary Objectives: • Determine the maximum tolerated dose and assess overall safety and tolerability

• Study Design: –Standard 3+3 design, dose escalation

• Dose Range: –12.5 mg to 750 mg p.o. BID in continuous 3 week cycles –Recommended phase 2 dose (RP2D) is 400mg PO BID

• Demographics: – Sex: 17M, 29F – Race: 43 white, 2 black, 1 other – Mean Age: 57.1years

26 Page Verastem, Inc. Confidential November 12, 2014

VS-6063 Phase I: Generally Well Tolerated with Few Grade 3 Events

Treatment-Emergent CTCAE Grade Adverse Events* Preferred Term Grade 1 Grade 2 Grade 3 Grade 4 Grade 5 Any Grade n (%) n (%) n (%) n (%) n (%) n (%) Nausea 16 (34.8) 3 (6.5) 0 (0.0) 0 (0.0) 0 (0.0) 19 (41.3) Fatigue 11 (23.9) 5 (10.9) 2 (4.3) 0 (0.0) 0 (0.0) 18 (39.1) Vomiting 12 (26.1) 3 (6.5) 0 (0.0) 0 (0.0) 0 (0.0) 15 (32.6) Hyperbilirubinaemia 5 (10.9) 9 (19.6) 1 (2.2) 0 (0.0) 0 (0.0) 15 (32.6) Decreased appetite 9 (19.6) 4 (8.7) 0 (0.0) 0 (0.0) 0 (0.0) 13 (28.3) Headache 11 (23.9) 1 (2.2) 1 (2.2) 0 (0.0) 0 (0.0) 13 (28.3) Diarrhoea 10 (21.7) 2 (4.3) 0 (0.0) 0 (0.0) 0 (0.0) 12 (26.1) Pyrexia 9 (19.6) 1 (2.2) 0 (0.0) 0 (0.0) 0 (0.0) 10 (21.7) Constipation 5 (10.9) 3 (6.5) 1 (2.2) 0 (0.0) 0 (0.0) 9 (19.6) Dizziness 9 (19.6) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 9 (19.6) Dehydration 1 (2.2) 6 (13.0) 0 (0.0) 0 (0.0) 0 (0.0) 7 (15.2) Cough 6 (13.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 6 (13.0) Chest pain 3 (6.5) 3 (6.5) 0 (0.0) 0 (0.0) 0 (0.0) 6 (13.0) Arthralgia 4 (8.7) 2 (4.3) 0 (0.0) 0 (0.0) 0 (0.0) 6 (13.0) Back pain 1 (2.2) 5 (10.9) 0 (0.0) 0 (0.0) 0 (0.0) 6 (13.0) Oropharyngeal pain 5 (10.9) 1 (2.2) 0 (0.0) 0 (0.0) 0 (0.0) 6 (13.0) Dyspnoea 3 (6.5) 3 (6.5) 0 (0.0) 0 (0.0) 0 (0.0) 6 (13.0) Hypertension 3 (6.5) 2 (4.3) 0 (0.0) 0 (0.0) 0 (0.0) 5 (10.9) Included data up to 28 days after last dose of study drug. Highest grade reported for each subject * Reported by >10% of Subjects in any dose group (n=46)

Page 27 Verastem, Inc. Confidential November 12, 2014 VS-6063 Phase 1 Study: Summary of Dose Escalation and DLTs (n=46)

* 400 mg po BID selected as RP2D

Page 28 Verastem, Inc. Confidential November 12, 2014 Ovarian Phase 1b in Combination with Paclitaxel

Page 29 Verastem, Inc. Confidential November 12, 2014 Combining VS-6063 with Paclitaxel for Patients with Ovarian Cancer Goals • Target cancer stem cells concurrently with chemotherapy • Evaluate feasibility of combination of VS-6063 with weekly paclitaxel - paves the way to several other indications where paclitaxel is standard of care Objectives • Evaluate safety and tolerability of combination of VS-6063 with weekly paclitaxel • Measure pharmacokinetics of paclitaxel in combination with VS-6063 • Confirm pharmacodynamic effect of VS-6063 on pFAK target Protocol permits single agent VS-6063 “maintenance” following paclitaxel

Phase 1 Phase 1b

Completed: 200mg, 400mg BID Completed Recruitment N=6 N=16

VS-6063 (dose escalation BID) VS-6063 (400mg BID) + paclitaxel (80mg/m2/week) + paclitaxel (80mg/m2/week)

Page 30 Novel Drugs Targeting Cancer Stem Cells November 12, 2014 Combination of VS-6063 and Weekly Paclitaxel Does not Impact Paclitaxel Pharmacokinetics

10000

Paclitaxel alone

1000 Paclitaxel + VS-6063

100 ( ng/ml) (

Paclitaxel concentration Paclitaxel 10

1 0 5 10 15 20 25 30 Time (hours)

The 24 hr serum concentration of paclitaxel (80 mg/m2) was determined on Day 1 in the absence of VS-6063

Following 14 days of continuous VS-6063 administration (200 or 400 mg BID) the 24hr serum concentration of paclitaxel was re-evaluated. (n=6)

Page 31 Novel Drugs Targeting Cancer Stem Cells November 12, 2014 Combination of VS-6063 and Weekly Paclitaxel Does not Worsen the Well-Known Side Effect Profile of Paclitaxel Alone

Most Frequently Reported Adverse Events ≥20% *Unlocked, in progress data, as presented at ASCO 2014 Novel Drugs Targeting Cancer Stem Page 32 Cells November 12, 2014 VS-6063 Inhibits FAK Activity in Patient Tumor Biopsies Within 10

Days

Score) - • Paired tumor biopsies were obtained in five patients following 10 days of VS-

pFAK (Y397; H (Y397; pFAK 6063 administration (400 mg BID ) Pre-treatment Post-treatment

Brown = pFAK (y397)

Page 33 Novel Drugs Targeting Cancer Stem Cells November 12, 2014 VS-6063 Reduces Cancer Stem Cell Markers in Ovarian Cancer Biopsies Within 10 Days

Paired tumor biopsies were obtained in five patients from before and after 10 days of VS- 6063 administration (400 mg BID) for measurement of Sox-2 RNA expression

Page 34 Novel Drugs Targeting Cancer Stem Cells Initial Data from the Combination Study of VS-6063 and Paclitaxel are Encouraging

Objective Response • 3 partial responses • 2 complete responses Objective Response or SD ≥ 6 months 6 months • Overall 9/22 (41%) 80% of Patients on Study Have Platinum Resistant Tumors Complete Response Partial Response Stable Disease *Off study

*Unlocked, in-progress data as of 30 Jun 2014

Page 35 Novel Drugs Targeting Cancer Stem Cells Mesothelioma Window of Opportunity Study

Page 36 Verastem, Inc. Confidential November 12, 2014 Window of Opportunity Study in Patients with Surgery-Eligible Mesothelioma

2nd Line Chemo 80% 4-6cyc Pem/Cis Treatment Holiday or Clinical Trial Surgery 20% Window of Opportunity

• 10 patients received VS-6063 (400 mg BID) for 12 days prior to surgery • Measure biomarkers in tumor biopsies • Evaluate tumor response by PET/CT using RECIST modified for mesothelioma • Provide guidance for future studies

Biopsy/Scan Biopsy/Scan Surgery

MPM that is VS-6063 30 days post-therapy resectable 400mg BID

0 12 Days ~42 Days Page 37 Novel Drugs Targeting Cancer Stem Cells VS-6063 Inhibits FAK Activity by 70% in Mesothelioma Biopsies

VS-6063 treatment at day 12 (core needle biopsy) was compared with Control (surgical biopsy at >30 days after VS-6063 treatment ceased)

Mean pFAK (Y397) reduced by 70% in the patients evaluated to date

Page 38 Novel Drugs Targeting Cancer Stem Cells VS-6063-203 VS-6063 Reduces Cancer Stem Cell Markers in Mesothelioma Biopsies

VS-6063 treatment at day 12 (core needle biopsy) was compared with matched controls (day 0 core needle biopsy or archival tissue sample from diagnosis) for CD133 RNA expression

Reductions following VS-6063 treatment observed across multiple CSC markers in the evaluable patients with matched control biopsies (7 of 10 patients to date)

Page 39 Novel Drugs Targeting Cancer Stem Cells VS-6063-203 Encouraging Early Signal After 12 Days of Treatment with VS-6063

Note PET/CT performed to guide biopsy and tumor response assessed using RECIST modified for mesothelioma

Unlocked, in-progress data as of Aug 2014 Novel Drugs Targeting Cancer Stem Page 40 Cells VS-6063-203 Mesothelioma COMMAND Study: Switch Maintenance Following Front Line Therapy

Page 41 Verastem, Inc. Confidential November 12, 2014 COMMAND: A Registration-Directed Study of VS-6063 to Maintain Tumor Control in Mesothelioma Goal • To support approval of VS-6063 on a global basis Patients • N ~ 350-400 Design • Multinational, randomized, double blind, placebo controlled • Stratification based on merlin status with an adaptive enrichment design • No cross-over allowed • Conducted and monitored as a pivotal study

Primary Objectives Secondary Objectives Exploratory Objectives Overall Survival (OS) Quality of Life (QoL) Time to new lesion (LCSS-Meso) Progression Free Survival (PFS) Objective Response Rate (ORR) Relationship of VS-6063 PK and outcome Safety and tolerability Population PK of VS-6063

Page 42 Novel Drugs Targeting Cancer Stem Cells COMMAND Schematic

2nd Line Chemo 80% 4-6cyc Pem/Cis COMMAND Study or Clinical Trial Surgery 20%

Placebo BID Merlin Low VS-6063 400mg BID

CT Scan CT Scan Key Endpoints

≥ 4 cycles PFS Platinum + PR/SD 350-400 OS pemetrexed QoL 0 2 4 6 8 weeks Placebo BID Merlin High VS-6063 400mg BID

Page 43 Novel Drugs Targeting Cancer Stem Cells November 12, 2014 Mesothelioma: VS-6063/VS-5584 Combination Study in Relapsed Mesothelioma

Page 44 Verastem, Inc. Confidential November 12, 2014 6063/5584 Novel Combo in Relapsed Mesothelioma • VS-6063 [400 mg BID] + dose escalation of 5584 intermittent dosing (M,W,F of each 21 Day cycle) • Relapsed/refractory Malignant Pleural Mesothelioma (ie patients NOT eligible for COMMAND) • Pre/post treatment biopsies where possible (assess target proteins in tumor and genomic analysis) • Platelet rich plasma for PD • To be conducted at select existing sites • Initiate by Q4 RP2D Archival / XXmg Optional Biopsy XXmg Optional Biopsy Biopsy XXmg XXmg XXmg

Expansion Cohort VS-6063 400mg BID + VS-5584 Dose Escalation (RP2D) Follow until disease 21 Day Cycle(s) progression

• Modified Fibonacci 3+3 design after starting dose of XXmg 5584 (50%, 40%, 33%) adjusted for available tablet strengths

Page Verastem, Inc. Confidential November 12, 2014 KRAS mutant NSCLC

Page 46 Verastem, Inc. Confidential November 12, 2014 VS-6063-201: Phase 2 Study in KRAS-mutated NSCLC • KRASm NSCLC outcome poor – median PFS 1.5 months (Douillard, JCO 2010) • Pre-clinical data suggests dysfunction of the tumor suppressors CDKN2A/INK4a/ARF (p16) and/or p53 appears requisite for efficacy of FAK inhibition in KRAS-driven NSCLC • Endpoints: PFS at 12 weeks, ORR and OS • Simon’s two-stage design: initial sample size is 11 patients per cohort –If 4 or more of 11 patients are progression free at 12 weeks will add 23 patients

KRAS p16 p53 Interim analysis

Cohort A VS-6063 400mg BID VS-6063 400mg BID

Cohort B VS-6063 400mg BID VS-6063 400mg BID

Cohort C VS-6063 400mg BID VS-6063 400mg BID

Cohort D VS-6063 400mg BID VS-6063 400mg BID Go/NoGo 12-week PFS in ≥4 patients? Determine mutation status Initial enrollment Expanded enrollment (up to 11 patients/arm) (up to 23 patients/arm)

Page Verastem, Inc. Confidential Verastem Combination Alliance Objectives

Page 48 Verastem, Inc. Confidential November 12, 2014 Verastem Objectives for CRUK Combination Alliance

• Combine VS-6063 with novel agents

• Some current combination interests with VS-6063 –Immune Checkpoint Antibodies • Proprietary preclinical rationale can be supplied under confidentiality –Cdk4/6 inhibitors • NF2/Merlin is often lost along with INK4a (p16/ARF) • Rationale to target NF2 loss with VS-6063 & p16 loss with cdk4/6 inhibitor

• Open to additional novel combos with scientific rationale

Page 49 Verastem, Inc. Confidential November 12, 2014