Investor Meetings October 2018

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1 Investor Meetings October 2018

2 Safe Harbor Statement To the extent that statements contained in this presentation are not descriptions of historical facts regarding TESARO, they are forward-looking statements reflecting the current beliefs and expectations of management made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of Words such as "may," "will," "expect," "anticipate," "estimate," "intend," and similar expressions (as well as other words or expressions referencing future events, conditions, or circumstances) are intended to identify forward-looking statements. Examples of forward-looking statements contained in this presentation include, among others, statements regarding the potential size of the current and future market opportunities for our various products and product candidates and our various assumptions related thereto, our lung cancer strategy, the design and expected timing of initiation, completion, and data readouts from our various ongoing and planned niraparib, TSR-042, TSR-033, TSR-022, and combination studies, the expected timing of various regulatory filings, and potential indications for our products and product candidates. Forward-looking statements in this presentation involve substantial risks and uncertainties that could cause our future results, performance, or achievements to differ significantly from those expressed or implied by the forward-looking statements. Such risks and uncertainties include, among others, risks related to competition, the uncertainties inherent in the execution and completion of clinical trials, uncertainties surrounding the timing of availability of data from clinical trials, uncertainties surrounding our ongoing discussions with and potential actions by regulatory authorities, risks related to manufacturing and supply, risks related to intellectual property, uncertainties related to our projected expenses, and other matters that could affect the availability or commercial potential of our products and product candidates. TESARO undertakes no obligation to update or revise any forward-looking statements. For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to the business of the Company in general, see TESARO's Annual Report on Form 10-K for the year ended December 31, 2017 and Quarterly Report on Form 10-Q for the quarter ended June 30,

3 Building a Leading Oncology Company Robust Oncology Portfolio Led by ZEJULA ZEJULA PARP Inhibitor Approved in U.S. and Europe Development programs ongoing with monotherapy and combinations in gynecologic and lung cancers TSR-042 anti-pd-1 TSR-022 anti-tim-3 TSR-033 anti-lag-3 Registration trial ongoing; BLA on track for 2H 2019 Enables strategic development and commercial flexibility in combination with ZEJULA, TSR-022, TSR-033 TSR-042 combination trial ongoing Anti-PD-1 experienced NSCLC patients TSR-042 combination trial ongoing Multiple tumor types TSR-075 anti-pd-1/lag-3 bispecific IND-enabling studies Multiple tumor types NSCLC: Non-small Cell Lung Cancer 3

4 Development Strategy Focused on Gynecologic and Lung Cancers Gynecologic Cancers: Ovarian, Endometrial Lung Cancer Ovarian Expand current ZEJULA label to treatment setting Move into front line Endometrial No approved drug in 2L endometrial Current agents provide 10-14% ORR Lung cancer Despite the availability of anti-pd-1 therapy, a large number of patients do not respond in the front-line setting anti-pd-1 monotherapy is now standard of care in patients with TPS >50% 2 nd /3 rd line PD-1 experienced market opportunity is growing rapidly ZEJULA (PARP) TSR-042 (PD-1) ZEJULA and TSR-042 Partnerships & Collaborations (Prostate, Bladder, Breast, Pancreatic) TPS: Tumor Proportion Score 4

5 ZEJULA Strategy to Expand PARPi Maintenance Use Aligned with KOLs to Drive Awareness to Providers & Patients Leverage KOL Awareness and Support Engagement of Providers Activation of Patients Collaborations in place with ovarian cancer thought leaders to raise awareness through several new initiatives: Publication of real-world evidence NCCN engagement to better reflect the importance of PARPi maintenance KOL position papers supporting maintenance treatment Launching unbranded peer-to-peer programs to engage community oncologists Engaging with EMR vendors and provider organizations to develop workflow and care plan enhancements that facilitate maintenance therapy decisions Expanded investment in Continuing Medical Education (CME) Launching new PR campaign to inform and educate patients & families Partnering with advocacy groups to encourage dialogue with physicians EU ZEJULA launch experience supports growth opportunity for U.S. PARPi adoption. 5

6 ZEJULA New Indications Would Address Every Stage of a Women s Journey with Ovarian Cancer OVARIAN CANCER PATIENT JOURNEY 1 st Line 2 nd Line 3 rd Line 4 th, 5 th, 6 th Line+ Treatment Maintenance Treatment Recurrent Maintenance Treatment Recurrent Maintenance Treatment Recurrent Maintenance ZEJULA clinical trials FIRST PRIMA OVARIO NOVA NOVA QUADRA NOVA AVANOVA AVANOVA AVANOVA TOPACIO Follow-on Study: Platinum Resistant Ovarian Cancer (ZEJULA +TSR-042) Women who respond to platinum for <6 months are considered platinum-resistant Current ZEJULA indication Fully enrolled / completed trials Enrolling / expected to enroll patients by year-end TSR-042: anti-pd-1 antibody; AVANOVA trial in collaboration with ENGOT 6

7 ZEJULA NOVA Study Primary Endpoint PFS Results 42% of patients estimated without progression or death 24 months following the start of chemotherapy gbrcamut Cohort 27% of patients estimated without progression or death 24 months following the start of chemotherapy Non-gBRCAmut Cohort Progression free Survival (%) Niraparib Placebo Progression free Survival (%) Niraparib Placebo Time Since Randomization (months) Time Since Randomization (months) Treatment Niraparib (N=138) Placebo (N=65) PFS Median (95% CI) (Months) Hazard Ratio (95% CI) p-value 21.0 (12.9, NR) (3.8, 7.2) (0.173, 0.410) p< % of Patients without Progression or Death 12 mo 18 mo 62% 50% 16% 16% Treatment Niraparib (N=234) Placebo (N=116) PFS Median (95% CI) (Months) Hazard Ratio (95% CI) p-value 9.3 (7.2, 11.2) (3.7, 5.5) (0.338, 0.607) p< % of Patients without Progression or Death 12 mo 18 mo 41% 30% 14% 12% Overall Survival (<20% patient deaths) HR 0.73 (95% CI, to 1.125; p=0.1545) PFS was analyzed using a 2-sided log-rank test using randomization stratification factors, and summarized using the Kaplan-Meier 7 methodology; Hazard ratios with 2-sided 95% confidence intervals were estimated using a stratified Cox proportional hazards model, with the stratification factors used in randomization

8 ZEJULA Moving to 1 st Line with PRIMA Ovarian Cancer With High Risk for Progression, Stage 3 or 4 (N=733) CR or PR Following Platinum Based Chemotherapy Enrolled 1 st line patients regardless of BRCA status Stratify on HRD (2:1 randomization) Niraparib 200 mg Daily Treatment 1 Placebo Daily Treatment 200 mg starting dose for most patients based on body weight & platelet count Blinded, pooled interim safety data at ESMO Primary Endpoint Endpoint Assessment Progression-free Survival (PFS) Top-line data expected in late 2019 Secondary Endpoints OS PFS2 Patient reported outcomes Safety & Tolerability Time to CA-125 progression 1 Trial was amended to incorporate a starting dose of 300 mg for patients 77 kg (170 lbs) and platelets 150K/uL, with a 200mg starting dose for all others 8

9 ZEJULA AVANOVA: Niraparib + Bevacizumab Recurrent, platinum-sensitive epithelial ovarian, fallopian tube, or primary peritoneal cancer w/high-grade serous/endometrioid histology Phase 1, N = 12 Phase 2, N=94 Stratify on HRD and PFI (>6-12 months or 12+ months) Objectives Phase 1/2 AVANOVA Trial Niraparib + Bevacizumab Niraparib: 300mg Bevacizumab: 15mg/kg Niraparib: 300mg Phase 1: Safety and tolerability of bevacizumabniraparib combination Phase 2: Progression-Free Survival (PFS) in niraparib vs. niraparib + bevacizumab Potentially synergistic activity via simultaneous inhibition of antiangiogenesis and DNA repair Chemotherapy free treatment regimen Goal to improve PFS with bevacizumab or niraparib monotherapy Supported by VEGFi + PARPi exploratory work (Avastin and others) Promising initial combination activity observed in AVANOVA Update of Phase 1 data at ESMO 2017 Disease control rate of 92% 6/12 (50%) ORR, including 1 CR and 5 PRs Median progression-free survival (PFS) was 49 weeks Phase 2 is ongoing 80% power for HR 0.57 (8 vs. 14 months) Phase 2 data in 1H 2019 Initial data presented at ASCO 2016, abstract 5555 AVANOVA is an Investigator Sponsored Trial (IST) SD: Stable disease CRC: Colorectal cancer HR: Hazard ratio GBM: Glioblastoma multiforme 9

10 TSR-042 Registration Strategies Focuses on Endometrial Cancers Accelerated Approval (U.S.) Population Endometrial Cancer 2L/3L Endometrial Cancer (GARNET) Includes MSS (70-75%) and MSI-H (25-30%) endometrial cancer ~7,600 patients treated in U.S ~7,600 patients treated in EU MSI-H Endometrial, MSI-H Colorectal and other MSI-H Tumors (GARNET) 2L/3L MSI-H Endometrial 2 MSI-H Cancers 3L/4L MSI-H Colorectal & Other MSI-H Tumors Phase 3 Randomized 1L Endometrial Cancer MSI-H Endometrial, MSI-H Colorectal and other MSI-H Tumors Full Approval Populations Includes MSS and MSI-H patients ~11,000 patients treated in U.S. ~11,000 patients treated in EU 2L/3L MSI-H Endometrial 2 3L/4L MSI-H Colorectal & Other MSI-H Tumors U.S. Market Opportunity: 1 $500M (2L/3L) to $1.5B (1L) Endometrial Cancer is an Area of High Unmet Need with No FDA Approved Therapies in 2L Endometrial 1 Based on market pricing of FDA approved anti-pd-1 therapies; 2 MSI-H Endometrial accounts for ~50% of MSI-H tumors Kantar Health estimated 2018 epidemiology numbers MSI-H: microsatellite instability-high 10

11 TSR-042 is the Foundation of our Lung Strategy PARP PD-1 TIM-3 Niraparib TSR-042 TSR-022 ZEJULA+ TSR-042 in 1L (JASPER) Data 1H 19 GARNET: 2L NSCLC n=65 Data Q4 18 P2 TSR-042 vs. SOC in 1L NSCLC FPI Q1 19 2/3L TSR TSR-022 in PD-1 experienced (AMBER) Data Q4 18 & 1H 19 Data to Guide Potential Registration Opportunities >450 patients, including >120 lung cancer patients have been treated with TSR

12 NSCLC Treatment Landscape Patients Treated Annually 1 TPS <49% 2/3 of 1L patients TPS 50% ~1/3 of 1L patients PD-1 Monotherapy PD-1 + Chemo First Line 110,000 (US) 135,000 (EU5) Platinum Containing Chemo Regimen PD-1 + Platinum Containing Chemo Regimen PD-1 Monotherapy TPS 50% KEYNOTE 024 (n=305) KEYNOTE 042 (n=1,274) KEYNOTE 189 (n=616) 2nd / 3rd Line 115,000 (US) 110,000 (EU5) PD-1 Monotherapy Platinum Containing Chemo Regimen ORR 45% 39.5% 61.4% mpfs 10.3 months 7.1 months 9.4 months Single-agent Chemo (e.g. docetaxel) PD-1 Experienced Efficacy Benchmarks ORR Single-agent Chemo (docetaxel) 3 ~10% Market research with KOLs and community oncologists support physician preference for PD-1 monotherapy in majority of first-line TPS 50% patients 2 Entinostat (HDACi) + pembrolizumab 4 10% (7/72) Durvalumab + tremelimumab 5 5% (4/78) Sitravatinib (TKI) + nivolumab 6 26% (6/23) mpfs: median PFS; NSCLC: Non-small cell lung cancer; TPS: Tumor Proportion Score 1 Stage IIIb and IV NSCLC excluding ALK/EGFRm patients, Kantar Health estimated 2018 epidemiology numbers; 2 IPSOS Oncology Monitor NSCLC, primary market research studies, external market research; 3 docetaxel PI studies TA317 and TAX320; 4 Hellmann et al.,wclc 2018; 5 Garon et al., ASCO 2018; 6 Mirati corp. presentation, includes unconfirmed responses; KEYNOTE 024, 042: squamous + non-squamous; KEYNOTE 189: non-squamous only 12

13 GARNET Data: 2/3L Lung Results by TPS Status Best Percent Change in Sum of Target Lesion Dimensions from Baseline (AACR 2018) 2L+ NSCLC GARNET TSR-042 TPS 0 TPS 1 49% TPS >50% and NA 50% 30% PD PD Ongoing Treatment Discontinued N 2/7 2/8 3/6 ORR [1,2] (%) 29% 25% 50% Percent Change 10% -10% -30% -50% -70% -90% SD SD PD SD SD SD PD SD 1 Opdivo USPI 2 Keytruda USPI 3 ASCO 2016; Abs # 9015 PD = progressive disease; PR = partial response; SD = stable disease; TPS: Tumor Proportion Score MSI-H EC = microsatellite instability-high endometrial cancer; R2PD = recommended phase 2 dose. SD SD SD SD PR PR PR Reference Data: Previously treated NSCLC ORR 20% (Checkmate - 017, squamous) 1 ORR 19% (Checkmate non-squamous) 1 ORR 18% (KN-010, TPS >1%, 2mg/kg) 2 PR PR PR PR 30% Decrease 2L+ NSCLC Keynote -010 Pembrolizumab TPS 0 TPS 1 49% TPS >50% ORR 3 (%) NA ~9 16% ~23 34% NSCLC irorr of ~29% [2,3] is similar ORR of approved anti-pd-1s; but is largely from a PD-L1 TPS < 50% population, demonstrating response rate not driven by PD-L1 status Data as of February 22, 2018 [1] Excludes patients that were not evaluable for tumor response [2] Includes both confirmed and unconfirmed responses [3] Patients who had at least 1 tumor assessment or did not have any tumor assessment but discontinued treatment NA = TPS status not available 13

14 Mechanisms by Which ZEJULA Could Potentiate an Immune Response DNA Repair Immunologically COLD Tumor PARP Inhibition Niraparib PARP Inhibition PD-1 Blockade TSR-042 Immune System Evasion Immunologically HOT Tumor Limited or no presence of activated anti-tumor immune cells in the tumor and a suppressive TME Presence of activated anti-tumor lymphocytes in the tumor and a supportive TME TME: tumor microenvironment *Brown, BJC

15 ZEJULA Rationale in Lung Cancer Effective in platinum responsive ovarian cancer (OC); lung cancer is a platinum responsive disease Both ovarian and lung cancers have high rates of HRD that infer platinum and PARPi sensitivity 1 Demonstrated activity in preclinical lung cancer models and 2 of 2 NSCLC patients in Phase 1 had tumor regression, even at low dose of niraparib (40mg, 316d; 110mg 175d) 2 Demonstrated positive effect on immune system and combination activity with anti-pd-1 in non-clinical models shows activity TOPACIO data indicative of potential positive clinical benefit from PARP + anti-pd-1 combination Phase 2 JASPER Trial 1L NSCLC Goal: Evaluate Safety and Efficacy of Niraparib + PD-1 PD-L1 TPS 50% Niraparib + anti-pd-1 mab Expression Frequency Low BRCA1/2 a 69% Low ERCC1 b 50% ATM loss c 40% PTEN loss d 20-30% Low MSH2 b 18-38% FA methylation e 14% ERCC1 low NSCLC further sensitized to niraparib 1. Marquard et al, Postel-Vinay Nature Rev Clin Onc 9: ; Postel-Vinay Oncogene , Lee et al Clin Can Res 13:832; 2. Sandhu et al Lancet Onc 2013; a. Clin Cancer Res ; b. Nat Rev Clin Onc 9: , c, oncotarget 2016 Villaruz et al, d, Rehman et al Nat Rev Clin Onc 7: , e, Oncogene 23:

16 JASPER Study: Preliminary Stage 1 Data for Niraparib in Combination with Anti-PD-1 in 1L NSCLC in Patients with TPS 50% Best Percent Change in Sum of Target Lesion from Baseline Objective responses by RECIST criteria following treatment with niraparib + pembrolizumab 16

17 TIM-3 is a Key Immune Checkpoint and a Next Generation Cancer Immunotherapy Target TIM-3 biology has been Implicated in T Cell Exhaustion AND Immune Suppression Mediated by Regulatory T Cells and Myeloid Cells CD4/8+ T Cell Exhaustion Myeloid Cells TIM-3 is expressed on macrophages and can also influence MDSC activity in TME* Dendritic Cells Regulatory T Cells T-cell TIM-3 negatively regulates T cell activation and is a marker of exhausted T cells TIM-3 is expressed on regulatory T cells and promotes survival and suppressive activity TIM-3 is expressed on tumor associated dendritic cells and may negatively regulate DC activation *TME = tumor microenvironment. Adapted from Anderson, A. Cancer Immunology Research

18 NSCLC Post-PD-1 Patient Case TSR anti-pd-1 combination dose escalation 63 year-old female diagnosed with Stage IV NSCLC Prior treatment included 1L chemotherapy, 2L anti-pd-1, 3L Tarceva TSR-022 (1 mg/kg) + anti-pd-1 >>> 72% shrinkage Feb Apr

19 AMBER Study: TSR-022 (anti-tim-3) + TSR-042 (anti-pd-1) in Post-PD-1 NSCLC Patients Part 1 TSR TSR-042 (500 mg) 300 mg 900 mg 100 mg Post-PD-1 NSCLC Data presentation at SITC Part 2 TSR TSR-042 (500 mg) Expansion Cohorts 100 mg 300 mg 900 mg = complete = enrolling *enrolled patients Patients must have progressed following treatment with an anti-pd(l)-1 antibody as assessed by the investigator Patients had median of 5 prior lines of therapy Biomarker Analysis: PD-L1, TIM-3, TMB 19

20 Several Key Milestones & Data Readouts Approaching 2H Gynecologic Lung Gynecologic Lung ESMO Congress: GARNET: MSI-H endometrial data with TSR- 042 PRIMA: blinded pooled interim safety data associated with a 200 milligram starting dose based upon baseline weight and platelet count SITC Annual Meeting: GARNET: TSR-042 data in NSCLC patients AMBER: TSR-022 plus TSR-042 combination initial data in post-pd-1 NSCLC CITRINO: TSR-033 monotherapy data QUADRA snda regulatory decision GARNET: TSR-042 data in MSS Endometrial patients submitted to SGO (Mar) AVANOVA P2 data of niraparib vs niraparib + bevacizumab in 1H 2019 PRIMA top-line data of niraparib in 1L OC in late 2019 BLA submission for TSR- 042 in 2H 2019 OVARIO top-line data of niraparib + bevacizumab in 1L OC in late 2019 Initial Phase 2 JASPER lung data with ZEJULA + TSR-042 in 1H 2019 Initiate Phase 2 registration enabling trial of TSR-042 versus standard of care in first-line NSCLC in early 2019 GARNET: final data for TSR-042 MSI-H and 2L Endometrial and NSCLC AMBER data for TSR TSR-042 CITRINO data TSR TSR-042 TSR-042: anti-pd-1; TSR-022: anti-tim-3; TSR-033: anti-lag-3 SITC: Society for the Immunotherapy of Cancers; BLA: Biologics License Application 20

21 Investor Meetings October 2018