Lonnie Moulder, CEO Leerink Global Healthcare Conference February 12, 2015

Transcription

1 Lonnie Moulder, CEO Leerink Global Healthcare Conference February 12, 2015

2 Safe Harbor Statement Statements made in this presentation about TESARO, Inc. that are not descriptions of historical facts are forward-looking statements reflecting the current beliefs and expectations of management. Forward-looking statements are sometimes identified by words such as plan, may, will, expect, and similar expressions referencing future events, conditions or circumstances. These forward-looking statements involve substantial risks and uncertainties that could cause our clinical development programs, future results, performance or achievements to differ significantly from those expressed or implied by the forward-looking statements, as a result of various factors, including, without limitation, the risks described in our Annual Report on Form 10-K for the year ended December 31, 2013 and our subsequent filings with the SEC. TESARO, Inc. undertakes no obligation to update or revise any forward-looking statement for any reason. 2

3 TESARO: An Overview STRATEGY Oncology-focused development and commercialization Commercialization experience in U.S., Europe and China Efficient external development model LEADERSHIP & EXECUTION Leadership team has built companies and launched products in oncology, including the CINV market Track record of successful in-licensing: 4 transactions and 8 programs Ability to rapidly develop, with 17 trials completed Few comparable companies in the oncology space Rich pipeline in exciting areas of oncology drug development All assets are wholly owned Multiple development & commercialization milestones in next 12 months OPPORTUNITY Well capitalized Long-term holders ~$257M in cash as of 12/31/14 (unaudited) Market capitalization >$1.0 B CAPITAL 3

4 A Balanced Portfolio of Product Candidates Compound Indication Discovery Pre-clinical Phase 1 Phase 2 Phase 3 Registration Rolapitant Oral NK-1 receptor antagonist Rolapitant IV Niraparib PARP Inhibitor CINV in A/C-breast cancer/ MEC treated patients CINV in cisplatin (HEC) treated patients CINV in cisplatin (HEC) treated patients CINV Ovarian Cancer Maintenance Ovarian Cancer Treatment BRCA+ Breast Cancer Niraparib + temozolomide Ewing s sarcoma* TSR-011 ALK and TRK Inhibitor NSCLC, others TSR-042 Anti-PD-1 mab Various tumor types Anti-TIM-3 mab Anti-LAG-3 mab Anti-TIM-3/PD-1 dual reactive mab Anti-LAG-3/PD-1 dual reactive mab Undisclosed mab Various tumor types Various tumor types Various tumor types Various tumor types Various tumor types CINV: Chemotherapy-induced nausea & vomiting mab: Monoclonal antibody A/C: anthracycline/cyclophosphamide. MEC: Moderately emetogenic chemotherapy; HEC: Highly emetogenic chemotherapy. NSCLC: Non-small cell lung cancer. * In collaboration with SARC, the Sarcoma Alliance for Research through Collaboration. 4

5 2015: Significant, Late-Stage Clinical Milestones Rolapitant Oral rolapitant PDUFA date September 5, 2015 Establish a full-scale oncology U.S. commercial organization by Q Submit NDA for IV rolapitant following regulatory approval of oral rolapitant Niraparib Initiate potential registration trial for ovarian treatment during Q1 Complete enrollment of the expanded non-gbrca cohort of NOVA in Q1 Report the initial data from NOVA during 2015 Initiate trials in SCLC and 1L ovarian cancer in 2H

6 Building an Ovarian Cancer Franchise 2 nd Line (Recurrent) Maintenance NOVA Trial PFS primary endpoint Efficacy analyses in prespecified gbrca mut and non-gbrca/hrd+ patients Initial data in 2015 Ovarian Treatment QUADRA Trial ORR primary endpoint Efficacy analyses in prespecified gbrca mut and HRD+ subgroups Phase 2 trial to begin Q st Line Maintenance PRIMA Trial PFS primary endpoint Will enroll gbrca mut and HRD+ patients Phase 3 trial to begin 2H 2015 Niraparib Dosing: 300 mg (3x100 mg capsules) Once Daily PFS: Progression free survival ORR: Overall response rate HRD: Homologous recombination deficiency 6

7 Phase 3 Trial of Niraparib in 2 nd Line (Recurrent) Ovarian Cancer Maintenance (NOVA Trial) High Grade Serous Ovarian Cancer, Platinum Sensitive, Relapsed Response to Platinum Treatment n=490 gbrca mut Non-gBRCA mut / HRD 2:1 Randomization 2:1 Randomization Niraparib Niraparib Placebo 300 mg 300 mg Placebo n=120 n=60 n=207 n=103 Endpoint Assessment Endpoint Assessment Primary Endpoint Secondary Endpoints PFS; >90% power to detect 4.5 month improvement (HR 0.50 in both cohorts) Assumption: 4.5 month PFS for control arms Overall survival, PFS 2, patient reported outcomes Expanded enrollment of non-gbrcamut cohort to complete 1Q 2015 PFS: Progression free survival TNBC: Triple negative breast cancer HRD: Homologous recombination deficiency 7

8 Registration Trial of Niraparib for Treatment of Ovarian Cancer (QUADRA Trial) High Grade Serous Ovarian Cancer, Platinum Resistant or Platinum Sensitive, gbrcamut or HRD Received 3 or More Lines of Chemotherapy N=225 Niraparib 300 mg Daily Treatment Endpoint Assessment Primary Endpoint Overall Response Rate (ORR) Secondary Endpoints Duration of Response, Disease Control Rate, Safety 8

9 Phase 3 Trial of Niraparib in 1 st Line Ovarian Cancer Maintenance (PRIMA Trial) High Grade Serous Ovarian Cancer Responded to 1 st Line Platinum Chemotherapy, with No Evidence of Progression, No Disease >2cm and Normal CA125 Tumor Biomarker Positive Ovarian Cancer 2:1 Randomization Niraparib N=192 Placebo N=96 Primary Endpoint PFS Power assumptions: 13* vs. 20 months, HR=0.625, 90% power Other Endpoints PFS2, OS, QOL, Safety *Control from ICON 7, OVAR 16 and erlotinib studies 9

10 PARP Inhibitor Market Opportunity in Ovarian Cancer of Approximately $4 Billion United States Europe 2L (Recurrent) Maintenance 2L (Recurrent) Maintenance Treatment Treatment 1L Maintenance 1L Maintenance Patients (000s) Patients (000s) gbrca mut non-gbrca mut /HRD + Non-gBRCA mut / HRD- Other/Ineligible Approximately 40,000 Eligible Patients in the U.S. and Europe 1L: 1 st Line; 2L: 2 nd Line; Treatment: 3 or more lines of previous therapy Dollar figures reflect current PARP inhibitor pricing. Source: Company estimates. 10

11 Breast Cancer: Phase 3 Treatment Trial Design (BRAVO Trial) gbrca mut, Advanced/Metastatic Breast Cancer (n=306) Up to Two Prior Treatments for Advanced/Metastatic Disease, Including Anthracycline and Taxane 2:1 Randomization 300 mg Niraparib Investigator Choice: Eribulin, Capecitabine, Gemcitabine or Vinorelbine Primary Endpoint Key Secondary Endpoint PFS >95% power to detect 3 month improvement (HR 0.50) Assumption: 3 month PFS for control: weighted average of 2.3 months for TNBC and 3.9 months for others vs. 6 months for niraparib; 60% of gbrca mut are TNBC Overall survival PFS: Progression free survival TNBC: Triple negative breast cancer 11

12 PARP Inhibitor Market Opportunity in gbrca mut Breast Cancer Exceeds $1 Billion U.S. Europe gbrca mut Patients (000s) 1L Patients 2L Patients 3L Patients Approximately 20,000 Eligible Patients in the U.S. and Europe 1L: 1 st Line metastatic/recurrent; 2L: 2 nd Line metastatic; 3L: 3 rd Line metastatic Dollar figures reflect current PARP inhibitor pricing. Source: Company estimates 12

13 Small Cell Lung Cancer: Design for Biomarker Identification and Registration Extensive Stage SCLC Relapsed After Response to 1 st Line Platinum Tissue Collection for Biomarker Analysis Niraparib 300 mg Daily Treatment Endpoint Assessment Biomarker Assessments Correlations of biomarkers to niraparib sensitivity Endpoints PFS, OS, Duration of Response, Safety *Assumes 10 v 14 mos., >90% power, HR =

14 PARP Inhibitor Market Opportunity in Small Cell Lung Cancer Exceeds $1 Billion U.S. Europe Patients (000s) In Response to a Platinum-Based Regimen Total Extensive Disease Population More than 20,000 Eligible Patients in the U.S. and Europe Dollar figures reflect current PARP inhibitor pricing. Source: Company estimates 14

15 PARP Inhibitor Market Opportunity Approximates $6 Billion for Current & Planned Indications Ovarian Cancer 2 nd Line Maintenance $2 Billion Treatment $1 Billion 1 st Line Maintenance $1 Billion Breast Cancer Small Cell Lung Cancer TOTAL $1 Billion $1 Billion $6 Billion More than 80,000 Eligible Patients in the U.S. and Europe Source: Company estimates. 15

16 Lonnie Moulder, CEO Leerink Global Healthcare Conference February 12, 2015

17 Appendix

18 Despite Available Therapies, Significant Unmet Need Remains in CINV NCCN Guidelines Version Antiemesis Perception vs. Reality 2 in Delayed CINV 91% Agent AC combination defined as either doxorubicin or epirubicin with cyclophosphamide s Cisplatin Carboplatin 1 Cyclophosphamide >1,500mg/m 2 Doxorubicin >60mg/m 2 Dacarbazine Epirubicin >90mg/m 2 Ifosfamide >2g/m per 2 dose Mechlorethamine Streptozocin 76% 43% 59% Start before chemotherapy Serotonin (5-HT 3 ) receptor antagonist AND Steroid AND Neurokinin 1 antagonist No Delayed Nausea Perception of HCPs No Delayed Vomiting Actual Patient Experience Opportunity to Educate HCPs Regarding Antiemesis Guidelines and Actual Patient CINV Experience 1 For selected patients as appropriate 2 J Support Oncol 2004;2(suppl 1):1-12 HCPs: Healthcare Providers 18

19 Rolapitant: A Differentiated NK-1 RA Product Candidate 1 2 Extended half life provides protection for 120-hour period of CINV risk Plasma half-life of ~180 hours High affinity for human NK-1 receptor (Ki = 0.7 nm); highly selective PET scan 5 days post-dose showed >90% NK-1 receptor occupancy following single 200mg oral dose + PET tracer Reduced potential for CYP3A4 interactions Approximately 60% of pharmaceutical products are metabolized via the CYP3A4 pathway 1 Rolapitant does not inhibit or induce CYP3A4 MDZ Mean (SD) Plasma Concentrations MRI Blocked PET (t00739) Baseline PET (t00729) 1 Ther Clin Risk Manag March; 1(1): Scale: kbq/ml PET data on file. 19

20 Rolapitant: Pivotal Program Design Phase 3 in MEC Reported Phase 3 in HEC1 Reported Phase 3 in HEC2 Reported 1,369 patients enrolled ~50% received A/C for breast cancer 5-HT 3 RA + dexamethasone vs. 200mg rolapitant + 5-HT 3 RA + dexamethasone 532 patients enrolled All received cisplatin 60 mg/m 2 5-HT 3 RA + dexamethasone vs. 200mg rolapitant + 5-HT 3 RA + dexamethasone 555 patients enrolled All receiving cisplatin 60mg/m 2 5-HT 3 RA + dexamethasone vs. 200mg rolapitant + 5-HT 3 RA + dexamethasone Endpoints Primary: Delayed complete response (CR) in the hr. period after chemotherapy Statistical plan required hierarchical analysis of the key secondary endpoints acute CR (0 to 24 hrs.) and overall CR (0 to 120 hrs.), and pre-specified adjustment for multiplicity for secondary endpoints Primary Endpoint Achieved in All 3 Trials; Safety Profile Consistent with Earlier Trials RA: receptor antagonist. MEC: moderately emetogenic chemotherapy. HEC: highly emetogenic chemotherapy. 20

21 Phase 3 Trials: Primary Endpoint Results mitt Population Complete Response Rate MEC Trial HEC Trial #1 HEC Trial #2 61.6% p < Delayed Phase (> hr) 71.3% 72.7% Control 58.4% p < Delayed Phase (> hr) Rolapitant 200mg 61.9% p = % Delayed Phase (> hr) 2 Each of the three Phase 3 trials achieved primary endpoint of CR in the delayed phase ( hours) 21

22 Phase 3 A/C-Based MEC Trial: Additional Supportive Endpoints Complete Protection* No Impact on Daily Life** Complete Response Rate 56.9% p = % Delayed Phase (> hr) Control (n=666) 53.2% p = % Overall Phase (0 120 hr) Rolapitant 200mg (n=666) Complete Response Rate Control (n=607) 67.4% p = % Overall Phase (0 120 hr) Rolapitant 200mg (n=605) CR Acute 83.5% vs. 80.3% (p=0.143), CR Overall 68.6% vs. 57.8% (p<0.001) Complete Protection endpoint favored rolapitant in the delayed and overall phases No Impact on Daily Life: Both the Nausea and Vomiting domains favored rolapitant (nausea p=0.019; vomiting p<0.001) * Complete Protection: No emesis, No rescue medication and maximum nausea score of <25mm on the VAS. ** No Impact on Daily Life measured by Functional Living Index-Emesis (FLIE) total score >108. All p values are unadjusted. 22

23 Phase 3 Cisplatin-Based HEC Trials: Additional Supportive Endpoints HEC-1: No Nausea Analysis (mitt) HEC-2: No Nausea Analysis (mitt) Complete Response Rate p = % p = % p = % 49.6% 41.6% 39.3% Complete Response Rate p = % 46.9% p = % 67.8% p = % 55.0% Delayed Phase Control (n=666) Acute Phase Overall Phase Rolapitant 200mg (n=666) Delayed Phase Control (n=666) Acute Phase Meaningful reduction in nausea demonstrated in both cisplatin-based HEC trials Overall Phase Rolapitant 200mg (n=666) HEC-1: CR Acute 83.7% vs. 73.7% (p=0.005), CR Overall 70.1% vs. 56.5% (p=0.001) HEC-2: CR Acute 83.4% vs. 79.5% (p=0.233), CR Overall 67.5% vs. 60.4% (p<0.084) 23

24 Rolapitant IV: Bioequivalence Program Underway to Address Largest Market Segment Log-Mean ± SE Rolapitant Plasma Concentration (ng/ml) 10, , REF (Oral) 200mg 185mg (IV) 30-min Infusion Time (h) Initial Results of a Human Dose Ascending Study Indicate that the IV Formulation is Likely to Achieve Bioequivalence to a 200 mg Oral Dose 24

25 $1.5B U.S. Market Opportunity for NK-1 RAs Annual U.S. Opportunity: 5 Million Day 1 Chemotherapy Administrations Market: NK-1 RA Doses 2012 Estimate (MM) 10 15% Cisplatin-Based Regimens (HEC) % 2 1 Estimated Unmet Targeted Market A/C-based Treatments for Breast Cancer & Carboplatin Regimens (MEC) 0 Current Potential Patients Receiving A/C for Breast Cancer and Other MEC Regimens Represent ~90% of the $1.5B Target U.S. Market Opportunity HEC: highly emetogenic chemotherapy MEC: moderately emetogenic chemotherapy A/C: anthracycline/cyclophosphamide 25

26 Our Opportunity: 5 Million Day One Doses Annually in the U.S. Significant Revenue Potential from Targeted Markets Rolapitant Potential Share: 25% 50% 75% Eligible Chemotherapy Initiations 1 IV Opportunity 4M Doses 1M doses $300 M 2M doses $600 M 3M doses $900 M IV 80% Oral Opportunity 1M Doses 0.25M doses $75 M 0.5M doses $150 M 0.75M doses $225 M 20% Oral Rolapitant is Positioned to Transform TESARO into an Integrated Development and Commercial Company 1 As reported by IMS National Sales Perspective Dollar figures reflect current NK-1 RA pricing of ~$300/cycle on average 26

27 Commercial Strategy: Plan to be U.S. Launch Ready by 3Q Key Account Collaborations Contracting Opportunity Leverage Clinical Trial Experience Long Standing Relationships Focus on Nurses 1 Differentiation Long Half-Life Sustained Efficacy for 5 Days Lack of CYP3A4 DDIs IV & Oral Formulations Key Success Factors 3 Educational Efforts Adherence to NCCN, ASCO Guidelines Increase Awareness of Need Established Reimbursement 2 Promotional Activities Primary Detail Position Focused, Right-Sized Commercial Organization (120) Opportunity for Significant Leverage: Anticipate Rolapitant P&L to Break Even at Annual Sales of ~$50 60M DDIs: Drug-Drug Interactions 27

28 TSR-011: Ant-tumor Activity in ALK+ Patients Currently Evaluating 120 mg Dose (Fractionated) Tumor Type Dose (mg) Prior ALKi Therapy (mo) Cycle ALK+NSCLC 480 > ALK+NSCLC 240 > ALK+NSCLC ALK+NSCLC 60* 1 ALK+NSCLC 60* 1 ALK+NSCLC 60* 7 ALK+NSCLC 60* unknown ALK+NSCLC 60* 24 ALK+NSCLC 120* 5 ALK+NSCLC 60* Naïve ALK+NSCLC 60* Naïve ALK+NSCLC 60* Naïve RECIST PR Non-RECIST PR RECIST PR Cycle 19 Cycle 14 Cycle of Response (PR) Near CR Blue bars denote progressive disease Unless otherwise stated, patients represented by green bars have stable disease * Fractionated as q8 or q12 Data as of November

29 TSR-011 Phase 1a Dose Escalation Adverse Events Preferred Term 20mg TID (N=11) n (%) All Grades Grades 3 40mg TID (N=3) n (%) Total (N=40) n (%) 20mg TID (N=11) n (%) 40mg TID (N=3) n (%) Total (N=40) n (%) Electrocardiogram QT prolonged (25.0) (7.5) Fatigue 3 (27.3) 0 10 (25.0) (2.5) Diarrhea 2 (18.2) 0 9 (22.5) Decreased appetite 2 (18.2) 0 7 (17.5) Headache 2 (18.2) 0 7 (17.5) (2.5) Vomiting 2 (18.2) 0 7 (17.5) Edema peripheral 1 (9.1) 0 6 (15.0) Urinary tract infection 1 (9.1) 0 6 (15.0) (2.5) Constipation 2 (18.2) 1 (33.3) 6 (15.0) Anemia 4 (36.4) 0 5 (12.5) 2* (18.2) 0 2 (5.0) Asthenia 1 (9.1) 0 5 (12.5) (2.5) Cough 2 (18.2) 0 5 (12.5) Dyspnea 1 (9.1) 0 5 (12.5) (2.5) Dehydration 2 (18.2) 0 4 (10.0) 1 (9.1) 0 1 (2.5) Dysgeusia (10.0) Hot flush 2 (18.2) 0 4 (10.0) Nausea 1 (9.1) 0 4 (10.0) *Gr 3 Anemia was observed in sarcoma and pancreatic NET pts, both after multiple lines of chemo- and radiation therapy 29

30 Lonnie Moulder, CEO Leerink Global Healthcare Conference February 12, 2015