Tuesday, March 20, Oppenheimer & Co. Annual Healthcare Conference

Transcription

1 ca Tuesday, March 20, 2018 Oppenheimer & Co. Annual Healthcare Conference

2 Forward-Looking Statements This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of In some cases you can identify these statements by forward-looking words, such as believe, may, will, estimate, continue, anticipate, intend, could, would, project, plan, potential, seek, expect, goal, or the negative or plural of these words or similar expressions. These forward-looking statements are subject to a number of risks, uncertainties and assumptions, and new risks emerge from time to time. In light of these risks, uncertainties and assumptions, the forward-looking events and circumstances discussed in this presentation may not occur and actual results could differ materially and adversely from those anticipated or implied in the forward-looking statements. Please refer to our Annual Report on Form 10-K that we filed with the SEC for a description of risks and uncertainties that could impact future results. Although we believe that the expectations reflected in the forward-looking statements are reasonable, we cannot guarantee that the future results, levels of activity, performance or events and circumstances reflected in the forward-looking statements will be achieved or occur. We undertake no obligation to update any forward-looking statements except as required by law. 2

3 NOW AVAILABLE IN THE U.S. 3

4 Bevyxxa: The First and Only Anticoagulant for VTE Prevention In Hospital to Home for days in Acute Medically Ill Patients WARNING: SPINAL/EPIDURAL HEMATOMAS MAY OCCUR IN PATIENTS TREATED WITH BEVYXXA WHO ARE RECEIVING NEURAXIAL ANESTHESIA OR UNDERGOING SPINAL PUNCTURE. THE RISK OF THESE EVENTS MAY BE INCREASED BY THE USE OF IN-DWELLING EPIDURAL CATHETERS OR THE CONCOMITANT USE OF MEDICAL PRODUCTS AFFECTING HEMOSTASIS. THESE HEMATOMAS MAY RESULT IN LONG-TERM OR PERMANENT PARALYSIS. CONSIDER THESE RISKS WHEN SCHEDULING PATIENTS FOR SPINAL PROCEDURES. 4

5 Pipeline of Innovative Products in Areas of Highest Medical Need Matching our R&D & Commercial Expertise COMMERCIAL / LATE STAGE Pre-clinical PHASE 1 PHASE 2 PHASE 3 FDA/ EMA Review Cerdulatinib Oral, Factor Xa Inhibitor Prophylaxis for hospitalized acute medically ill patients at risk for VTE FXa inhibitor antidote/ reversal agent Hospitalized patients with major bleeding or requiring surgery Oral, Syk/JAK inhibitor Relapsed/refractory B- and T-cell malignancies FDA APPROVED AND AVAILABLE EMA REVIEW ONGOING BREAKTHROUGH DESIGNATION May 4, 2018 PDUFA EMA REVIEW ONGOING PHASE 2A STUDY ONGOING (Three Cohorts) EARLY STAGE R&D Cerdulatinib PRT2761 Topical, Syk/JAK inhibitor Mild to moderate atopic dermatitis Ocular, Syk inhibitor Allergic conjunctivitis Licensed to Dermavant Joint Venture with Ora, Inc. 5 Venous thromboembolism (VTE)

6 G7 G7 Addressable Market Market (US $M) (US $M) WW WW Sales Sales US (US $ (mln) $M) Portola s Leading Position in Two Blockbuster Growth Markets WW Oral Factor Xa Market Addressable market $22B* $11B* $3-4B VTE Px Acute Medically ill G7 Xa Reversal Market Addressable market 10,000 9,000 8,000 7,000 6,000 5,000 4,000 3,000 >$2B Anticoagulant Antidote 2,000 1, *Evaluate Pharma Jan 5, 2018; Truven, Portola estimates

7 CUMULATIVE 180 DAY PROBABILITY (%) Urgent Need to Prevent VTE In Hospital to Home in Acute Medically Ill Patients >24 Million Acute medical patients indicated for VTE prevention (G7) >1 Million Will suffer a blood clot within 35 days 70% 60% 50% 40% 30% 20% 10% 0 SYMPTOMATIC VTE IN ACUTE MEDICAL PATIENTS DAYS AFTER ADMISSION 2.5% 2.0% 1.5% 1.0% 0.5% SYMPTOMATIC VTE RATE (%) 150,000 Estimated to survive condition but die of VTE every year Cumulative and persistent VTE risk starting at hospital admission Bevyxxa is the first and only drug approved for this indication 7 Piazza G et al. Thromb Haemost. 2009;102(3):

8 More Major Bleeding Event Rate (%) VTE Events Previous VTE Prophylaxis Studies Failed Due to Significant Increase in Major Bleeding and Limited Efficacy 6 EXCLAIM (Failed Interim Futility) Enoxaparin* vs. Extended Enoxaparin N=5,963 MAGELLAN Enoxaparin vs. Rivaroxaban N=8, % RRR=22.8% ARR=1.31% P= % 4.4% 3.3% 2.5% 2.4% % P< % Standard Enoxaparin (6-14d)* Extended Enoxaparin (24-32d) 0.4% P< % Standard Enoxaparin (6-14d) Extended Rivaroxaban (31-39d) 8 EXCLAIM efficacy analysis based on revised eligibility criteria and enrollment after DSMB stopped trial for futility. * Patients in both study arms received open label enoxaparin for 6-14 days followed by placebo or extended duration enoxaparin. Cohen AT et al. N Eng J Med. 2013;368(6): ; Hull RD et al. Ann Intern Med. 2010;153(1):8-18.

9 Bevyxxa has Unique Properties with the Potential to Reduce VTE Without an Increase In Major Bleeding Once-daily half life Low renal clearance Not metabolized by CYP3A4 (Commonly used CYP3A4 inhibitors e.g., clarithromycin, erythromycin, HIV protease inhibitors, fluconazole, itraconazole) BETRIXABAN RIVAROXABAN ENOXAPARIN Half Life hrs * 5-9 hrs hrs Renal Excretion 11-18% 36% >40% CYP3A4 Interactions No Yes No 9 *Betrixaban s pharmacological half life

10 APEX Study: Betrixaban and a New Treatment Paradigm Compared to the Old Standard STANDARD PROPHYLAXIS EXTENDED PROPHYLAXIS EVALUATION 6-14 DAYS DAYS ENROLLMENT (N=7513) Enriched extended VTE risk R Enoxaparin 40 mg SC daily Placebo Loading Dose - Betrixaban 80 mg oral once daily Primary Endpoint VTE including VTE death DAYS Follow-Up Safety Including Bleeding and Stroke DAYS Dosing adjustments: In severe renal insufficiency (CrCl 15 to <30 ml/min): Betrixaban 40 mg (80 mg loading dose) and enoxaparin 20 mg SC daily In patients taking concomitant strong P-gp inhibitors: Betrixaban 40 mg (80 mg loading dose), no dose adjustment for enoxaparin 10 Cohen AT et al. N Engl J Med. 2016;375:534-44

11 Reduction in VTE Including VTE-Related Deaths Compared to Standard of Care (mitt population) VTE and VTE Death DAY 42 Major Bleeding DAY 42 7% 6% 5% 4% 3% Enoxaparin/Placebo Betrixaban 6.0% 223/3720 RRR=25% ARR=1.56% P=0.003 NNT=65 4.4% 165/3721 7% 6% 5% 4% 3% Enoxaparin/Placebo Betrixaban RR=1.19 P=0.55 2% 1% 0% 2% 1% 0% 0.6% 0.7% 21/ / mitt=modified intent-to-treat; RRR=relative risk reduction BEVYXXA [Package Insert], Portola Pharmaceuticals, Inc. Cohort 1 (D-Dimer > 2x ULN): Cohort 2 (Age > 75 OR D-Dimer > 2x ULN: OVERALL POPULATION 7.2% vs. 5.7%, RRR=21%, 95% CI [0.63, 0.98], P= % vs. 4.7%, RRR=22%, 95% CI [0.64, 0.96], P=0.018

12 VTE-related Death (%) Reduction in VTE-Related Death New results published in The American Heart Journal VTE-Related Death (80 mg) HR = 0.46 (95% CI: ) p = ARR = 0.45% NNT = 223 Enoxaparin 0.79% Betrixaban 0.34% 12 Gibson et al. Symptomatic event reduction with extended-duration betrixaban in acute medically ill hospitalized patients. Am Heart J. 2018; 198:84-90.

13 Reduction in VTE-Related Death and Hospitalization Peer-Reviewed and Published New Data (Ad Hoc Analyses) VTE-Related Death and VTE Hospitalization 2.00% 1.75% HR = 0.53 ( ) ARR = 0.77% NNT = 130 Enoxaparin/Placebo Betrixaban 1.64% 1.50% 1.25% P = % 0.75% 0.87% 0.50% 0.25% VTE-related death Chi G et al. Circulation. 2017;136:A VTE Hospitalization Chi G et al. Circulation. 2018; 137(1):91-94 Composite data on file, PERFUSE Study Group

14 Bevyxxa Effectiveness and Safety Drives New Standard of Care in Highest-Risk Acute Medically Ill Patients Clinical Benefit Compared to Old Standard of Care Efficacy 25% Composite VTE 45% Symptomatic VTE 47% VTE rehospitalizations & death Safety No increase 41% Major bleeding (ISTH criteria) Stroke 14

15 Scaling Sales and Medical Affairs to Increase Impact Aug-Dec 2017 IH H 2018 Sales Reps Hospital Targets ~1,000 ~1,200 ~1,500+ % APEX Patients 50% 70+% 80+% *Not including field based MSLs; 1:8 ratio MSL/reps 15

16 Compelling Data Drive Positive Health Economic Story Cost Per Fatal and Irreversible Event* Saved ARR NNT Duration of Treatment Cost Cost/ Event Saved 0.9% 114 Chronic $4,400/ yr $500, % 100 Chronic $4,500/ yr $450, % 200 Chronic $10,000/ yr ~$2,000,000 80mg 1.8% days ~$600 $33, *Events include annualized addition of CV Deaths, MIs, Strokes & PEs minus ICHs & Fatal Bleeds Eliquis based on ARISTOTLE trial (CV Deaths, MIs, Strokes, PEs, ICHs, Fatal Bleeds) Entresto based on PARADIGM-HF trial (MACE at 27 months showed 2.2% ARR -- adjusted to 1.0% annually) Repatha based on FOURIER trial (CV Deaths, MIs and Strokes combined ARR 1.5% over 36 months adjusted to 0.5% annually) Bevyxxa based on APEX 80mg mitt analysis (CV Deaths, MIs, Strokes, PEs, ICHs, Fatal Bleeds)

17 Early Launch Indicators 12 major publications and 30+ scientific presentations Validated HECON model developed by leading thrombosis academic group CENTER FOR OUTCOMES RESEARCH Formulary wins including flagships Payer coverage 17

18 Urgent Need to Address Factor Xa Inhibitor Bleeding: A Major and Growing Cause of Hospital Admissions and Death G7 Bleeding Admissions due to Oral Factor Xa Inhibitor 440, ,000 ICH Mortality & Morbidity 295, % mortality at 30 days 215, days in hospital 27% CAGR Top 20% with costs >$100, Source: Calculations based on IMS Health, Truven and Evaluate Pharma Analyst Xa Class projections

19 Andexanet Alfa has Potential to be the First and Only Antidote For Universal FXa Inhibitor Reversal Only agent designed to reverse the anticoagulant activity of these FXa inhibitors * In clinical trials, only agent to reduce anti-fxa activity Ongoing confirmatory trial in bleeding patients Bevyxxa (betrixaban) Xarelto (rivaroxaban) Eliquis (apixaban) Savaysa (edoxaban) Lovenox (enoxaparin) Arixtra (fondaparinux) Unfractionated Heparin Placebo (N = 8) Andexanet 400mg bolus + 400mg (x 2hr) infusion (N = 23) >250 patients currently enrolled in the U.S. and EU Siegal et al. N Engl J Med 2015; 373: Xarelto and Eliquis (Phase 3); Bevyxxa, Savaysa and Lovenox (Phase 2); Arixtra and unfractionated heparin (preclinical) Healthy volunteers treated with apixaban The ongoing phase 3b/4 study is evaluating reversal of apixaban, edoxaban, enoxaparin and rivaroxaban with andexanet

20 20 Clinical Hemostatic Efficacy

21 Thrombosis/Mortality Rates in Bleeding Patients in Recently Completed ICH Enriched and Non ICH Studies Study ANNEXA-4 * (2018) REVERSE-AD (2017) Sarode (2013) Sarode (2013) Reversal Agent Anticoagulant Andexanet FXa Inhibitors Idarucizumab Dabigatran 4F-PCC Warfarin Plasma Warfarin Number Hemostatic Efficacy (95% CI) Thrombotic Event Rate (95% CI) Mortality (95% CI) Total % ICH Total ICH Total ICH Total ICH % (76-89) 81% (72-90) 11% (7-16) % a NR b 5% (3-8) % (64-81) 65% (56-75) 42% (15-72) 58% (28-85) 8% (3-15) 6% (3-13) 12% (7-19) 6% (2-13) NR NR 12% (8-18) 14% (10-18) 6% (2-12) 5% (2-10) 12% (7-20) 16% (10-25) NR NR Ezekwudo (2017) None VKA 60%/ FXai 35% N/A N/A 15% (9-23) 15% (9-23) 45% (36-54) 45% (36-54) 4F-PCC = Four factor prothrombin complex concentrate; CI = Confidence interval; ICH = Intracranial hemorrhage; N/A = Not applicable; NR = Not reported a 68% had investigator-determined, non-adjudicated time to hemostasis within 24 hours b Time to hemostasis not calculated in ICH patients 21

22 AndexXa Recommended in Key Guidelines In patients with oral Factor Xa related life-threatening bleed Suggest Andexanet Suggest NOT using 4F-PCC For serious bleeds on NOACs: Recommend general measures followed by specific antidote 22

23 Cerdulatinib: A SYK-JAK Inhibitor for Resistant or Relapsed Hematological Cancers and Other Diseases B cell lymphoma BCR pathway chronically active T cell lymphoma Syk over expressed (not expressed in healthy T-cells) Uniquely inhibits 2 targets that mediate critical survival signals in B- and T-cell malignancies CERDULATINIB B cell lymphoma JAK-related cytokines support survival T cell lymphoma IL-2 drives T cell growth and survival; some activating JAK mutations seen PI3 K Tumor derived cytokines IL-6, IL-10 Gilead Zydelig Verastem IPI-145 Pharmacyclics Imbruvica TM Incyte Jakafi 23

24 Advancing Cerdulatinib 91 Patients (79 evaluable) now enrolled Efficacy ~50% response rate across 3 tumor types Complete responses in PTCL Safety Consistent with other trials in same patient populations Next Steps (Q2) FDA discussion regulatory path Complete enrollment Present Phase 2a study results 24

25 Capitalized to Drive Momentum $534.2M Cash, Cash Equivalents & Investments as of 12/31/17 United States Q1 Q2 Q3 Q4 U.S. Launch Initiated FDA PDUFA (Gen 1) May 4 FDA Supplemental Decision (Gen 2) November (assuming 6-mo review) Cerdulatinib Europe Betrixaban CHMP OE Conducted Determining Next Steps FDA Discussion & Phase 2a Data Presentation Q1 Q2 Q3 Q4 Andexanet CHMP OE Conducted Add l Data Requested CHMP Opinion 25

26 NASDAQ: PTLA