Credit Suisse Healthcare Conference November 2014

Transcription

1 Credit Suisse Healthcare Conference November 2014

2 Safe Harbor Statement This presentation may contain forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of Such forward-looking statements are characterized by future or conditional verbs such as may, will, expect, intend, anticipate, believe, estimate and continue or similar words. You should read statements that contain these words carefully because they discuss future expectations and plans, which contain projections of future results of operations or financial condition or state other forward-looking information. Such statements are only predictions and our actual results may differ materially from those anticipated in these forward-looking statements. We believe that it is important to communicate future expectations to investors. However, there may be events in the future that we are not able to accurately predict or control. Factors that may cause such differences include, but are not limited to, those discussed under Risk Factors and elsewhere in our Annual Report on Form 10-K for the year ended December 31, 2013, as filed with the Securities and Exchange Commission, including the uncertainties associated with product development, the risk that products that appeared promising in early clinical trials do not demonstrate safety and efficacy in larger-scale clinical trials, the risk that we will not obtain approval to market our products, the risks associated with dependence upon key personnel and the need for additional financing. We do not assume any obligation to update forward-looking statements as circumstances change. This presentation does not constitute an offer or invitation for the sale or purchase of securities or to engage in any other transaction with Synergy or its affiliates. The information in this presentation is not targeted at the residents of any particular country or jurisdiction and is not intended for distribution to, or use by, any person in any jurisdiction or country where such distribution or use would be contrary to local law or regulation. Credit Suisse Healthcare Conference 2

3 Our Focus: Pioneering GI Research & Development NATURAL Advanced clinical programs with multiple value drivers PHYSIOLOGY MEETS BREAKTHROUGH SCIENCE Platform technology based on a naturally occurring human GI hormone Exclusive worldwide rights Strong patent portfolio Experienced management team Credit Suisse Healthcare Conference 3

4 Our Platform: Discovered & Developed by Synergy COMPOUND INDICATION PHASE 1 PHASE 2 PHASE 3 PLECANATIDE Chronic Idiopathic Constipation (CIC) SP-333 Irritable Bowel Syndrome with Constipation (IBS-C) Opioid-Induced Constipation (OIC) Ulcerative Colitis (UC) Credit Suisse Healthcare Conference 4

5 Our Approach: Based on a Natural Human GI Hormone - Uroguanylin UROGUANYLIN (Natural GI Hormone) PLECANATIDE CIC/IBS-C SP-333 OIC/UC Credit Suisse Healthcare Conference 5

6 Physiological Mechanism of Action Cross Section of GI Tract 1 3 Plecanatide SP Uroguanylin (UroG) activates GC-C receptors in the gut GC-C receptor stimulates cyclic GMP synthesis C-GMP activates CFTR, moving fluid into the intestine for normal digestion 4 Plecanatide/SP-333 activate GC-C, restoring normal GI function Credit Suisse Healthcare Conference 6

7 Plecanatide: Novel Analog of Natural Uroguanylin Uroguanylin Plecanatide NDDCELCVNVACTGCL NDECELCVNVACTGCL KEY AMINO ACID SUBSTITUTION Binding constant to GC-C receptor is 8-fold higher than (1) uroguanylin Activity mimics natural uroguanylin (ph-regulated) Essentially non-systemic Once-daily oral tablet Efficacy and superior tolerability validated in CIC and IBS-C clinical trials (1) D. Liu, et. al., Anticancer Research, 29: (2009) Credit Suisse Healthcare Conference 7

8 Natural GC-C Agonist vs. Bacterial Enterotoxin Uroguanylin: Natural GC-C Agonist Plecanatide: Uroguanylin Analog NDDCELCVNVACTGCL NDECELCVNVACTGCL ST Peptide: E. coli Bacteria Linaclotide: Enterotoxin Analog NSSNYCCELCCNPACTGCY CCEYCCNPACTGCY Linaclotide is a truncated version of a bacterial enterotoxin Credit Suisse Healthcare Conference 8

9 Plecanatide CIC Clinical Program

10 Plecanatide Phase 2b/3 CIC Trial: Study Overview Aim: Assess the safety and efficacy of 0.3, 1.0 and 3.0 mg plecanatide doses vs. placebo in CIC patients Patient Population: 951 patients with CIC (Modified Rome III Criteria) Primary Endpoint: Design: Proportion of Durable Overall Responders (fulfills 3 CSBMs + 1 CSBM from baseline per week, for 9/12 weeks, including 3 of the last 4 weeks) FDA Approval Endpoint Screening up to 4 weeks Baseline 2 weeks Treatment 12 weeks Post-Tx 2 weeks Credit Suisse Healthcare Conference 10

11 Plecanatide Phase 2b/3 CIC Trial: Primary Endpoint (FDA Endpoint) % of Responders Proportion of Durable Overall Responders= fulfills 3 CSBMs + 1 CSBM from baseline per week, for 9/12 weeks, including 3 of the last 4 weeks) Placebo n= mg n= mg n= mg n=237 = p<0.05; = p<0.01 Credit Suisse Healthcare Conference 11

12 Change from Baseline/ LS Mean Change from Baseline/ LS Mean Plecanatide Phase 2b/3 CIC Trial: Secondary Endpoints - Clear Dose-Response Change from Baseline/ LS Mean Change from Baseline/ LS Mean Placebo n=236 CSBM Frequency mg n= mg n= mg n= Placebo n=236 SBM Frequency mg n= mg n= mg n= Stool Consistency (BSFS Scale) 0.81 Placebo n= mg n= mg n= mg n= Placebo n=236 Mean Straining Change mg n= mg n= mg n=237 = p<0.05; = p < 0.01; = p < Credit Suisse Healthcare Conference 12

13 % Responders Plecanatide Phase 2b/3 CIC Trial: Demonstrated Immediate & Sustained Effect Bristol Stool Form Scale Score Weekly Responder Rates Stool Consistency (BSFS) r/o Placebo 0.3 mg 1.0 mg 3.0 mg Treatment Week = p<0.05; = p < 0.01; = p < r/o Treatment week Placebo 0.3 mg 1.0 mg 3.0 mg Credit Suisse Healthcare Conference 13

14 Plecanatide Phase 2b/3 CIC Trial: Safety Summary Safe and well tolerated with <10% diarrhea at 3.0 mg dose Serious Adverse Events (AE) Treatment-emergent (TE) AEs AEs leading to withdrawal Placebo n= mg n= mg n= mg n=237 5 (2.1%) 1 (0.4) 1 (0.4) 2 (0.8%) 96 (40.7%) 99 (41.8) 103 (43.3) 106 (44.7%) 8 (3.4%) 9 (3.8) 16 (6.7) 13 (5.5%) All Diarrhea TEAEs 3 (1.3%) 13 (5.5) 20 (8.4) 23 (9.7%) Severe Diarrhea TEAEs (1.7) 1 (0.4%) Withdrawal due to Diarrhea 1 (0.4%) 2 (0.8) 8 (3.4) 7 (3.0%) Credit Suisse Healthcare Conference 14

15 Plecanatide Pivotal Phase 3 CIC Trials: Program Overview Aim: Two, randomized, 12-week, double-blind, placebo-controlled trials to confirm the safety and efficacy of plecanatide in CIC patients Treatment Groups: 3.0 and 6.0 mg oral tablet plecanatide or placebo once-daily Estimated Enrollment: 1350 CIC patients per trial (2700 patients total) Primary Endpoint: Design: Proportion of Durable Overall Responders Screening up to 4 weeks Baseline 2 weeks Treatment 12 weeks Post-Tx 2 weeks Credit Suisse Healthcare Conference 15

16 Plecanatide CIC Registration Program: Anticipated Events & Timelines Nov 2013 April Q Q Q Started Registration Trial 1 Started Registration Trial 2 Top-line Data (Trial 1) Top-line Data (Trial 2) CIC NDA Filing Plecanatide FDA approval for CIC CIC Open Label Studies Ongoing Credit Suisse Healthcare Conference 16

17 Plecanatide IBS-C Clinical Program

18 Plecanatide Phase 2b IBS-C Trial: Study Overview Aim: Assess the efficacy and safety of 0.3, 1.0, 3.0 and 9.0 mg plecanatide doses vs. placebo in IBS-C patients Population: Rome III Criteria for IBS-C Primary Endpoint: Mean change from baseline in CSBM frequency Study Design: Screening up to 6 weeks Baseline 2 weeks Treatment 12 weeks Post-Tx 2 weeks Credit Suisse Healthcare Conference 18

19 Change from Baseline over 12 weeks ( LS Mean) Plecanatide Phase 2b IBS-C Trial: Primary Endpoint Mean Change from Baseline in CSBM Frequency Placebo n= mg n= mg n= mg n= mg n=85 = p < 0.05; = p < Note: mitt population Credit Suisse Healthcare Conference 19

20 Plecanatide Phase 2b IBS-C Trial: Secondary Endpoint Stool Consistency Bristol Stool Form Scale Score Placebo 0.3 mg 1.0 mg 3.0 mg 9.0 mg r/o Treatment week = p<0.05; = p < 0.01; = p < Note: mitt population Credit Suisse Healthcare Conference 20

21 % Responder Plecanatide Phase 2b IBS-C Trial: Secondary Endpoint - Abdominal Pain Responder Abdominal Pain Responder= 30% reduction in pain in 9 out of 12 treatment weeks (75%) % 27.4% 32.5% 38.4% 40.0% Placebo n= mg n= mg n= mg n= mg n=85 = p < 0.05 Note: mitt population Credit Suisse Healthcare Conference 21

22 Plecanatide Phase 2b IBS-C Trial: Secondary Endpoint- Overall Responder (FDA Endpoint) % Responder Overall Responder= fulfills both 30% reduction in worst abdominal pain and Increase of 1 CSBMs from baseline in the same week for at least 50% of the weeks (6/12 weeks) = p < 0.05 Note: mitt population 24.7% Placebo n= % 0.3 mg n= % 1.0 mg n= % 3.0 mg n=86 40% 9.0 mg n=85 Credit Suisse Healthcare Conference 22

23 % Responder Plecanatide Phase 2b IBS-C Trial: Ability to Relieve IBS-C Symptoms How would you rate the ability of your study drug treatment to provide relief from your IBS-C symptoms? Responder= Patient s response is considerable or completely improved Week 2 Week 4 Week 8 Week 12 Placebo 0.3 mg 1.0 mg 3.0 mg 9.0 mg = p< 0.05; = p 0.01; = p Note: mitt Population Credit Suisse Healthcare Conference 23

24 Plecanatide Phase 2b IBS-C Trial: Summary of Adverse Events (AEs) Placebo n= mg n= mg n= mg n= mg n= 85 Treatment-emergent adverse events (TEAEs) 30 (34.9%) 37 (43.5%) 41 (48.2%) 37 (43.0%) 40 (47.1%) Serious AEs 0 1 (1.2%) 0 1 (1.2%) 2 (2.4%) Mild Diarrhea (5.9%) 3 (3.5%) 2 (2.4%) Moderate Diarrhea 0 1 (1.2%) 2 (2.4%) 5 (5.8%) 5 (5.9%) Severe Diarrhea 0 2 (2.4%) 1(1.2%) 0 3 (3.5%) All Diarrhea TEAEs 0 3 (3.5%) 8 (9.4%) 8 (9.3%) 10 (11.8%) Discontinued due to any TEAE 1 (1.2%) 1 (1.2%) 5 (5.9%) 7 (8.1%) 6(7.1%) Discontinued due to Diarrhea (1.2%) 5 (5.8%) 3 (3.5%) No signals in vital signs, hematology, serum chemistries, urinalysis or ECG Credit Suisse Healthcare Conference 24

25 % Diarrhea Plecanatide: Consistent Tolerability Profile for CIC & IBS-C % Diarrhea CIC Phase 2b Trial IBS-C Phase 2b Trial % 9.7% % 9.3% 11.8% 5 1.3% 5.5% 5 3.5% 0 Placebo n= mg n= mg n= mg n=237 0 Placebo n= mg n= mg n= mg n=86 9 mg n=85 Note: This is a cross trial comparison. Plecanatide phase 2b CIC trial did not include 9.0 mg dose. Credit Suisse Healthcare Conference 25

26 Plecanatide Pivotal Phase 3 IBS-C Trials: Program Overview Aim: Two, randomized, 12-week, double-blind, placebo-controlled studies to confirm the safety and efficacy of plecanatide in IBS-C patients Treatment Groups: 3.0 and 6.0 mg oral tablet plecanatide or placebo once-daily Estimated Enrollment: 1,050 IBS-C patients per trial (Rome III Criteria) Primary Endpoint: Design: Overall Responder endpoint Screening up to 6 weeks Baseline 2 weeks Treatment 12 weeks Post-Tx 2 weeks Credit Suisse Healthcare Conference 26

27 Plecanatide IBS-C Registration Program: Anticipated Events & Timelines 4Q H H H H Start Registration Trial 1 Start Registration Trial 2 Top-line Data (Trial 1) Top-line Data (Trial 2) IBS-C NDA Filing Plecanatide FDA approval for IBS-C IBS-C Open Label Studies Credit Suisse Healthcare Conference 27

28 SP-333 Clinical Program

29 SP-333: Superior Stability Expands the Potential Next-Generation Uroguanylin Analog Uroguanylin SP-333 NDDCELCVNVACTGCL dndecelcvnvactgcdl Resistant to proteolysis in simulated intestinal fluid Highly potent and stable peptide Activity mimics natural physiology (ph-regulated) Essentially non-systemic Once-daily oral tablet Single letters denote different amino acids. Colored lines denote disulfide bonds. Credit Suisse Healthcare Conference 29

30 SP-333 Phase 2 OIC Trial: Study Overview Aim: Assess the safety and efficacy of SP-333 in OIC patients receiving chronic opioid therapy for 3 months Treatment Groups: 1.0, 3.0 and 6.0 mg SP-333 vs. placebo once-daily Estimated Enrollment: 260 OIC patients Treatment Duration: 4 weeks Primary Endpoint: Mean change from baseline in the number of SBMs during week 4 of the Treatment Period Top-line data expected in the fourth quarter of this year Credit Suisse Healthcare Conference 30

31 Corporate Summary

32 SP-333 Plecanatide Anticipated Milestones Phase 2b/3 Positive Top-line Data CIC EOP2 Meeting CIC Phase 3 Pivotal Program Top-line Data US NDA Filing Phase 2b Trial Positive Top-line Data IBS-C EOP2 Meeting IBS-C Phase 3 Pivotal Program US NDA Filing OIC UC Completed SAD/MAD Phase 1 Trials Phase 2 Trial Top-line Data Proof of Concept Study Credit Suisse Healthcare Conference 32

33 Financial Summary Nov. 3, 2014: Synergy successfully completed $200 million private offering Company is now fully funded to drive plecanatide pivotal phase 3 development in CIC and IBS-C through to NDA filing Credit Suisse Healthcare Conference 33

34 Our Team: GI Expertise & Proven Track Record of Execution Gary Jacob, Ph.D. Chairman & CEO Kunwar Shailubhai, PhD Chief Scientific Officer Over 25 years of experience in pharma and biotech across multiple disciplines, including: R & D, operations and business development Major discoverer of Plecanatide and SP-333 for GI indications Over 20 years experience at G.D. Searle/Monsanto Co. and NIH Patrick Griffin, MD Chief Medical Officer Laura Barrow, PharmD SVP, Clinical Operations Board-certified, internal medicine and gastroenterology Over 25 years of experience; Sanofi-Aventis, Forest Laboratories, Private practice Over 25 years experience in clinical development Hoffmann La-Roche, Bristol-Myers Squibb, Pfizer Paul Eng, PhD SVP, Drug Development Marino Garcia SVP, Corporate Development Bernard Denoyer, CPA SVP, Finance Former Director of GI Clinical Development, Forest Laboratories Successfully led CIC/IBS-C phase 3 trials to NDA and drug approval Former VP of Global BD, Aptalis Pharmaceuticals Aspreva Pharmaceuticals, Eli Lily, Schering Plough, Pfizer Former CFO of META Group Inc. SVP, Finance and Secretary, Callisto Pharmaceuticals Credit Suisse Healthcare Conference 34