UBS 2016 Health Care Conference May 24, 2016

Transcription

1 Leading the Microbiome Revolution UBS 2016 Health Care Conference May 24, 2016

2 Forward Looking Statements Some of the statements in this presentation constitute forward looking statements under the Private Securities Litigation Reform Act of Such statements are subject to factors, risks and uncertainties (such as those detailed in the Company s periodic filings with the SEC) that may cause actual results to differ materially from those expressed or implied by such forward looking statements. 2

3 Investment Highlights 1 Leading Microbiome Therapeutics Company Clinically demonstrated approach for treating disease by restoring a dysbiotic (unhealthy) microbiome to a healthy state Integrated discovery and manufacturing platform 2 C. Difficile Franchise; Positive Phase 1b/2 results for lead candidate SER-109 Potential first-in-field indication for recurrent C. difficile infection (CDI) Ph1b/2 study results: 97% clinical cure rate; 87% achieving efficacy endpoint per protocol; no drug-related SAEs Granted Breakthrough Therapy Status & Orphan Designation by FDA 3 Expanding Pipeline Encompassing Inflammatory, Metabolic, and Infectious Diseases SER-287 for Ulcerative Colitis: Phase 1b study initiated SER-262 expected to enter clinic in mid-2016 for Primary CDI Additional pre-clinical programs in IBD, metabolic and infectious diseases 4 Strong Financial and Strategic Position Strong cash position Strategic collaboration with Nestlé Health Science for CDI and IBD assets for ex-us / Canadian markets Founded by VentureLabs, innovation foundry of Flagship Ventures 3

4 Ecobiotic Drugs Potential New Frontier in Medicine Microbiome s Impact on Health Ecobiotic Drugs Microbiome maintains normal function Pathogen resistance Immune system function Energy metabolism Dysbiotic microbiome linked to multiple diseases Infectious diseases (e.g., C. difficile) Inflammatory and Immune diseases (e.g. Ulcerative Colitis & Crohn s) Metabolic diseases (e.g. Diabetes, Obesity & NASH) Novel treatment paradigm bacteria as therapy Restore dysbiotic microbiome to healthy state Consortia of microbes designed to deliver targeted functions Oral drugs No current approved microbiome therapeutics 4

5 Business Strategy Prioritizes Indications with Strongest Clinical Data and Scientific Rationale Pipeline Growth Recurrent C. Diff. Infection (SER-109 *, Ph2 ongoing) Ulcerative Colitis (SER-287 *, Ph1b ongoing) Primary C. Diff. Infection (SER-262*) Infection & GVHD after allo-hsct (SER-155) Liver Diseases (NASH) Crohn s Disease * Metabolism: Diabetes and Obesity Rare Metabolic Diseases Immunooncology Process Evolution Biologically sourced (SER-109; SER-287) Synthetic fermented (SER-262; SER-301; SER-155) Today Future 5

6 Collaboration with Nestlé Health Science Nestlé Health Science global reach and GI market focus to support worldwide development and commercialization Licensing rights for Seres C. difficile and inflammatory bowel disease assets for markets outside the US / Canada $120M upfront, additional $30M of milestones expected in 2016 Potential for over $1.9B in development & commercial milestones. Tiered royalties on sales ranging from high single digits percentages up to the high teens for all products. Additional resources to support R&D efforts in new indications Seres maintains global rights for all product candidates outside CDI and IBD Collaboration announced January 11,

7 Robust Microbiome Therapeutics Pipeline SER-109 Recurrent C. difficile Discovery Preclinical Phase I Phase II Phase III Study enrollment complete SER-262 Designed Ecobiotic for Primary C. difficile SER-287 IBD (Ulcerative Colitis) SER-155 Drug resistant bacteria HSCT GvHD + Bacteremia SER-301 Designed Ecobiotic IBD Metabolic Diseases (Liver disease and noninsulin dependent Type 2 Diabetes) 7

8 Clostridium difficile is the #1 Hospital Acquired Infection in U.S. Standard Antibiotic Treatments Have High Recurrence in C. diff Primary infection (~ k patients) After antibiotic treatment: ~25% No response to certain antibiotics: 8% First relapse/retx (~ k) Second relapse/retx (~85-110k) Third relapse/retx (~50-65k) Recurrence ~40% 60% CDC Designated Urgent Threat C. difficile disease is an inflammatory infection of the colon which occurs after gut microbes are killed by broad spectrum antibiotic use Most common nosocomial infection in U.S.; ~29,000 deaths annually (Lessa et al NEJM) Growing burden: increased from 4.5 to 8.2 per 1000 patients discharged from 2001 to 2010 (Reveles 2014) Economic burden of as much as $4.8B in U.S. acute-care facilities(dubberke 2012) Cost per episode: primary CDI ~$5K, recurrent CDI ~$18K (Ghantoji 2010) Breaking the recurrence cycle can result in over $50K per patient savings 8

9 SER-109 : Ecobiotic Drug Candidate with Rapid, Capital Efficient Development Path Seres most advanced product candidate focused on Recurrent C. difficile Disruptive potential therapy that treats the root cause of the disease Oral, single dose drug candidate: Rationally designed Delivers bacteria in spore form to recolonize the gut Rapid, capital efficient development path Pre-clinical toxicology / carcinogenicity not required Phase 1A study not required, no PK to measure Dose-ranging studies not required Drug : Drug interaction studies not required as no systemic bioavailability Granted Breakthrough Therapy Status & Orphan Designation by FDA 9

10 Phase 1b/2 Study Overview Objective: Determine whether SER-109 can prevent CDI recurrence Leading Clinical Centers: Massachusetts General Hospital, Boston Mayo Clinic, Rochester Miriam Hospital, Providence Emory Medical School, Atlanta Patient Population: 3 episodes of CDI in 12 months Primary Efficacy: Absence of CDI through 8 weeks post treatment Safety: Assessed over 24 weeks post treatment Dose Cohorts: Cohort 1: Mean dose of 1.7 x 10 9 spores (range 3 x 10 7 to 2 x ) Cohort 2: Fixed dose of 1.0 x 10 8 spores 10

11 Positive SER-109 Phase 1b/2 Results 29/30 subjects (97%) were CDI free 8 weeks after treatment 87% of patients achieved efficacy endpoint per protocol 3 patients with transient diarrhea and positive C. difficile test; none required antibiotics; all went 8 weeks without CDI C. difficile carriage at 8 weeks: 24/27 (89%) were C. difficile negative by PCR or toxin assay Safety: AEs consistent with post-antibiotic recovery from CDI No drug-related serious adverse events Approximately 90% long-term efficacy post 8 week time point Khanna et al, Journal of Infectious Disease

12 SER-109 Phase 2 Study: Target Enrollment Complete, Results Expected in Mid-2016 Study design: Randomized, double-blind, placebo-controlled parallel group study with 2:1 randomization (SER-109 vs. Placebo) 89 patients at ~40 U.S. sites Patients will complete standard course of antibiotic therapy, and then take single dose of SER-109 (1x10 8 spores) on Day 1 Primary Efficacy endpoint: Absence of recurrent CDI in 8-week period following treatment Recurrence defined as diarrhea ( 3 unformed stools/day for 2 days) with positive C. difficile test requiring antibiotic treatment Open label extension study for patients who recur in Phase 2 study to provide active treatment and expand safety database Phase 2 study: Enrollment complete, results expected in mid-2016 Phase 3 study expected to begin by end of

13 Favorable SER-109 Profile Verses Potential Competitors Modality Fecal Transplant Antibiotics Antibodies Vaccines Characteristics Invasive procedures (colonoscopy or NGtube) with risk of adverse events Potential for transmission of human pathogens 60% relapse of recurrent CDI Causes and perpetuate dysbiosis underlying CDI susceptibility Suppress toxins to ameliorate symptoms Do not address microbiome dysbiosis, the root cause of disease IV infusion, high COGs Unproven efficacy until Phase 3 is complete Complex marketing effort to identify and vaccinate elderly at-risk groups SER-109 Highly efficacious Rapid, durable repair of dysbiosis Favorable safety Single oral dose 13

14 SER-262: Designed Synthetic Fermented Product Candidate for Primary C. difficile Potent efficacy demonstrated in C. difficile murine model SER-109 SER-262 C. diff * Expect SER-262 Phase 1b initiation in mid

15 SER-109 and SER-262: An Opportunity for Clostridium difficile SER-109 Recurrent CDI SER-262 Primary CDI Approximately K patients in U.S. Approximately K patients in U.S. Fast-to-Market, Potential First-in-Field Potential Best-in-Class Designed Ecobiotic C. difficile Cost Burden of $4.8 Billion in U.S. Alone Dubberke & Olsen,

16 SER-287 Phase 1b Study in Ulcerative Colitis SER-287 Overview Diverse spore ecology derived from healthy donors Repeat administration provides chronic ecological pressure to correct microbiome dysbiosis Therapeutic Rationale Multiple repeat-dose placebo-controlled FMT studies show significant clinical response 1 Preclinical studies in multiple animal models of colitis provide evidence that administration results in reduced pathology Formulation Proprietary methods to enable repeat dosing Development Phase 1b study initiated in December 2015 Results expected in Moayyedi, P, et al., Gastroenterology. 2015; Rossen, N, et al., Gastroenterology 2015; Kump P. et al., United European Gastroenterology Week,

17 SER-287 Phase 1b Will Provide Insight into Efficacy and Mechanism in UC Patients Arm A (n=15): Placebo pre-treatment / Once weekly dosing for 8 weeks Primary Objective Change in composition of intestinal microbiome at 8 weeks 55 mildmoderate UC patients failing standard-ofcare Arm B (n=10): Placebo pre-treatment / Once daily placebo for 8 weeks Arm C (n=15): Vancomycin pre-treatment / Once daily dosing for 8 weeks Arm D (n=15): Vancomycin pre-treatment / Once weekly dosing for 8 weeks Safety and tolerability Secondary Objectives Clinical responses, including complete remission, and endoscopic improvement Change in serum and fecal biomarkers Complement of microbiome metabolic pathways from stool, urine and blood Immunological and pathologic changes in mucosal biopsies 17

18 SER-155: To Reduce Hematopoietic Stem Cell Transplantation-Associated Mortality SER-155 Overview Designed Ecobiotic drug candidate for prevention of allogeneic HSCT associated infection and Graft vs. Host Disease (GvHD) Microbiome Profile Correlates with GvHD Mortality Risk 2 Prevention of HSCT Infection Supporting Data Prevention of GvHD Supporting Data Opportunity HSCT conditioning results in dysbiosis, and increased risk of bacteremia from gut pathogens SER-109 Phase 1b demonstrated significant reduction of carriage of Gram(-) and Gram(+) pathogens 1 Increased microbiome diversity may improve intestinal barrier function and modulate inflammatory tone GvHD mortality associated with immune dysregulation due to microbiome changes ~22,000 allo-hsct per year with high hospitalization and treatment cost (US and EU data) 1 Khanna et al, Journal of Infectious Disease Jenq, et al, Biology of Blood and Marrow Transplantation 2015, 3 Taur, et al., Blood Overall Survival Favors no GvHD related mortality HSCT Patient Microbiome Health Correlates with Overall Mortality Risk 3 Time (Years) Favors GvHD related mortality 67% 60% 36%

19 Broad Opportunities for Microbiome Therapies Disease Rare genetic disease (e.g., urea cycle disorders, hepatic encephalopathy) Non-Alcoholic Steatohepatitis (NASH) Immuno-oncology Therapeutics Supportive Publications Therapeutic Objective for Microbiome Modulation Reduce toxic ammonia in blood derived from bacterial urea metabolism Increase production of beneficial signaling molecules (i.e., secondary bile acids, short chain fatty acids) to reduce bacterial translocation, modulate liver inflammation, and normalize lipid metabolism in liver Improve clinical response to therapeutic checkpoint inhibitors Reduce anti-ctla4 induced colitis by providing microbial ecologies correlated with improved patient outcomes Urea cycle disorders: Shen et al., JCI, NASH: Le Roy et al., Hepatology, Immuno-oncology: Vetizou M et al., Science 2015.; Slvan A. et al., Science 2015.; Dubin et al., Nature, 2016.

20 Collaborations with Leading Microbiome Experts to Accelerate R&D Progress Target Indication Recent Academic Collaborations Immuno-oncology Therapeutics Hematopoietic Stem Cell Transplantation Rare genetic metabolic diseases (e.g., urea cycle disorders, hepatic encephalopathy) Inflammatory Bowel Disease Collaboration announcements: Memorial Sloan Kettering, University of Pennsylvania, see May 12, 2016 press releases; Medical University of Graz and Research Institute of St. Joseph s Hamilton, see May 4, 2016 press release. 20

21 Proprietary Drug Discovery and Development Platform Bedside-to-Bench-to-Bedside Clinical Trials & Cohort Studies Computational Discovery Screening Formulation & Manufacturing Discovery advanced by POC in humans Strong collaborations Proprietary computational design algorithms derive functional ecologies & prioritize targets & therapeutic hits Vast, proprietary strain library Disease targeted functional & efficacy screens Unique manufacturing know-how to translate microbial ecologies into drugs Fermenter titer [CFU/mL] Flask titer [CFU/mL] Seres Ecobiotic discovery pipeline leverages human data from the outset 21

22 SER-109: Novel Biologic Using Proven Approach Follow blood and tissue product paradigms for regulation Established purification process Established formulation process Conventional biologics cold chain Donor Collection Solvent Inactivation Spore Purification Drug Substance QC Formulation & Encapsulation Drug Product QC Labeling & Distribution Well-established inactivation and validation Paradigms Multi-component, high potency active is analogous to other biologics: IVIG, Premarin, Otosporin Highly stable drug product Live vaccine-like product Provide small, potent spore inoculum Single dose, using the human gut as bioreactor to amplify ~ K recurrent CDI U.S. patient base addressed by< 20 healthy donors 22

23 Clinical Manufacturing Processes for Designed Ecobiotic Drugs are Simple, Cost-effective, Robust Drug Substance Platform Process Master Cell Bank Clonal Characterized Production Fermentation Single strain cultures cgmp-acceptable media Single-use technology Platform format Cell (Spore) Harvest Robust, scalable Drug Substance Conventional storage format Drug Product Process Multiple Drug Substances Formulation Adjust composition Add excipients Capsule Filling Machine filling Capsule sealing Multi-strain Drug Product Liquid-filled capsule product Target shelf-stable 23

24 Broad IP Portfolio and Regulatory Exclusivity Bolster Market Potential 4 ISSUED PATENTS + LICENSED IP* Demonstrates rationally designed ecologies of spores and microbes are patentable Composition of matter and method claims Claims related to SER-109/CDI, colitis, & Crohn s lead candidates through PORTFOLIO Families of Applications 8 Nationalized 2 4 Pending PCT Pending Provisionals REGULATORY EXCLUSIVITY 12 years for new 10 years for new drug biological composition * Includes additional rights to intellectual property including a worldwide exclusive license to Memorial Sloan Kettering Cancer Center patent applications related to the use of bacterial compositions for treating HSCT patients and related areas. 24

25 Selected Achievements and Projected Upcoming Value-Driving Milestones Successful SER-109 Phase 1b/2 study results SER-109 breakthrough + orphan drug designations SER-109 Phase 2 study enrollment completed SER-287 Phase 1b ulcerative colitis study initiated NHS collaboration (CDI & IBD ex North America) Academic collaborations to drive R&D progress Recurrent CDI: SER-109 Phase 2 read-out Phase 3 initiation Primary CDI: SER-262 Phase 1b initiation Ulcerative Colitis: SER-287 Phase 1b read-out Advancing new pipeline programs (infectious, inflammatory and metabolic diseases) 1H H

26 Leading the Microbiome Revolution