Seres Therapeutics Overview
Eric Shaff, Chief Executive Officer
Oppenheimer Fall Healthcare Summit
September 23, 2020
Forward looking statements
Some of the statements in this presentation constitute "forward looking statements" under the Private Securities Litigation Reform Act of 1995, including, but not limited to, our development plans, the promise and potential impact of any of our microbiome therapeutics, the ability of our clinical trials to support approval, the timing of clinical studies, the timing and ultimate results of the SER-109 safety data, the size of the market for SER-109, the sufficiency of cash to fund operations, and the potential benefits of Seres' collaborations. Such statements are subject to important factors, risks and uncertainties, such as those discussed under the caption "Risk Factors" in the Company's Quarterly Report on Form 10-Q filed on July 28, 2020, and its other filings with the SEC, that may cause actual results to differ materially from those expressed or implied by such forward looking statements. Any forward looking statements included herein represent our views as of today only. We may update these statements, but we disclaim any obligation to do so.
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SER-109 Phase 3 success highlights that the time for microbiome therapeutics is now
Seres' mission: To transform the lives of patients worldwide with revolutionary microbiome therapeutics
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Seres is developing a novel drug modality that modulates the gut microbiome
Ecobiotic® microbiome therapeutics are encapsulated consortia of commensal bacteria with specific pharmacologic properties
Formulated for | Designed to |
oral delivery using | target inflammatory |
current Good | & immunological |
Manufacturing | disease pathways |
Practices (cGMP) | simultaneously |
Consortia capture | Mechanisms |
breadth of | includes microbial |
biological & | engraftment in GI |
functional diversity | tract to restructure |
the microbiome |
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Industry-leading,in-house research engine for drug discovery, development & manufacturing
Disease Target
Identification
Microbiome
Biomarker Discovery
Clinical sample
biorepository
Proprietary genomic
- metabolomic analytics
World-class
collaborations
Hit-to-Lead
Identification
Consortia Design
Broad strain library & culturing know-how
Genomic & host
function screening
In-silico drug design for functional targets
Lead Optimization
& Bioprocess
Pharmacological
Properties Validation
Ex vivo & in vivo disease modeling
Fermentation &
formulation optimization platforms
End-to-End GMP Manufacturing
Oral formulation
Donor-derived & multi-
strain fermentation
Anaerobic, spore &
lyophilized
technologies
Late clinical stage
drug release assays
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Broad opportunities for microbiome therapeutics
Infectious Disease
Preclinical | Phase 1b | Phase 2b | Phase 3 | Collaborators |
SER-109 | Recurrent C. difficile | Phase 3 | |
SER-155 | Infection, Bacteremia & GvHD in HSCT for cancer | ||
(Rationally-designed, fermented) | |||
Inflammatory
Oncology
SER-287 | Ulcerative colitis | |
SER-301 | Ulcerative colitis | |
(Rationally-designed, fermented) | ||
SER-401 | Metastatic melanoma | |
in combination with anti-PD-1 MAb | ||
Immuno- | Improve response to check-point therapies; potential | |
Oncology | synergies with AZ pipeline |
Phase 2b
Phase 1b
- Collaboration with Nestlé Health Science, announced Jan. 11, 2016, regarding C. difficile and IBD programs for markets outside of North America
- Collaboration with University of Texas MD Anderson Cancer Center and the Parker Institute for Cancer Immunotherapy, announced Nov. 14, 2017, regarding evaluation of microbiome therapies to improve the outcomes of cancer patients treated with immunotherapy. The Parker Institute is the IND application holder for SER-401.
- Collaboration with AstraZeneca, announced Mar. 11, 2019, regarding advancing mechanistic understanding of the microbiome in augmenting the efficacy of cancer immunotherapy, including potential synergy with AstraZeneca compounds.
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C. difficile Infection
Overview and SER-109 Phase 3 study
August 2020: Positive ECOSPOR III Phase 3 study read-out
- Multiply recurrent
C. difficile patients (n=182) - All subjects treated with standard of care antibiotics
SER-109 (n = 90) | ||||
Primary endpoint: | Safety | |||
C. diff. recurrence, | follow-up to | |||
at up to 8 weeks | 24 weeks |
Placebo (n = 92) | ||||
0 weeks | 8 weeks | 24 weeks |
Toxin testing to ensure | Substantially higher dose vs. | Placebo arm to provide | ||
inclusion of subjects with | Phase 2 designed to result in | invaluable safety and efficacy | ||
active rCDI, and for accuracy | greater and earlier microbiome | data that cannot be obtained in | ||
of endpoint | restoration | open-label trials | ||
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Topline SER-109 Phase 3 study efficacy results
Primary efficacy endpoint results:
SER-109 | Placebo | p-Value | ||
Time point | (N =90) | (N =92) | RR (95%CI) | |
(p1/p2) | ||||
n (%) | n (%) | |||
Week 8 | 10 (11.1) | 38 (41.3) | 0.27 (0.15, 0.51) | <0.001 / <0.001 |
- Sustained clinical response rate (i.e., percentage of patients who remain free of CDI at 8 weeks): SER-109 was effective in 88.9% of SER-109 subjects vs. 58.7% of subjects in the placebo arm.
- Results were statistically significant in both age stratified subgroups: 18-64 years old, or 65 and over
- Highly statistically significant 30.2% absolute reductionin the rate of CDI recurrence compared to placebo
- Number needed to treat = approximately 3
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Favorable safety profile observed in Phase 3
- SER-109was well tolerated, with no treatment-relatedserious adverse events (SAEs) observed in the active arm, and an adverse event profile similar to placebo
- Overall incidence of patients who experienced AEs during the eight-week study period was similar between SER-109and placebo arms
- Most commonly observed treatment-related AEs were flatulence, abdominal distention and abdominal pain, which were generally mild to moderate in nature, and these were observed at a similar rate in both the SER-109 and placebo arms
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Substantial recurrent C. difficile infection market opportunity
Infectious disease caused by toxin-producing bacteria, resulting in diarrhea, abdominal pain, fever and nausea
Leading cause of hospital-acquired infection in the U.S.
- ~ 453K cases of primary CDI within the U.S. each year
- ~ 170K episodes per year (100K episodes of first recurrence; ~ 73K episodes of 2+ recurrences)
- Estimated ~ $5B in healthcare burden each year
25% of primary C. difficile recur
Over 20,000 deaths per year
• Potential broad FDA label covering rCDI patients
11 Source: * Desai et al., Epidemiological and economic burden of Clostridium difficile in the United States: estimates from a modeling approach, BMC Infectious Diseases (2016) 16:303; Guh AY et al. NEJM 2020
FMT safety concerns highlight the need for improved, FDA-approved treatment options for C. difficile infection
• In contrast to FMT, SER-109 is comprised of a highly purified consortia of spore-based bacteria manufactured under GMP conditions to ensure product quality and consistency
• Unique manufacturing process to inactivate potential pathogens
• Process inactivates many emerging potential pathogens where diagnostic assays may not yet be widely available, such as SARS-CoV-2
Since July 2020, the largest U.S. provider of FMT has | |
12 | quarantined supply and halted shipments |
Amplifying efforts for market preparation and launch
Scaling Market Education
Efforts
Enhancing Understanding of Commercial Opportunity
Building Infrastructure to
Launch
- Medical communications strategy
- KOL mapping
- Develop and deploy payer value proposition
- Deeper patient journey analysis
- Pricing analysis
- Customer segmentation
- Identify options for go-to-market model
- Scale Medical Affairs organization and deploy MSL team
- Hire key commercial leadership roles
- Key external strategic partners on board
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SER-109: Investigational, spore-based therapeutic designed to break the cycle of recurrent C. difficile infection
SER-109
Oral formulation of Firmicute bacteria spores
Strong clinical & scientific data
- Dramatic reduction in CDI recurrence rate
- Spore-formingFirmicute bacteria prevent C. difficile germination and growth
Oral formulation
- Spores are resistant to gastric acid, facilitating oral delivery to gastrointestinal tract
Favorable safety profile
- Favorable tolerability & safety profile with no imbalance in adverse event
- Spore purification mitigates risk of transmission of known and unknown infectious agents
FDA regulatory designations
- Breakthrough designation
- Orphan drug status
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SER-287 and Ulcerative Colitis
Ulcerative colitis overview
Serious chronic condition characterized by inflammation of the colon and rectum resulting in abdominal pain, bowel urgency and diarrhea
Significant need for improved | |
therapies - Many drugs are | |
immunosuppressive, limiting use to | |
more severe patients | ~700K in the United States |
Only ~1/3 achieve remission |
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The dysbiotic microbiome may be a trigger of inflammation in ulcerative colitis
Gut Lumen
Gut Epithelium
Lamina Propria
Blood vessel
Microbiome
Steroids
Thiopurines / MTX
Anti-TNFs
JAK Inhibitors
Anti IL12/23
Anti-Integrins S1P1 Agonists
Microbiome therapeutics may drive therapeutic benefit
- May address drivers of inflammation, barrier integrity, innate immune activation, and adaptive immune education and cell trafficking
- Effector molecules may include short chain fatty acids, secondary bile acids, tryptophan metabolites, and TLR ligands
Microbial consortia can likely target multiple pathways simultaneously
Opportunity to develop both first-line and combination therapies
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Published study regarding microbiota transplantation provided clinical proof-of-concept in ulcerative colitis
30% | 27% | P= 0.027 | ||||
25% | ||||||
20% | ||||||
15% | ||||||
8% | ||||||
10% | ||||||
5% | ||||||
0% | ||||||
Steroid-free clinical remission and endoscopic remission or
response
Microbiota transplant | Placebo | ||
18Note: SER-287 was not involved in this study
SER-287 Phase 1b ulcerative colitis study
Placebo pre-treatment for 6 | Placebo once daily for 8 | (n=11) | ||
days | weeks | |||
Vancomycin pre-treatment | SER-287 once daily for 8 | (n=15) | ||
for 6 days | weeks | |||
58 mild-to- | ||||
moderate | WEEKLY | |||
ulcerative | ||||
colitis patients | Placebo pre-treatment for 6 | SER-287 once weekly for 8 | (n=15) | |
days | weeks | |||
Vancomycin pre-treatment | SER-287 once weekly for 8 | (n=17) | ||
for 6 days | weeks | |||
Primary
Objectives
- Safety and tolerability
- Change in composition of intestinal microbiome at 8 weeks
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Phase 1b study results - Statistically significant clinical remission improvement observed in Vanco/SER-287 daily treatment arm
% patients achieving remission
40%
30%
20%
10%
0%
40.0% | ||||||||||||||||
(6/15) | ||||||||||||||||
p = 0.0237 | ||||||||||||||||
17.7% | ||||||||||||||||
(3/17) | ||||||||||||||||
13.3% | ||||||||||||||||
(2/15) | ||||||||||||||||
0.0% | ||||||||||||||||
(0/11) | ||||||||||||||||
Placebo | Vancomycin | Placebo | Vancomycin | |||||||||||||
pretreatment / | pretreatment / | pretreatment / | pretreatment / | |||||||||||||
Placebo | SER-287 daily | SER-287 weekly | SER-287 weekly |
20 | Remission = Total Modified Mayo score ≤ 2 AND endoscopic subscore ≤ 1 |
Note: Missing data treated as failure; statistical significance not found in SER-287 weekly arms | |
Illustrative endoscopy improvement - Vanco/SER-287 daily treatment
Pre-treatment endoscopy showing
the sigmoid colon with spontaneousPost-treatmentday 64 endoscopy bleeding and ulceration
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SER-287 Phase 1b safety results show safety profile comparable to placebo
- SER-287daily arm demonstrated a similar safety profile to placebo
- No serious drug-related adverse events
- Reduced gastrointestinal adverse events provide an independent assessment of efficacy as the GI adverse events likely reflect ulcerative colitis disease activity
• SER-287 daily arm GI AEs: 2/15 (13.3%) vs. placebo arm: 5/11 (45.5%)
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Phase 1b study results - SER-287 bacteria engrafted in subjects and was durable to four weeks after dosing
Henn et al. (in review)
- Significant engraftment observed starting one week post-dosing
- Engraftment is significantly higher in arms with vancomycin pre-conditioning
- Engraftment in vancomycin arms is dose-dependent; significantly greater in daily dosing arm (arm with greatest efficacy)
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SER-287 Phase 1b study results published
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Ongoing SER-287ECO-RESET Phase 2b study in patients with mild-to-moderate active ulcerative colitis
10-week induction period | |||||||
Pbo | |||||||
pre- | Placebo | ||||||
treat | |||||||
Mild to moderate | 26-week | ||||||
Vanco | |||||||
UC patients with | exploratory | ||||||
pre- | SER-287 daily high dose | ||||||
active disease | maintenance | ||||||
treat | |||||||
N=201 | follow-up | ||||||
Vanco | SER-287 daily high dose | ||||||
pre- | |||||||
followed by step down dose | |||||||
treat | |||||||
Primary endpoint: | |||||||
Clinical remission |
- FDA Fast Track designation
- FDA feedback: Phase 2b study results, in conjunction with data from a second pivotal study, could support BLA submission
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Earlier stage development programs: SER-401,SER-301,SER-155
Immuno-oncology - Microbiome signature in melanoma patient responder to anti-PD-1
- SER-401composition driven by bacteria consistent with responder profile
- All spore formers that leverage deep Seres expertise in the biology and manufacturing of these organisms
27 Gopalakrishnan et al, Science 2017
Ongoing SER-401 Phase 1b study
Study Objectives
SER-401; biologically sourced
product to match microbiome Primary endpoint = safety and tolerability signature of anti-PD-1 responders
Patients with
(n=20)
All patients = CT scans with RECIST week 12
Secondary endpoints = engraftment,
response and correlative studies
Placebo (n=10)(immune correlates in blood and tumor, metabolites)
metastatic melanoma treated with anti-PD-1 (nivolumab)
Day -14 | Day -7 | Day 0 | Day +7 | Day +14 | Day +28 | Day +56 | Day +84 | |
SER-401 / Placebo | Daily dosing | |||||||
Biospecimens: | Blood | |||||||
Stool | ||||||||
Biopsy |
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Additional study arm may be added including fecal microbiota obtained from responders
SER-301:Next-generation, rationally designed fermented microbiome therapeutic candidate for ulcerative colitis
- Reduces induction of pro-inflammatory activity
- Improves epithelial barrier integrity & TNF-α driven inflammation in IECs
- Modulates UC-relevantanti-inflammatory, innate & adaptive immune pathways
- Activities to initiate clinical development ongoing
- Human Research Ethics Committee approval in Australia
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SER-155:Rationally-designed, fermented microbiome therapeutic candidate for infection, bacteremia & GvHD
- Decreases infection by antibiotic resistant bacteria in the gastrointestinal tract that lead to bacteremia
- Enhances epithelial barrier integrity to prevent bacterial translocation to the blood stream
- Modulates local and systemic immunomodulatory responses to decrease graft versus host disease
- Collaboration with:
Catalyzes changes in the microbiome & microbe-derived metabolites to prevent bacteremia
Antibiotic resistant pathogens can dominate the GI microbiome
Compromised epithelial layer with thin mucus layer
Basal
TLRs
- Lead candidate nominated
- U.S. regulatory submission preparation in process
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SER-109 success validates our microbiome therapeutic approach, presenting opportunity in multiple additional areas
- Deep understanding of the broad role of the microbiome in health:
- Resistance to pathogens
- Gut & systemic inflammation
- Innate & adaptive immunity
- Regulation of metabolism
- Novel drug discovery and development platform
- Option to pursue multiple diseases with high unmet need
Highly productive R&D engine
pursing multiple promising
potential opportunities
Infectious (e.g. Antibiotic resistant
infections)
Inflammatory (e.g. Crohn's, RA)
Oncology (e.g. tumor progression &
bacteremia)
Immune modulation & autoimmune
disease
Metabolic & Cardiovascular (e.g. NASH)
Neurologic & CNS disease
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Differentiated CMC capabilities producing rationally designed fermented products
Seres in-house GMP manufacturing and quality control capabilities
Cell banking & inoculum | Drug substance | Drug product | Quality control |
- Potential best-in-class clinical profile based on species specific properties
- Fermented approach enables efficient and highly scalable manufacturing process to serve large markets
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Broad IP portfolio and regulatory exclusivity
PATENT PORTFOLIO OF OWNED & LICENSED PATENTS AND APPLICATIONS*
- Have obtained issued patents in the US, demonstrating that rationally designed ecologies of spores and microbes are patentable
- Portfolio includes composition of matter and method claims, including option to license foundational IP from MD Anderson related to the use of bacteria in combination with checkpoint inhibitors. Portfolio also includes exclusive licenses to Memorial Sloan Kettering Cancer Center IP related to use of bacteria to treat gastrointestinal disorders and cancer relapse.
- Issued claims related to SER-109/C. difficile & SER-287 /ulcerative colitis lead candidates extend through 2033
- 13 Issued US Patents obtained
21 | Families of Applications | |
15 Nationalized
1 | Pending Provisionals | |
PROJECTED BIOSIMILAR REGULATORY EXCLUSIVITY
12 | years for new | 10 drugyears for new |
biological composition |
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Seres is well positioned to harness core microbiome capabilities advance pipeline
SER-109
SER-287
SER-401
SER-301
SER-155
Additional R&D opportunities
Positive ECOSPOR III Phase 3 study results expected to serve as single study to support BLA; Plan to meet with FDA to discuss filing
Ulcerative colitis - Phase 2b study ongoing
Metastatic melanoma - Phase 1b study ongoing
Rationally designed fermented composition;
Activities to initiate clinical development ongoing
Rationally designed fermented composition;
Plan to initiate development to prevent infections and GvHD
Multiple earlier stage programs under consideration as new development opportunities
Strong balance sheet, following August 2020 | |
34 | capital raise of $264 M |
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Seres Therapeutics Inc. published this content on 23 September 2020 and is solely responsible for the information contained therein. Distributed by Public, unedited and unaltered, on 23 September 2020 16:24:02 UTC