Seres Therapeutics : HC Wainwright Annual Global Investor Conference Presentation

Seres Therapeutics Overview

Eric Shaff, Chief Executive Officer

HC Wainwright Annual Global Investor Conference

September 16, 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 drug discovery, development & manufacturing platforms

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	Phase 2b
SER-301	Ulcerative colitis
(Rationally-designed, fermented)
SER-401	Metastatic melanoma	Phase 1b
in combination with anti-PD-1 MAb
Immuno-	Improve response to check-point therapies; potential
Oncology	synergies with AZ pipeline

1. Collaboration with Nestlé Health Science, announced Jan. 11, 2016, regarding C. difficile and IBD programs for markets outside of North America
2. 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.
3. 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

SER-109 (n = 90)

•	Multiply recurrent
		Primary endpoint:		Safety
	C. difficile patients (n=182)
			C. diff. recurrence,		follow-up to
•	All subjects treated with
		at up to 8 weeks		24 weeks
	standard of care antibiotics
				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.

1. ~ 453K cases of primary CDI within the U.S. each year

1. ~ 170K episodes per year (100K episodes of first recurrence; ~ 73K episodes of 2+ recurrences)

1. 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
• Preparations for commercialization are underway

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

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%				P= 0.027
27%
25%
20%
15%
							8%
10%
5%
0%
Steroid-free clinical remission and endoscopic remission or
				response
			Microbiota transplant		Placebo

16Note: 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
ulcerative		WEEKLY
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

40.0%

40%

(6/15)

30%

p = 0.0237

17.7%

20%

(3/17)

13.3%

(2/15)

10%

0.0%

0%

(0/11)

Placebo

Vancomycin

Placebo

Vancomycin

pretreatment /

pretreatment /

pretreatment /

pretreatment /

Placebo

SER-287 daily

SER-287 weekly

SER-287 weekly

18	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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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

• 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

24 Gopalakrishnan et al, Science 2017

Ongoing SER-401 Phase 1b study

SER-401; biologically sourced product to match microbiome signature of anti-PD-1 responders (n=20)

Placebo (n=10)

Patients with

metastatic melanoma treated with anti-PD-1 (nivolumab)

Day -14

Day -7

Day 0

SER-401 / Placebo

Biospecimens: Blood

Stool

Biopsy

Study Objectives

Primary endpoint = safety and tolerability

All patients = CT scans with RECIST week 12

Secondary endpoints = engraftment,

response and correlative studies

(immune correlates in blood and tumor,

metabolites)

Day +7

Day +14

Day +28

Day +56

Day +84

Daily dosing

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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

Catalyzes changes in the microbiome & microbe-derived metabolites to prevent

	to bacteremia
•	Enhances epithelial barrier integrity to prevent
	bacterial translocation
•	Modulates local
	immunomodulatory
	graft versus host disease
•	Collaboration with:

bacteremia

Basal

TLRs

Antibiotic resistant pathogens can dominate the GI microbiome

Compromised epithelial layer with thin mucus layer

• Lead candidate nominated
• U.S. regulatory submission 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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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 capital raise of $264 M

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