UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549
FORM
CURRENT REPORT
Pursuant to Section 13 or 15(d)
of the Securities Exchange Act of 1934
Date of Report (Date of earliest event reported):
(Exact name of Registrant as Specified in Its Charter)
| (State or other jurisdiction of incorporation) |
(Commission File Number) |
(IRS Employer Identification No.) |
| |
||
| (Address of principal executive offices) | (Zip Code) |
Registrant’s telephone number, including area code:
Not Applicable
(Former Name or Former Address, if Changed Since Last Report)
Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:
| Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425) |
| Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12) |
| Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b)) |
| Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c)) |
Securities registered pursuant to Section 12(b) of the Act:
| Title of each class |
Trading |
Name of each exchange on which registered | ||
Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§ 230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§ 240.12b-2 of this chapter).
Emerging growth company
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐
| Item 2.02. | Results of Operations and Financial Condition. |
On May 9, 2023, Seres Therapeutics, Inc. (the “Company”) announced its financial results for the quarter ended March 31, 2023 and provided operational updates. The full text of the press release issued in connection with the announcement is furnished as Exhibit 99.1 to this Current Report on Form 8-K (the “Current Report”).
The information in this Item 2.02 of this Current Report, including Exhibit 99.1 attached hereto, shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended (the “Securities Act”), or the Exchange Act, except as expressly set forth by specific reference in such filing.
| Item 7.01. | Regulation FD Disclosure. |
On May 9, 2023, the Company posted an updated corporate presentation in the “Investors and News” portion of its website at www.serestherapeutics.com. A copy of the slide presentation is attached as Exhibit 99.2 to this Current Report and incorporated herein by reference.
On May 9, 2023, the Company posted a slide presentation on the initial clinical data from the SER-155 Phase 1b open-label study cohort 1 in the “Investors and News” portion of its website at www.serestherapeutics.com. The Company also issued a press release in connection with the foregoing. A copy of the slide presentation and press release are attached as Exhibit 99.3 and Exhibit 99.4, respectively, to this Current Report and incorporated herein by reference.
The information in Item 7.01 of this Current Report, including Exhibit 99.2, Exhibit 99.3 and Exhibit 99.4 attached hereto, is intended to be furnished and shall not be deemed “filed” for purposes of Section 18 of Exchange Act, or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act or the Exchange Act, except as expressly set forth by specific reference in such filing. The Company undertakes no obligation to update, supplement or amend the materials attached hereto as Exhibit 99.2, Exhibit 99.3 and Exhibit 99.4.
| Item 9.01. | Financial Statements and Exhibits. |
(d) Exhibits
The following Exhibits 99.1 through 99.4 relate to Item 2.02 or Item 7.01 and shall be deemed to be furnished, and not filed:
| Exhibit No. |
Description | |
| 99.1 | Seres Therapeutics, Inc. Press Release issued May 9, 2023 | |
| 99.2 | Seres Therapeutics, Inc. Corporate Presentation as of May 2023 | |
| 99.3 | Seres Therapeutics, Inc. SER-155 Phase 1b Cohort 1 Study Results Slide Presentation as of May 2023 | |
| 99.4 | Seres Therapeutics, Inc. SER-155 Phase 1b Cohort 1 Study Results Press Release issued May 9, 2023 | |
| 104 | Cover Page Interactive Data File (embedded within the Inline XBRL document) | |
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
| SERES THERAPEUTICS, INC. | ||||||
| Date: May 9, 2023 | By: | /s/ Thomas J. DesRosier | ||||
| Name: | Thomas J. DesRosier | |||||
| Title: | Chief Legal Officer and Executive Vice President | |||||
Exhibit 99.1
Seres Therapeutics Reports First Quarter 2023 Financial Results and Provides Business Updates
– VOWSTTM microbiota-based therapeutic approved for prevention of recurrence of C. difficile infection in adults following antibacterial treatment for recurrent CDI; product availability expected in June –
– New SER-155 Phase 1b Cohort 1 clinical data show favorable tolerability, successful drug bacteria engraftment and a significant reduction in pathogen domination in the gastrointestinal microbiome; Cohort 2 data readout anticipated in mid-2024 –
– Strengthened balance sheet with up to $250 million debt facility with Oaktree, Seres received $110 million upon agreement closing; Seres to receive $125 million milestone payment from Nestlé Health Science related to VOWST approval –
– Conference call at 8:30 a.m. ET today –
CAMBRIDGE, Mass., May 9, 2023 — Seres Therapeutics, Inc. (Nasdaq: MCRB), a leading microbiome therapeutics company, today reported first quarter 2023 financial results and provided business updates.
“We were thrilled to recently announce the FDA approval of VOWST, the first and only FDA-approved orally administered microbiota-based therapeutic, and with the favorable label indication received from the FDA. Adult recurrent C. difficile infection patients who could benefit from using VOWST, per the label, can access it, including those with first recurrence. The approval of VOWST marks Seres’ transformation to a commercial organization and provides definitive validation of the promise of our microbiome technology platform,” said Eric Shaff, President and Chief Executive Officer at Seres. “We are looking forward to launching VOWST in the United States in June alongside our collaborator, Nestlé Health Science.
“We also continue to advance our earlier-stage pipeline, including SER-155, designed to prevent infections and/or graft-versus-host disease in patients undergoing allogeneic hematopoietic stem cell transplant, or allo-HSCT. We are also very pleased to report today new Phase 1b data from study Cohort 1 that support our therapeutic objective of reducing serious enteric infections, resulting bloodstream infections and GvHD. These encouraging initial data support the continued development in the ongoing placebo-controlled study Cohort 2.
“Finally, we have substantially strengthened our balance sheet and expect to further enhance our cash position with the receipt of a $125 million milestone payment from Nestlé based on the FDA approval.”
First Quarter and Recent Program and Corporate Updates
FDA Approval of VOWST: In April 2023, Seres and Nestlé Health Science announced the Food and Drug Administration (FDA) approval of VOWST (fecal microbiota spores, live-brpk), formerly called SER-109, an orally administered microbiota-based therapeutic to prevent recurrence of C. difficile Infection (CDI) in adults following antibacterial treatment for recurrent CDI (rCDI). VOWST is thought to facilitate restoration of the gut microbiome. The Company anticipates VOWST product availability and launch in June.
The FDA approval of VOWST was supported by a robust Phase 3 development program that included the ECOSPOR III and ECOSPOR IV studies. VOWST was previously granted Breakthrough Therapy and Orphan Drug Designations by the FDA.
ECOSPOR III was a multicenter, randomized, placebo-controlled study in individuals with rCDI, the results of which were published in the New England Journal of Medicine. The study’s primary objective was to demonstrate the reduction of CDI recurrence with VOWST. In ECOSPOR III, VOWST was shown to reduce CDI recurrence at eight weeks, with approximately 88% of individuals recurrence-free at eight weeks post-treatment, compared to 60% in participants who received placebo. In addition, at six months post-treatment, 79% of the VOWST group were demonstrated to be recurrence-free, compared to 53% in the placebo group. No treatment-related serious adverse events were observed in the active arm and the frequency of treatment-related adverse events was similar between the VOWST and placebo arms. The most common adverse reactions through eight weeks in VOWST treated participants versus placebo were solicited events of abdominal distention (31.1% VOWST versus 29.3% placebo), fatigue (22.2% VOWST versus 21.7% placebo), constipation (14.4% VOWST versus 10.9% placebo), chills (11.1% versus 7.6% placebo), and unsolicited event of diarrhea (10.0% versus 4.3% placebo).
ECOSPOR IV was an open-label, single arm study evaluating VOWST in 263 adult participants with rCDI. Study results were published in the JAMA Network Open. The ECOSPOR IV study results contributed to the VOWST safety database and supported product approval.
Seres and Nestlé Health Science are committed to helping appropriate patients who have been prescribed VOWST obtain access. Additional details about VOWST access programs will be available at launch. Please see vowst.com for further information.
In July 2021, Seres and Nestlé Health Science entered into an agreement to jointly commercialize VOWST in the U.S. and Canada. Nestlé Health Science is leveraging its global pharmaceutical business and assuming the role of lead commercialization party, including the utilization of its existing infrastructure, 150-person gastrointestinal sales force, payer access team and a recently hired 20-person hospital salesforce.
New SER-155 Phase 1b Cohort 1 Study Results: In a separate press release issued today, Seres announced new safety and pharmacology study data including:
| • | favorable tolerability profile observed, with no serious adverse events attributed to SER-155 administration; |
| • | bacteria in the SER-155 consortia engrafted into the gastrointestinal (GI) microbiome, with a magnitude and kinetics consistent with expectation from prior clinical results from other Seres microbiome therapeutics; and |
| • | cumulative incidence of domination with ESKAPE pathogen families was rare and observed at substantially lower incidence rates than observed in a reference population of allo-HSCT patients.1 |
SER-155 is an investigational, oral, 16 strain, cultivated microbiome therapeutic designed to prevent colonization and reduce the abundance of ESKAPE pathogens (e.g., from families such as Enterococcaceae, Enterobacteriaceae, Streptococcaceae, Staphylococcaceae) in the GI tract to reduce the risk of enteric driven bloodstream infections and other downstream consequences such as GvHD in patients receiving allo-HSCT. SER-155 has the potential to also impact antimicrobial resistance (AMR), including infections caused by carbapenem-resistant Enterobacteriaceae (CRE) and vancomycin-resistant Enterococci (VRE). The development of SER-155 is supported by SER-109 Phase 3 ECOSPOR III study exploratory results showing the decolonization of gut pathogens, including bacterial carrying antibiotic resistance genes, in the GI microbiome following SER-109 administration.
The ongoing SER-155 Phase 1b study includes two cohorts with Cohort 1 designed to assess safety and drug pharmacology, including the engraftment of drug bacteria in the gastrointestinal tract.
Enrollment of the Cohort 2 study is ongoing, incorporating a randomized, double-blinded placebo-controlled design to further evaluate safety and engraftment, as well as clinical outcomes, and will enroll approximately 60 subjects administered either SER-155 or placebo at a 1:1 ratio. The Company anticipates obtaining Cohort 2 study data in mid-2024.
Infection Protection research: The Company continues to conduct research to bring forward new microbiome therapeutics as a novel approach for Infection Protection for medically compromised individuals, including those with cancer neutropenia, cirrhosis or solid organ transplant. Preclinical studies are evaluating the potential to reduce the abundance of targeted pathogens to decrease the potential for pathogen transmission, strengthen epithelial barriers to further reduce translocation and the frequency of bloodstream infections, and to modulate immune responses to tackle medical complications such as graft-versus-host disease (GvHD). The Company plans to announce an additional Infection Protection clinical development program in 2023.
Ulcerative Colitis (UC) research: The Company previously reported clinical, microbiome and metabolomic data from the SER-287 Phase 2b study and the first cohort of its SER-301 Phase 1b study. Available data for these investigational microbiome therapeutics suggest that there may be an opportunity to utilize biomarker-based patient selection and stratification for future studies. Research activities remain ongoing to inform potential further development activities.
Financial Results
Seres reported a net loss of $71.2 million for the first quarter of 2023, as compared with a net loss of $56.6 million for the same period in 2022.
Research and development expenses for the first quarter of 2023 were $44.0 million, compared with $39.6 million for the same period in 2022. The research and development expenses were primarily related to Seres’ VOWST clinical development program and manufacturing costs, as well as personnel expenses. Included in the first quarter 2023 R&D expenses of $44 million is approximately $16 million of commercial manufacturing costs for VOWST. Following the approval of VOWST, R&D expenses in the P&L will no longer include VOWST commercial manufacturing costs, as these costs will be capitalized and recognized on Seres’ balance sheet.
General and administrative expenses for the first quarter of 2023 were $22.5 million, compared with $18.6 million for the same period in 2022. General and administrative expenses were primarily related to personnel expenses, professional fees, including VOWST commercial readiness and pre-launch expenses, and facility costs.
The Company has expanded its capabilities across the organization in support of VOWST approval and launch and is focused on driving operational efficiencies and pursuing opportunities to optimize its cost structure.
Seres ended the first quarter of 2023 with $106.5 million in cash, cash equivalents and investments as compared with $181.3 million at the end of 2022.
In April 2023, Seres announced that it had entered into a new $250 million senior secured debt facility provided by funds managed by Oaktree Capital Management, L.P. The Company drew the first tranche of $110 million at closing, with three additional tranches available. These additional tranches include $90 million that will be available in two tranches of $45 million each based upon the achievement of certain applicable VOWST sales targets, and an additional $50 million will be available to the Company at Oaktree’s discretion to support potential future business development activities. Of the $110 million advanced by Oaktree at closing, approximately $53 million retires outstanding debt, and after deducting fees and expenses, the net proceeds to the Company were approximately $50 million.
Seres is also due to receive a $125 million milestone payment from Nestlé Health Science associated with the FDA approval of VOWST. The Company also anticipates the receipt of proceeds from the supply of VOWST initial inventory to Nestlé.
Seres pro-forma cash balance as of March 31, 2023, is approximately $282 million, including the VOWST approval milestone and the net proceeds from its debt financing with Oaktree.
Conference Call Information
Seres’ management will host a conference call today, May 9, 2023, at 8:30 a.m. ET. To access the conference call, please dial 800-715-9871 (domestic) or 646-307-1963 (international) and reference Conference ID 5098595. To join the live webcast, please visit the “Investors and News” section of the Seres website at www.serestherapeutics.com.
A webcast replay will be available on the Seres website beginning approximately two hours after the event and will be archived for at least 21 days.
INDICATION AND IMPORTANT SAFETY INFORMATION FOR VOWST
INDICATION
VOWST is indicated to prevent the recurrence of Clostridioides difficile infection (CDI) in individuals 18 years of age and older following antibacterial treatment for recurrent CDI (rCDI).
Limitation of Use: VOWST is not indicated for treatment of CDI.
IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS
Transmissible infectious agents: Because VOWST is manufactured from human fecal matter, it may carry a risk of transmitting infectious agents. Report any infection that is suspected to have been transmitted by VOWST to Aimmune Therapeutics, Inc. at 1-833-246-2566.
Potential presence of food allergens: VOWST may contain food allergens. The potential to cause adverse reactions due to food allergens is unknown.
ADVERSE REACTIONS
The most common adverse reactions (reported in ≥5% of participants) were abdominal distension (31.1%), fatigue (22.2%), constipation (14.4%), chills (11.1%), and diarrhea (10.0%).
To report SUSPECTED ADVERSE REACTIONS, contact Aimmune Therapeutics at 1-833-AIM-2KNO (1-833-246-2566), or the FDA at 1-800-FDA-1088, or visit www.fda.gov/MedWatch.
DRUG INTERACTIONS
Do not administer antibacterials concurrently with VOWST.
Please see Full Prescribing Information and Patient Information
About Seres Therapeutics
Seres Therapeutics, Inc. (Nasdaq: MCRB) is a commercial-stage company developing novel microbiome therapeutics for serious diseases. Seres’ lead program, VOWSTTM, obtained U.S. FDA approval in April 2023 as the first orally administered microbiota-based therapeutic to prevent recurrence of C. difficile infection (CDI) in adults following antibacterial treatment for recurrent CDI and is being commercialized in collaboration with Nestlé Health Science. Seres is evaluating SER-155 in a Phase 1b study in patients receiving allogeneic hematopoietic stem cell transplantation to reduce incidences of gastrointestinal infections, bloodstream infections and graft-versus-host disease as well as additional preclinical stage programs targeting Infection Protection in medically compromised patients. The Company is also conducting research to inform further development of microbiome therapeutics for ulcerative colitis. For more information, please visit www.serestherapeutics.com.
About SER-155
SER-155 is a consortium of bacterial species selected using Seres’ reverse translation discovery and development platform technologies. The design incorporates microbiome biomarker data from human clinical data and nonclinical human cell-based assays and in vivo disease models. The SER-155 composition aims to decrease the colonization and abundance of bacterial pathogens that can harbor antibiotic resistance and to enhance epithelial barrier integrity in the GI tract to both reduce the likelihood of pathogen translocation and decrease the incidence of bloodstream infections. Further, SER-155 is designed to modulate host immune responses to decrease GvHD.
Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including the timing of commercial launch, the availability of VOWST, the commercial success of VOWST, the timing and results of clinical studies, the ability for microbiome therapeutics to modulate the microbiome and treat or prevent infection, our ability to achieve sales targets and the receipt of future milestones and debt tranches, and other statements which are not historical fact.
These forward-looking statements are based on management’s current expectations. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including, but not limited to, the following: we have incurred significant losses, are not currently profitable and may never become profitable; our need for additional funding; our limited operating history; the impact of the COVID-19 pandemic; our unproven approach to therapeutic intervention; our reliance on third parties and collaborators to conduct our clinical trials, manufacture our product candidates and develop and commercialize VOWST and any other product candidates, if approved; the unknown degree and competing factors of market acceptance for VOWST; the competition we will face; our ability to protect our intellectual property; and our ability to retain key personnel and to manage our growth. These and other important factors discussed under the caption “Risk Factors” in our Annual Report on Form 10-K filed with the Securities and Exchange Commission (SEC), on March 7, 2023, and our other reports filed with the SEC could cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. Any such forward-looking statements represent management’s estimates as of the date of this press release. While we may elect to update such forward-looking statements at some point in the future, we disclaim any obligation to do so, even if subsequent events cause our views to change. These forward-looking statements should not be relied upon as representing our views as of any date subsequent to the date of this press release.
SERES THERAPEUTICS, INC.
CONDENSED CONSOLIDATED BALANCE SHEETS
(unaudited, in thousands, except share and per share data)
| March 31, | December 31, | |||||||
| 2023 | 2022 | |||||||
| Assets |
||||||||
| Current assets: |
||||||||
| Cash and cash equivalents |
$ | 94,841 | $ | 163,030 | ||||
| Short term investments |
11,703 | 18,311 | ||||||
| Prepaid expenses and other current assets |
9,537 | 13,423 | ||||||
|
|
|
|
|
|||||
| Total current assets |
116,081 | 194,764 | ||||||
| Property and equipment, net |
24,306 | 22,985 | ||||||
| Operating lease assets |
108,914 | 110,984 | ||||||
| Restricted cash |
8,185 | 8,185 | ||||||
| Restricted investments |
1,401 | 1,401 | ||||||
| Other non-current assets |
11,307 | 10,465 | ||||||
|
|
|
|
|
|||||
| Total assets |
$ | 270,194 | $ | 348,784 | ||||
|
|
|
|
|
|||||
| Liabilities and Stockholders’ (Deficit) Equity |
||||||||
| Current liabilities: |
||||||||
| Accounts payable |
$ | 12,297 | $ | 17,440 | ||||
| Accrued expenses and other current liabilities (1) |
44,361 | 59,840 | ||||||
| Operating lease liabilities |
4,784 | 3,601 | ||||||
| Short term portion of note payable, net of discount |
— | 456 | ||||||
| Deferred revenue—related party |
2,376 | 4,259 | ||||||
|
|
|
|
|
|||||
| Total current liabilities |
63,818 | 85,596 | ||||||
| Long term portion of note payable, net of discount |
51,234 | 50,591 | ||||||
| Operating lease liabilities, net of current portion |
106,692 | 107,942 | ||||||
| Deferred revenue, net of current portion—related party |
94,835 | 92,430 | ||||||
| Other long-term liabilities |
1,486 | 1,442 | ||||||
|
|
|
|
|
|||||
| Total liabilities |
318,065 | 338,001 | ||||||
|
|
|
|
|
|||||
| Commitments and contingencies (Note 12) |
||||||||
| Stockholders’ (deficit) equity: |
||||||||
| Preferred stock, $0.001 par value; 10,000,000 shares authorized at March 31, 2023 and December 31, 2022; no shares issued and outstanding at March 31, 2023 and December 31, 2022 |
— | — | ||||||
| Common stock, $0.001 par value; 200,000,000 shares authorized at March 31, 2023 and December 31, 2022; 126,592,604 and 125,222,273 shares issued and outstanding at March 31, 2023 and December 31, 2022, respectively |
127 | 125 | ||||||
| Additional paid-in capital |
887,685 | 875,181 | ||||||
| Accumulated other comprehensive loss |
2 | (12 | ) | |||||
| Accumulated deficit |
(935,685 | ) | (864,511 | ) | ||||
|
|
|
|
|
|||||
| Total stockholders’ (deficit) equity |
(47,871 | ) | 10,783 | |||||
|
|
|
|
|
|||||
| Total liabilities and stockholders’ (deficit) equity |
$ | 270,194 | $ | 348,784 | ||||
|
|
|
|
|
|||||
| [1] | Includes related party amounts of $24,958 and $34,770 at March 31, 2023 and December 31, 2022, respectively |
SERES THERAPEUTICS, INC.
CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS AND COMPREHENSIVE LOSS
(unaudited, in thousands, except share and per share data)
| Three Months Ended March 31, |
||||||||
| 2023 | 2022 | |||||||
| Revenue: |
||||||||
| Collaboration revenue—related party |
$ | (522 | ) | $ | 1,493 | |||
|
|
|
|
|
|||||
| Total revenue |
(522 | ) | 1,493 | |||||
| Operating expenses: |
||||||||
| Research and development expenses |
43,969 | 39,649 | ||||||
| General and administrative expenses |
22,470 | 18,571 | ||||||
| Collaboration (profit) loss sharing—related party |
3,607 | (976 | ) | |||||
|
|
|
|
|
|||||
| Total operating expenses |
70,046 | 57,244 | ||||||
|
|
|
|
|
|||||
| Loss from operations |
(70,568 | ) | (55,751 | ) | ||||
|
|
|
|
|
|||||
| Other (expense) income: |
||||||||
| Interest income |
1,032 | 384 | ||||||
| Interest expense |
(1,948 | ) | (912 | ) | ||||
| Other income (expense) |
310 | (345 | ) | |||||
|
|
|
|
|
|||||
| Total other expense, net |
(606 | ) | (873 | ) | ||||
|
|
|
|
|
|||||
| Net loss |
$ | (71,174 | ) | $ | (56,624 | ) | ||
|
|
|
|
|
|||||
| Net loss per share attributable to common stockholders, basic and diluted |
$ | (0.57 | ) | $ | (0.61 | ) | ||
|
|
|
|
|
|||||
| Weighted average common shares outstanding, basic and diluted |
125,862,975 | 92,164,419 | ||||||
|
|
|
|
|
|||||
| Other comprehensive income (loss): |
||||||||
| Unrealized gain (loss) on investments, net of tax of $0 |
12 | (155 | ) | |||||
| Currency translation adjustment |
2 | — | ||||||
|
|
|
|
|
|||||
| Total other comprehensive income (loss) |
14 | (155 | ) | |||||
|
|
|
|
|
|||||
| Comprehensive loss |
$ | (71,160 | ) | $ | (56,779 | ) | ||
|
|
|
|
|
|||||
References:
| 1. | Peled, J, Gomes, A, Devlin, S, et al. (2020). Microbiota as Predictor of Mortality in Allogeneic Hematopoietic-Cell Transplantation. N Engl J Med. 382(9), 822–834. DOI: 10.1056/nejmoa1900623 |
IR and PR Contact:
Carlo Tanzi, Ph.D.
ctanzi@serestherapeutics.com
###
Seres Therapeutics Corporate Overview May 2023 Exhibit 99.2
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 timing of VOWST product availability; the anticipated supply and degree of market acceptance of VOWST; the potential for microbiome therapeutics to protect against infection; the timing of clinical development; our development opportunities and plans; the ultimate safety and efficacy data for our products; the sufficiency of cash to fund operations; the receipt of milestone payments and access to additional debt tranches; and other statements which are not historical fact. Such statements are subject to important factors, risks and uncertainties, such as those discussed under the caption "Risk Factors" in the Company’s Annual Report on Form 10-K filed on March 7, 2023, 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. Forward Looking Statements Seres Therapeutics, Inc. © 2023
VOWSTTM is the First FDA Approved Orally Administered Microbiota-Based Therapeutic VOWSTTM is indicated to prevent the recurrence of C. difficile infection (CDI) in individuals 18 years of age or older following antibacterial treatment for recurrent CDI (rCDI). Seres is pioneering a new modality, led by VOWSTTM Seres Therapeutics, Inc. © 2023
Seres Mission: Transforming the Lives of Patients Worldwide with Revolutionary Microbiome Therapeutics Encapsulated consortia of commensal bacteria designed to target multiple disease-relevant pathways simultaneously Bacterial Consortia Orally-formulated, using current Good Manufacturing Practices (cGMP) Disease susceptible baseline microbiome Engraftment of drug species Restructure microbiome composition Change in microbiome function Change in host function Bile acids Short-chain fatty acids Tryptophan metabolites Other Seres Therapeutics, Inc. © 2023
Strategic Priorities | Expanding Microbiome Therapeutic Leadership Successfully commercialize VOWSTTM, first-in-class oral microbiome therapeutic Maximize opportunities in Infection Protection Continue research to inform further development in ulcerative colitis and immune modulation FDA approved on April 26, 2023 to prevent the recurrence of C. difficile infection (CDI) in adults following antibacterial treatment for recurrent CDI (rCDI) Anticipated launch in June Co-commercialization agreement with Nestlé Health Science SER-155 Phase 1b study in allo-HSCT* patients for prevention of bacterial infections and acute GvHD* New SER-155 Phase 1b Cohort 1 Day 100 data support continued development Broad preclinical portfolio to prevent infection in medically compromised patients, including cancer neutropenia, cirrhosis and solid organ transplant Potential for biomarker-based patient selection in Ulcerative Colitis SER-155 GvHD results may further inform path forward in immune modulation * allo-HSCT: allogeneic hematopoietic stem cell transplant; GvHD: graft versus host disease SER-155 is an investigational microbiome therapeutic that has not been approved by any regulatory authority, including the U.S. Food and Drug Administration (FDA) 5 Seres Therapeutics, Inc. © 2023
Immunotherapy Collaborators INFECTION PROTECTION Preclinical Phase 1b Phase 2b FDA Approval SER-155 Bloodstream and antimicrobial-resistant bacterial infections & GvHD in allogenic hematopoietic stem cell transplant patients IMMUNE MODULATION SER-287 Ulcerative colitis4 SER-301 Ulcerative colitis4 Modulate host immunity/inflammation to improve response and tolerability of cancer treatments Programs targeting antimicrobial-resistant infections in medically compromised groups (e.g., cancer neutropenia, solid organ transplant) VOWST (fecal microbiota spores, live-brpk) Recurrent C. difficile 1,2 3 Oncology Research ongoing to determine future ulcerative colitis development plans 1 1 Collaboration with Nestlé Health Science, announced Jan. 11, 2016, regarding C. difficile and IBD programs for markets outside of North America. VOWST co-commercialization agreement for North America with Nestlé Health Science announced July 1, 2021 SER-155 preclinical work was supported in part by CARB-X Translational research activities are ongoing, informed by learnings from SER-287 Phase 2b and SER-301 Phase 1b study data, to evaluate the potential to utilize biomarker-based patient selection and stratification in future clinical development efforts Cohort 2 proceeding VOWST is the First Approval from Our Pipeline of Oral Microbiome Therapeutics Phase 3 Seres Therapeutics, Inc. © 2023
VOWSTTM and Recurrent C. difficile Infection Seres Therapeutics, Inc. © 2023
C. difficile Infections Are an Urgent Public Health Threat High probability of recurrence >20%, usually within 1-2 weeks after completion of antibiotic therapy Symptoms include colitis and severe, watery diarrhea with up to 15 bowel movements a day Spore-forming, toxin-producing, gram-positive, anaerobic bacteria Acute onset of severe symptoms leads to hospitalization for many patients Risk of recurrence escalates once a patient has an initial recurrence, which can trap patients in a vicious cycle 40-50% 20,000+ CDI deaths per year (U.S.) CLOSTRIDIOIDES DIFFICILE THREAT LEVEL URGENT ~156K Recurrent CDI cases estimated for 2023 (U.S.) 1. US CDC. Antibiotic Resistance Threats in the United States, 2019. US Department of Health and Human Services, CDC; 2019. doi:10.15620/cdc:82532 2. Feuerstadt P et al. J Med Econ. 2020;23(6):603-609. 3. Chilton CH et al. Clin Microbiol Infect. 2017;24(5):476-482. 4. Ofosu A. Ann Gastroenterol. 2016;29(2):147-154. 5. Cole SA, Stahl TJ. Clin Colon Rectal Surg. 2015;28(2):65-69. doi:10.1055/s-0035-1547333. 6. Wilcox MH et al. Open Forum Infect Dis. 2020;7(5):ofaa114. doi:10.1093/ofid/ofaa114 7. Centers for Disease Control and Prevention. Your risk of C. diff. Accessed January 28, 2022. https://www.cdc.gov/cdiff/risk.html 8. Jiang ZD et al. Aliment Pharmacol Ther. 2017;45(7):899-908.9. McFarland LV et al. Am J Gastroenterol. 2002;97(7):1769-1775, https://www.fda.gov/news-events/press-announcements/fda-approves-first-fecal-microbiota-product. Seres Therapeutics, Inc. © 2023
Time point VOWST (N =90) Placebo (N =92) Relative risk (95%CI) p-value (p1/p2) n (%) of recurrences n (%) of recurrences Week 8 11 (12.4) 37 (39.8) 0.32 (0.18-0.58) <0.001 / <0.001 TRIAL DESIGN VOWST ECOSPOR III Study Results Primary endpoint: C. diff. recurrence, at up to 8 weeks VOWST (n = 90) Multiply recurrent C. difficile patients (n=182) All subjects treated with standard of care antibiotics Placebo (n = 92) 0 weeks 8 weeks 24 weeks Safety follow-up to 24 weeks PRIMARY EFFICACY ENDPOINT RESULTS Note: Sustained clinical response % is calculated as 100% minus % with recurrence * Compared to 60% in the placebo arm Feuerstadt P et al. N Engl J Med. 2022;386(3):220-229. Approximately 88% Recurrence-free rate at 8 weeks* Seres Therapeutics, Inc. © 2023
VOWST Phase 3 Results Published in Premier Journals January 20, 2022 Extended Follow-up of Microbiome Therapeutic SER-109 Through 24 Weeks for Recurrent Clostridioides difficile infection in a Randomized Clinical Trial RESEARCH LETTER Survival Function for Time to Clostridioides difficile Infection Recurrence October 19, 2022 Recurrence of C. difficile Infection up to 8 Weeks (Intention-to-Treat Population). Seres Therapeutics, Inc. © 2023
ECOSPOR III Data: VOWST Was Well-Tolerated Adverse Events (AEs) Through 8 Weeks (Safety Population)2 SER-109 (n=90) n (%) Placebo (n=92) n (%) Any adverse event 84 (93) 84 (91) Adverse event related or possibly related to SER-109 or placebo 46 (51) 48 (52) Serious adverse event3 7 (8) 15 (16) Adverse event of special interest that occurred or worsened after initiation of SER-109 or placebo 1 (1) 1 (1) Serious adverse event or an adverse event of special interest that occurred or worsened after initiation of SER-109 or placebo and was related or possibly related to SER-109 or placebo 0 0 Serious adverse event leading to withdrawal from the trial 0 1 (1) Adverse event leading to death4 2 (2) 0 1. Feuerstadt P et al. N Engl J Med. 2022;386(3):220-229. 2. Adverse events were coded with the use of the Medical Dictionary for Regulatory Activities, version 20.0. Adverse events of special interest included invasive infections such as bacteremia, meningitis, and abscess. 3. Many of the serious adverse events were related to the primary endpoint of recurrent C. difficile infection, which was more common in the placebo group than in the SER-109 group. 4. Three deaths occurred in the SER-109 group, all of which were reported by the investigator as being unrelated to SER-109; 2 of the participants had onset of fatal adverse events within the 8-week period after dosing, but only 1 of these 2 participants died during that period. Seres Therapeutics, Inc. © 2023
ECOSPOR III Data: VOWST Was Well-Tolerated Adverse Events (AEs) Through 8 Weeks (Safety Population)2 SER-109 (n=90) % Placebo (n=92) % Solicited* Abdominal distension 31.1 29.3 Fatigue 22.2 21.7 Constipation 14.4 10.9 Chills 11.1 7.6 Unsolicited Diarrhea 10.0 4.3 Source: VOWST Package Insert * Solicited adverse events were recorded by participants in a diary for 7 days after completion of the 3-day regimen of VOWST or placebo. Participants were monitored for unsolicited events by queries during visits for a period of 8 weeks after the first dose of study drug. Seres Therapeutics, Inc. © 2023
ECOSPOR IV Data: VOWST Was Well-Tolerated * 4 VOWST participants discontinued ECOSPOR III and enrolled in ECOSPOR IV **TEAE: treatment-emergent adverse event; SAE: serious adverse event Sims et al. JAMA Netw Open. 2023 Feb 1;6(2):e2255758.; adverse reactions from Package Insert Seres Therapeutics, Inc. © 2023 Overall safety profile through 24-week follow-up showed that VOWST was well tolerated, consistent with the safety profile observed in ECOSPOR III Overall, 141 (53.6%) subjects experienced a total of 476 TEAEs** 33 (12.5%) subjects experienced a total of 77 SAEs; none were deemed related or possibly related to the study drug 8 deaths reported; none were deemed related or possibly related to study drug by investigators Most common adverse reactions included flatulence (4.2%), diarrhea (3.4%) and nausea (3.0%). The majority of adverse reactions were mild to moderate in severity ECOSPOR IV summary Phase 3, open-label, single-arm trial of 263* adults with history of CDI Purpose is to describe safety and tolerability of VOWST Completed to meet FDA predefined requirements for a BLA submission
ECOSPOR IV Study (n=263) Published in JAMA Network Open Open label design study to assess overall safety profile through 24-week follow up: SER-109 was well-tolerated, consistent with safety profile in ECOSPOR III, and extended the safety population Recurrence-free rate: 91% similar to 88% rate observed in ECOSPOR III Recurrence-free rate in patients with first recurrence: 94% Cohen S. et al., Journal of the American Medical Association, 2022. Results Extended ECOSPOR III Data and Supported FDA Approval Seres Therapeutics, Inc. © 2023
Full prescribing information available at vowst.com Highlights of Prescribing Information Indication statement VOWST is indicated to prevent the recurrence of Clostridioides difficile infection (CDI) in individuals 18 years of age and older following antibiotic treatment for recurrent CDI (rCDI) Limitations of use VOWST is not indicated for the treatment of CDI Dosing and administration Oral dosing (4 capsules once daily for 3 consecutive days following antibiotic treatment and laxative) Storage No refrigeration requirements Store in original packaging New Oral Treatment Option for Adults with rCDI Seres Therapeutics, Inc. © 2023
“ VOWST is Highly Anticipated by Healthcare Professionals Source: GI and ID survey (n=300), 2021 Dr. Carl Crawford, M.D. Assistant Professor of Clinical Medicine Division of Gastroenterology, Weill Cornell Medicine Recurrent C. difficile infection is a highly debilitating and life-threatening disease, and antibiotics alone do not address the underlying cause of rCDI, dysbiosis of the gut microbiome. The approval of VOWST provides an important new oral treatment option for this disease, and I am pleased to now be able offer this medicine to patients that have experienced a CDI recurrence. Definitely or probably will not Probably will Might or might not Definitely will of surveyed HCPs definitely or probably will prescribe VOWSTTM 22% 52% 25% 1% ~75% HCP Intent to Prescribe VOWSTTM ” Seres Therapeutics, Inc. © 2023
Prevention of recurrences is seen as a top treatment goal for rCDI patients Despite it being the top goal, physicians perceive standard of care as lacking efficacy at preventing recurrences As a result, preventing recurrences is also the biggest unmet need leading to heightened appetite for a product like VOWST HCP Enthusiasm for VOWST Driven by Desire to Prevent Recurrences and Limitations of Current Options 17 Top 5 rCDI Treatment Goals % Ranked in Top 3 Prevention of recurrences Prevention of morbidity / mortality Restoring patient QoL Symptom relief Restoration of gut microbiome Preventing subsequent recurrences Sustained efficacy / durability Restore gut microbiome More affordable Tx More rapidly address symptoms Top 5 Unmet Needs % Ranked in Top 3 59% 48% 40% 35% 25% 66% 57% 38% 34% 29% Source: Seres physician survey data (2022) Seres Therapeutics, Inc. © 2023
Expect HCP Use of VOWST to Broaden with Product Experience Source: Seres market research Seres Therapeutics, Inc. © 2023 Expected initial patient types The first patient I'd give it to would be somebody who probably has it from being on prolonged antibiotics, doesn't have a lot of other comorbid illness, and has just had enough of it so they're willing to try an alternative. – ID doctor This idea is what we're looking for. I guess this is the holy grail. You might want to hit everyone with this even at 1st recurrence. – ID doctor Young, Motivated High Risk Historical Recurrent ‘Healthy’ Multiply Recurrent FMT Patient Broadened use after experience Any appropriate rCDI patient
Combined Field Teams to Cover Highest Potential rCDI Prescribers Prioritize top volume and early adopting HCPs w/150 person GI sales force GI sales force covers 85% of GI practices for current inline Nestle product Average 10 years industry experience & 5 years in GI Drove ZENPEP® acceleration over last 3 years Prioritize ~300 top HCOs w/20-person hospital team Includes ID engagement; ~1500 ID specialists see > 2 rCDI patients/year Deployed Q1 ‘23; profiled top institutions Activate a broader HCP audience via non-personal and patient promotion All HCPs with recurring patients in Symphony Claims Data, May 2022 – Date Range Nov ‘20- Oct ’21 Seres Therapeutics, Inc. © 2023
Engaging with Key Commercial and Medicare Part D Plans to Initiate Broad Coverage * New To Market Block (NTMB) deny insurance coverage of a new therapy until it can be reviewed and covered by the health plan. Seres Therapeutics, Inc. © 2023 VOWST Launch Up to Launch + 12 months Payers utilize NTMBs* to limit demand Launch + 18 months Medicare coverage begins Launch + 12 months Medicaid coverage begins 54% Commercial 37% Medicare 6% Medicaid Payer mix Path to coverage for VOWST
*Subject to specific eligibility and financial criteria Sources: 1. Rodrigues et al Infect Control Hosp Epidemiol. 2017 Feb;38(2):196-202. ; inflation adjusted from $34K in 2016 dollars to 2023 dollars 2. Optum Burden of Illness data on file VOWST Delivers Compelling Value Proposition We Are Committed to Broad Patient Access 21 Seres Therapeutics, Inc. © 2023 Uniquely addresses #1 unmet need of preventing recurrence, with robust efficacy and an established safety profile with an orally administered regimen Innovative product; first and only FDA-approved orally administered microbiota-based therapeutic Addresses costly burden of rCDI: $43,000 cost / patient1 Commitment to patient access and affordability Providing financial and treatment support for eligible patients*
Laying the Foundations to Ultimately Transform Standard of Care and Achieve Potential Initial Focus Expanded Focus Increase HCP awareness and trial of an entirely new modality Provide positive experience Enhance hospital outflow Engage payers to build coverage Drive repeat use among higher-volume HCPs Increase reach to lower-volume HCPs Optimize payer coverage with a focus on commercial plans Seres Therapeutics, Inc. © 2023
Co-commercializing VOWST in the United States with 50/50 profit sharing per July 2021 agreement, extending our global strategic collaboration Seres Therapeutics, Inc. © 2023
Seres and Nestlé Health Science Have Full Suite of Resources and Complementary Capabilities to Support VOWSTTM Launch Market Access and Reimbursement Specialty Product Distribution Patient Support Services Medical Affairs Data and Insights Commercial Infrastructure Key Customer Relationships Seres Therapeutics, Inc. © 2023
Well Positioned to Supply Commercial Demand at Launch and Beyond VOWSTTM commercial supply Note: Seres and Bacthera collaboration press release issued Nov. 10, 2021 + 10+ years of Seres technology & facility investment for anaerobic bacterial therapeutics Joint venture between Chr. Hansen and Lonza with offices in Switzerland and Denmark Bacthera collaboration provides redundancy and expands upon existing commercial supply capacity Launch batches manufactured; anticipate Bacthera commercial drug production in 2024 for release in 2025, as the expected number of patients treated expands Seres Therapeutics, Inc. © 2023 Seres in-house GMP Manufacturing and Quality Control High-quality CMO support
SER-155 and Infection Protection Franchise Seres Therapeutics, Inc. © 2023
Antimicrobial Resistant Infections - Urgent Public Health Threat Limited innovation despite substantial and growing impact Declared “one of the world’s most urgent threats” $20 billion excess direct healthcare costs 35,000 deaths per year in US Major burden to society Many high-risk patient populations Allogeneic HSCT recipients at risk for bloodstream infections Additional patients with suppressed immune systems (e.g., transplant recipients, cancer patients) Patients with chronic diseases (e.g., cirrhosis) Seres Therapeutics, Inc. © 2023
SER-155 May Represent a Novel Solution to Reduce GI Pathogen Abundance and Infection & GvHD in Allogeneic HSCT Enrollment ongoing in SER-155 Phase 1b Cohort 2 a randomized, double-blind, placebo-controlled study Expect to release topline results in mid-2024 SER-155 is an oral, cultivated consortium, designed to reduce abundance of pathogens linked to infections and GvHD in allogeneic HSCT recipients* SER-155 Phase 1b study Cohort 1 SER-155 was well-tolerated through 100 Days post HSCT SER-155 bacterial strain engraftment was as expected GI pathogen domination was rare and transient in patients after SER-155 treatment compared to expected rates from prior cohort studies *Note: SER-155 is an investigational therapeutic and has not been approved by any regulatory authority, including the US Food & Drug Administration Seres Therapeutics, Inc. © 2023 Seres Therapeutics, Inc. © 2023
SER-155 Designed to Modulate Targets that Address Leading Causes of Mortality Following Allogeneic HSCT (allo-HSCT) Consortium of unique, human commensal bacterial strains Cultivated and encapsulated for oral delivery Strain selection based on broad pre-clinical screening for defined functions and insights from microbiome clinical data Preclinical data show SER-155 leads to multi-log reductions of Enterococcus (including VRE) and Enterobacteriaceae (including CRE) linked to GvHD in allo-HSCT patients* SER-155 is a 16 strain cultivated bacterial consortium optimized using MbTx Platform Allo-HSCT recipients are medically vulnerable; 50% 3 year mortality Organ failure 7-9% GVHD 19-23% Primary disease 46-60% Second Malignancy 1% Infection 17-21% * Seres data shared in Jan 2022 Infection Protection Investor Event; VRE = vancomycin-resistant Enterococci; CRE = carbapenem-resistant Enterobacterales; VRE and CRE both included in US CDC Antibiotic Resistance Threats ** CIBMTR 2020 SER-155 specifically designed to reduce infections and GvHD in allo-HSCT recipients Causes of allo-HSCT mortality at 1 year** Seres Therapeutics, Inc. © 2023 Seres Therapeutics, Inc. © 2023
ESKAPE pathogen domination* in SER-155 administered subjects observed at rates substantially lower than reference cohort ESKAPE Pathogen Domination was Rare and Transient in Cohort 1 SER-155 Cohort 1 From HSCT Day 0-30, 11% of patients (1 subject, Fig.1 blue line) From HSCT day 0-100, 22% of patients (2 subjects, not shown) All instances of pathogen domination were transient Reference Patient Cohort (MSKCC; Peled et al. 2020) Day 0 through 30, 64% of patients (Fig.1 black line) Pathogen domination has been shown to be associated with risk of blood stream infections (Taur, CID 2012) and GvHD (Jenq Bio BMT 2015; Stein-Thoeringer Science 2019) Cumulative Incidence HSCT Day Fig.1 Cumulative Domination Incidence Reference Cohort Incidence 64% (459 subjects) SER-155 Cohort-1 Incidence 11% (9 subjects) * i.e., the families: Enterococcaceae, Enterobacteriaceae, Streptococcaceae & Staphylococcaceae Seres Therapeutics, Inc. © 2023 Seres Therapeutics, Inc. © 2023
SER-155 Was Generally Well-Tolerated in Cohort 1 (Day 100 Data) TEAE: treatment-emergent adverse event; SAE: serious adverse event; AESI: adverse event of special interest; SUSAR: suspected unexpected serious adverse reaction TEAEs observed as expected in this patient population All subjects experienced at least 1 TEAE 1 TEAE resulted in study discontinuation (unrelated to SER-155 administration) GI disorders were most common, with diarrhea being the most common AE No SAEs were considered related to SER-155 No SUSARs observed Majority of SAEs and AESIs occurred during vulnerable time for patients (from HSCT to neutrophil recovery, start of SER-155 Course 2) Data Safety Monitoring Board approved advancement to Cohort 2 Data Safety Monitoring Board met at predefined points, including at Day 100 data cut for Cohort 1, to review all safety events No deaths prior to Day 100; 3 after Day 100, none considered related to drug Seres Therapeutics, Inc. © 2023 Seres Therapeutics, Inc. © 2023
SER-155 Could Become Core Part of Allogeneic HSCT Treatment Regimen Unique potential clinical and economic value for allogeneic HSCT patients Double benefit of reducing infections and GvHD, 2 of 3 leading causes of mortality at 1 year Avoids costs of post-transplant complications: $181K average additional costs for US patients with complications Sources: CIBMTR 2020; Passweg et al Bone Marrow Transplantation 57 (2022) 742-752; Perales et al Biol Blood Marrow Transplant 23 (2017) 1788–1794; Broder, et al. “The Cost of Hematopoietic Stem-Cell Transplantation in the United States” Am Health and Drug Benefits 10 (2017) 366–374; https://data.cms.gov/provider-summary-by-type-of-service/medicare-inpatient-hospitals/medicare-inpatient-hospitals-by-geography-and-service/data/2019; Seres physician interviews Favorable safety profile appropriate for use across HSCT population Substantial impact for patients: almost 30,000 transplants / year across US and Europe Seres Therapeutics, Inc. © 2023 Seres Therapeutics, Inc. © 2023
Seres’ Path Forward Seres Therapeutics, Inc. © 2023
VOWST rCDI SER-155 BSI & GvHD in allogeneic HSCT recipients Broad preclinical portfolio Driving to an additional clinical development program in 2023 Potentially 2+ additional programs within 3 years SER-155: Therapeutic adjacency to SER-109 Phase 1b study ongoing in cohort 2 Additional Opportunities Now Approved Active Clinical Development Pre-clinical Portfolio Autologous HSCT Cancer Neutropenia Solid Organ Transplant Cirrhosis Maximizing the Opportunity in Infection Protection Broadly Target Antimicrobial Resistant Infections Seres Therapeutics, Inc. © 2023
Seres is Well Positioned to Bring VOWST to Patients and Advance Our Pipeline $125 million milestone due to Seres with approval Secured up to $250 million debt facility; $110 million funded at closing Replaces existing debt facility * Net of payout to retire existing debt and fees 3/31/2023 cash balance: $107 million 3/31/2023 pro-forma cash balance: $282 million including $125 million VOWSTTM approval milestone and net proceeds* received at closing from Oaktree Seres Therapeutics, Inc. © 2023
SER-155 Phase 1b in Cohort 2 with successful engraftment and reduced pathogen domination in Cohort 1 Ongoing preclinical programs with potential to address large immunocompromised patient populations Well Positioned to Extend Microbiome Therapeutic Leadership in 2023 Opportunities in Infection Protection Continued research in UC and microbiome therapeutic platform Ongoing research to inform plans for continued development in UC Extend industry-leading microbiome therapeutic platform capabilities Potential SER-109 BLA approval and successful launch for rCDI VOWST approved April 26, 2023; product available in June Working closely with Nestlé to prepare for commercial launch Producing supply to support commercial demand $125M milestone payment from Nestlé due with FDA approval March 31, 2023 pro-forma* cash balance: $282 million * Including $125 million VOWST approval milestone and net proceeds received from Oaktree at closing of new debt facility Seres Therapeutics, Inc. © 2023
Continued Microbiome Therapeutic Leadership, Anticipated Compelling Growth and Value Creation Advancing opportunities in Infection Protection and other therapeutic areas VOWSTTM approved; commercialization underway in rCDI VOWSTTM transforming standard of care for a broad population of rCDI patients SER-155 in late-stage clinical development 2+ additional Infection Protection candidates in clinical development Extend industry-leading microbiome therapeutic platform 2023 2025 Seres Therapeutics, Inc. © 2023
SER-155 Phase 1b Cohort 1 Day 100 Data May 2023 Exhibit 99.3
SER-155 May Represent a Novel Solution to Reduce GI Pathogen Abundance and Infection & GvHD in Allogeneic HSCT Enrollment ongoing in SER-155 Phase 1b Cohort 2 a randomized, double-blind, placebo-controlled study Expect to release topline results in mid-2024 SER-155 is an oral, cultivated consortium, designed to reduce abundance of pathogens linked to infections and GvHD in allogeneic HSCT recipients* SER-155 Phase 1b study Cohort 1 SER-155 was well-tolerated through 100 Days post HSCT SER-155 bacterial strain engraftment was as expected GI pathogen domination was rare and transient in patients after SER-155 treatment compared to expected rates from prior cohort studies *Note: SER-155 is an investigational therapeutic and has not been approved by any regulatory authority, including the US Food & Drug Administration Seres Therapeutics, Inc. © 2023
Beneficial Bacteria Protect the GI Tract from Potential Microbial Pathogens A healthy, diverse microbiome is essential to preventing colonization and infection with pathogens Antibiotics and other insults can drive the loss of beneficial microbes, enabling pathogens and drug-resistant bacteria to rapidly expand and dominate in GI tract Domination with pathogens and drug-resistant bacteria in patients can increase intestinal permeability and is associated with increased risk of blood stream infections and other medical complications Antibiotics Microbiome Therapeutics Sources: Pamer, E., Science 2016; Kim et al, Nature, 2019; McGovern et al, CID 2020, Ubeda et al, J.Clin Invest 2010; Taur et al, Clin Infect Dis, 2012, Tamburini et al, Nat Med 2018 Seres Therapeutics, Inc. © 2023
Microbiome Therapeutics are a Potential Novel Approach to Address Infections, Antimicrobial Resistance, & Associated Complications Antibiotic resistant pathogens can dominate the GI microbiome Compromised epithelial layer Bacterial translocation/blood stream infections and GI inflammation Lamina propria Intestinal lumen Epithelial barrier Mucus layer Disrupted gastrointestinal microbiome has disease-relevant consequences Seres microbiome therapeutics MbTx Platform enables: Identification of microbial species and functional targets linked to disease-specific outcomes Identification of bacterial strains that engraft successfully and that modulate disease functional pathways Preclinical and SER-109 ECOSPOR III exploratory results demonstrate microbiome therapeutics may decolonize pathogens with the potential for clinical outcomes * Feuerstadt P NEJM 2022; 386:220-9; post hoc analysis of VOWST Phase 3 study data; presented at IDWEEK 2021 conference Seres Therapeutics, Inc. © 2023
SER-155 Designed to Modulate Targets that Address Leading Causes of Mortality Following Allogeneic HSCT (allo-HSCT) Consortium of unique, human commensal bacterial strains Cultivated and encapsulated for oral delivery Strain selection based on broad pre-clinical screening for defined functions and insights from microbiome clinical data Preclinical data show SER-155 leads to multi-log reductions of Enterococcus (including VRE) and Enterobacteriaceae (including CRE) linked to GvHD in allo-HSCT patients* SER-155 is a 16 strain cultivated bacterial consortium optimized using MbTx Platform Allo-HSCT recipients are medically vulnerable; 50% 3 year mortality Organ failure 7-9% GVHD 19-23% Primary disease 46-60% Second Malignancy 1% Infection 17-21% * Seres data shared in Jan 2022 Infection Protection Investor Event; VRE = vancomycin-resistant Enterococci; CRE = carbapenem-resistant Enterobacterales; VRE and CRE both included in US CDC Antibiotic Resistance Threats ** CIBMTR 2020 SER-155 specifically designed to reduce infections and GvHD in allo-HSCT recipients Causes of allo-HSCT mortality at 1 year** Seres Therapeutics, Inc. © 2023
SER-155 Phase 1b: Two-Cohort Study to Evaluate SER-155 in Allogeneic HSCT Patients Evaluate safety, tolerability of SER-155 dosed before and after allogeneic HSCT Evaluate the engraftment (PK) of SER-155 strains in the GI microbiome Assess the impact of SER-155 engraftment on gastrointestinal microbiome domination Continue to evaluate safety, tolerability, PK/PD Explore clinical outcomes of infection & GvHD and candidate biomarkers associated with clinical impact and mechanism Enrolling Day 100 data available Cohort 1 – open-label 15 patients Cohort 2 - randomized, double-blind, placebo-controlled ~60 patients Seres Therapeutics, Inc. © 2023
SER-155 Cohort 1 Enrollment Summary: Majority of Subjects Retained Post Transplant 15 enrolled 13 received study drug 11 received allogeneic stem cell transplant 10 reached Day 100 (*9 subjects with evaluable samples for PK/PD) 2 enrolled but untreated due to disease progression/withdrawal of consent (not SER-155 related) 2 discontinued prior to transplant due to disease progression/COVID (not SER-155 related) Pharmacology population* Safety Population HSCT Population Seres Therapeutics, Inc. © 2023
SER-155 Was Generally Well-Tolerated in Cohort 1 (Day 100 Data) TEAE: treatment-emergent adverse event; SAE: serious adverse event; AESI: adverse event of special interest; SUSAR: suspected unexpected serious adverse reaction TEAEs observed as expected in this patient population All subjects experienced at least 1 TEAE 1 TEAE resulted in study discontinuation (unrelated to SER-155 administration) GI disorders were most common, with diarrhea being the most common AE No SAEs were considered related to SER-155 No SUSARs observed Majority of SAEs and AESIs occurred during vulnerable time for patients (from HSCT to neutrophil recovery, start of SER-155 Course 2) Data Safety Monitoring Board approved advancement to Cohort 2 Data Safety Monitoring Board met at predefined points, including at Day 100 data cut for Cohort 1, to review all safety events No deaths prior to Day 100; 3 after Day 100, none considered related to drug Seres Therapeutics, Inc. © 2023
GI Microbiome Pathogen Domination as a Driver of Infection & GvHD in Allo-HSCT has been Reported in Peer-Reviewed Literature Seres ongoing 7-year partnership with Memorial Sloan Kettering Cancer Center (MSKCC) to elucidate role of microbiome in HSCT: Gastrointestinal (GI) microbiome domination, a state in which a single type of bacteria is unusually abundant, is a common occurrence in HSCT patients. Cumulative incidence of GI microbiome domination was observed in majority of subjects by Day 30 after HSCT* Similar rates were observed at 3 other centers Domination with ESKAPE pathogens was common Cumulative incidence of domination in HSCT patients * Peled et al, NEJM 2020; Seres-supported study Seres Therapeutics, Inc. © 2023
GI Microbiome Pathogen Domination is Associated with Worse Clinical Outcomes in Allo-HSCT Recipients * Taur et al, Clin Inf Dis 2012; extended in Tamburini et al Nat Med, 2018 ** Stein-Thoringer et al Science 2019; also supported by Jenq et al Bio BMT 2015 Dominated Not dominated Dominated Not dominated Domination increases bloodstream infection risk with the dominating bacteria* Enterococcus domination is a risk factor for acute GvHD and mortality** Seres Therapeutics, Inc. © 2023
ESKAPE pathogen domination* in SER-155 administered subjects observed at rates substantially lower than reference cohort ESKAPE Pathogen Domination was Rare and Transient in Cohort 1 SER-155 Cohort 1 From HSCT Day 0-30, 11% of patients (1 subject, Fig.1 blue line) From HSCT day 0-100, 22% of patients (2 subjects, not shown) All instances of pathogen domination were transient Reference Patient Cohort (MSKCC; Peled et al. 2020) Day 0 through 30, 64% of patients (Fig.1 black line) Pathogen domination has been shown to be associated with risk of blood stream infections (Taur, CID 2012) and GvHD (Jenq Bio BMT 2015; Stein-Thoeringer Science 2019) Cumulative Incidence HSCT Day Fig.1 Cumulative Domination Incidence Reference Cohort Incidence 64% (459 subjects) SER-155 Cohort-1 Incidence 11% (9 subjects) * i.e., the families: Enterococcaceae, Enterobacteriaceae, Streptococcaceae & Staphylococcaceae Seres Therapeutics, Inc. © 2023
SER-155 Bacterial Strains Engrafted in Cohort 1 Patients Engraftment magnitude and kinetics were consistent with our expectations Engraftment is the colonization of the GI tract by metabolically active drug product strains; assessed throughout the study period via proprietary genomic technologies. Most of the strains engrafted in a majority of the individuals evaluated. These engraftment data, as well as those that will come from Cohort 2, will be used to inform Phase 2 trial design. Seres Therapeutics, Inc. © 2023
SER-155 Phase 1b Cohort 2: What We Expect to Learn SER-155 safety, strain engraftment (PK) and pathogen abundance (PD) in the context of placebo comparator arm Further elucidate mechanism of action of SER-155 Explore impact of SER-155 on clinical outcomes, including the incidence of enteric infections, BSI, BSI with enteric bacteria, and GvHD, with contemporaneous placebo rates Broaden dosing experience in allo-HSCT patients to confirm optimal dosing strategy Cohort 2 topline data expected in mid-2024 Seres Therapeutics, Inc. © 2023
SER-155 Could Become Core Part of Allogeneic HSCT Treatment Regimen Unique potential clinical and economic value for allogeneic HSCT patients Double benefit of reducing infections and GvHD, 2 of 3 leading causes of mortality at 1 year Avoids costs of post-transplant complications: $181K average additional costs for US patients with complications Sources: CIBMTR 2020; Passweg et al Bone Marrow Transplantation 57 (2022) 742-752; Perales et al Biol Blood Marrow Transplant 23 (2017) 1788–1794; Broder, et al. “The Cost of Hematopoietic Stem-Cell Transplantation in the United States” Am Health and Drug Benefits 10 (2017) 366–374; https://data.cms.gov/provider-summary-by-type-of-service/medicare-inpatient-hospitals/medicare-inpatient-hospitals-by-geography-and-service/data/2019; Seres physician interviews Favorable safety profile appropriate for use across HSCT population Substantial impact for patients: almost 30,000 transplants / year across US and Europe Seres Therapeutics, Inc. © 2023
Exhibit 99.4
Seres Therapeutics Reports SER-155 Phase 1b Cohort 1 Results Showing Successful Drug Bacteria Engraftment and Substantial Reduction in Pathogen Domination in the Gastrointestinal Microbiome
– Tolerability profile observed supports continued development in Cohort 2, with no treatment attributed serious adverse events –
– Reduction in incidences of microbiome pathogen domination provides support for intended SER-155 clinical activity –
–SER-155 Phase 1b placebo-controlled Cohort 2 data readout anticipated in mid-2024 –
– Conference call at 8:30 a.m. ET today –
CAMBRIDGE, Mass., May 9, 2023 — Seres Therapeutics, Inc. (Nasdaq: MCRB), a leading microbiome therapeutics company, today reported initial clinical data about SER-155. SER-155 is an oral, cultivated bacterial consortia investigational therapeutic designed to prevent enteric-derived infections and resulting blood stream infections, as well as induce immune tolerance responses to reduce the incidence of graft-versus-host disease (GvHD) in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Gastrointestinal (GI) microbiome data from the first 100 days post HSCT in Cohort 1 of the SER-155 Phase 1b open-label study showed the successful engraftment of SER-155 bacterial strains and a substantial reduction in the cumulative incidence of pathogen domination, a biomarker associated with the risk of serious enteric infections and bloodstream infections, as well as GvHD. The tolerability profile observed was favorable, with no serious adverse events attributed to SER-155 administration. Enrollment in the placebo-controlled Cohort 2 portion of the study is ongoing and topline results are anticipated in mid-2024.
“We are pleased with these initial SER-155 Phase 1b study results from Cohort 1, which provide encouraging evidence to support our clinical objective of reducing enteric-derived infections, resulting bloodstream infections, and graft-versus-host disease in individuals undergoing allo-HSCT for cancers and other serious conditions,” said Lisa von Moltke, M.D., Chief Medical Officer at Seres. “The tolerability profile of SER-155 was favorable, with no serious adverse reactions associated with SER-155 administration. Enrollment in the placebo-controlled Cohort 2 study is proceeding, and we look forward to gaining further insights into the therapeutic potential of SER-155 to benefit this highly medically compromised patient population.”
SER-155 Phase 1b Study Design and Summary of Cohort 1 Results
SER-155 is an investigational, oral, 16 strain, cultivated microbiome therapeutic designed to prevent colonization and reduce the abundance of ESKAPE pathogens (e.g., from families such as Enterococcaceae, Enterobacteriaceae, Streptococcaceae, Staphylococcaceae) in the GI tract to reduce the risk of enteric driven bloodstream infections and other downstream consequences, such as GvHD, in patients receiving allo-HSCT. SER-155 has the potential to impact antimicrobial resistance (AMR), including infections caused by carbapenem-resistant Enterobacteriaceae (CRE) and vancomycin-resistant Enterococci (VRE).
The development of SER-155 is informed by preclinical data that showed that allo-HSCT patients across multiple study sites had disrupted microbiomes and were susceptible to pathogen overgrowth in the GI tract, as well as in vivo studies that demonstrated SER-155’s ability to significantly decolonize VRE and CRE, and further modulate epithelial barrier integrity and T cell biology or relevance to GvHD. Previously published exploratory results from the SER-109 ECOSPOR III Phase 3 study showed decolonization of gut pathogens, including bacteria that carry antibiotic resistance genes, providing clinical proof-of-concept for the SER-155 program.
The SER-155 Phase 1b study includes two cohorts, with Cohort 1 designed to assess safety and drug pharmacology, including the engraftment of drug bacteria in the gastrointestinal tract. Cohort 1 included 13 subjects who received any dosing of the SER-155 regimen, with 11 of these subjects subsequently receiving an allo-HSCT. Nine subjects had evaluable samples for microbiome data analyses. The average age in Cohort 1 was 60, and most subjects had acute myeloid leukemia, myelodysplastic syndrome or myeloproliferative neoplasia as their primary disease and received reduced-intensity conditioning pre-transplant. Most subjects received peripheral blood stem cells from a matched unrelated donor. Neutrophil engraftment was observed in all subjects. The majority of subjects received a tacrolimus-based regimen for GvHD prophylaxis.
“The Phase 1b data provide important mechanistic insights that support the potential utility of microbiome therapeutics such as SER-155 to individuals receiving allo-HSCT,” said Matthew Henn, Ph.D., Chief Scientific Officer at Seres. “Study data from Cohort 1 suggest that SER-155 administration results in substantially lower incidence rates of gastrointestinal pathogen domination with ESKAPE pathogens of clinical concern, including Enterococcaceae, Enterobacteriaceae, Streptococcaceae and Staphylococcaceae. These are bacteria that can include antibiotic resistant strains such as carbapenem-resistant Enterobacteriaceae (CRE) and vancomycin-resistant Enterococci (VRE).”
Published data have demonstrated an association between the incidence of GI domination with ESKAPE pathogens in allo-HSCT patients and the risk of serious infections, GvHD, and mortality.1,2,3 Reducing the incidence of domination of ESKAPE pathogens in the GI microbiome through administration of a microbiome therapeutic has the potential to meaningfully reduce enteric infections, enteric driven blood stream infections and GvHD in this medically compromised patient population and more broadly.
“Allogeneic hematopoietic stem cell transplantation can be a highly effective approach to treat serious cancers, however, the process results in a high risk of complications, including infections and graft-versus-host disease,” said Marcel van den Brink, M.D., Ph.D., Head, Division of Hematologic Malignancies at Memorial Sloan Kettering Cancer Center (MSK). “Microbiome therapeutics have the potential to address underlying mechanisms that may be involved in many of the issues faced during allo-HSCT. These encouraging initial SER-155 results, particularly the very low levels of gastrointestinal pathogen domination observed, provide support for the promise of these approaches to lead to important clinical benefits.”
Enrollment of Cohort 2 is ongoing, incorporating a randomized, double-blinded placebo-controlled design to further evaluate safety, drug strain engraftment, and incidence of gastrointestinal ESKAPE pathogen domination, as well as the incidence of enteric infections, enteric driven blood stream infections and GvHD. Cohort 2 will enroll approximately 60 subjects administered either SER-155 or placebo at a 1:1 ratio. The Company anticipates obtaining top-line placebo-controlled day-100 data from study Cohort 2 in mid-2024.
Seres believes that the medical benefit and commercial potential for SER-155 is substantial. Nearly 30,000 allo-HSCT procedures are performed in the U.S. and Europe per year.4 Complications are frequent and costly, with additional costs for patients with complications averaging approximately $180,000/year.5,6 Infections and GvHD are estimated to result in nearly half of mortality associated with allo-HSCT.4 With the exception of an exclusive license from MSK, Seres fully owns worldwide rights for commercialization of SER-155. In addition to SER-155, the Company is evaluating other microbiome therapeutic preclinical programs for additional medically compromised patient populations who are at risk of life-threatening infections.
Conference Call Information
Seres’ management will host a conference call today, May 9, 2023, at 8:30 a.m. ET to discuss Q1 2023 financial results and provide a business update, including a discussion of new SER-155 study results. Prior to the conference call, the Company plans to provide slides to accompany the conference call on the ‘Investors and News’ section of the Seres website at www.serestherapeutics.com.
To access the conference call, please dial 800-715-9871 (domestic) or 646-307-1963 (international) and reference Conference ID 5098595. To join the live webcast, please visit the ‘Investors and News’ section of the Seres website at www.serestherapeutics.com.
A webcast replay will be available on the Seres website beginning approximately two hours after the event and will be archived for at least 21 days.
About Seres Therapeutics
Seres Therapeutics, Inc. (Nasdaq: MCRB) is a commercial-stage company developing novel microbiome therapeutics for serious diseases. Seres’ lead program, VOWSTTM, obtained U.S. FDA approval in April 2023 as the first orally administered microbiota-based therapeutic to prevent recurrence of C. difficile infection (CDI) in adults following antibacterial treatment for recurrent CDI and is being commercialized in collaboration with Nestlé Health Science. Seres is
evaluating SER-155 in a Phase 1b study in patients receiving allogeneic hematopoietic stem cell transplantation to reduce incidences of gastrointestinal infections, bloodstream infections and graft-versus-host disease as well as additional preclinical stage programs targeting Infection Protection in medically compromised patients. The Company is also conducting research to inform further development of microbiome therapeutics for ulcerative colitis. For more information, please visit www.serestherapeutics.com.
About SER-155
SER-155 is a consortium of bacterial species selected using Seres’ reverse translation discovery and development platform technologies. The design incorporates microbiome biomarker data from human clinical data and nonclinical human cell-based assays and in vivo disease models. The SER-155 composition aims to decrease the colonization and abundance of bacterial pathogens that can harbor antibiotic resistance and to enhance epithelial barrier integrity in the GI tract to both reduce the likelihood of pathogen translocation and decrease the incidence of bloodstream infections. Further, SER-155 is designed to modulate host immune responses to decrease GvHD.
Forward-Looking Statements and Disclosures
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including the timing of additional clinical data, the ability of microbiome therapeutics to prevent or reduce infections, the ultimate safety and efficacy data of SER-155, final study results, and other statements which are not historical fact.
These forward-looking statements are based on management’s current expectations. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including, but not limited to, the following: we have incurred significant losses, are not currently profitable and may never become profitable; our need for additional funding; our limited operating history; the impact of the COVID-19 pandemic; our unproven approach to therapeutic intervention; our reliance on third parties and collaborators to conduct our clinical trials, manufacture our product candidates and develop and commercialize VOWST or any other product candidates, if approved; the unknown degree and competing factors of market acceptance for VOWST; the competition we will face; our ability to protect our intellectual property; and our ability to retain key personnel and to manage our growth. These and other important factors discussed under the caption “Risk Factors” in our Annual Report on Form 10-K filed with the Securities and Exchange Commission (SEC), on March 7, 2023, and our other reports filed with the SEC could cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. Any such forward-looking statements represent management’s estimates as of the date of this press release. While we may elect to update such forward-looking statements at some point in the future, we disclaim any obligation to do so, even if subsequent events cause our views to change. These forward-looking statements should not be relied upon as representing our views as of any date subsequent to the date of this press release.
SER-155 is covered by certain intellectual property exclusively licensed to Seres from MSK. Drs. van den Brink and Peled have financial interests related to Seres. MSK has institutional financial interests related to Seres.
IR and PR Contact
Carlo Tanzi, Ph.D.
ctanzi@serestherapeutics.com
References:
| 1. | Peled, J, Gomes, A, Devlin, S, et al. (2020). Microbiota as Predictor of Mortality in Allogeneic Hematopoietic-Cell Transplantation. N Engl J Med. 382(9), 822–834. DOI: 10.1056/nejmoa1900623 |
| 2. | Stein-Thoeringer, C, Nichols, K, Lazrak, A, et al. (2019). Lactose drives Enterococcus expansion to promote graft-versus-host disease. Science. 366(6469), 1143–1149. DOI: 10.1126/science.aax3760 |
| 3. | Taur, Y, Xavier, J, Lipuma, L, et al. (2012). Intestinal Domination and the Risk of Bacteremia in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation. Clinical Infectious Diseases. 55(7), 905–914. DOIL 10.1093/cid/cis580 |
| 4. | Center for International Blood and Marrow Transplant Research |
| 5. | Broder, M, Quock, T, Chang, E, et al. (2017). The Cost of Hematopoietic Stem-Cell Transplantation in the United States. American Health & Drug Benefits. 10(7), 366–374. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5726064/ |
| 6. | Seres internal estimates |
###