Our Programs

Seres’ microbiome therapeutics represent an entirely new class of medicines with promise across a wide range of diseases.

INFECTION PROTECTION
Preclinical
Phase 1b
Phase 2b
Phase 3
Collaborators
INFECTION PROTECTION
1,2

Product overview

SER-109 is a first-in-class investigational microbiome therapeutic administered orally following antibiotics to reduce recurrence of C. difficile infection (CDI) in patients with recurrent CDI. SER-109 is comprised of purified Firmicutes spores, based on their modulatory role in the life cycle of C. difficile and disease pathogenesis. The FDA has granted SER-109 Breakthrough Therapy Designation and Orphan Drug Designation. In a Phase 3 clinical trial, SER-109 achieved high rates of sustained clinical responses with a favorable safety profile comparable to placebo in patients with recurrent CDI. Data suggests enriching for Firmicutes spores achieves high efficacy, while mitigating risk of transmitting infectious agents beyond donor screening alone. For information on the prior clinical studies of SER-109, see here. Seres has completed enrollment in the SERES-013 ECOSPOR IV open-label study for SER-109. The open-label study is expected to expand the SER-109 safety database to support a Biologics License Application (BLA) with the US FDA. For more information about the open-label study of SER-109 see here.

Mechanism of action

SER-109 is a multifunctional consortium of commensal bacteria based on human clinical insights. It is designed to modulate the following microbiome functions →

Unmet need in C. difficile

C. difficile has been classified as one of the greatest microbial threats to human health by the Centers for Disease Control and Prevention (CDC) since 2019. It is the leading cause of hospital-acquired infection in the United States and is responsible for the deaths of more than 20,000 Americans each year.

There are few options for the treatment of recurrent CDI; vancomycin pulse taper regimens are recommended by guidelines but have modest efficacy because they do not address the disrupted microbiome (McDonald, 2018).

SER-109 engraftment is associated with compositional and functional changes in the microbiome that are critical to a sustained clinical response.

Status of clinical program

Seres has completed enrollment of a Phase 3 ECOSPOR study assessing the safety and efficacy of SER-109 for the treatment of recurrent C. difficile. Seres has also completed enrollment in the SERES-013 ECOSPOR IV open-label study for SER-109.

Learn more about our current clinical trials.

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Product overview

SER-155 is an investigational, oral, rationally designed, fermented microbiome therapeutic designed to reduce the incidence of gastrointestinal infections, bacteremia, and graft versus host disease (GvHD) in immunocompromised patients, including patients receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT).

Mechanism of action

SER-155 is a multifunctional consortium of commensal bacteria designed based on human clinical insights. SER-155 is designed to augment the following microbiome functions, which are associated with better survival and lower rates of infection and GvHD in patients undergoing stem cell transplantation →

Unmet need in antibiotic-resistant infections and GvHD

Antibiotic-resistant infections, GvHD, and mortality are frequent, serious complications of organ or stem cell transplantation. Antibiotics used to treat infections in this patient population are not always effective and can have significant side effects. Current therapies for the prevention of GvHD rely on broad immunosuppression, which increases the risk of infection and has limited efficacy for a significant proportion of patients.

Status of clinical development

Phase I study now enrolling.

 
IMMUNE MODULATION
 
 
 
 
 
IMMUNE MODULATION
Research ongoing to determine future ulcerative colitis development plans
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Research ongoing to determine future ulcerative colitis development plans
1
 

Scientific literature

Black R, et al. The burden of illness associated with recurrent Clostridioides difficile infection: a claims-based analysis. Presented at IDWeek 2021; October; Virtual.

Wilcox, et al. The efficacy and safety of fecal microbiota transplant for recurrent Clostridioides difficile infection: current understanding and gap analysis. Open Forum Infect. 2020;7(5):ofaa114. doi:10.1093/ofid/ofaa114

SER-109

Publications:

McGovern BH, et al. SER-109, an investigational microbiome drug to reduce recurrence after Clostridioides difficile infection: lessons learned from a phase 2 trial. Clin Infect Dis. 2021;72(12):2132-2140. doi:10.1093/cid/ciaa387

Khanna, et al. A novel microbiome therapeutic increases gut microbial diversity and prevents recurrent Clostridioides difficile infection. J Infect Dis. 2016;214(2):173-81. doi:10.1093/infdis/jiv766

Conference Talks and Posters:

Cohen SH, Louie T, Sims M, et al. Investigational microbiome therapeutic SER-109 reduces recurrence of Clostridioides difficile infection (rCDI) compared to placebo, regardless of risk factors for recurrence. Presented at: IDWeek Conference 2021; October; virtual.

Hohmann E, Feuerstadt P, Oneto C, et al. The impact of investigational purified microbiome therapeutic SER-109 on health-related quality of life (HRQoL) of patients with recurrent Clostridioides difficile infection (rCDI) in ECOSPOR-III, a placebo-controlled clinical trial. Presented at: IDWeek Conference 2021; October; virtual.

Louie T, Sims M, Nathan R, et al. Time to recurrence of Clostridioides difficile infection (rCDI) is rapid following completion of standard of care antibiotics: results from ECOSPOR-III, a phase 3 double-blind, placebo-controlled randomized trial of SER-109, an investigational microbiome therapeutic. Presented at: IDWeek Conference 2021; October; virtual.

McChalicher C, Abdulaziz A, Halvorsen E, et al. Manufacturing Processes of SER-109, a purified investigational microbiome therapeutic, reduce risk of transmission of emerging and undetected infections in donor stool. Presented at: IDWeek Conference 2021; October; virtual.

Sims M, Khanna S, Pardi D, et al. Diagnostic testing among patients with suspected recurrent Clostridioides difficile infection (rCDI) in ECOSPOR-III a phase 3 clinical trial: implications for clinical practice vs clinical trials. Presented at: IDWeek Conference 2021; October; virtual.

Kraft CS, Lombardo MJ, Louie T, et al. Characterization of ribotypes among study participants in a phase 3 trial of investigational microbiome therapeutic SER-109 to reduce recurrent Clostridioides difficile infection (RCDI). Presented at: World Microbe Forum 2021; virtual.

Korman L, Lashner B, Kraft CS, et al. 24 week efficacy and safety data from Ecospor III: a phase 3 double blind, placebo controlled, randomized trial of SER-109, an investigational microbiome therapeutic for recurrent Clostridioides difficile infection. Presented at: Digestive Disease Week (DDW) 2021; May; virtual.

Bryant JA, Liyang D, O’Brien EJ, et al. Rapid conversion of primary to secondary bile acids in subjects with recurrent Clostridioides difficile infection (CDI) following SER-109, an investigational microbiome therapeutic. Presented at: Digestive Disease Week (DDW) 2021; May; virtual.

Fonte A, Berenson C, Korman L, et al. Ecospor III: a phase 3 double blind, placebo controlled randomized trial of SER-109 an investigational microbiome therapeutic for treatment of recurrent Clostridioides difficile infection (RCDI). Presented at: Making a Difference in Infectious Diseases (MAD-ID) Annual Meeting 2021; May; virtual.

Berenson C, Korman L, Kraft CS, et al. ECOSPOR-III: a phase 3 double blind, placebo controlled randomized trial of SER-109 an investigational microbiome therapeutic for treatment of recurrent Clostridium difficile infection (RCDI). Presented at: Society of Hospital Medicine 2021; May; Virtual.

McGovern BH, Sims M, Lashner B, et al. Efficacy and safety of investigational microbe drug SER-109 for treatment of recurrent Clostridioides difficile infection (RCDI). Presented at: Society of Healthcare Epidemiology of America 2021; April; virtual.

Almomani SA, Button JE, Schuster BM, et al. Inactivation of vegetative bacteria during production of SER-109, a microbiome-based therapeutic for recurrent Clostridioides difficile infection. Presented at: ASM Microbe Conference 2016; June; Cambridge, MA.

O’Brien EJ, Henn MR. Comparisons of microbiomes from US and European populations suggest that SER-109 may have clinical utility in broad geographic locations for the treatment of patients with recurrent Clostridioides difficile infection. Presented at: 26th European Congress of Clinical Microbiology and Infectious Diseases 2016; April; Cambridge, MA.

Lombardo MJ, Vulic M, Ohsumi T, et al. Vancomycin-Resistant Enterococcal (VRE) titers diminish among patients with recurrent Clostridioides difficile infection after administration of SER-109, a novel microbiome agent. Presented at: IDWeek Conference 2015; October; Boston, MA.

Wortman JR, Lombardo MJ, Vulic M, et al. Engraftment of SER-109 Spores was rapid and durable in patients with recurrent Clostridioides difficile infection. Presented at: ICCAC Conference 2015; September; Boston, MA.

Henn, et al. A Phase 1b safety study of SER-287, a spore-based microbiome therapeutic, for active mild to moderate ulcerative colitis. Gastroenterology. 2021;160(1):115-127.e30. doi:10.1053/j.gastro.2020.07.048

Sartor & Wu. Roles for intestinal bacteria, viruses, and fungi in pathogenesis of inflammatory bowel diseases and therapeutic approaches. Gastroenterology. 2017;152(2):327-339.e4. doi:10.1053/j.gastro.2016.10.012

Lloyd-Price, et al. Multi-omics of the gut microbial ecosystem in inflammatory bowel diseases. Nature. 2019;569(7758):655-662. doi:10.1038/s41586-019-1237-9

Rubin, et al. ACG clinical guideline: ulcerative colitis in adults. Am J Gastroenterol. 2019;114(3):384-413. doi:10.14309/ajg.0000000000000152

SER-287

Conference Talks and Posters:

Wortman JR. SER-287, an investigational microbiome therapeutic, induces widespread transcriptional changes related to clinical remission in a placebo-controlled, double-blind randomized trial (SERES-101) in patients with active mild-to-moderate ulcerative colitis. Presented at: Digestive Disease Week (DDW) 2019; May 18-21; San Diego, CA.

SER-301

Conference Talks and Posters:

Nelson T, Oka A, Liu Bo, et al. In vivo characterization of SER-301, a rationally designed investigational microbiome therapeutic for patients with active mild to moderate ulcerative colitis. Presented at: Digestive Disease Week (DDW) 2021; May 21-23; virtual.

Gopalakrisnan, et al. Gut microbiome modulates response to anti-pd-1 immunotherapy in melanoma patients. Science. 2018;359(6371):97-103. doi:10.1126/science.aan4236

Matson, et al. The commensal microbiome is associated with anti-pd-1 efficacy in metastatic melanoma patients. Science. 2018;359(6371):104-108. doi:10.1126/science.aao3290

Routy, et al. Gut microbiome influences efficacy of pd-1-based immunotherapy against epithelial tumors. Science. 2018;359(6371):91-97. doi:10.1126/science.aan3706

SER-401

Publications:

Gopalakrishnan, et al. Intervention strategies for microbial therapeutics in cancer immunotherapy. IOTECH. 2020; (awaiting formal publication) doi:10.1016/j.iotech.2020.05.001

Conference Talks and Posters:

Sceneay J, Srinivasan S, Desjardins C, et al. Leveraging gut microbiota networks to impact tumor immunotherapy Presented at: American Association for Cancer Research Conference 2019; May. Cambridge, MA.

Sceneay J, Srinivasan S, Halley K, et al. Leveraging gut microbiota to impact tumor immunotherapy Presented at: American Association for Cancer Research Conference 2018; April. Cambridge, MA.

Gooley, et al. Reduced mortality after allogeneic hematopoietic cell transplantation. N Engl J Med. 2010;363(22):2091-2101. doi:1056/NEJMoa1004383

Gratwohl, et al. Hematopoietic stem cell transplantation: a global perspective. JAMA. 2010;303(16):1617-24. doi:1001/jama.2010.491

SER-155 / Infection & GvHD

Taur, et al. The effects of intestinal tract bacterial diversity on mortality following allogeneic hematopoietic stem cell transplantation. Blood. 2014;124(7):1174-1182. doi:10.1182/blood-2014-02-554725

Stein-Thoeringer, et al. Lactose drives enterococcus expansion to promote graft-versus-host disease. Science. 2019; 366;1143-1149. doi:10.1126/science.aax3760

Peled, et al. Microbiota as predictor of mortality in allogeneic hematopoietic-cell transplantation. N Engl J Med. 2020; 382:822-34. doi:1056/NEJMoa1900623

Conference Talks and Posters:

Halvorsen E, Vulić M, O’Brien E, et al. Design and preclinical characterization of SER-155, an investigational cultivated microbiome therapeutic to restore colonization resistance and prevent infection in patients undergoing Hematopoietic Stem Cell Transplantation (HSCT). Presented at: IDWeek Conference 2021; October; virtual.