Our Programs

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

Pre-Clinical
Phase 1
Phase 2
Phase 3
Collaborators

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. A SER-109 open label study label study in patients with recurrent CDI, including first recurrence, is ongoing. The open-label study is expected to expand the SER-109 safety database to support a Biologics License Application (BLA) with the U.S. 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) in 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. Patients may still enroll in an open-label study.

Learn more about our current clinical trials.

Product overview

SER-287 is an investigational, oral, biologically-derived microbiome therapeutic for the treatment of ulcerative colitis (UC). SER-287 is a consortium of multiple bacterial spores manufactured by fractionating and purifying targeted bacteria from stool of healthy human donors. SER-287 has been granted Fast Track designation and Orphan Drug designation by the FDA. A completed SER-287 Phase 1b clinical study demonstrated a statistically significant difference in the clinical remission rate between patients with active mild-to-moderate ulcerative colitis treated with vancomycin followed by daily SER-287 for 8 weeks compared to the placebo group, and a favorable safety profile.

Mechanism of action

SER-287 is a multifunctional consortium of commensal bacteria based on human clinical insights. It is designed to modulate the following microbiome functions →

Unmet need in UC

Ulcerative colitis (UC) is a serious chronic condition marked by persistent inflammation in the digestive tract which can greatly reduce an individual’s quality of life. Although the pathogenesis of UC remains unclear, changes in the gastrointestinal microbiome and associated metabolites appear to be important. The relationship between the immune system and the gut microbiome also appears to play a role in the disease.

First-line therapies for UC are only modestly effective. Non-responders have limited treatment options because potent immunosuppressive therapies have serious side effects which are hard to justify in patients with mild-to-moderate disease. An unmet need exists for a safer and more efficacious oral therapy.

SER-287 is designed to improve symptoms and reduce colonic inflammation by acting on multiple disease-relevant pathways.

Status of clinical program

Seres has completed enrollment in the Phase 2b ECO-RESET study, designed to assess the safety and efficacy of SER-287 in patients with active mild-to-moderate ulcerative colitis.

Learn more about our current clinical trials.

Product overview

SER-301 is an investigational, oral, rationally-designed, fermented microbiome therapeutic for the treatment of mild-to-moderate ulcerative colitis (UC). SER-301 is a consortium of multiple bacterial strains that is manufactured by fermenting each strain individually and then combining to form drug product.

Mechanism of action

SER-301 is a multifunctional consortium of commensal bacteria designed based on clinical insights from our SER-287 Phase 1b study in UC patients. SER-301 is designed to modulate the following microbiome functions →

Unmet need in UC

UC is a serious chronic condition marked by persistent inflammation in the digestive tract which can greatly reduce an individual’s quality of life, and there is no curative treatment. Though genetic factors contribute to a person’s risk for UC, the relationship between the immune system and the gut microbiome also appears to play a role in triggering the disease.

First-line therapies for UC are only modestly effective. Non-responders have limited treatment options because potent immunosuppressive therapies have serious side effects which are hard to justify in patients with mild-to-moderate disease. An unmet need exists for a safer and more efficacious oral therapy.

SER-301 is designed to improve the symptoms of UC and decrease colonic inflammation by simultaneously acting on multiple disease-relevant pathways to address disease.

Status of clinical program

A Phase 1b trial of SER-301 for the treatment of ulcerative colitis has been initiated in Australia and New Zealand.

Learn more about our current clinical trials.

Product overview

SER-155 is an investigational, oral, rationally-designed, fermented microbiome therapeutic for the prevention of antibiotic-resistant bacterial infections and graft-versus-host disease (GvHD) in patients following solid organ and allogeneic stem cell transplantation. SER-155 is a consortium of multiple bacterial strains that is manufactured by fermenting them individually and then combining to form drug product.

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

Initiation of clinical development in process.

Seres is advancing its research and development efforts in cancer and applying learnings obtained from the SER-401 trial in metastatic melanoma to future programs.

Learn more about our current clinical trials.

Scientific literature

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

SER-109

Publications:

McGovern et al. SER-109, an investigational microbiome drug to reduce recurrence after Clostridium 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 Clostridium difficile infection. J Infect Dis. 2016;214(2):173-81. doi:10.1093/infdis/jiv766

Conference Talks and Posters:

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 Clostridium difficile infection. Presented at: Digestive Disease Week (DDW) 2021; May; virtual.

McGovern BH, Sims M, Lashner B, et al. Efficacy and safety of investigational microbe drug SER-109 for treatment of recurrent Clostridium difficile infection (RCDI). Presented at: Society of Healthcare Epidemiology of America 2021; April; 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 Clostridium difficile infection (RCDI). Presented at: Making a Difference in Infectious Diseases (MAD-ID) Annual Meeting 2021; May; virtual.

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

Almomani S.A. Button J.E, Schuster B.M, et al. Inactivation of vegetative bacteria during production of SER-109, a microbiome-based therapeutic for recurrent Clostridium 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 Clostridium 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 Clostridium 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 Clostridium difficile infection. Presented at: ICCAC Conference 2015; September; Boston, MA.

SER-262

Conference Talks and Posters:

Wortman JR, Lachey J, Lombardo MJ, et al. Design and Evaluation of SER-262: a fermentation-derived microbiome therapeutic for the prevention of recurrence in patients with primary Clostridium difficile infection. Presented at: ASM Microbe Conference 2016; June; Cambridge, MA.

Bryant J, Ford C, Litcofsky K, et al. Engraftment of investigational microbiome drug, SER-262, in subjects treated with vancomycin is associated with reduced rates of recurrence after primary Clostridium difficile infection (CDI). Presented at: IDWeek Conference 2019; October; Washington D.C.

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

Our latest
news

Recurrent C. diff study now enrolling
An open-label study of SER-109

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Target enrollment achieved in Phase 2b SER-287 study
Topline clinical data expected in mid-2021

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