FDA authorizes new IND to evaluate impact of multi-strain probiotic DS-01tm on gut microbiota of patients with IBS

BOSTON, Sept. 29, 2020 /PRNewswire/ -- Seed Health, a microbial sciences company, today announced U.S. Food and Drug Administration (FDA) authorization of its Investigational New Drug (IND) application for DS-01tm, a broad spectrum multi-species, multi-strain probiotic. The regulatory acceptance enables a team of gastroenterologists at Beth Israel Deaconess Medical Center, a teaching hospital of Harvard Medical School, to initiate a Phase II randomized, triple-blind, and placebo-controlled clinical trial to investigate the role of the gut microbiome in patients with Irritable Bowel Syndrome (IBS), as well as the impact of DS-01tm on both intestinal cells and metabolic output of the native intestinal microbial communities.

IBS is the most common gastrointestinal condition worldwide, with an estimated prevalence of 10-15% in the U.S. population and nearly 12% of all primary care patients, contributing to 3.1 million ambulatory care visits each year.^2,3 Characterized by a combination of chronic or recurring abdominal pain or discomfort, IBS is associated with symptoms ranging from diarrhea and constipation to bloating and distension, and is often accompanied by psychosocial distress and impaired quality of life.

While specific aspects of IBS like chronic constipation can be treated pharmacologically, treatment for many symptoms are currently limited to experimental dietary and lifestyle recommendations. This chronic disorder impacts the lives of millions of people and is a significant health care burden.

Although the underlying cause of IBS is unknown, recent studies⁴ have shown a link between IBS and an altered gut immune response, particularly as related to disruption of the intestinal microbiota. The current working hypothesis is that an abnormal microbiota drives impaired intestinal permeability and dysregulated immune responses, causing gastrointestinal distress.^5,6 Various efforts are now in development to target the gut microbiota and gastrointestinal (GI) tract with live microorganisms, though previous trials have had limited success due to empiric strain selection, small population size, and inadequate trial design to control for high placebo response⁷ rates.

The upcoming study, led by gastroenterologist Dr. Anthony Lembo, of the Division of Gastroenterology, Hepatology and Nutrition at Beth Israel Deaconess Medical Center, will use novel functional biomarkers to understand the role of the host microbiota in IBS, and to assess the impact of DS-01tm on the gut microbiota of patients with IBS. Patient recruitment has already begun, and participants with multiple subtypes of IBS (IBS-C and IBS-M) will be included?half will be administered DS-01tm and half will receive a placebo throughout the 12-week trial. The trial will assess metagenomic stability, measured through shotgun metagenomic DNA sequencing, alongside metabolic output of the gut microbiota, daily abdominal pain, daily stool consistency, IBS symptom severity, IBS adequate relief, daily abdominal discomfort, daily abdominal bloating, number of bowel movements per day, gut permeability, and overall quality of life. Participants will also use a mobile companion application to report the day-to-day gastrointestinal symptoms and quality of life inputs, whereas previous studies have relied on often inconsistent, low-compliant manual reporting.

This trial follows a recent update by the American Gastroenterology Association (AGA) that highlights 'major variation' in probiotic formulations while recommending 'well defined clinical trials' to establish the safety of specific formulations on clinical conditions relevant to gastroenterology.⁸

Principal investigator Dr. Lembo and his team are considered world experts in the burden and treatment of multiple IBS subtypes. He has conducted clinical trials on both pharmacological and non-pharmacological treatments, pioneered investigations into the placebo response, and has published widely on these topics.

"IBS is one of the most common conditions globally, but previous research on microbiota-based interventions for IBS has been inconsistent and inconclusive," said Dr. James Versalovic, Seed Health Advisor, Professor of Pathology and Immunology at Baylor College of Medicine, and early pioneer in the field of metagenomic medicine. "Seed Health's upcoming interventional trial represents a new approach to studying IBS by focusing not only on gut microbiota composition, but also on the thousands of bioactive metabolites it produces."

DS-01tm, developed with Dr. Gregor Reid, is a broad spectrum probiotic with 24 genetically distinct microorganisms across 12 species, including strains with novel mechanistic data that have been investigated in multiple randomized, double-blind, placebo-controlled human clinical trials. "Acceptance of the IND is an exciting advancement for the field of probiotic research," said Dr. Gregor Reid, Seed Health CSO, past-President of the International Scientific Association of Probiotics and Prebiotics (ISAPP), and former Chair of the UN-World Health Organization Expert Panel that authored the global scientific definition of probiotics. "This study is the first of several that will generate both mechanistic and clinical data in randomized, triple-blind, placebo-controlled interventional trials to investigate DS-01tm."

As part of the Seed Health's commitment to further transparency and accountability in science communication, they have included their conflict of interest statement below.

Dr. Anthony Lembo is a physician at Beth Israel Deaconess Medical Center (BIDMC) affiliated with Harvard Medical School and has no conflict of interest.

Dr. Christopher Mason is an Associate Professor of Physiology and Biophysics at Weill Cornell Medicine and will be analyzing microbiota samples via metagenomic shotgun sequencing. Patient data will remain blinded during sequencing and analysis. Dr. Mason has no conflict of interest.

Dr. James Versalovic is a Professor of Pathology and Immunology at Baylor College of Medicine and Physician-in-Chief at Texas Children's Hospital. Dr. Versalovic is a member of Seed Health's Scientific Advisory Board and is not involved in the trial.

Dr. Gregor Reid is a Distinguished Professor of Microbiology and Immunology at Western University, and the Endowed Chair in Human Microbiome and Probiotics at Lawson Health Research Institute. Dr. Gregor Reid is the Chief Scientist of Seed Health.

References

1. Belmonte, L., Beutheu Youmba, S., Bertiaux-Vandaële, N., Antonietti, M., Lecleire, S., Zalar, A.,... Ducrotté, P. (2012). Role of toll like receptors in irritable bowel syndrome: differential mucosal immune activation according to the disease subtype. PloS one, 7(8), e42777. DOI: 10.1371/journal.pone.0042777.
2. Occhipinti, K., & Smith, J. W. (2012). Irritable bowel syndrome: a review and update. Clinics in Colon and Rectal Surgery, 25(1), 46?52. DOI: 10.1055/s-0032-1301759.
3. Saito, Y. A., Schoenfeld, P., & Locke, G. R., 3rd (2002). The epidemiology of irritable bowel syndrome in North America: a systematic review. American Journal of Gastroenterology, 97(8), 1910?1915.  DOI: 10.1111/j.1572-0241.2002.05913.x.
4. Chey, W.D., Kurlander, J., & Eswaran, S. (2015). Irritable Bowel Syndrome: A Clinical Review. JAMA, 313(9):949?958. DOI: 10.1001/jama.2015.0954.
5. Black, C. J., & Ford, A. C. (2020). Global burden of irritable bowel syndrome: trends, predictions and risk factors. Nature reviews. Gastroenterology & hepatology, 17(8), 473?486. https://doi.org/10.1038/s41575-020-0286-8
6. Quigley E. (2017). Gut microbiome as a clinical tool in gastrointestinal disease management: are we there yet? Nature reviews. Gastroenterology & hepatology, 14(5), 315?320. https://doi.org/10.1038/nrgastro.2017.29
7. Ballou, S., Beath, A., Kaptchuk, T. J., Hirsch, W., Sommers, T., Nee, J., Iturrino, J., Rangan, V., Singh, P., Jones, M., & Lembo, A. (2018). Factors Associated With Response to Placebo in Patients With Irritable Bowel Syndrome and Constipation. Clinical Gastroenterology and Hepatology, 16(11), 1738?1744.e1. DOI: 10.1016/j.cgh.2018.04.009.
8. Su, G.L., Ko, C.W., Bercik, P., Falck-Ytter, Y., Sultan, S., Weizman, A.V., Morgan, R.L. (2020). AGA Clinical Practice Guidelines on the Role of Probiotics in the Management of Gastrointestinal Disorders. Gastroenterology, DOI:10.1053/j.gastro.2020.05.059.

Seed Health
Seed Health is a microbial sciences company pioneering applications of bacteria to impact human and environmental health. In collaboration with leading academic partners, they accelerate breakthrough science into live biotherapeutics and innovations for consumer health under a unique foundry model. Each portfolio venture is built on its own proprietary platform to target pervasive, unmet medical needs for which bacteria may become or replace the primary standard of care. The current pipeline includes interventions for infectious disease, allergy, and inflammatory conditions across various body sites and windows of development. All consumer innovations in probiotics are commercialized under Seed®. seedhealth.com / seed.com

Contact:
Jonathon O'Leary
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