Frontrunner in Microbiome Therapeutics

Elena - Stock.adobe.com

It has been reported that interest in the gut microbiome and its relevance to human health has increased significantly over the past decade (1). As noted in a recent article by James McIlroy—who has been cited on the Forbes 30 Under 30 Europe Healthcare and Science list (2)—founder and CEO of EnteroBiotix, a clinical stage microbiome therapeutics company, “Instead of viewing bugs as bad, we’re embracing them as being part of a symbiosis” (1).

Harnessing the power of the microbiome

EnteroBiotix is a clinical-stage microbiome therapeutics company which leverages the gut microbiome to develop novel medicinal products that restore health and prevent disease, with a specific focus on drug-resistant bacterial infections and gastrointestinal conditions. Established in 2017, EnteroBiotix is headquartered in Glasgow, United Kingdom, and operates research laboratories and Medicines and Healthcare products Regulatory Agency (MHRA)-licensed good manufacturing practice (GMP) pharmaceutical manufacturing sites in Glasgow and Aberdeen, UK.

The company has developed a differentiated platform manufacturing technology that has broad potential applicability across the spectrum of microbiome therapeutic approaches. EnteroBiotix have created a trademark-protected donor brand and online portal called the ‘Number 2 Donor Programme’ for recruiting healthy donors (3). The company’s MHRA-licensed cleanroom facility in Aberdeen ensures that starting material is accepted, tested, and processed in a regulatory compliant manner. The platform delivers investigational medicinal products that contain diverse and viable communities of donor-derived microorganisms which target multiple functional pathways.

Enterobiotix’s competitors include Evolve Biosystems Inc. (United States), Ilya Pharma AB (Sweden), Novome Biotechnologies Inc. (US), and RedHill Biopharma (Israel). EnteroBiotix ranks 19th among 169 active competitors according to data published by Tracxn Technologies (4).

Diseases and conditions linked to the human microbiome

Research shows that imbalances within the gut microbiome may be associated with a wide range of medical ailments ranging from acute intestinal infections such as those caused by the bacterium C. difficile, to complex chronic conditions like inflammatory bowel disease and colorectal cancer (5). However, it is thought that modulation of the microbiome offers an exciting and largely unexplored therapeutic avenue to treating an array of infectious intestinal diseases and Multidrug Resistant Organism (MDRO) infections, as well as conditions linked to the brain and liver, metabolic diseases, and those in immuno-oncology.

EnteroBiotix, therefore, believes that one of the best established and most powerful means of modulating the microbiome is through Intestinal Microbiota Transfer (IMT), which involves the transfer of microbiome communities from a healthy person into the intestinal tract of another person suffering from a microbiome mediated condition (6). The company produces capsules that contain diverse ecosystems of microbiota obtained from healthy and rigorously screened donors, which provide a compositionally consistent, safer, and non-invasive alternative to current methods for transferring microbiota from donors to patients (1).

Clinical efficacy of IMT

IMT is a gold-standard therapeutic intervention for patients suffering from recurrent C. difficile infection (rCDI) and has shown promise in other diseases areas associated with substantial unmet clinical need (7). For example, this has also been demonstrated in indications that affect the liver such as liver cirrhosis, hepatic encephalopathy, and hepatitis (6). Globally, more than 90 randomized controlled trials (RCTs) investigating the therapeutic utility of IMT have been conducted in a wide array of patient populations suffering from extra-intestinal and intestinal diseases, all of which have consistently reported good efficacy and safety supporting this route of treatment (8).

Investor interest in EnteroBiotix

EnteroBiotix has raised total funding of US$24 million (€22.5 million) over four rounds (4). In September 2021, the company secured US$21.5 million (€20.3 million) in a series A financing round to advance a pipeline of drugs targeting the microbiome (9). The funding round was led by Scottish investment firm Thairm Bio with investments from Scottish Enterprise, SIS Ventures, and US-based Kineticos Ventures. With these funds, EnteroBiotix will expand its headcount to 50, and advance its pipeline for multiple disease areas, as well as develop its in-house manufacturing capabilities. According to data derived from Crunchbase, venture capitalists invested US$1 billion (€94.3 million) into microbiome start-ups between 2015 to 2020 (10).

Granting of IMP licensure

In October 2022, EnteroBiotix announced that it had been granted a manufacturer’s licence for Investigational Medicinal Products (IMP) by the MHRA to manufacture microbiome product candidates for clinical trials (11). Located at the Strathclyde Business Park in Glasgow, the 20,000-square-foot facility incorporates an in-house quality control (QC) hub and analytical department that is designed to meet regulatory biologics requirements and product analysis while providing the company end-to-end control of its supply chain (12).

EnteroBiotix’s manufacturing capabilities include its novel proprietary AMPLA platform that enables the rapid preparation of dry powder from hydrated starting material at static temperature (11). The company believes this technology has potential applicability across the entire spectrum of microbiome therapies that are currently dried using traditional methods, including lyophilization, making this approach superior to others being currently pursued. The GMP-certified manufacturing facility is the most advanced of its kind in Europe and is designed to operate as a flexible and scalable manufacturing centre. According to Douglas Thomson, non-executive chairman at EnteroBiotix, “The board has backed the vision of establishing control of the supply chain and to develop in-house manufacturing and analytical capabilities as a strategic asset” (13). Looking ahead, the company is aiming to initiate a Phase II clinical trial for its lead microbiome therapeutic asset, EBX-102, in patients with liver cirrhosis by the end of 2022.

Partnership with Imperial College London

In November 2022, EnteroBiotix entered into a collaboration with Imperial College London (ICL) to assess the potential of IMT administration in patients with blood cancer prior to bone marrow transplant as a means of altering their gut microbiome with the aim of achieving improved outcomes. The Phase IIa, investigator-initiated trial, will evaluate how EBX-102 impacts the outcomes of bone marrow transplant patients with blood cancer. This trial forms part of the Microbiota Transplant Prior to Allogeneic Stem Cell Transplantation study, that is being conducted across six of the UK’s leading blood cancer centres including, Imperial College, University College London Hospitals, the Royal Marsden, King’s College London, Leeds Teaching Hospitals, and University Hospitals Birmingham (14).

According to Professor Julian Marchesi of ICL, Department of Metabolism, Digestion and Reproduction, “Patients with blood cancers are a group whose gut microbiome is particularly under attack … as they often receive strong chemotherapy, which has side effects of mouth ulcers and gut inflammation” (14). These patients receive antibiotics frequently due to their high rate of infections, with many inevitably being colonised with antibiotic-resistant bacteria. As a result, patients are at high risk of getting an infection which is untreatable. The products developed by EnteroBiotix hold the promise of manipulating the gut microbiome in such patients, thereby reducing the need for antibiotics and improving health outcomes.

The clinical trial, which is funded by the Medical Research Council and supported in-kind by EnteroBiotix, will build on Imperial’s successful pilot study (in the same patient population) which demonstrated preliminary data suggesting that IMT can reduce complications and improve survival rates (14). Through this partnership, Imperial will increase its exploration into the efficacy of this approach for a range of diseases and will aim to strengthen the pathway to commercialization through the conduct of systematic research.

The future of microbiome therapeutics

In addition to helping explore the safety, tolerability, and efficacy of IMT-based drugs for a range of conditions, the partnership between Imperial and EnteroBiotix is expected to help place microbiome research onto a sounder footing, supported by systematic learning about the gut microbiome and the very specific mechanisms that make microbiome treatments work in patients with variable gut ecologies. Microbiome therapeutics have the potential to provide short- and long-term changes to the gut and liver, and may provide an alternative means of treating disabling and life-threatening conditions such as inflammatory bowel disease, colorectal cancer, and liver cirrhosis, in the near future.

References

1. Silverman, D. Imperial Partnering with EnteroBiotix to Advance Microbiome Medical Treatments. Imperial.ac.uk, 10 Nov. 2022.
2. Jennings, K.; Pratap, A.; Valet, V.; Conklin, J. Under 30 Europe 2022: Meet the Entrepreneurs Innovating from the Microbiome to the Psyche. Forbes, 3 May 2022.
3. EnteroBiotix. Number 2 Donor Programme. Number2.org (accessed 21 Feb. 2023).
4. Tracxn. EnteroBiotix. Tracxn.com, 21 Feb. 2023 (accessed 21 Feb. 2023).
5. Guinane, C.M.; Cotter, P.D. Role of the Gut Microbiota in Health, and Chronic Gastrointestinal Disease: Understanding a Hidden Metabolic Organ. Therap. Adv. Gastroenterol. 2013, 6 (4), 295–308.
6. EnteroBiotix. Intestinal Microbiota Transfer (IMT). EnteroBiotix.com (accessed 21 Feb. 2023).
7. Quraishi, M.N.; Widlak, M.; Bhala, N.; et al.Systematic Review with Meta-Analysis: The Efficacy of Faecal Microbiota Transplantation for the Treatment of Recurrent and Refractory Clostridium Difficile Infection. Aliment. Pharmacol. Ther. 2017, 46 (5), 479–493.
8. Cammarota, G.; Masucci, L.; Ianiro, G.; et al. Randomised Clinical Trial: Faecal Microbiota Transplantation by Colonoscopy vs. Vancomycin for the Treatment of Recurrent Clostridium difficile Infection. Aliment. Pharmacol. Ther. 2015, 41 (9), 835–843.
9. Lucas, E. EnteroBiotix Secures $21.5M Series A to Advance Microbiome Drug Pipeline. Fierce Biotech, 8 Sep. 2021.
10. Hall, C. Startups Focused on Gut Microbiome for Health Clues Raised $1B in VC Funding. Crunchbase News. 8 Dec. 2020.
11. EnteroBiotix. EnteroBiotix Receives MHRA MIA (IMP) Licensure of State‑of-the-Art GMP Manufacturing Facility for Producing Microbiome Therapeutics. Press Release, 11 Oct. 2022.
12. Keenan, J. EnteroBiotix Completes New Manufacturing Facility Focused on Gut Microbiome Therapies. Fierce Pharma, 27 Oct. 2021.
13. Laws, L. License Granted to EnteroBiotix for Manufacture of Microbiome Product Candidates. LABIOTECH.eu, 11 Oct. 2022.
14. EnteroBiotix. EnteroBiotix Partners with Imperial College London to Develop Microbiome Therapeutics. Press Release, 10 Nov. 2022.

About the author

Bianca Piachaud-Moustakis is lead writer at Pharmavision, Pharmavision.co.uk.

Article details

Pharmaceutical Technology Europe
Vol. 35, No. 3
March 2023
Pages: 12–13, 15

Citation

When referring to this article, please cite it as Piachaud-Moustakis, B. Frontrunner in Microbiome Therapeutics. Pharmaceutical Technology Europe, 2023, 35 (2), 12–13, 15.