A new class of drugs, microbiome therapeutics are gaining prominence. The obvious initial therapeutic area for gut microbiome modalities is in infectious diseases as evidenced by the recent approvals. There are three approved microbiome based drugs. Seres Therapeutics' VOWST and Ferring Pharmaceuticals’ REBYOTA  have been approved by the US FDA. BiomeBank’s Biomictra has received approval from Therapeutic Goods Administration (TGA) in Australia. All three are approved for Clostridium difficile bacteria infection.

According to GlobalData's Pharma Intelligence Centre, there are currently 388 microbiome therapeutics under development. The most targeted therapy areas for these agents are gastrointestinal conditions, with 106 agents, followed by infectious diseases with 74 agents, and oncology with 65 agents.

Cancer

Researchers and companies are actively exploring the potential of microbiome-based therapies in oncology. Various studies evaluating microbiome-based therapies to enhance the efficacy of cancer immunotherapy are currently underway. 

In 2022, South Korean firm Genome & Company collaborated with American pharma giant Merck, for a phase 2 trial involving its cancer blockbuster drug Keytruda. The trial aimed to evaluate the efficacy of Genome & Company's lead product, GEN-001, in treating biliary tract cancer patients.

Genome & Company's lead pipeline GEN-001 is said to be the first candidate for an immuno-oncology microbiome therapeutic in Korea. Currently, clinical studies (Phase I/Ib) targeting multiple solid cancer patients (non-small cell lung cancer, head and neck cancer, urothelial cancer) are being conducted in the US and Korea. 

UK-based 4D pharma is another firm evaluating microbiome therapeutics role in modulating anticancer drug efficacy. In 2021, the firm partnered with American pharma giants Merck and Pfizer to evaluate bavencio in combination with MRx0518 – a single strain live biotherapeutic product in development for the treatment of cancer – as a first-line maintenance therapy for patients with locally advanced or metastatic urothelial carcinoma.

South Korea’s GI Biome is another leading player in the space. In February 2023, the firm received approval from the Korean regulator for its phase 1 investigational new drug (IND) submission for GB104, a microbiome candidate for colorectal cancer.

“Patients with hematologic malignancies such as leukaemia receive intensive chemotherapy, stem cell transplantation and broad-spectrum antibiotics, which can create a state of dysbiosis, i.e. an imbalance in the gut microbiota (the opposite of symbiosis). This dysbiosis leads to inflammation and infections, resulting in a negative impact on the patient's health and the efficacy of treatments. By restoring the immune homeostasis in patients with cancer, we believe that microbiol therapies will become a new pillar in cancer treatment, alongside radiotherapy, conventional chemotherapy, monoclonal antibodies, small molecules, and immunotherapies,” said  Hervé Affagard, CEO and Co-Founder of MaaT Pharma, France.  The firm focuses on restoring the symbiosis between the host (patients) and the gut microbiome before and during the patient's treatment to fight cancers.

Autoimmune disorders

The correlation between microbiota composition and autoimmune disorders has opened up avenues for novel treatments in this field.

In 2022, Microba Life Sciences from Australia and Ginkgo Bioworks from the US joined forces to identify single-strain, live bacteria products (LBPs) that could be used to treat autoimmune disorders. Similarly, in 2021,  Viome Life Sciences in the US expanded its partnership with UK-based GSK to conduct clinical research and explore the development of new therapeutic interventions, focusing on chronic diseases such as autoimmune disorders and cancers.

Neurological disorders

Several studies have linked gut microbiome’s role in neurological disorders such as parkinson’s disease, Alzheimer's and autism etc. This paves the way for new treatment modalities for these debilitating diseases.

“Recent studies have highlighted the importance of the microbiota-gut-brain axis and the impact of the gut microbiome in brain diseases, and especially shedding some light on the role of the gut microbiome, linking abnormalities to diseases such as Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease,” said Hervé Affagard. In January 2023, MaaT Pharma, initiated a phase 1b trial in France in ALS.

In February 2023, US-based LISCure Biosciences, a clinical-stage biotech developing advanced microbiome technology with precision targets, announced a multi-year strategic R&D collaboration with South Korean firm Celltrion to identify novel microbiome therapy for parkinson's disease.

Another frontrunner is US-based Axial Therapeutics, a clinical-stage biopharmaceutical company dedicated to the development of gut-targeted, small molecule therapeutics for neurological conditions and oncology. Axial Therapeutics is currently conducting a phase 2b clinical trial for their lead product candidate, AB-2004, which aims to treat irritability associated with autism. Additionally, they are in the preclinical evaluation stage for AB-5006, a development candidate targeting parkinson's disease.

Challenges 

Despite the promising potential of microbiome therapies, there are still several challenges to overcome. These include the need for a better understanding of the microbiome's intricacies, standardisation of therapeutic approaches, and ensuring safety and efficacy in clinical applications.

“Lack of standardised methodologies in analysing content and composition of the microbiota in diseased and healthy states is a major issue that needs to be resolved soon. Engraftment of the microbes in the host (human) is not well understood and hence proper research and elucidation is required,” said Dr Debojyoti Dhar, Co-Founder and Director (Business Development and Innovation), Leucine Rich Bio, India. It is a microbiome based diagnostic company. 

The regulatory landscape for microbiome therapies is evolving, with few guidelines for their development and approval.

“With the growth in scientific possibilities and definitions of how microbiome therapies will work – it is essential that the legislative and regulatory environment worldwide keeps pace to ensure patients benefit from these advances as early as possible. Regulatory frameworks which are multidisciplinary and proactive create international harmonisation, support academic research and enable clinical trials; which will build clinical confidence among healthcare practitioners to apply these new therapies,” said Carl Bilbo, Senior Vice President – Microbiome, Ferring Pharmaceuticals, Switzerland. 

Manufacturing of such live microbiome therapies pose another challenge. “The manufacturing of microbiome-based therapies requires specialised expertise and infrastructure. Most contract development and manufacturing organisations (CDMOs) have limited expertise with microbiome-based drugs and struggle to maintain viability of the microorganism throughout the entire manufacturing process, a critical component to success. At MaaT Pharma, we have chosen to develop in-house cGMP manufacturing capabilities to ensure full control and scalability of our manufacturing capacities and know-how from clinical batches to commercialisation,” said Hervé Affagard.

The past decade has witnessed significant growth in the field of microbiome therapies, setting the stage for a promising future. Market research firms also predict the global microbiome therapeutics to boom. It will be worth $1.5 billion by 2027, according to BCC Research. 

Ayesha Siddiqui