BiomeBank Interview with Sam Costello: The Future of Microbial Therapies and Gut Health

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BiomeBank, a pioneer in microbiome therapeutics, is making significant strides in addressing diseases linked to microbiome imbalance. Pharma Technology Focus and BiomeBank CEO Sam Costello recently discussed the company’s progress and future plans. In this Q&A, Sam provides insights into the science behind BiomeBank’s therapies, their market potential, and the innovative Consortiome platform that promises to revolutionise microbial treatments.

Sam Costello: Gut microbes are critical to human health. They perform many essential functions for us, and when we lose these microbes, we can also lose the functions they perform. This loss can manifest as disease. An increasing number of diseases have been linked to the loss of human gut microbes, and there is increasing recognition that the gut microbiome is effectively an organ of the human body.

Sam Costello: There are numerous diseases linked to microbiome loss. Many are directly related to the gut, such as inflammatory bowel disease (ulcerative colitis and Crohn's disease) and liver disorders like non-alcoholic steatohepatitis. Metabolic diseases such as type 2 diabetes, insulin resistance, and obesity have also been linked, as are various allergic and autoimmune conditions. There are also associations with cancers and neurological conditions like autism.

Sam Costello: The potential market is huge given the link to many common diseases. Approved donor-derived microbiome therapies are now the standard of care for recurrent C. difficile infection, and that’s a relatively small market. However, there are significant opportunities in inflammatory bowel diseases such as ulcerative colitis and Crohn’s disease that represent total addressable markets of greater than $10B each. In other areas of gastroenterology, diseases like irritable bowel syndrome and liver diseases present further opportunities. Oncology also holds promise, as a depleted microbiome often predicts poor responses to cancer treatments. By restoring microbiome diversity through FMT, studies show that therapies like checkpoint inhibitors can have enhanced efficacy. There is the opportunity to develop disease specific cultured microbiome therapies for each of these indications.

Sam Costello: The evidence varies. There is high-level evidence supporting the use of donor-derived therapies like fecal transplants for recurrent C. difficile infection. It's now really a standard of care for that particular condition. There is also evidence for their efficacy in inducing remission in ulcerative colitis, with multiple randomised control trials supporting this. There’s emerging evidence supporting FMT's efficacy in a number of other diseases too, demonstrating that replacing missing microbes can be quite an effective therapy.

Sam Costello: There are only three approved donor-derived therapies worldwide. Two approved in the United States for recurrent C. difficile, and our therapy, Biomictra™, which is approved in Australia for recurrent C. difficile infection. We now supply over 70 hospital networks around Australia, and we've seen increasing uptake. I think the great thing about these approvals is it demonstrates a clear regulatory path for potential approval of other microbiome-based therapies targeting much larger markets.

Sam Costello: Donor-derived therapies, such as FMT, show efficacy in several indications but can present challenges due to their variable composition which limits the ability to target specific disease focused mechanism of action. Cultured microbiome therapies offer advantages over donor-derived therapies, particularly in rationally selecting microbes that have favourable efficacy and safety profiles. In addition, they have advantages in scalability and cost-effective production. However, cultured therapies have traditionally been limited to single strains or small consortia because each strain requires its own bioreactor for production, limiting their composition.

Sam Costello: Exactly. BiomeBank's solution to this is the Consortiome platform, which can co-culture a diverse array of microbes, encompassing over 90% of the gene families and functions found in a healthy human microbiome or FMT-based product. Consortiome allows for the creation of diverse microbial communities with emergent therapeutic properties, which are not evident in individual strains. For example, the therapy for ulcerative colitis demonstrates a potent ability to reduce and consume hydrogen sulfide, a property arising from the diverse community rather than individual strains. 

These emergent properties explain why donor-derived therapies have been effective, due to the therapeutic functions that arise from diverse microbial compositions. The Consortiome platform enhances this effect by selecting specific strains to target a particular mechanism of action, making it a more targeted and rationally designed therapy compared to traditional FMT.

Sam Costello: Manufacturing therapy in a bioreactor allows for more effective scaling compared to relying on donors. The co-culturing methodology means we don’t need many bioreactors for a consortia of many organisms, greatly reducing production costs and streamlining manufacture.

Sam Costello: It positions us very uniquely against donor-derived therapies and small consortia, which enables us to produce therapies with commercial advantages from controlled composition and targeted mechanisms of action. Our goal is to produce best-in-class therapies using this approach.

Sam Costello: BB265 is our first therapy developed using the Consortiome platform. Starting with our donor-derived product, we used it in a clinical trial for ulcerative colitis and identified a mechanism of action. We selected strains from our culture collection based on their ability to consume hydrogen sulfide, which was linked to remission in discovery trials. This consortia has similar genetic diversity and gene function as a donor-derived product but is enhanced for a specific mechanism of action, making it highly promising for treating ulcerative colitis. In terms of the clinical trial timeline, we aim to start the phase 1b/2a study in 2025.

Sam Costello: The total market for ulcerative colitis is about $13 billion annually, with current therapies having less than 50% clinical and endoscopic remission rates. Many therapies also have significant annual loss of response rates and work through immune suppression, which can be associated with adverse events. BB265 offers a novel, non-immunosuppressive approach, presenting significant opportunities for efficacy and safety. It may also be paired with other therapies without additive immunosuppressive effects.

Want to learn more? Get in touch with the BiomeBank team below.