There is considerable interest and excitement about the human microbiome, the complex community of micro-organisms such as bacteria, fungi, and viruses and their genes. The authors of this recent review in Nature ask whether the field provides viable opportunities for biopharma companies to develop innovative therapies, or whether it been overhyped?
I agree with the authors that the opportunity is real however there are still significant challenges and barriers to development and commercialisation and probably a little over-excitement along the way...
The article reviews challenges around clinical development, trial design and regulation given the daily changes to gut bacterial composition and donor bacterial populations. Clearly the regulatory environment is still immature and concerns have been raised regarding the limited understanding of mechanisms of action, reinforcing the need for more robust data and safety evidence. Developing novel therapies from living microbial organisms will require new manufacturing standards and there will be IP challenges with naturally occurring genes, microbes and proteins which are may not be patentable. There will also be additional ethical and legal implications such as who owns the IP rights to microbes, the information that arises from them and what about patient data transparency and confidentiality?
Despite these issues and challenges - academia, new biotechs, nutritional companies and large pharma are accelerating investment in this area – looking to leverage the mutually beneficial relationship between microbes and their human hosts to develop novel therapeutics.
Various approaches, tapping into the microbiome, are already in development including:
1. Faecal microbiota transplantation (FMT) through companies such as Rebiotix
2. Probiotics introduced into patients to promote growth of beneficial microbes; the focus of firms such as Seres Therapeutics.
3. Prebiotics which induce growth of desirable microbial populations are being targeted by companies such as Ritter Pharmaceuticals to tackle Lactose intolerance.
4. It is estimated that one-third of circulating metabolites are produced by the gut microbiota. Companies such as Second Genome are investigating these host-microbiome interaction pathways as changes in the microbiome can trigger changes which result in disease or disease progression
5. Other firms are looking at next generation antibiotics which avoid major side effects on the microbiome
6. Additionally companies are now looking at combining microbiome science and gene editing techniques to produce genetically engineered bacteriophages
This is definitely more than hype and as the authors’ note, with time the series of unknowns will gradually be addressed. We are starting to see pipeline advances in areas such as IBD and oncology and increased excitement building around connections between the gut and the brain, suggesting CNS conditions may be next. We are not going to see transformational microbiome-derived therapies overnight but they are most certainly coming…
does the microbiome field provide viable opportunities for biopharma companies to develop innovative therapies, or has it been overhyped? Here, we argue that the opportunity is real, but that multiple questions remain related to the science, clinical development, regulation and business models for microbiome-based therapies.