Shaken not stirred your bacteriophage cocktail
A look at the relationship between gut bacteria and therapeutics for common and not-so-common illnesses
The usefulness of microbes and microbiota as treatments for conditions such as inflammatory bowel disease (IBD), Parkinson’s disease and cancer are being explored by established pharmaceutical players and start-ups alike. Here we highlight some of the latest developments in preclinical and Phase I trials.
Press Read more and then select the following links for insights into the preclinical and clinical development of monoclonal microbials, phage cocktails and conventional single molecule therapies, which hope to shape how we view the relationship between gut bacteria and therapeutics for common and not-so-common illnesses.
Monoclonal microbials
Cloned compositions of specific strains of naturally-occurring microbes, termed monoclonal microbials, are one of the most exciting developments. Evelo Biosciences are currently developing and testing multiple monoclonal microbials.
EDP 1066 is currently in phase I studies for psoriasis, atopic dermatitis, and ulcerative colitis. The monoclonal microbial EDP 1815 is being developed to treat inflammatory diseases.
In preclinical testing, EDP 1815 showed immunomodulatory activity on human immune cells and anti-inflammatory activity in discrete tissues, including skin, joints, gut and the central nervous system. Evelo have recently started a Phase I clinical trial for EDP 1815 in treating psoriasis and atopic dermatitis. Meanwhile EDP 1503 is in preclinical trials for oncology – colorectal, renal cell carcinoma, and melanoma.
Microbiome modification
A potential application for microbiomes is the development of treatments for psychiatric and neurological disorders, particularly for Parkinson’s disease. Studies are being advanced by Axial Biotherapeutics, who are looking to lead the way with microbiome modification.
“Our team is conducting advanced clinical research, which suggests that disorders like Parkinson’s are not just a brain condition but very likely have origins in the GI system” said Carrolee Barlow, M.D., Ph.D., Chief Executive Officer, Parkinson’s Institute and Clinical Center.1
“We are excited to join forces with Axial Biotherapeutics and their team to investigate an intervention with the potential to eradicate and block these microbial effects and improve GI function. It is our ultimate goal to determine if this approach can stop PD from progressing. Partnerships like this, along with financial donations, will make our goal of finding a solution for PD a reality.”1
Meanwhile Nextbiotix is developing microbiome-based therapies using single microbial strains that interact with human cells in the gut to tackle inflammatory bowel disease.
Acting more effectively on immunomodulatory pathways, they are intended to significantly improve the lives of patients suffering from inflammatory bowel diseases.2
Nextbiotix state their ambition to bring gut microbiota back into the therapeutic equation using a bacterium called Faecalibacterium prausnitzii.2
Keto Diet as protection against epileptic seizures
US-based Bloom Science is exploring the way that a ketogenic diet increases the abundance of certain gut bacteria that seems to offer protection against epileptic seizure. The company hopes to be able to mimic the diet’s action on the microbiome.
Shaken not stirred – your bacteriophage cocktail
Israeli startup BiomX hopes to tackle inflammatory bowel disease (IBD) which BiomX believe is derived from certain gut bacteria. Using a phage cocktail to kill these bacteria, its lead candidate is BX 002, a bacteriophage cocktail developed to target and eradicate pro-inflammatory gut bacteria believed to be implicated in IBD.
Discussing the findings by Dr. Kenya Honda, Professor of Microbiology and Immunology at Keio University School of Medicine, which were shown to potentially have a role in the onset and aggravation of IBD, Jonathan Solomon, CEO of BiomX stated:3
“Professor Honda’s pioneering discoveries in the understanding of the role of bacteria in modulating the microbiome have been major drivers in advancing the microbiome field…. we are now capable of selectively eradicating targeted components of the microbiome as they specifically relate to IBD.”3
The findings were recently published in Science magazine.3
A more conventional approach
Other companies are developing more conventional single molecule therapies. For instance, Enterome Biosciences is working in partnership with Nestlé Health Science to develop drug candidates that can influence the health of the microbiome. Its lead product is EB 8018, a small molecule designed to selectively disarm virulent FimH-expressing bacteria without disrupting the gut microbiome. EB 8018 is currently in phase I trials for the treatment of Crohn’s disease. Enterome is also working with Johnson & Johnson to take its other drugs EB 110 and 220 into preclinical and phase I trials for Crohn's disease, and is exploring other pharmaceuticals with Takeda, AbbVie and BMS.
Second Genome, in partnership with Pfizer and Roche, is developing SG 1019, a small molecule P2X7 inhibitor, to target tissue injury and inflammation through inhibition of an inflammasome activation pathway. SG 1019 is in early trials aimed at nonalcoholic steatohepatitis and inflammatory bowel disease.
Stay tuned for part IV – we’ll be looking at what’s over the horizon and why microbiome treatment represents a potentially large market – suggested to be worth $2.2 billion in 2020, reaching $3.2 billion by 2024.
References
1. Axial Biotherapeutics. Parkinson’s Institute and Clinical Center and Axial Biotherapeutics Announce Collaboration to Target Gastrointestinal Metabolites that May Contribute to Parkinson’s Disease. Available at www.axialbiotherapeutics.com.
2. Press release. Nextbiotix raises € 7m in a Series A round to tackle inflammatory bowel diseases. Available at www.docs.wixstatic.com.
3. Press release. BiomX Licenses Novel Bacterial Targets for the Treatment of IBD. Available at www.biomx.com.
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