The excrement experiment that may cure cancer 💩
Why poop could become the last resort to fight infections
Hello and welcome to Careviser by Marie Loubiere, the weekly newsletter that cuts through the healthcare noise with a single focus: productization of the latest research and tech breakthroughs.
Faecal microbiota transplantation has become a hot topic in the past few years. We have made significant progress in terms of understanding the microbiome, and how bacteria can impact or restore it, potentially curing deadly diseases such as Clostridioides difficile or cancer.
Faecal microbiota transplantation for Clostridioides difficile: mechanisms and pharmacology by Khoruts, A., Staley, C. & Sadowsky, M.J.
🗝️ Why it matters: The Clostridioides difficile is a bacteria that causes infections. It leads to about 15,000 deaths each year in the US. It is highly contagious and can live for longer periods of time on surfaces. Its strains produce toxins which can cause diarrhea and inflammation in infected patients. It is getting increasingly difficult to treat Clostridioides difficile with antibiotics due to increased antibiotic resistance in developed countries.
🔎 The Faecal Microbiota Transplantation (FMT) treatment: it is a fairly new treatment. It is a completely new branch of pharmacology. Regulatory authorities need to take into account that it is neither a drug nor a human transplant and adjust approvals accordingly.
It is extremely promising. It has been shown to cure 90% of patients with Clostridioides difficile that had previously failed a treatment attempt with antibiotics alone.
It is becoming more accepted by the medical community. It was initially used by a limited number of physicians who were basing the treatment on fresh donor stools. Nowadays standardized FMT products are now available, and it is a treatment option endorsed by professional societies.
✅ Opportunities that come with the development of Faecal Microbiota Transplantations:
FMT is different from conventional drugs as it is made of live microbiota that are variable in composition. They will interact with the host gut microbiota which is also affected by external factors (dietary nutrient flow, medication, lifestyle…). The host can be more or less cooperative to the FMT.
Centralized manufacturing of Faecal Microbiota needs to happen to ensure the quality and consistency of the output (donor testing, production processes…). Currently stool banks mostly provide faecal microbiota to individual physicians in a rather artisanal fashion. That’s not a scalable way to prepare and distribute the material for large-scale treatments as the microbiota needs to be separated from faecal material. The material also needs to be stored over time through industrial freezing methods. It also needs to be encapsulated based on how the delivery is planned (delayed, or release in the colon etc…). These are numerous and complex variables that need to be taken into account for the manufacturing processes. The regulatory aspect of such manufacturing needs to take them into account so that each new type of transplantation does not need to be approved every time a small modification is made.
Matching of patients to the right faecal microbiota donors could be done using stratification software.
There still needs to be done more research on the long-term effects of FMTs on the host gut microbiota. For instance, many patients who have Clostridioides difficile also show irritable bowel syndrome symptoms. FMTs seem to show faster improvement of these than antibiotics, but this remains to be proven with large study groups. The impact on microbiome stability, relicience and functionality also needs to be assessed, as well as the risk of transmitting infectious diseases from the donor.
Finch Therapeutics was launched in 2016 by the former founder of OpenBiome the first non-profit stool bank in the US. They have developed a pipeline of microbiome therapeutics that are aimed to be administered orally.
💊 The product: They use a drug development approach based on existing research studies on FMTs. They apply machine learning techniques to these outcomes to identify patterns associated with successful outcomes. In a nutshell, they start with what has worked in existing studies to generalize it as opposed to discover drugs from the ground up with in vitro or animal models. It is supposed to be less risky.
📈 Progress: Their most advanced candidate targets C. difficile and completed a successful Phase II in June 2020. They have been awarded Fast Track and Breakthrough Therapy designations by the FDA. They have raised over US$180m since their inception. In the meantime, they have been building manufacturing capabilities, so that they would be able to quickly distribute their products based on the results of Phase III in upcoming years.
🚀 Next steps: going public to fund Phase III and their go-to-market?
Microbiota is a super impressive company in that space. Spun-out from the Wellcome Trust Sanger Institute in 2016, they have achieved a pretty amazing range of milestones since then. They raised a round of £8m at funding with Cambridge Innovation Capital and IP Group which was later completed by £4m from Seventure.
💊 The product: They use microbiome science to discover live bacterial therapeutics and biomarkers. They rely on 10 years of research carried at the Wellcome Trust Sanger Institute which was a leader in the Human Genome Project.
They claim to have the world’s leading microbiome Culture Collection, proprietary Reference Genome Database and microbiome AI.
They apply these to microbiome precision medicine meaning they are able to isolate all the gut bacteria from any one human. They analyse big clinical datasets, and match specific bacterial signatures associated with patient phenotypes which paths the way for drugs or biomarkers discovery.
📈 Progress: They have programs in inflammatory bowel disease (IBD), immuno-oncology and Clostridium difficile. Their IBD program led them to sign a whooping $534m deal with Genentech where they will test drug microbiome responses for Genetech’s clinical trials. That deal was signed only 18 months after they launched the business, which is pretty incredible. Genentech believes it can help them better predict the patient response to the drug candidates, identify the bacteria identified with good response and deliver them to the gut through FMT so that non-responders could become responsive to the drug candidate.
🚀 Next steps: Genentech works on its own sets of drugs candidates that are currently in early stages so we’ll have to wait a few more years until they could reach the market.
That’s a wrap for today! Don’t hesitate to reply to this email with comments, I read and answer all emails :)