From Cynicism to Success

A fourth century Chinese handbook for emergency medicine outlined how FMT can be used to treat food poisoning and diarrhea. Though the ancient manuscript cannot describe the implications of gut microbiota on human health in the way we can today, it does highlight the fact that people have known and believed in the central role of the gut in human disease for centuries. We now have the science to back up the fact that the microbiome is important and can affect our health – and the medicines we take. We now have the opportunity to use emerging knowledge and technologies to fill in the blanks pertaining to the chemical mechanisms of the microbiome and the consequences for us.

Microbiome research is still a relatively new field and in the fledgling years there has been some  skepticism about what could realistically be achieved. There were several companies who started out at the same time as our company, Pendulum, and we all faced cynicism. But analytical technologies have helped identify novel targets that could be used to develop interventions for a range of human health issues. Many companies entering the microbiome space initially focused on developing therapeutics for traditional gut-related infections and diseases, but we decided to pursue a different therapeutic area, and started working on metabolic disorders. It is estimated that 415 million people live with diabetes worldwide and we wanted to create options for those patients. Patients with type 2 diabetes (T2D) are often deficient in the bacterial strains capable of metabolizing essential fibers into short-chain fatty acids like butyrate. Butyrate is a small molecule that binds to G-protein coupled receptors (GPCR), which signals for the release of GLP1. GLP1 is a small molecule that enhances the secretion of insulin and reduces blood glucose levels. Without the microbes to metabolize fibrous foods into butyrate, the potential for natural insulin production is lost.

Integrating long-read and high-throughput DNA sequencing, we have assembled genomic-based hypotheses about diabetes, rather than simply categorizing the strains associated with the disease present in the gut. With this knowledge, we have developed our first product designed specifically for people living with T2D.

A double-blinded, randomized, placebo-controlled clinical trial has shown that the product Pendulum T2D Glucose Control  is successfully able to reduce hemoglobin A1C (glycated hemoglobin) levels by 0.6 percent versus placebo(for example, from 6.5 to 5.9) and post-meal blood sugar spikes in T2D patients by 60 percent. It’s a massive success for the Pendulum team! Not only have we been able to create an efficacious product comprised of naturally-occurring bacterial strains, but we have validated our discovery platform – something our early critics thought impossible.

No guts, no glory

With any novel intervention, the main challenge is determining which pathways and targets will ultimately impact the disease. Is there any value to a therapeutic that offers nothing new to patients? The answer is obvious. Companies developing microbiome-derived therapeutics not only have to tackle this issue but the fact that there are very few tools available for their production. The tools  available for the creation of traditional drugs are the product of decades worth of enhancements and innovation. They suit the needs of conventional drug development and manufacturing. The newness of the microbiome means that companies must figure out the essentials of building a lab and how to manage the challenges that come with logistics. How can partners in the supply chain help get products from A to B? As our T2D product contains live strains of bacteria, a robust cold chain strategy must be enforced to ensure that people receive quality products.

Patient education is also an important consideration for pharmaceutical companies. Though people are increasingly aware of the microbiome and its implications for human health, have we educated them enough to truly understand what the field has to offer? Do they know the difference between a microbiome-derived small molecule, FMT, a probiotic, a prebiotic,  and a medical food? Are they aware of the risks of “do-it-yourself” treatments? There is a constant stream of information that people are able to access through the Internet and social media, and while it is positive that patients are engaging with this area of research, it can be difficult to understand everything that is happening in the field. Patients are certainly receptive to microbiome research and are looking for solutions to their medical problems; therefore, from a commercial standpoint, we must make sure that we help patients understand what a product can (and can’t) do and what value it may add to the management of their disease. 

Patient excitement mirrors our own. Companies are creating solutions that go beyond traditional medicine making, and in the next five years we could see microbiome-based therapeutics for GI disorders, metabolic syndrome and CNS disorders becoming part of the pharmaceutical landscape. The link between nature and science has always been a point of discussion, but for the first time in history we have the tools to truly marry the two together. 

We should all be prepared to stand in awe of the new wave of innovation that microbiome products stand to offer!