Therapeutically Targeting the Interconnected Biology of the Gut

Over 100 million neurons and approximately 70–80% of your body's immune cells are found in the gastrointestinal tract or "gut". These cells share their "home" with trillions of microbial cells that make up the "microbiota". Together these three components make up the "enteric signaling network" or ESN.

The ESN acts as a gateway for the communication between the brain and the gut, and has been linked to disease – presenting itself as a potential therapeutic target.

We recently had the pleasure of interviewing Paul-Peter Tak, CEO of Kintai Therapeutics. Tak discusses how Kintai Therapeutics are exploiting the power of big data and machine learning to unravel the interconnected biology of the gut, and explains how the enteric signaling network can be therapeutically targeted. Tak also touches on the lead drug candidates in Kintai's pipeline and the various indications they are being developed for. 

Laura Lansdowne (LL): For our readers who may be less familiar with Kintai, could you tell us a little about the company history and mission?

Paul-Peter Tak (PPT): Kintai is a biotech company that is uniquely focused on developing therapeutics to unlock the power of the enteric signaling network and its role in health and disease. We have amassed ground-breaking, extensive knowledge on the interconnected biology of the microbiota, immune cells, and neurons and their role in diseases across different therapy areas. With this intricate knowledge, our multidisciplinary scientific approaches, and an emphasis on molecular therapeutics, we have created a platform technology that fuels development of small molecules that are designed to target these signals and address them for the greatest impact.

LL: Could you tell us more about the enteric signaling network and how it can be targeted therapeutically?

PPT: We are focused on the gut microbiome, the gut immune system and the enteric nervous system, all of which make up the enteric signaling network. Parkinson’s disease is a clear example of the critical importance of the interconnected biology of the gut, as the gut microbiome, immunoinflammatory cells and transport of misfolded proteins through the vagus nerve to the brain have all been implicated in its pathogenesis.

Our PEM™ discovery platform relies on our unprecedented “mapping” of the entire enteric system and enables both identification of therapeutic molecules and optimized locational precision. This enables the development of PEM™ compounds, or novel small molecule therapeutics that are activated in the location expected to result in optimal benefit–risk for patients.

Credit: Kintai Therapeutics

LL: How is Kintai using big data and machine learning to unravel this interconnected biology of the gut?

PPT: Kintai has created a library of unique biosamples. These samples allow us to truly explore the depths of human biology and increase the proability of success in drug discovery. We utilize state-of-the-art molecular techniques to quantitatively evaluate the biomolecules that drive the enteric signaling networks. These measurements allow us to evaluate with high precision and accuracy both the human and microbial systems in the human “super-organism”, in both normal and diseased physiological states. We leverage advanced quantitative and analytical techniques from a number of fields, including ‘omics, statistics, and machine learning. These methodologies allow us to both integrate and distill the complex high-dimensional data for our human biological samples into actionable therapeutically relevant hypotheses.

The gut is the site of some of the most sophisticated and intricate biology in the body and only through Kintai’s state of the art integrated approach is the company able to interpret robust data sets to produce compelling new discoveries.

LL: Could you tell us more about your lead product candidates and the indications they are being developed for?

PPT: Kintai’s most advanced programs are targeting disease origins within the gut for quick proof-of-concept and potential accelerated path through the development process. These include programs in obesity and chronic kidney disease. Simultaneously, we are also advancing earlier stage discovery programs in oncology and neuroscience, using our cutting edge science to develop medicines that may, for example, turn non-responders to checkpoint inhibitors for the treatment of cancer into responders. These recently introduced immunotherapies have demonstrated amazing results but only in a minority of the patients. There is growing evidence demonstrating a link between the microbiome and checkpoint inhibitor efficacy through metabolic pathways; Kintai is in a unique position to leverage these insights and bypass the microbes through its PEM approach.

We are also looking to further understand the role that microbiome enteric signaling biology plays in patients, often children, with therapy-resistant epilepsy. Here again, we aim to switch non-responders to responders in the future.

Paul-Peter Tak was speaking with Laura Elizabeth Lansdowne,
Science Writer for Technology Networks.