Harnessing the gut-brain axis to create gut-restricted small molecules for metabolic and neurological diseases

Fierce 15

CEO: Nancy Thornberry
Based: New York City
Founded: 2015
Clinical focus: CNS and metabolism

The scoop: The gut-brain axis is a red-hot field of research. Fueled by interest in the microbiome, the annual number of references to “gut-brain axis” in the academic literature increased by more than 1,000% from 2009 to 2017. That surge in activity has uncovered bidirectional communication between the brain and gut, reshaping our understanding of major diseases and unlocking new ways to treat them.

Kallyope is poised to realize the therapeutic opportunities created by this blossoming of research into the axis. Equipped with a platform capable of mapping gut-brain circuits, the New York-based biotech is translating evidence of links between microbiome metabolites and disease into gut-restricted small molecules that act on metabolic and neurological diseases.

What makes Kallyope fierce: Evidence of the link between the gut and neurological conditions such as Parkinson’s disease and epilepsy has accrued in recent years. The question now is how to use this knowledge to create new drugs. Kallyope’s answer is a platform that combines a variety of high-tech approaches—single-cell sequencing, optogenetics, chemogenetics, neural tracing and more—to map and validate gut-brain circuits.

These maps serve as the basis for Kallyope’s drug research programs, which bypass the thorny issue of getting molecules into the brain by acting on the other end of the circuit instead.

“Our approach is to use gut-restricted molecules to target the circuits at their origin,” Kallyope CEO Nancy Thornberry said. “That is a fundamentally new way of thinking about therapeutics. One could characterize it as a safe way to the brain.”

Kallyope spent its first two years putting together its technologies and building out its platform and drug discovery teams. In February, Kallyope started on the next stage of its development by pulling in a $66 million series B round. The money equips Kallyope to move its lead programs toward the clinic over the next two to three years, while using the output of its platform to discover new early-stage assets.

“We're starting to really dig into the data to elucidate new circuits that can be targeted with small molecule therapeutics,” Thornberry said. In parallel, Kallyope is working with Novo Nordisk to discover peptide treatments for obesity and diabetes, leaving its internal teams free to focus on small molecules.

These internal teams are made up of academics from New York’s research institutions, ex-pharma researchers from the New Jersey corridor and scientists who left the city because of a lack of jobs, only to leap at the chance to return to work for Kallyope. With a limited number of companies competing for these workers, Thornberry thinks Kallyope has an advantage over its peers in the congested biotech hotspots of California and Massachusetts.

“From a recruiting perspective, I believe we really have an edge over other hubs as it’s an untapped talent pool,” the CEO said.

An analysis of recent Fierce 15 winners gives an indication of just how untapped the New York City talent pool is. Over the past five years, biotechs based in 10 U.S. states and five European companies have won the Fierce 15 award. California and Massachusetts have racked up more than 50 wins between them.

Neither New York nor its eponymous city have contributed a winner. By the metric of Fierce 15 winners, the New York biotech scene has been less productive than Canada, Connecticut, Illinois, Maryland, Texas, the Netherlands and a clutch of other places.

New York is pushing hard to change that, putting together a $500 million financing package in a bid to quadruple R&D space in the city. In Kallyope, the city has a startup that could become the poster child for its drive to become a leading biotech hub.

Investors: Lux Capital, The Column Group, Polaris Partners, Illumina Ventures, Alexandria Venture Investments, Euclidean Capital and Two Sigma Ventures