Just before the world shut down in 2020 due to COVID-19, Hao Shi, Ph.D. '20, finished the last experiment for his doctoral research. He had developed an advanced imaging tool that visualizes the gut microbiome - the community of bacteria and other tiny organisms that live in human intestines - and saw the innovation's potential for real-world impact for fighting disease.
"I wanted to do something that will make a real difference I can feel in my lifetime," Shi said. "The pandemic really gave me this drive to actually try to do something now."
Shi is now chief technology officer of a company leveraging his work to start clinical trials with cancer patients.
That year, Shi launched Kanvas Biosciences with his Ph.D. advisor, Iwijn De Vlaminck, and medical microbiologist Matt Cheng. The team licensed the technology through Cornell's Center for Technology Licensing and joined the Center for Life Science Ventures, where they explored potential markets for the mapping platform. Eventually, they identified cancer immunotherapy as an area where their innovation could meet an urgent demand.
"As we're building this company, we found that this technology we developed was ideally suited as a platform to develop microbiome therapeutics," said De Vlaminck, associate professor of biomedical engineering in Cornell Engineering.
Kanvas' mapping platform, HiPR FISH, identifies the microorganisms present in the microbiome, pinpoints their locations and reveals complex interactions among different species. These insights inform the company's development of live biotherapeutics, drugs that utilize living microorganisms to treat disease by modifying the microbiome's contents.
The drugs can be used in immunotherapy, which empowers a patient's own immune systems to fight disease. Over the last decade, immunotherapy has revolutionized cancer treatment. It is generally less toxic than chemotherapy and radiation, but only about one in 10 patients respond to it.
Some patients who have responded exceptionally well to immunotherapy have donated their stool to help others. The fecal matter, which contains diverse microbial species, is transplanted into the patient's intestinal tract. These fecal transplants from "super donors" can dramatically improve patients' responses, proving the critical role of the microbiome for this treatment method.
"The problem with fecal transplants is you can't replicate them, you can't optimize them and you couldn't manufacture this at scale," said Cheng, who now serves as Kanvas' CEO. "We thought, can you replicate what makes a super donor so special and develop a therapy to treat other patients?"
To answer those questions, the team created a drug candidate, KAN-001, using their platform technology. A live biotherapeutic, KAN-001 effectively serves as a synthetic stool donation: the drug primes patients' microbiomes for immunotherapy treatment to enhance their response.
In studies in mice, KAN-001 worked better than stool from a super donor to improve patients' response to immunotherapy, and the drug is set to begin phase I testing in humans soon.
"We believe we have a unique therapy here that can really improve outcomes in these vulnerable patients," Cheng said. "We're really excited to use it to treat these patients in our upcoming clinical trials."
The startup has also developed a biotherapeutic to manage colitis, a common adverse effect of immunotherapy, using a similar approach. KAN-004 aims to help patients better tolerate their treatment by restoring gut health and reducing inflammation. Clinical trials for the drug could begin as early as next year.
While Kanvas is currently focused on advancing the two drug candidates through the trials process, the team sees broader applicability for their mapping platform in epidemiology, biology and health care.
"Our technology essentially allows you to understand the microbiome system," said Shi. "I think it will help us get a lot more information about how the microbiome, which we think of as a new organ system, works in our body. That will have implications beyond cancer."
Bridget Hagen is a marketing communications specialist for Cornell Research and Innovation.
