Proposed model of retinoid signaling in Type 2 diabetes demonstrates disease modifying mechanism for Kayothera therapies.

Kayothera, an early-stage therapeutics company developing 1st-in-class, orally-available antagonists of the retinoid pathway, announces that it is advancing a program to treat and reverse cardiometabolic diseases, with a focus on Type 2 Diabetes. The clinical use of retinoids has long been associated with rapid weight gain, hypertriglyceridemia and hyperlipidemia, while preclinical studies have suggested a causal role for retinoid signaling in pancreatic degeneration. Kayothera has advanced a series of potential therapies to reverse these retinoid-dependent effects and treat the underlying cause of Type 2 Diabetes, a disease which affects more than 500 million people, or 5% of the world’s population.

A recent publication in Nature Communications co-authored by Kayothera founders, Dr. Mark Esposito and Dr. Yibin Kang, along with Columbia University researchers, demonstrated that Kayothera’s therapies could reverse Type 2 Diabetes progression. This work demonstrated that Beta cell loss in Type 2 Diabetes is driven by ALDH1a3 activity, leading to retinoid signaling and progressive degeneration. Treatment by oral administration with Kayothera therapies reversed pancreatic decline in these mice and results in a disease-treating effect that persisted for weeks after treatment stopped.  Kayothera recently presented this work at the Keystone Symposium focusing on new strategies to treat Type 2 Diabetes.

Kayothera compound KOTX1 reverses Beta cell decline in preclinical models of Type 2 Diabetes and restores Insulin production.

Advanced candidates in Kayothera’s pipeline are safe and effective, with no dose-limiting toxicities observed to date and with the ability to restore the function of diseased pancreatic islets in preclinical models of obesity and Type 2 diabetes. Kayothera plans to nominate a development candidate for cardiometabolic disease in Q4 2023.

Images from Son et al, 2023. Nat Comms. 

The Tiger Entrepreneur Award will be presented at this year’s Celebrate Princeton Innovation reception on Thursday, October 13. The 2022 winners, in alphabetical order:

Mark Esposito *17

Esposito is co-founder and vice president of Kayothera, a startup developing small molecule immunotherapies to treat solid cancers. Kayothera is a spinout from the lab of Yibin Kang, Warner-Lambert/Parke-Davis Professor of Molecular Biology at Princeton, with whom Esposito earned his Ph.D. and also was a postdoctoral researcher. Kang and Esposito co-founded Kayothera in 2019 with seed funding from the New Jersey Health Foundation. Earlier this year, Kayothera raised a $8 million Series A round, led by Accelerator Life Science Partners. In addition to his work at Kayothera, he is Director of Biology at Optimeos, another Princeton spinout, as well as Principal at Meagi, LLC, a biotechnology consulting firm.

The original Princeton University press release. 

“As part of BIO’s commitment to growing the biotechnology ecosystem, 2021 Start-Up Stadium successfully increased awareness of these 16 innovative start-up finalists to hundreds of potential investors and development partners,” said Bernard V. Fallon, BIO’s Managing Director of Industry Research, Investor Outreach, and Education.  “Given the diversity of exciting technologies presented and in biotech investors’ specialties, BIO has already received feedback on dozens of equity investment conversations for finalists proceeding as outputs from the Start-Up Stadium contest, beyond the prize benefits that will go to this year’s one winning company, Kayothera.”

The winning company receives a one-year membership at BIO and a “fast-track” accelerator application and nomination into the final selection phase for up to a $10,000 sequencing grant (Illumina Accelerator).

“The start-up stadium was a fantastic opportunity to craft Kayothera’s narrative while reaching a broad audience of stakeholders in the cancer immunotherapy field,” noted Mark Esposito, CEO of Kayothera Inc. “We made several high-value investor introductions through the Start-up stadium that have led to fruitful discussions since the event.”

A full list of 2021 Start-Up Stadium participants and judges can be found here.

Press release authored and released by BIO: Link

At Kayothera, we care deeply about making new therapies that transform outcomes for patients with difficult-to-treat cancers. By developing therapies with the potential to produce deep responses in patients with metastatic or advanced disease, we hope to give patients a new lease on life.

Note: A non-paywall link is available here.

Additional press on this discovery can be found at Princeton University, a commentary at Nature Cell Biology, and the original article.

Kayothera is developing therapies to treat late-stage and metastatic cancers, including breast, lung, pancreatic, colorectal, brain, and kidney cancers. Currently, prospects for patients facing such diseases are grim: These cancers are fairly resistant to current chemotherapy and pharmaceutical companies have found it difficult and challenging to pursue new treatments.

But discoveries made in the laboratory of Princeton University Professor Yibin Kang point to novel approaches to overcome the defenses of cancer cells. Kang, the Warner-Lambert/Parke-Davis Professor of Molecular Biology, and Mark Esposito, a postdoctoral research associate in the Kang lab, have cofounded Kayothera to pursue the development of therapies based on the Kang lab work.

According to Professor Kang, Kayothera’s lead programs have considerable biological validation. “Genetic and pharmacological studies in my laboratory have identified and validated a family of key enzymes that protect cancer cells under stressful conditions, such as metastasis, drug treatment and attack by the immune system.  The development of small molecule inhibitors against these enzymes will potentially improve the efficacy of chemotherapy and immunotherapy against advanced cancers.”

The company presented the type of opportunity to make a difference that the New Jersey Health Foundation had in mind when it worked with Princeton University to create a funding framework last fall: The two organizations share a goal to accelerate the progress of Princeton-related life-science innovation toward real-world impact.

“The mission of the New Jersey Health Foundation is to promote the advancement of health-related research and education throughout the state,” said George F. Heinrich, M.D., Vice Chair and CEO. “We are excited that our funding will advance Kayothera’s research to help address some of the toughest challenges in cancer therapy with the ultimate goal of extending patient lives. We hope this is the first of many opportunities we have to support the progress of Princeton research toward real-world impact.”

Mark Esposito, Kayothera CEO, laid out the company’s next steps and what the funding means to the company. “This partnership with NJHF enables us to move our two therapeutic programs from basic scientific discovery to clinical development. Ultimately, this is an investment in improving the quality of life of patients and giving hope to those affected by terminal cancer diagnoses.”

Story originally reported by Princeton University.