A new drug therapy for cancer treatment, spun out of research performed in a CU Boulder biochemistry lab, may provide better results for patients with solid cancers and hematologic cancers, such as leukemia and lymphoma.
OnKure Therapeutics recently began phase 1 of a first-in-human clinical trial, testing investigational anti-cancer agent OKI-179—a novel and Class-selective HDAC inhibitor—in patients with advanced solid tumors. The trial is taking place in partnership with CU Cancer Center on the Anschutz Medical Campus, and the patient is doing well, according to reports.
OKI-179 is a potent and selective inhibitor of a family of enzymes known as histone deacetylases (HDACs). While previous HDAC inhibitors have shown promise in preclinical studies, clinical benefit has generally been limited by toxicity, something OnKure aims to resolve with OKI-179.
"We're very optimistic that OKI-179 will fill a hole in what is currently available," said Dr. Anthony D. Piscopio, president and CEO of OnKure, in a press release. "It also stands out from FDA-approved HDAC inhibitors based on its unique potency and selectivity profile."
The compound is an analog of the naturally occurring chemical largazole, named for Key Largo, Florida, where largazole is bio-manufactured by a type of coral-colonizing bacteria indigenous to the region. After its structure and anti-proliferative effects were discovered in 2008, work by Dr. Xuedong Liu showed that largazole and the optimized analog that would become OKI-179 achieves its anti-proliferative effects through the mechanism of HDAC inhibition.
Dr. Liu, a CU Boulder professor of chemistry and bioschemistry and chief science officer and co-founder of OnKure, initially received a grant through the state of Colorado’s Bioscience Discovery Evaluation and Development (BDEG) program in 2010 to iterate and improve upon the natural compound. In OnKure's pre-clinical trials, OKI-179 was the lead candidate and showed that it safely reduced the growth rate of tumors when dosed by itself or in combination with other targeted therapies.
"Basically, HDAC enzymes remove a kind of speed limiter from cells, allowing them to proliferate more readily and HDAC inhibitors like OKI-179 block this effect," said Dr. Jennifer Diamond, medical director of the CU Cancer Center Cancer Clinical Trials Office, co-director of the Women's Cancer Developmental Therapeutics Program, and principal investigator of the OKI-179 phase 1 clinical trial.
OnKure exclusively licensed OKI-179 from Venture Partners at CU Boulder in 2011, and later added further oncology assets, also developed in Dr. Liu’s lab, in a second license in 2015. OKI-179 has also received issued patents in 37 different countries.
"OnKure’s story includes several key takeaways about innovating new medicines," said Brynmor Rees, assistant vice chancellor for Research & Innovation and managing director of Venture Partners: