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CU Boulder spinout OnKure Therapeutics enrolls first cancer patient in clinical trial

<p>A new聽drug therapy for cancer treatment, spun out of research performed in a <a href=" Boulder biochemistry lab</a>,聽may provide better results for patients with solid cancers and hematologic cancers, such as leukemia and lymphoma.</p>
<p>OnKure Therapeutics <a href=" began</a> phase 1 of a first-in-human clinical trial, testing investigational anti-cancer agent OKI-179鈥攁 novel and Class-selective HDAC inhibitor鈥攊n 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.</p>
<p>OKI-179 is a potent and selective inhibitor of a family of enzymes known as histone deacetylases (HDACs).聽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.</p>
<p>"We're very optimistic that OKI-179 will fill a hole in what is currently available," said Dr. Anthony D. Piscopio, president and CEO聽of OnKure, in a <a href=" release</a>. "It also stands out from FDA-approved HDAC inhibitors based on its unique potency and selectivity profile."</p>
<p>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聽in 2008, work by Dr. Xuedong Liu聽showed that largazole and the optimized analog that would become OKI-179 achieves its anti-proliferative effects through the mechanism of HDAC inhibition.聽</p>
<p>Dr. Liu, a CU Boulder professor of chemistry and bioschemistry and聽chief science officer and co-founder of OnKure, initially聽received a grant聽through the state of Colorado鈥檚 Bioscience Discovery Evaluation and Development (BDEG) program in 2010 to iterate and improve upon the natural compound.聽 In OnKure's pre-clinical trials, OKI-179 was the lead candidate and showed that it safely reduced the growth rate of tumors when聽dosed by itself or in combination with other targeted therapies.</p>
<p>"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,聽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.聽</p>
<p>OnKure exclusively licensed OKI-179 from <a href=" Partners at CU Boulder</a> in 2011, and later added further oncology assets, also developed in Dr. Liu鈥檚 lab, in a second license in 2015.聽 OKI-179 has also received issued patents in 37 different countries.聽</p>
<p>"OnKure鈥檚 story includes several key takeaways about innovating new medicines," said Brynmor Rees, assistant vice chancellor for Research &amp; Innovation and managing director of Venture Partners:</p>
<ul class="list-style-icon-3">
<li>Firstly, the source of the discovery (largazole) stems from the rich biodiversity found in nature, our best source of drug candidates.聽</li>
<li>Secondly, Dr. Liu鈥檚 team was able to translate a promising natural compound into an optimized analog with both an improved therapeutic profile and also novel composition of matter intellectual property.聽 These are key requirements in drug development.聽</li>
<li>Lastly, OnKure鈥檚 success draws on Colorado鈥檚 strong entrepreneurial ecosystem, including the leadership of a local serial entrepreneur, Dr. Tony Piscopio, and the critical grant funding provided to OnKure by the Office of Economic Development and International Trade.</li>
</ul>
<p>Visit <a href=" Partners at CU Boulder</a>聽to learn more about CU Boulder inventions and related support, or learn more about <a href=" Therapeutics</a>.</p>

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