On April 19, 2018 Onconova Therapeutics, Inc. (NASDAQ:ONTX), a Phase 3 clinical-stage biopharmaceutical company focused on discovering and developing novel products to treat cancer, reported an advance in pre-clinical development and the presentation of new data for investigational ON 123300, a novel dual inhibitor of CDK4/6 + ARK 5 with potential application across a variety of cancers (Press release, Onconova, APR 19, 2018, View Source [SID1234525549]).
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CDK inhibitors have emerged as promising and potentially targeted large market cancer therapies. ON 123300 has the potential to overcome many of the limitations of current generation CDK4/6 inhibitors. Onconova believes that ON 123300 may act as a single agent, due to the unique targeting of ARK5, as well as CDK 4 and 6, making it potentially suitable for indications that may not be responsive to the current generation of CDK4/6 inhibitors.
Onconova and HanX Biopharmaceuticals, the Company’s Greater China collaboration partner for ON 123300, recently completed the pre-Investigational New Drug (pre-IND) consultation with the U.S. Food and Drug Administration (FDA). These discussions provided guidance for the manufacturing of ON 123300 and the pre-clinical development plan for the submission of an IND application.
The data from preclinical studies demonstrates that there is a differential metabolism of ON 123300 in male versus female rodents. As a result, the drug exposure is almost 2-3 fold higher in female rats. Based upon preclinical animal liver microsome studies, this differential effect appears to be limited to rodents, and is not observed in preclinical studies with human liver microsomes. Based on the metabolism data from other species, relevant species have been selected along with the dosing strategy to be implemented in GLP toxicological studies to be conducted by HanX. As a part of the pre-clinical development program, Onconova and HanX announced a collaborative program in December 2017, wherein the remaining IND enabling studies will be funded by and conducted by HanX.
Onconova previously reported that ON 123300 was found to be as active as Palbociclib (Pfizer’s Ibrance) in a preclinical Rb + ve xenograft model. Moreover, the molecule may have the potential advantage of reduced neutropenia when compared to Palbociclib based upon this model.
Ramesh Kumar, President and CEO of Onconova, commented, "At the end of March, we received pre-IND guidance from the FDA, which provides a path towards filing an IND and then starting clinical trials. Our partner, HanX, has initiated GMP manufacturing and will be initiating GLP pre-clinical studies based on the guidance provided by the FDA, and we look forward to advancing ON 123300 into clinical development."
Faming Zhang, Ph.D., founder and Chairman of HanX, commented, "We are pleased to have completed the process chemistry and have initiated GMP manufacturing for ON 123300. GLP toxicology studies are planned and we will be undertaking additional preclinical studies to enhance the profile of this novel compound. In collaboration with Onconova, our goal is to simultaneously file the IND in the USA and China, as soon as possible. Once an IND is in place, HanX plans to initiate Phase 1 studies in China and also participate in more advanced global clinical trials."
A copy of the presentation is available by visiting the Scientific Presentations section of Onconova’s website.