On March 15, 2023 Onconova Therapeutics, Inc. (NASDAQ: ONTX), ("Onconova"), a clinical-stage biopharmaceutical company focused on discovering and developing novel products for patients with cancer, reported the publication of two abstracts that have been accepted for poster presentations at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, which is taking place at the Orange County Convention Center in Orlando, Florida from April 14 – 19, 2023 (Press release, Onconova Therapeutics, MAR 15, 2023, View Source [SID1234628833]).
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The full texts of the published abstracts can be found on the AACR (Free AACR Whitepaper) Annual Meeting website. The corresponding posters will be presented during the "Cyclin-dependent Kinases and Cyclin-dependent Kinase Inhibitors" poster session, which is taking place from 9:00 a.m. – 12:30 p.m. ET on April 19, 2023. Additional information on the posters is shown below.
Poster Title: Synergistic activity of the CDK4/6 antagonist narazaciclib (ON123300) with irreversible BTK inhibition in ibrutinib-resistant mantle cell lymphoma
Abstract Number: 5974
This poster will describe studies evaluating narazaciclib in preclinical models of mantle cell lymphoma (MCL). Results from these studies demonstrated narazaciclib’s single-agent antitumor activity in MCL cell lines independent of their sensitivity to ibrutinib, which is a Bruton’s tyrosine kinase inhibitor (BTKi) approved by the U.S. Food and Drug Administration (FDA) for the treatment of MCL. When combining narazaciclib with ibrutinib, synergistic increases in antitumor activity against both BTKi-resistant and BTKi-sensitive MCL cell lines were observed.
Additional analyses showed that narazaciclib’s antitumor activity against the evaluated MCL cell lines was superior to that of the FDA-approved CDK 4/6 inhibitors palbociclib and ribociclib, and similar to that of the FDA-approved CDK 4/6 inhibitor abemaciclib. Treatment with narazaciclib also led to tumor growth inhibition without detectable toxicity in a chicken embryo chorioallantoic membrane (CAM) xenograft model of MCL.
Poster Title: Differential targets engaged by narazaciclib in comparison to the approved CDK4/6 inhibitors contribute to enhanced inhibition of tumor cell growth
Abstract Number: 5987
This poster will describe cell-based, in vitro, and bioinformatic analyses comparing narazaciclib and palbociclib. Results from a cell-based murine mammary carcinoma model showed a stronger induction of programmed cell death with narazaciclib compared to palbociclib. In vitro and cell-based analyses revealed multiple targets that are engaged by narazaciclib but not by palbociclib. These targets included BUB1, the overexpression of which is correlated with poor survival in triple negative breast cancer. The results of additional cell-based assays that will be described in the poster suggest that narazaciclib may promote antitumor immunity and show that combining narazaciclib with autophagy inhibitors sensitizes breast cancer cells to cell death.