On April 19, 2023 Onconova Therapeutics, Inc. (NASDAQ: ONTX), ("Onconova" or "the Company"), a clinical-stage biopharmaceutical company focused on discovering and developing novel products for patients with cancer, reported new preclinical data on narazaciclib in two poster presentations at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting (Press release, Onconova, APR 19, 2023, View Source [SID1234630321]).
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"Data being presented at AACR (Free AACR Whitepaper) further highlight how narazaciclib’s differentiated inhibitory profile may allow it to overcome the shortcomings of FDA-approved CDK 4/6 inhibitors," said Steven M. Fruchtman, M.D., President and Chief Executive Officer of Onconova. "Kinases recently identified as targets of narazaciclib, but not of the most widely prescribed CDK 4/6 inhibitor include BUB1, the overexpression of which was shown to be associated with poor survival in subtypes of endometrial and breast cancer. In addition, data featured in the AACR (Free AACR Whitepaper) posters provide additional evidence of narazaciclib’s potential to combine synergistically with therapeutic agents in a variety of drug classes. Looking forward, the learnings from these studies will be a valuable asset as we advance narazaciclib’s Phase 1/2a trial in endometrial cancer and evaluate potential opportunities for its clinical study in additional indications and with combination approaches to promote efficacy in resistant tumors."
Poster 5987: Differential targets engaged by narazaciclib in comparison to the approved CDK 4/6 inhibitors contribute to enhanced inhibition of tumor cell growth.
Featured in this poster are data characterizing narazaciclib’s mechanism of action and activity in preclinical cancer models. Results showed that, in addition to inhibiting kinases such as CDK 4/6, narazaciclib treatment led to the degradation of other kinases not targeted by the FDA-approved CDK 4/6 inhibitor palbociclib. These kinases included BUB1, the overexpression of which was shown to be associated with poor prognosis in breast cancer and uterine corpus endometrial carcinomas. Data from PYMT murine breast cancer cells showed a stronger induction in apoptosis (programmed cell death) with narazaciclib compared to palbociclib and another FDA-approved CDK 4/6 inhibitor, abemaciclib. In addition, data from multiple cell lines suggest that inhibiting autophagy may sensitize breast cancer cells to narazaciclib treatment.
Poster 5974: Synergistic activity of the CDK 4/6 antagonist narazaciclib (ON123300) with irreversible BTK inhibition in ibrutinib-resistant mantle cell lymphoma.
Data featured in this poster demonstrate narazaciclib’s potent antitumor activity against mantle cell lymphoma (MCL) cell lines, independent of their sensitivity to the FDA-approved Bruton’s tyrosine kinase inhibitor ibrutinib. Narazaciclib’s activity against MCL cell lines was shown to be 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. Combining narazaciclib with ibrutinib led to synergistic increases in antitumor activity against both ibrutinib-sensitive and ibrutinib-resistant MCL cell lines. In addition, narazaciclib exhibited significant antitumor activity without detectable toxicity when combined with ibrutinib in an in vivo model of MCL (embryo chorioallantoic membrane xenograft model).
Copies of the AACR (Free AACR Whitepaper) posters will be available on the on the "Scientific Presentations" section of the Onconova website following the conclusion of the conference.