Onconova Therapeutics Announces Abstract At The ASCO Annual Meeting Highlighting Narazaciclib’s Differentiated Inhibitory And Improved Safety Profile In Preclinical Models
Onconova Therapeutics, Inc. (NASDAQ: ONTX), a clinical-stage biopharmaceutical company focused on discovering and developing novel products for patients with cancer, today announced the publication of an abstract at the American Society of Clinical Oncology (ASCO) Annual Meeting. Featured in the abstract are preclinical data from in vitro and cell-based assays that demonstrate how narazaciclib’s inhibitory profile differentiates it from the FDA-approved CDK4/6 inhibitors palbociclib, ribociclib, and abemaciclib.
Key data and conclusions from the abstract include:
- Narazaciclib, abemaciclib, palbociclib, and ribociclib each have strong affinity for CDK4/cyclin D1, with Kd values of 0.18 nM, 0.08 nM, 0.75 nM, and 1.3 nM, respectively.
- Narazaciclib and abemaciclib have similar affinities against CDK family members, including nM activity against CDK2/cyclin A, which may play a role in resistance to palbociclib and ribociclib.
- Narazaciclib’s inhibitory activity against GSK3β, a kinase whose inhibition putatively causes tolerability issues related to diarrhea, is ~29 times less than that of abemaciclib.
- Cellular kinase assays showed narazaciclib’s highest inhibitory activity to be against CDK4/6, CSF1R, (supports pro-tumor immune suppression), and NUAK1/ARK 5 (associated with poor prognosis in multiple cancers and implicated in cancer cell migration, invasion, and metastasis).
- Cellular Thermal Shift Assay (CETSA) and integrative Inferred Kinase Activity (INKA) analysis showed that narazaciclib is associated with and modulated unique signaling pathways resulting in specific deregulated phosphorylation patterns when compared to palbociclib treated cells.
Steven M. Fruchtman, M.D., President and Chief Executive Officer of Onconova and co-author of the abstract, commented, “Though revolutionary and commercially successful, currently available CDK4/6 inhibitors are limited by tolerability and safety issues as well as the unfortunate reality of primary and acquired drug resistance. This creates a pressing unmet need for novel agents that may overcome these shortcomings and provide patients with durable clinical benefit. Narazaciclib’s decreased affinity for targets associated with poor tolerability, together with its increased inhibitory activity against kinases implicated in metastasis, cancer cell survival, immune suppression, and drug resistance, suggests it may address this need. We continue to explore this hypothesis in narazaciclib’s clinical program and remain on track to establish a recommended Phase 2 dose by the end of the year.”
A copy of the abstract, titled, “Narazaciclib’s kinase inhibitory activity is differentiated from approved CDK4/6 inhibitors in preclinical models,” is available on the ASCO Annual Meeting website.
About Onconova Therapeutics
Onconova Therapeutics is a clinical-stage biopharmaceutical company focused on discovering and developing novel products for patients with cancer. The Company has proprietary targeted anti-cancer agents designed to disrupt specific cellular pathways that are important for cancer cell proliferation.
Onconova’s novel, proprietary multi-kinase inhibitor narazaciclib (formerly ON 123300) is being evaluated in two separate and complementary Phase 1 dose-escalation and expansion studies. These trials are currently underway in the United States and China.
Onconova’s product candidate rigosertib is being studied in an investigator-sponsored study program, including in a dose-escalation and expansion Phase 1/2a investigator-sponsored study with oral rigosertib in combination with nivolumab for patients with KRAS+ non-small cell lung cancer.