Invited speaker presentation details: | |
Title: | Discovery of ORIC-944, a novel inhibitor of PRC2 with best-in-class properties for the treatment of prostate cancer |
Session Title: | New Drugs on the Horizon: Part 1 |
Date & Time: | |
Presenter: | |
Abstract: | Embargoed until |
Oral presentation details: | |
Title: | ORIC-944, a potent and selective allosteric PRC2 inhibitor with best-in class properties, demonstrates combination synergy with AR pathway inhibitors in prostate cancer models |
Abstract Number: | 6856 |
Date & Time: | |
Session Category: | Experimental and Molecular Therapeutics |
Session Title: | Novel Antitumor Agents 5 |
Presenter: | |
Abstract Highlights
ORIC-944, a potent, highly selective, orally bioavailable inhibitor of PRC2 demonstrated single agent tumor growth inhibition in a spectrum of AR-positive in vivo prostate cancer models, including those expressing AR mutants or ARv7. Combining ORIC-944 with an AR inhibitor was synergistic in multiple prostate cancer cell line models, and combination efficacy for ORIC-944 with AR inhibition was confirmed in vivo. RNA-seq analysis of transcriptional changes induced by ORIC-944 provided mechanistic insight into the role of PRC2 in prostate cancer lineage plasticity and combination response. These results position ORIC-944 as a potential best-in-class PRC2 inhibitor for combination with AR inhibitors in patients with prostate cancer.
Poster presentation details: | |
Title: | ORIC-613, a potential first- and best-in-class, orally bioavailable, potent and selective PLK4 inhibitor with synthetic lethality in TRIM37 high cancer models |
Abstract Number: | 594 |
Date & Time: | |
Session Category: | Experimental and Molecular Therapeutics |
Session Title: | Kinase and Phosphatase Inhibitors 1 |
Location: | Poster Section 25 |
Abstract Highlights
ORIC-613 is an orally bioavailable, potent and exquisitely selective small molecule inhibitor of PLK4, which is synthetic lethal in tumor cells with high levels of TRIM37. ORIC-613 is highly selective against the kinome, including against the closely related aurora kinases and other PLK family members. Preclinical assessment in cancer cell lines revealed the synthetic lethality, with ORIC-613 having stronger potency in TRIM37-high cells as evidenced by inducing tumor cell death specifically in TRIM37-high versus TRIM37-wildtype cells. Analysis of genomic data from adult tumors indicates that increased TRIM37 copy number is found across a breadth of cancers, with notable prevalence in breast cancer. Oral dosing of ORIC-613 resulted in tumor growth inhibition and regressions in TRIM37-high xenograft breast tumors. These results position ORIC-613 as a potential first- and best-in-class development candidate, which demonstrates synthetic lethality in TRIM37-high tumors and has the potential to benefit these patients.
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Cautionary Note Regarding Forward-Looking Statements
This press release contains forward-looking statements as that term is defined in Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. Statements in this press release that are not purely historical are forward-looking statements. Such forward-looking statements include, among other things, statements regarding the potential best-in-class properties of ORIC-944; ORIC-613 as a potential first- and best-in-class development candidate; the development plans for ORIC-944 and ORIC’s other product candidates; the potential advantages of ORIC-944, ORIC-613 and ORIC’s other product candidates and programs; and plans underlying ORIC’s clinical trials and development. Words such as “believes,” “anticipates,” “plans,” “expects,” “intends,” “will,” “goal,” “potential” and similar expressions are intended to identify forward-looking statements. The forward-looking statements contained herein are based upon ORIC’s current expectations and involve assumptions that may never materialize or may prove to be incorrect. Actual results could differ materially from those projected in any forward-looking statements due to numerous risks and uncertainties, including but not limited to: risks associated with the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics and operating as an early clinical stage company; ORIC’s ability to develop, initiate or complete preclinical studies and clinical trials for, obtain approvals for and commercialize any of its product candidates; changes in ORIC’s plans to develop and commercialize its product candidates; the potential for clinical trials of ORIC’s product candidates to differ from preclinical, initial, interim, preliminary or expected results; negative impacts of health emergencies, economic instability or international conflicts on ORIC’s operations, including clinical trials; the risk of the occurrence of any event, change or other circumstance that could give rise to the termination of ORIC’s license and collaboration agreements; the potential market for ORIC’s product candidates, and the progress and success of competing therapeutics currently available or in development; ORIC’s ability to raise any additional funding it will need to continue to pursue its business and product development plans; regulatory developments in
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