On March 5, 2024 ORIC Pharmaceuticals, Inc. (Nasdaq: ORIC), a clinical stage oncology company focused on developing treatments that address mechanisms of therapeutic resistance, reported that multiple abstracts have been accepted for presentation, including two oral presentations on ORIC-944, a potent and selective allosteric inhibitor of PRC2, at the 2024 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting taking place April 5-10, 2024, in San Diego, CA (Press release, ORIC Pharmaceuticals, MAR 5, 2024, View Source [SID1234640804]).

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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: Sunday, April 7, 2024, 1:00 p.m. – 2:30 p.m. PT
Presenter: Lori Friedman, Ph.D., Chief Scientific Officer
Abstract: Embargoed until April 7, 2024

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: Tuesday, April 9, 2024, 2:30 p.m. – 4:30 p.m. PT
Session Category: Experimental and Molecular Therapeutics
Session Title: Novel Antitumor Agents 5
Presenter: Anneleen Daemen, Ph.D., Executive Director of Translational Medicine

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: Sunday April 7, 2024, 1:30 p.m. – 5:00 p.m. PT
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.

All regular abstracts are available for viewing via AACR (Free AACR Whitepaper)’s online itinerary planner located, here. Invited speaker abstracts will be available for viewing the morning of their associated session.