On August 5, 2020 ORIC Pharmaceuticals, Inc. (Nasdaq: ORIC), a clinical stage oncology company focused on developing treatments that address mechanisms of therapeutic resistance, reported it has entered into an exclusive worldwide license agreement with Mirati Therapeutics, Inc. (Nasdaq: MRTX), a leading targeted oncology company dedicated to advancing novel therapeutics (Press release, ORIC Pharmaceuticals, AUG 5, 2020, View Source [SID1234562914]). ORIC will have exclusive worldwide rights for the development activities and commercialization of a small molecule allosteric inhibitor program directed towards the polycomb repressive complex 2 (PRC2), a validated oncogenic target across several cancers with promising therapeutic potential in prostate cancer, among other indications.

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"We are excited to add another program to our pipeline that is well aligned with our mission of overcoming cancer resistance and our expertise in hormone-dependent cancers, key tumor dependencies and precision oncology," said Jacob Chacko, M.D., president and chief executive officer of ORIC. "Our lead program, ORIC-101, and the rest of our innovative, wholly-owned pipeline of precision medicines have thus far been internally generated by our fully integrated drug discovery and development team. This PRC2 inhibitor is the first externally sourced program we’ve added to our pipeline and, based on work conducted at ORIC, we believe Mirati’s novel approach in targeting PRC2 may address an area of significant unmet medical need in treatment-resistant prostate cancer."

"We are pleased to enter into this agreement with ORIC, which enables the continued advancement of Mirati’s PRC2 inhibitors" said James G. Christensen, Ph.D., executive vice president and chief scientific officer of Mirati. "With ORIC’s focus on novel treatments for prostate cancer, ORIC is an ideal partner to further the research and development of this program."

Mirati has developed highly selective allosteric inhibitors of PRC2, including a lead candidate now designated as ORIC-944, that target its regulatory embryonic ectoderm development (EED) subunit and may represent a best-in-class approach for the treatment of advanced prostate cancer. Prior to entering into the license agreement with Mirati, ORIC generated compelling in vivo efficacy data in enzalutamide-resistant prostate cancer models with ORIC-944. ORIC expects to file an IND for ORIC-944 in the second half of 2021.

Under the terms of the agreement, in exchange for an exclusive worldwide license to develop and commercialize Mirati’s PRC2 inhibitor program, ORIC paid to Mirati a one-time non-cash payment of $20 million in shares of ORIC common stock. The number of shares issued to Mirati was based on a price of $34.00 per share, representing a premium of 10% to the 60-day trailing volume-weighted average trading price of ORIC’s common stock. ORIC is not subject to any future milestone or royalty payment obligations to Mirati.

Webcast and Conference Call

ORIC will host a webcast and conference call today, August 5th, at 4:30 p.m. ET. To participate in the conference call, please dial (866) 393-4306 (domestic) or (734) 385-2616 (international) and refer to conference ID: 5167646. Please join the conference call at least 15 minutes early to register. A live webcast will be available in the Investors section of the company’s website at www.oricpharma.com. The webcast will be archived for 60 days following the presentation.

About PRC2

The polycomb repressive complex 2 (PRC2) has methyltransferase activity required for long term epigenetic silencing of chromatin and plays a critical role in cancer. PRC2 core subunits EED, EZH2, and SUZ12 function as part of a complex to selectively repress gene expression by regulating the transfer of methyl groups to a distinct lysine residue on histone proteins associated with DNA. Overexpression and/or mutations in PRC2 can result in aberrant methylation activity, leading to tumorigenesis in multiple solid tumors and hematological malignancies. In particular, PRC2 dysfunction can lead to decreased expression of tumor suppressor genes and other target genes that have been associated with poor prognosis in patients with metastatic prostate cancer.

First-generation PRC2 inhibitors, which target the catalytic EZH2 subunit, have demonstrated clinical activity in several cancers, and one has been approved by the FDA for the treatment of epithelioid sarcoma and follicular lymphoma. More recent scientific advances have focused on developing allosteric inhibitors of PRC2, which may help to address several limitations of first-generation PRC2 inhibitors. Research conducted at ORIC demonstrated that allosteric inhibitors of PRC2 are more efficacious in treatment-resistant prostate cancer models than has been reported by traditional non-allosteric PRC2 inhibitors.