Syros Pharmaceuticals Licenses Clinical-Stage RARα Agonist to Develop and Commercialize for Genomically-Defined Cancer Populations Identified by Gene Control Platform

- Phase 2 clinical trial in acute myeloid leukemia (AML) / myelodysplastic syndrome (MDS) patients with gene control biomarker discovered by Syros planned in the first half of 2016 -

- Provides validation for proprietary gene control target and biomarker discovery and development platform -

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Syros Pharmaceuticals, the industry pioneer in gene control, announced today that it entered into an exclusive license agreement with the Japanese oncology company TMRC Co. Ltd., to develop and commercialize tamibarotene in North America and Europe for cancer. Tamibarotene is a first-in-class selective agonist to retinoic acid receptor alpha (RARα), a nuclear hormone receptor which regulates transcription. Using Syros’ proprietary gene control discovery and development platform, the Company discovered a cancer dependency to RARα and a biomarker to identify patients with this dependency who may respond to RARα agonist therapy. Syros plans to initiate a Phase 2 clinical trial with tamibarotene in the first half of 2016 in this genomically-defined subset of patients with AML and MDS. Tamibarotene is marketed in Japan for acute promyelocytic leukemia (APL), a form of AML characterized by a different genomic alteration of RARA (gene encoding RARα).

“Tamibarotene represents a promising therapeutic option for a genomically-defined subset of cancer patients, and we are moving rapidly to bring this therapy to patients,” said Nancy Simonian, MD, Chief Executive Officer of Syros. “Using our proprietary gene control target discovery and development platform, we discovered a novel cancer dependency to RARα, and we were delighted then to identify tamibarotene, a first- and best-in-class selective RARα agonist with a well characterized efficacy and safety profile. By in-licensing this drug, we are able to accelerate Syros to a clinical-stage organization and in so doing demonstrate the power of our platform to identify gene-control targets and biomarkers, while we continue to advance our own internally discovered drug candidates to gene control targets.”

Syros’ proprietary gene control platform systematically analyzes human disease tissue to uncover gene regulatory programs which have been altered or dysregulated in disease and which may be suitable targets for therapeutic intervention. In this case, Syros discovered a biomarker associated with RARα dependency in subsets of AML and breast cancer patients based on analysis of their tumors. Syros then demonstrated in patient-derived xenograft models of AML that tumors with the biomarker for RARα dependency responded to tamibarotene while the tumors without the biomarker did not respond to the therapy. Treatment with tamibarotene extended survival in animals with the patient-derived tumors with the biomarker. Syros observed the elevated biomarker in approximately 25% of AML patient samples analyzed. Syros plans to research the potential role of this biomarker in other cancers, including in breast cancer.

The Company plans to initiate a Phase 2 clinical trial in AML and MDS patients in early 2016 with tamibarotene (which going forward will be referred to as SY-1425). The objective of the single-arm, single-agent study will be to determine the efficacy of tamibarotene in patients with high levels of the RARα biomarker. The dose and schedule to be used in the trial will be the same as those used in the approved APL indication in Japan.

Financial terms of the agreement were not disclosed.

About Syros Pharmaceuticals

Syros Pharmaceuticals is a therapeutics company harnessing breakthroughs in gene control to revolutionize the treatment of cancer and other diseases. Syros’ proprietary platform identifies the master switches for disease genes, opening a whole new approach to novel therapeutics and biomarkers. The Company’s founders are pioneers in gene control research and translation. Co-founded by Flagship Ventures and ARCH Venture Partners, Syros Pharmaceuticals is located in Cambridge, Mass. For more information, visit www.syros.com.

About Tamibarotene

Tamibarotene, also called retinobenzoic acid, is an orally active, synthetic retinoid. It is currently marketed in Japan for the treatment of patients with relapsed or refractory APL. To date, over 1,500 patients have been treated with tamibarotene. Published data from clinical studies show that tamibarotene induces a complete remission in 36-58% of relapsed or refractory APL patients. Tamibarotene is well tolerated. Adverse events include elevated cholesterol and lipids, skin rash, headache and retinoic acid syndrome. (Tobita, et al. Blood, August 1997; Sanford D, et al. British Journal of Haematology, July 2015)