SY-5609 :: Syros Pharmaceuticals, Inc. (SYRS)

Decreasing Expression of Cancer-Driving Genes with CDK7

SY-5609 is a highly selective and potent oral inhibitor of the cyclin-dependent kinase 7 (CDK7) that is expected to enter a Phase 1 clinical trial in patients with select solid tumors, including breast, lung and ovarian cancers, as well as solid tumors of any histology with a specific molecular signature.

SY-5609 represents a new approach to treating cancer that we believe has potential in a range of difficult-to-treat cancers. It has induced deep and sustained tumor growth inhibition, including complete regressions, as a single agent in preclinical models of breast, ovarian and lung cancers. SY-5609 has also shown substantial anti-tumor activity in combination with fulvestrant in hormone receptor (HR)-positive breast cancer models that are resistant to CDK4/6 inhibitors. SY-5609 has also been shown preclinically to preferentially kill cancer cells over non-cancerous cells.

A Promising Approach for Difficult-to-Treat Cancers

Cancer cells adapt to hijack or thwart the body’s normal processes to grow out of control, forming tumors and crowding out healthy cells. SY-5609 has the potential to disrupt two important processes that cancer cells use to survive and thrive: increased expression of cancer-promoting genes, and uncontrolled cell cycle progression.

Potent and Highly Selective CDK7 Inhibitor

Program	Indication	Discovery	Preclinical	Early Clinical	Mid-Stage Clinical	Pivotal	Commercial Rights
SY-5609 (Oral CDK7 inhibitor)	SY-5609 (Oral CDK7 inhibitor) Cancer	Discovery Phase complete	Preclinical Phase in progress	Early Clinical Phase not started	Mid-Stage Clinical Phase not started	Pivotal Phase not started Syros (Global)	Syros (Global)

PRECLINICAL EVALUATION OF PK, PD, AND ANTI-TUMOR ACTIVITY OF THE ORAL, NON-COVALENT, POTENT AND HIGHLY SELECTIVE CDK7 INHIBITOR, SY-5609, PROVIDES RATIONALE FOR CLINICAL DEVELOPMENT IN MULTIPLE SOLID TUMOR INDICATIONS

LIV JOHANNESSEN, SHANHU HU, NAN KE, ANTHONY D’IPPOLITO, NISHA RAJAGOPAL, PRIYANKA SAWANT, KRISTIN HAMMAN, JASON MARINEAU, ANNELI SAVINAINEN, WILLIAM ZAMBONI, GRAEME HODGSON
31^st EORTC-NCI-AACR MOLECULAR TARGETS AND CANCER SYMPOSIUM
ABSTRACT NUMBER: C091
2019

SY-5609, AN ORALLY AVAILABLE SELECTIVE CDK7 INHIBITOR, DEMONSTRATES BROAD ANTI-TUMOR ACTIVITY IN VIVO

Shanhu Hu, Jason Marineau, Kristin Hamman, Michael Bradley, Anneli Savinainen, Sydney Alnemy, John Carulli, Claudio Chuaqui and Eric Olson
American Association for Cancer Research (AACR) Annual Meeting
Abstract Number: 4421
2019

AN ORAL AND SELECTIVE CDK7 INHIBITOR DEMONSTRATES SUBSTANTIAL ANTI-TUMOR EFFECT IN BREAST AND OVARIAN CANCER MODELS

Shanhu Hu, Jason Marineau, Michael Bradley, Kristin Hamman, Sydney Alnemy, Danielle Smith, John Carulli, Claudio Chuaqui
30th EORTC-NCI-AACR Molecular Targets and Cancer Therapeutics Symposium
Abstract Number 96
2018

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SY-5609