A gene control pathway mapper working directly in human disease tissue, Syros Pharmaceuticals Inc. pulled down $40 million by way of its preferred stock transaction to advance SY-1425 (tamibarotene), described as a first-in-class selective agonist to retinoic acid receptor alpha (RARα), into a phase II trial.

The Cambridge, Mass.-based firm is able with its approach to manipulate gene "switches" and pinpoint those patients with the best chances of benefiting from drugs that do so. In the case of SY-1425, which will be tested in a genomically defined subset of patients with acute myelogenous leukemia and myelodysplastic syndromes, Syros discovered a cancer dependency to RARα and a biomarker to identify patients with that dependency who may respond to agonist therapy. A spokesperson for Syros said no one from the company was available for comment.

Syros, which raised $53 million in a series B round in the fall of 2014, was co-founded and backed by Flagship Ventures and Arch Venture Partners, and was spun out of the Whitehead Institute and Dana-Farber Cancer Institute. The firm was named after a Greek island, like another Flagship/Arch project, Agios Pharmaceuticals Inc. CEO Nancy Simonian formerly served as chief medical officer of Cambridge, Mass.-based Millennium: The Takeda Oncology Co., and was responsible for the development of Velcade (bortezomib) – originally approved in the U.S. in 2003 for multiple myeloma and expanded to other various oncology indications – as well as other drugs. (See BioWorld Today, Oct. 27, 2014.)

Launched in April 2013 with a $30 million series A round, Syros said it has industrialized the mapping of gene control regions and put together the largest known collection of human gene regulatory circuits, integrated into advanced biology and chemistry. Researchers have found that the genes regulated by "super-enhancers" (discovered by the company's founders) reside in insulated regions of the genome called "neighborhoods" – a link that points to the relationship between super-enhancers and chromosomal structure and zeroes in on a crucial aspect of gene expression: the integrity of those "neighborhoods."

H.C. Wainwright analyst Andrew Fein called super-enhancers his "favorite platform," and tagged privately held Syros "one of the most interesting companies leveraging high-powered academic work," plus a solid pedigree. The gene control discovery effort "is expected to help identify targets upstream of multiple key disease-causing genes," he wrote in a December research report. "Super-enhancer analyses and interpretation is a very complex errand by today's epigenetic standards, and potentially a mega-project best pursued within the walls of a Harvard lab rather than at a private company. However, Eric Olson, the head of discovery and development at Syros, is just about the only person whom we believe could tease out high-yield applicability in a sophisticated paradigm: he was formerly the head of the cystic fibrosis program at Vertex Pharmaceuticals Inc. and, in our view, should be singlehandedly credited with making the cystic fibrosis transmembrane conductance regulator program what it is today, while the rest of Vertex was busy pushing ahead towards the ultimate implosion of the hepatitis C virus franchise."

New investor Deerfield Management Co. led the latest Syros financing, which included new investor Casdin Capital as well as existing investors Fidelity Management and Research Co., Wuxi Healthcare Ventures, Polaris Partners, Redmile Group, Aisling Capital and Alexandria Venture Investments.

Syros also plans an investigational new drug application for a phase I/II study with its second pipeline program.