Heal thyself—with a little boost

OXFORD, U.K.—Targeted toward discovering how the body’s own immune system can be tweaked to fight cancer, Sitryx Therapeutics Ltd., a biopharmaceutical company focused on regulating cell metabolism, is collaborating with Nottingham, U.K.-based contract research organization Sygnature Discovery Ltd. to develop disease-modifying therapeutics in immuno-oncology and immuno-inflammation.

Sygnature Discovery comes to the table with an established reputation as a provider of premium integrated drug discovery and preclinical services, while the Sitryx team brings an extensive track record of success in the discovery and development of novel drugs, states a Nov. 7 joint news release.

“We will combine our considerable know-how and expertise to deliver new, highly effective disease-modifying therapeutics,” Dr. Neil Weir, Sitryx CEO tells DDNews. “We are still at the early stages in discovery,” he notes, but if all goes as planned, “hopefully, human trials could begin by 2020-21.”

Sitryx scientists are exploring multiple metabolic pathways within immune cells to identify potential druggable targets for the development of new therapies to treat cancer and inflammation, Weir says. Sitryx supports the key hypothesis that it is possible to manipulate intracellular metabolic pathways in specific cells to alter their activity and attempt to defeat disease.

“We are pleased to have been selected by Sitryx to support their groundbreaking research efforts to develop disease-modifying therapeutics across multiple biological targets in immuno-oncology and immuno-inflammation,” says Sygnature’s CEO and founder, Dr. Simon Hirst. “Our considerable in-house knowledge of immuno-oncology and immunology discovery will enable us to efficiently navigate these complex areas of biology to support the identification and optimization of novel and selective small molecules, while developing a deep understanding of their mode of action.”

The energetic status of cells has been shown to be pivotal in controlling the behavior of disease associated cells in immuno-oncology and immuno-inflammation, according to Sygnature. Correcting immune cell function and/or inhibiting tumor cell growth through targeting metabolic pathways has the potential to deliver new complementary and highly differentiated approaches to treat a wide range of severe diseases.

Weir says that ideally, some of the newly discovered therapies could be used in addition to chemotherapy and other drugs to treat cancer patients, while other therapies might be designed to replace the challenging regimen of chemo and radiation.

Rather than killing cancer cells from outside of the body, the immune cells would be manipulated to treat cancer from the inside, using the body’s own immune system, he says.

Private equity-backed since 2017, Sygnature operates research facilities in Nottingham and Alderley Park, U.K., housing over 200 research scientists. The company says its “drug hunters” have the know-how required to undertake the most demanding of research programs and drive them from target validation through hit identification, hit-to-lead and lead optimization to preclinical development. Since 2011, Sygnature says it has delivered 14 drug candidates to clients which have subsequently entered Phase 1 and 2 clinical trials.

Sitryx set the stage for the Sygnature collaboration with the announcement on Oct. 8 of the closing of its Series A financing round. Founded with seed funding from SV Health investors, Sitryx raised $30 million from a syndicate of specialist international healthcare investors co-led by SV Health Investors, Sofinnova Partners, the Longwood Fund and the global healthcare company, GlaxoSmithKline (GSK).

Immunometabolism is also a fast-emerging area of investigation into the role of metabolic pathways in immune cell function. Changes to these pathways have been shown to be pivotal in the development of a number of severe diseases, including a range of cancers and autoimmune conditions.

Correcting immune cell function and/or inhibiting tumor cell growth through immunometabolic therapies have the potential to be key, complementary and highly differentiated approaches to treating disease, Weir says.

Sitryx consults the world-leading scientific expertise of its founders in the field of immunometabolism to address a broad range of immunometabolic targets, he notes. Through differentiated chemistry approaches, including small molecules, proteolysis targeting chimera (PROTACS) and topical formulations, Sitryx has built a portfolio of projects addressing oncology and immuno-inflammatory indications.

Sitryx’s proprietary science is supported by GSK’s drug discovery and chemistry experts, as well as having access to certain GSK technologies and the licensing of intellectual property, including chemical matter.

GSK’s interest in Sitryx arose from work within the Immunology Network, a unique open collaboration initiative connecting GSK to the work of academic scientists and their novel immunology research, Weir explains.

Sitryx was co-founded by a team of world-leading scientists from the United States and Europe, who have contributed significantly to the field, he says. This includes Houman Ashrafian, partner at SV Health Investors; Luke O’Neill, professor of biochemistry, School of Biochemistry and Immunology at Trinity College Dublin; Jonathan Powell, professor of oncology and associate director, Institute for Cancer Immunotherapy, Johns Hopkins University and Paul Peter Tak, former chief immunology officer and senior vice president at GSK and professor of medicine at Amsterdam University Medical Centre.

“Immunometabolism is an extremely exciting and compelling scientific area and, at Sitryx, we have seen that modulation of these key cellular pathways has broad therapeutic potential across multiple disorders with unmet medical needs,” Weir said in October. “Together with our proprietary chemistry, deep biological insights and world leading team of immunometabolism experts, Sitryx is well positioned to become a leader in immunometabolism.”

John Lepore, senior vice president of research at GSK, said: “Immunology is at the heart of GSK’s new approach to R&D. Through our Immunology Network, we believe the emerging field of immunometabolism that Sitryx is focusing on has the potential to bring new therapeutic opportunities to patients for a broad range of diseases including cancer.

“Our investment in Sitryx will allow us to access this exciting science through working closely with world-renowned academic scientists in an open, collaborative way.”