GSK-Backed Sitryx Launches With Six Immunometabolism Eggs In Its Basket

GlaxoSmithKline, SV Health Investors and Sofinnova are among the backers of a new Oxford-based biotech which has raised $30m in series A financing and boasts a strong line-up of academic founders. CEO Neil Weir outlines Sitryx’s raison d’etre.

Who created Sitryx?

Chemical assets from GlaxoSmithKline PLC and target biology insights from high-profile academic founders form the basis for new company Sitryx, which has been launched with $30m in series A funding. Focused on developing disease-modifying treatments for autoimmune/inflammatory conditions and cancer, it is working on six early-stage projects to target immunometabolic pathways with small-molecule candidates. The company sprang out of the Immunology Network set up at GSK by Paul Peter Tak, who last month left the company after seven years and who is a co-founder of Sitryx.

“We have set ourselves up to be leaders in the field of immunometabolism,” explained CEO Neil Weir, who joined the company as its first employee in April 2018. He was previously SVP Discovery at UCB Pharma. The company’s assets include the tangible assets from GSK and “biological insights into pathways and as yet unpublished data from the founders’ labs around the connectivity of targets to human disease,” Weir told Scrip. “We’ve not encamped in one specific area; our targets cover a broad range of metabolic pathways through the insights that have come from our founders in glycolysis, the TCA [tricarboxylic acid] cycle and in pathways that feed into the TCA cycle.”

Sitryx has six academic founders from the world of immunology and metabolism:

Houman Ashrafian – Partner at SV Health Investors and Visiting Professor and Head of Experimental Therapeutics at University of Oxford

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

Jeff Rathmell – Professor of Cancer Biology and Director, Vanderbilt Center for Immunobiology

Michael Rosenblum – Assistant Professor, UCSF School of Medicine

Paul Peter Tak – formerly Chief Immunology Officer and SVP at GlaxoSmithKline, and Professor of Medicine at Amsterdam University Medical Centre

What is immunometabolism?

Tak explained to Scrip that it had been Luke O’Neill through his work with GSK’s Immunology Network who had helped identify immunometabolism as “potentially the next big thing in immunology.” Unlike previous work targeting metabolic pathways to starve tumor cells, “this is a fundamentally different approach where you actually target metabolic pathways to interfere with the immune system and thereby target the tumor cell,” Tak said, noting that such an approach is also relevant to diseases of auto-immunity.

While the fundamentals of metabolism are a fairly well understood already, attempting to drug metabolic pathways to change the behaviour of immune cells is still an emerging field, explained Weir. “And from what we can see and with the way we’re pursuing our targets, we’re not seeing other competitors.” With the breadth of experience of the founders and knowledge around different targets, Sitryx “doesn’t have all our eggs in one basket,” added the CEO: “There’s a breadth of portfolio here, it’s not just a single project. And it covers both innate and adaptive immune responses.”

The Future of Immuno-Oncology

The company is still at an early stage, and does not expect to begin identifying candidates to take into the clinic until late 2019, with first in human trials not expected before 2020.

To date, immuno-oncology has focused in large part on stimulating cell surface receptors using antibody treatments, but Sitryx is looking to develop small molecule oral and topical therapies that influence processes inside the cells. There may be potential to develop such treatments to be complementary to other therapies, but the company’s starting point is to view its candidates as standalone therapies, Weir said.

The programs are split between autoimmune/inflammatory and oncology conditions but “we will follow where the biology takes us, having set out on a path which starts off with a hypothesis as to where it’s pertinent,” the CEO noted, adding that the approach could also be applied to fibrosis.

Sitryx will have its own labs in Oxford Science Park but it will also work with founders, placing post-docs in their labs, as well as working with CROs. And GSK will support the company, for example helping it to understand and apply PROTACS (proteolysis targeting chimera) technology.

The series A round was co-led by SV Health Investors and Sofinnova Partners, with GSK and Longwood Fund also investing. GSK has no special rights on candidates emerging from Sitryx’s pipeline.

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