Grey Wolf Therapeutics has raised £10 million ($14 million) to advance small molecules that help the immune system recognize tumors. The series A, which was backed by Andera Partners and Canaan, will fund preclinical work on drugs that may render more tumors vulnerable to checkpoint inhibitors.
In recent years, evidence of the limitations of checkpoint inhibitors has fueled research into ways to make tumors more visible to the immune system. One way to achieve this goal is to modulate the immune system, for example by administering neoantigen vaccines to prime T cells to recognize markers on the surface of tumor cells. Another, less pursued path, is to directly alter the tumor cells.
Oxford-based Grey Wolf thinks it can make tumors more visible to the immune system by modulating enzymes their cells use to display antigens. These enzymes, ERAP1 and ERAP2, cut peptides to length ready for binding to the MHC class I complex.
This trimming and binding enable the immune system to determine whether a cell is an invader that needs attacking or a normal part of the body that should be ignored. However, ERAP1 and ERAP2 also overtrim neoantigens and antigens, thereby preventing their presentation on the cell surface. This creates a problem for the immune system and an opportunity for Grey Wolf.
“We're modulating the activity of these enzymes to essentially overcome that problem. By doing so, we'll regulate neoantigen presentation and we'll also elicit new neoantigens to be presented,” Grey Wolf CEO Peter Joyce said.
The idea is built on research from the University of Southampton, notably a 2013 paper that found giving the small molecule aminopeptidase inhibitor leucinethiol to mice with cancer prolonged their survival. ERAP1 and ERAP2 are aminopeptidases.
Working with seed funding from its executive chairman—former Spinifex Pharmaceuticals CEO Tom McCarthy—and CRO Sygnature Discovery, Grey Wolf has built on the research done at Southampton and taken its program through hit generation. The research done so far suggests the approach works as a monotherapy and boosts the efficacy of anti-PD-1 drugs.
With the series A money in the bank, Grey Wolf is now positioned to move through lead optimization and to the cusp of IND-enabling studies. Along the way, Grey Wolf plans to generate efficacy data in vitro and in mice as well as gather dose-ranging results and some early toxicology data. If all goes to plan, Grey Wolf will then either raise a series B round or deliver an early exit for its investors.
The potential to render tumor cells visible to the immune system using simple small molecules, not complex and costly biologics, could prove attractive to the big names in immuno-oncology. And it has already landed Grey Wolf notable backers.
Andera is the fund formerly known as Edmond de Rothschild Investment Partners, while Canaan is a big early-stage investor in the U.S. that has been absent from the U.K. biotech scene until now. The involvement of McCarthy, who Canaan worked with at Spinifex en route to its takeover by Novartis, led the fund to take a look at Grey Wolf.