Quench targets lupus and rare diseases with R&D into new drug class

Quench Bio has emerged from stealth mode with $50 million of committed funding, bidding to be the first company to target Gasdermin D (GSDMD) in inflammatory disease indications poorly served by existing drugs.

This protein and others in its class are of significant interest to big pharma – Gasdermin D is the best understood and is associated with many autoimmune diseases including rheumatoid arthritis, lupus, multiple sclerosis, and non-alcoholic steatoheptatitis (NASH).

But according to one of its backers Quench is unlikely to target the big indications such as RA where there are a wealth of already-approved drugs - instead opting for diseases such as lupus and other rare diseases that could be used as proof of concept trials.

Founding investors Arix and Atlas Venture led a Series A funding round and were joined by AbbVie Ventures and RA Capital, with $50 million providing enough cash to last around three years.

AbbVie’s investment brings guidance and expertise from the parent company, which of course produces the inflammatory diseases mega-blockbuster Humira.

Quench has been working in secret since 2018 and hopes that by tackling Gasdermin D, and other related proteins, it can prevent cells from dying in ways that cause an immune response, thus limiting the symptoms seen with those diseases.

By stopping an explosive form of cell death called pyroptosis, or attacks from neutrophil white blood cells known as NETosis, Quench thinks it will find drugs promoting less chaotic and inflammatory reactions and treat the root cause of the conditions.

At the helm is CEO Samantha Truex, the former chief business officer of Padlock Therapeutics, acquired by Bristol-Myers Squibb for $600 million in 2016.

Chief technology officer Mark Tebbe has co-founded the company together with head of biology Mike Nolan, who both have “entrepreneur in residence” roles at Atlas.

Arturo Zychlinsky and Herbert Waldmann, both directors at The Max Planck Institute, are also co-founders after collaborating with the Lead Discovery Center on inhibitors of NETosis and gasdermin.

Josh Resnick, managing director and co-head of ventures at RA Capital and Adam Houghton, head of AbbVie Ventures will join the board, alongside existing directors Jonathan Tobin of Arix Bioscience and Bruce Booth of Atlas Venture.

Arix’s John Cassidy will continue his role as board observer.

In an interview with pharmaphorum, Tobin said that the company has been “reliably informed” that it is currently leading the way into Gasdermin research, although there are likely to be other teams working in the area who are not yet in the public domain.

“We have got almost certainly the biggest research effort in identifying the first Gasdermin D inhibitors.

“You can never be 100% sure in this businesss, but if other groups start working on this problem that is great and an advantage, as the more validation from independent groups, the higher the confidence in the groups and the greater the interest.

“Any competition is good, it’s a difficult problem to crack and the more people working on it, the better.”

Tobin said that within its three year funding window the company expects to have at least nominated a development candidate and have it close to clinical trials.

Research is unlikely to target well-served diseases such as rheumatoid arthritis and relapsing/remitting MS – instead likely first indications could include progressive MS where there are fewer drugs on the market.

According to Tobin the “bar is low” in lupus, where GlaxoSmithKline’s Benlysta was FDA approved almost nine years ago and rivals such as AstraZeneca are struggling to make headway.

Vasculitis could be another area for research along with rarer diseases that could be used as clinical proof of concept.

Any compound that makes it through to the clinic will also be a small molecule drug that could be taken orally, giving an immediate convenience advantage over injected biologics such as Humira.

Tobin stressed that Quench is not a “Max Planck Institute spin-out” and has a licence to develop intellectual property it identified from the institute’s research, with the expertise from Truex and her team.

“The founders are really the guys who have added value,” he said.