Introducing Quench Bio: a new approach to treating immune system disorders

27th January 2020

Today we announced the Series A financing and launch of Quench Bio, a company that we created and seeded with Atlas Venture in June 2018. (Read the press release here)

This is the first company we have co-founded and formed from scratch, combining scientific discoveries from professors in Germany with entrepreneurs and co-investors in Boston. It encapsulates the benefits of Arix’s transatlantic footprint and culture.

So, with this financing, we are officially launching Quench Bio out of ‘stealth mode’. Here is the story.

The origins of Quench

The embryo from which Quench came traces itself back to a project from the Lead Discovery Center (LDC), which helps to translate scientific discoveries from Max Planck Institutes in Germany into drug discovery projects for partnering with pharma or spin outs. LDC is an academic partner of Arix, and after reviewing many of their early stage projects, we were instinctively attracted to a project from Prof Arturo Zychlinsky, who is a prominent immunologist in Berlin and responsible for the discovery of neutrophil extracellular traps (NETs).

A bit of science

NETosis is the biological equivalent of Spider Man capturing his enemies in his web: NETs are released by dying neutrophils as a way of snaring invading bacteria in a sticky web of DNA and proteins. This process can become overly active, which can contribute to chronically debilitating autoimmune diseases such as lupus, rheumatoid arthritis, and multiple sclerosis. Prof Zychlinsky had teamed up with the LDC and Prof Herbert Waldmann to discover the proteins responsible for this process, thinking this might potentially lead to a new drug target. After years of experiments, the evidence implicated a new player in the NETosis process – Gasdermin D protein. The idea to create the first small molecule inhibitors of this never before drugged target was the germination of Quench Bio.

The role of Gasdermin D in inflammatory cell death was first published in 2015 in Nature by Feng Shao’s lab in China, and since then it is becoming clearer that it is central to several key processes that are misregulated in inflammatory and autoimmune disease. Gasdermin is a fascinating molecule that exists as a monomer in resting cells, but when stimulated is chopped into two fragments, one of which self-organises into a complex of 27 subunits that spontaneously forms a pore in the cell membrane. This pore allows inflammatory molecules to leak out of the cell, stimulating a cascade that leads to chronic inflammation. Furthermore, pore formation causes changes in the fluid balance inside the cell leading to a form of cell death called pyroptosis, which exposes the insides of cells to the immune system, perpetuating inflammation.

This simplified diagram below shows how Gasdermin activation can lead to pore formation causing pyroptosis or NETosis in affected cells.

In several chronic diseases, the processes of pyroptosis and NETosis are exacerbated and may be responsible for disease progression. Quench’s hypothesis was that inhibiting Gasdermin D as a central node in both cellular processes might have therapeutic applications in a multitude of serious diseases. We needed to start a company to test this and try to develop the first Gasdermin-targeting drug.

Gasdermin was not going to be a straightforward target to drug – it is not part of one of the typical classes of proteins easily inhibited by a small molecule that can be taken as a once-daily tablet, such as an enzyme, ion channel, or receptor. There was no published molecular structure to aid drug discovery, no known assays of protein function or activity, and little was known of the biology and function of the protein. This was going to be a high risk project in need of a hugely talented and hungry team of expert drug hunters.

However, the prize is large and worth the risk, as evidenced by recent acquisitions of similar companies in this burgeoning field of innate immunity. These included Padlock Therapeutics (acquired by BMS in 2016 for up to $600m), IFM Tre (acquired by Novartis in 2019 for up to $1.575bn), Delinea (acquired by Celgene in 2017 for up to $775m), Jecure (acquired by Genentech in 2018 for an undisclosed sum). The deal values for these preclinical projects clearly point to the promise of these approaches as important avenues for new therapeutics in an area where innovation has been eclipsed by oncology. The therapeutic promise of inhibitors of inflammatory cell death processes could be realised in diverse diseases such as lupus, asthma, Parkinson’s disease, multiple sclerosis, and kidney diseases.

In the summer of 2018, after many discussions with the founders and in-depth scientific due diligence on Gasdermin as a potential drug target, its potential clinical applications and likely commercial appetite for such a product, we teamed up with Boston-based early-stage life science specialists Atlas Venture, who had a large amount experience in innate immunology, having co-founded a number of successful companies that discovered inhibitors for novel inflammatory targets, including Padlock Therapeutics, IFM, and Delinea. We agreed terms for a license to the founders’ IP and technology, and Quench Bio was formed in June 2018.

Building the Quench team

In parallel with closing the seed funding, Atlas had recruited a couple of its entrepreneus-in-residence to start work on the project. The first employee was Chief Technology Officer Mark Tebbe, a medicinal chemist and drug hunter with over 20 years’ experience, including a long stint at Eli Lilly before moving into biotech. Mark had worked for years in Germany and so spoke the same language as the academic founders. In August of 2018 we were fortunate to have Samantha Truex join as CEO. Sam had previously had senior business roles at the two Boston biotech giants Biogen and Genzyme, before becoming Chief Business Officer of Padlock Therapeutics, negotiating its successful exit to BMS. She had subsequently become an Entrepreneur in Residence at Atlas and has taken on advisory roles within numerous companies.

Quench quickly got started with this team of three and a small room in Atlas’s office. Sam then convinced Iain Kilty to leave Pfizer after 18 years and take his first foray into a biotech, going from a company with over one hundred thousand employees to one with just four. Iain had been responsible for early stage immunology and inflammation drug research at Pfizer and was attracted to the novelty of the science Quench was pursuing, and the vision and energy of the team. In 2019 the company took its first wet lab bench space at Lab Central in Cambridge, MA. They hired their first bench scientist and have now grown the lab team significantly, including the appointment of Wei Li, an immunologist with over 20 years’ experience in companies Pfizer and Millennium Pharmaceuticals.

Building the board

In parallel with building the team, we formed a small but highly functional board. This included Chairman and co-founding investor Bruce Booth from Atlas; me representing Arix as co-founding investor; Prof Herbert Waldmann representing the founders; and Sam Truex. Sam then hired Jo Viney, a veteran immunologist who had done stints at Amgen, Immunex, Biogen before co-founding her own immunology company, Pandion. Jo brought deep immunology drug discovery expertise to the board, as well as the experience of building a top performing scientific team. The Quench team quickly put together a world-class scientific advisory board to give deep insights into the biology of this new target as well as potential clinical applications, and the company has developed productive collaborations with several of these advisors.

The Series A fund raise

Fast forward to the summer of 2019, and despite being only 12 months in, the team was making great progress validating Gasdermin as an exciting target and cracking the chemistry needed to deliver small molecule inhibitors. At the same time, literature was emerging independently from labs around the world highlighting the importance and centrality of Gasdermin in an increasing number of clinical indications. We put together a plan to raise a Series A to accelerate progress and push towards a development candidate that could ultimately be taken into the clinic.

The board hand picked a small number of like-minded investors we thought would also make helpful board members. We facilitated introductions and the Quench team started pitching in the autumn of 2019. We were fortunate there was strong demand for the story, largely driven by the quality of the team and the excitement in the groundbreaking science. Abbvie Ventures (also co-investors in Arix portfolio company Artios) and RA Capital (co-investors in Arix portfolio company Imara) put their hands up to take part in the round, and together with us and Atlas quickly agreed the terms of the Series A, bringing the total raised by the company to $50m. The company went from first presentation to signed term sheet in less than six weeks – a record by biotech standards. We feel this syndicate has the firepower and expertise to ensure Quench achieves its maximum potential: Abbvie is the world’s leading immunology pharma company, manufacturers of Humira, the best selling drug of all time ($20bn of sales in 2018). RA is a prolifically successful life science investors, with over $2bn under management and a strong track record of returns.

What did we like about Quench Bio?

Similar to our other early stage investments going after scientific white space, Artios and STipe, the investment thesis was based on the combination of superb science with top quality entrepreneurial management. An aligned and straightforward syndicate, providing the right amount of capital, gives the company the best platform for success. Quench ticked these boxes:

  • Great academic founders with strong track records and critical findings that had been corroborated elsewhere, and were willing to “share” their baby with an industrially-focused team to drive a product towards development
  • A strong and investable team that had discovered drugs and negotiated deals in similar areas before who have the skills and mental fortitude and resilience to prosecute a tough and unprecedented target. The tractability of the project is exponentially enhanced by the quality of the team, and Arix’s mantra is to be uncompromising on the people we back, particularly at early stages of investment where we have high percentage ownership and influence on the composition of the management and the strategy the company takes
  • A syndicate experienced in early stage drug discovery who understands the challenges, and what “good” and “bad” look like – when to be patient and when changes need to be made
  • Novel and exciting science that has the potential to be developed into a drug that could have a large impact on multiple diseases, both niche and more common

So we are genuinely excited about the journey ahead for Quench. It is a privilege to be involved with setting up a new company with such high quality investors and entrepreneurs, and this is going to be the first of a number of new companies that Arix helps create.