Cells die all the time in a controlled manner that’s perfectly normal. But the way cells die matters. Sometimes cell death is violent, sparking inflammation believed to contribute to disease.
Quench Bio aims to develop drugs that stop the uncontrolled forms of programmed cell death, potentially halting inflammatory disease. The Cambridge, MA-based startup has come out of stealth with $50 million in Series A financing intended to produce a drug candidate ready for tests in humans in about three years.
Quench’s research focuses on gasdermin, a family of proteins that scientists have found plays a role in multiple signaling pathways that lead to inflammatory cell death. One of these proteins, gasdermin d, is activated in two forms of inflammatory cell death: pyroptosis and NETosis. These activated proteins form pores on the cellular membrane, which leak inflammatory cytokines, says Quench CEO Samantha Truex. Eventually, the cell ruptures and spills more of the inflammation-causing contents. Gasdermin d is the trigger for this cellular demise.
“It’s the executioner of inflammatory cell death,” Truex says.
There are biological approaches to inflammation, such as medicines that block the inflammatory cytokine IL-1 beta. The Novartis (NYSE: NVS) anti-inflammatory canakinumab (Ilaris) is one such drug. Experimental approaches to stopping inflammation include drugs that block NLRP3, a complex of proteins that plays a role in the inflammatory response. Novartis expanded its anti-inflammatory pipeline last year with the acquisition of IFM Tre, a Boston biotech that was developing a drug intended to block NLRP3.
Truex says NLRP3 is a “great target” that she hopes works for patients. But she adds that even if NLRP3 is blocked, it’s possible that other protein complexes can go on to trigger inflammation. Gasdermin d is downstream of the activity of NLRP3 and other inflammasomes, and it seems to be where the inflammatory responses all lead. By blocking gasdermin d, a small molecule Quench drug could potentially stop the formation of the pores that leak a cell’s contents, the creation of which sets that cell on course for a violent death.
Research about gasdermin’s role in inflammation is relatively new; the first scientific papers about the proteins were published in 2015. Truex says the research that led to the formation of Quench stems from the Max Planck Society, where scientists were looking for drugs to block the NETosis inflammatory cell death pathway. Those researchers collaborated with two venture capital firms, Atlas Venture of Cambridge, MA and Arix Bioscience of London, which co-founded Quench in 2018 and provided seed funding. The startup has been incubating within Atlas’s Cambridge office and also has some operations at nearby LabCentral, a shared laboratory space for biotech startups.
Truex says that Quench has identified more than 25 autoinflammatory and autoimmune diseases associated with inflammatory cell death, including rheumatoid arthritis, lupus, multiple sclerosis, and nonalcoholic steatohepatitis. But she says that the field of gasdermin research is so new that it’s not clear which diseases could be addressed by blocking gasdermin d.
With the new financing, Truex says Quench will study patient samples to try to determine which diseases are driven by gasdermin d activation. With that information, the company will prioritize which diseases it can target. Concurrent with that research, Quench will try to discover gasdermin d inhibitors that could become drug candidates.
Truex expects the cash latest financing will last for three years, at which point the company aims to have a small molecule drug ready for clinical testing. She adds that Quench will also try to find out whether it makes sense to target other gasdermin proteins as a way of treating disease.
RA Capital led the investment, joined by AbbVie Ventures, the venture arm of AbbVie (NYSE: ABBV). Atlas Venture and Arix also participated in the financing.