Quartet Medicine

About Quartet Medicine

Quartet Medicine, Inc. was a biotechnology company operating in the pharmaceutical sector, specifically focused on developing non-opioid therapeutics for chronic pain and inflammation. The company was founded in 2013, emerging from a collaboration between scientists at Boston Children's Hospital, the École Polytechnique Fédérale de Lausanne (EPFL) in Switzerland, and the venture capital firm Atlas Venture. The founding scientific team included Clifford Woolf, M.D., Ph.D., and Kai Johnsson, Ph.D., along with Kevin Pojasek, Ph.D., who co-founded the company while serving as an entrepreneur-in-residence at Atlas Venture and became its acting CEO. Woolf's research, dating back to 2006, identified the crucial role of tetrahydrobiopterin (BH4) synthesis in modulating neuropathic and inflammatory pain. Pojasek brought extensive experience in corporate development and leadership from previous roles at several biotech companies.

The company's central business strategy was to develop small molecule drugs to modulate the BH4 synthesis pathway. Human genetics suggested that lower levels of BH4, a key cofactor in neuronal and immune cell function, were associated with a reduced risk of chronic pain. Quartet's product development aimed to safely restore normal BH4 levels, thereby addressing neuronal hypersensitivity and chronic immune cell activation without the side effects and addiction risks associated with opioids. The company's research was heavily biomarker-driven, using sepiapterin as a specific biomarker to measure target engagement both preclinically and in planned clinical trials. This approach was intended to de-risk the clinical development process for its lead program, which focused on inhibiting sepiapterin reductase (SPR), the final enzyme in the BH4 synthesis pathway.

Quartet Medicine successfully raised a total of $23.25 million in its Series A financing round by October 2015, with investors including Atlas Venture, Novartis Venture Funds, Pfizer Venture Investments, and Partners Innovation Fund. In a significant milestone, the company entered into a "built-to-buy" agreement with Merck in January 2016. This deal provided up to $20 million in initial funding to advance its lead candidate through Phase IIa clinical trials, with an option for Merck to acquire the company for up to $575 million. However, in August 2017, the company encountered a critical setback. During a final preclinical toxicology study, unexpected and concerning neurologic effects were observed. The signal was believed to be a direct result of the drug's mechanism of action, making it difficult to engineer around. Faced with a low probability of technical success for its primary and backup compounds, the company and its investors made the decision to cease operations, and the wind-down was nearly complete by the end of 2017.