Mineralys emerges with a new take on an old idea for the treatment of hypertension and $40M to play with
Aldosterone, a hormone linked to increased blood pressure, has long been a target of interest for the treatment of hypertension, but selectivity has been a challenge. Now a new company has emerged from stealth to improve where others have failed.
Mineralys Therapeutics uncloaked early Monday morning with $40 million in Series A funds to prep their lead candidate — a selective aldosterone synthase inhibitor licensed from Japan’s Mitsubishi Tanabe — for a pivotal study. The company was launched by Catalys Pacific, the VC firm founder BT Slingsby put together to create new biotechs around Japanese innovation.
Aldosterone synthase inhibition is not a new idea. Novartis, Eli Lilly and Boehringer Ingelheim have all pursued it, Slingsby said. At higher levels, aldosterone basically tells the body to retain more sodium, and thus more water, leading to an increase in blood volume and pressure. CEO Jon Congleton compared the situation to a water hose: The more water in the hose, the higher the pressure.
The idea is to inhibit CYP11B2, an enzyme responsible for aldosterone synthesis. But the challenge is doing so without off-target effects. Another enzyme in proximity, CYP11B1, controls the synthesis of cortisol. If a candidate isn’t selective enough, it could inhibit both pathways — and reducing cortisol essentially counters the blood pressure lowering effect of aldosterone reduction, Congleton said.
From the results of four Phase II trials conducted by Novartis and published back in 2013:
Unfortunately, the observed increase in 11-deoxycortisol levels indicated off-target inhibition of the 11β-hydroxylase activity of CYP11B1 that resulted in the stimulation of the HPA feedback axis.
Mineralys believes it has a more selective aldosterone synthase inhibitor than past attempts. The biotech is about to head into a Phase II proof-of-concept study in Q2, and Congleton expects to read out data in the second half of 2022 which he hopes will pave the way for a pivotal study launch at the beginning of 2023.
The Series A funds should allow the company to do that, as well as preclinical CMC and clinical pharmacology work, and have cash going into 2023, he said.
Congleton joined Mineralys back in October as employee No. 1. That was shortly after he left Impel NeuroPharma, where he served as president and CEO. The commute led him to leave Impel, he joked, adding that weekly trips from Philadelphia to Seattle were weighing on him. But what attracted him to Mineralys was the chance to bring a targeted approach to the diagnosis, management and treatment of hypertension.
In January, the company tapped miRagen, Vertex and Novartis Institutes for Biomedical Research veteran David Rodman as CMO.
“We think really bringing a more targeted approach to the diagnosis management and treatment of hypertension is long overdue,” Congleton said.