Nivalis Therapeutics, Inc.

Mineralys Therapeutics’ hypertension drug candidate could offer a new treatment option for patients who don’t adequately respond to currently available blood pressure medicines. The once-daily pill is nearing a pivotal test, and Mineralys has raised $192 million in IPO cash to finance its clinical trial plans. When Mineralys set preliminary terms for the IPO last week, it planned to sell 10 million shares in the range of $14 to $16 per share. The Radnor, Pennsylvania-based company ended up adding 2 million shares to the offering, which priced late Thursday at the top of the projected price range. Those shares began trading Friday on the Nasdaq under the stock symbol “MLYS.” Many patients who have hypertension take multiple medications to manage the condition. However, more than half of the 115 million people in the U.S. with sustained elevated blood pressure fail to meet their blood pressure reduction goals, Mineralys says in its IPO filing. That failure puts these patients at greater risk of death due to cardiovascular disease or stroke. Standard-of-care drugs include angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs), which work by lowering levels of aldosterone, a hormone that regulates blood pressure. Another class of drugs work by blocking aldosterone’s activity at the called mineralcorticoid receptor. Mineralys aims to address aldosterone, but in a different way than currently available medications. Its small molecule drug, lorundrostat (previously known as MLS-101), is an aldosterone synthase inhibitor (ASI). It blocks aldosterone synthase, an enzyme key to the synthesis of the hormone. The company says its molecule is highly selective, hitting its enzyme target without also hitting other targets, such as the hormone cortisol. “Several large pharmaceutical companies have tried to develop ASIs, but their efforts have been hampered due to insufficient selectivity for aldosterone, resulting in off-target toxicities associated with cortisol inhibition,” Mineralys said in the filing. “These challenges have led to the discontinuation of many ASIs in development to date.” Last November, Mineralys reported preliminary data from a placebo-controlled Phase 2 test enrolling 200 patients with uncontrolled or treatment-resistant hypertension. Those participants had been taking up to two anti-hypertensive drugs to manage their blood pressure. Results showed the study met its blood pressure reduction goals. Furthermore, the study drug was well tolerated by patients. Serious adverse events were reported in three participants. In two of them, the effects were deemed unrelated to the drug. The third patient had pre-existing below normal sodium levels in the blood, which reversed after stopping treatment with the Mineralys drug. The next step for lorundrostat is another Phase 2 study to evaluate the safety and efficacy of the molecule when used as an add-on therapy in patients who are taking two or three anti-hypertensive medications. This double blind, placebo-controlled study will enroll up to 240 adults and will start in the first half of this year. Meanwhile, Mineralys plans to start a Phase 3 study in the second half of this year. The trial design will be similar to that of the Phase 2 study except it will have more patients—up to 1,000 adults with uncontrolled or treatment-resistant hypertension. Preliminary data are expected in mid-2025. Mineralys also wants to see how its drug works addressing hypertension in patients with chronic kidney disease. A Phase 2 study is expected to start in the middle of this year. Mineralys is pursuing its clinical trial plans as rival CinCor Pharma prepares for a pivotal test of its aldosterone synthase inhibitor, baxdrostat. Despite failing in Phase 2 last November, the biotech reported encouraging results in a subgroup of patients that it said could inform the design of a Phase 3 study. AstraZeneca apparently sees potential in the CinCor drug. Last month, it agreed to pay $1.3 billion to acquire CinCor. Lorundrostat traces its origins to Mitsubishi Tanabe, which discovered the molecule and advanced it as far as Phase 1 testing. Venture capital firm Catalys Pacific founded Mineralys in 2019, according to the filing. The following year, Mineralys licensed global rights to lorundrostat, paying $1 million up front. The deal includes milestone payments of up to $9 million for development and $155 million if the drug reaches the market. Mineralys has raised $158 million since its inception, most recently a $118 million Series B financing last June led by RA Capital and Andera Partners. According to the prospectus, Catalys Pacific is Mineralys’s largest shareholder, owning a 24.1% post IPO stake, followed by Samsara Capital’s 9.7% stake. Mineralys’s CEO is Jon Congleton, a veteran of Impel NeuroPharma, Nivalis Therapeutics, and Teva Pharmaceutical Industries. The company reported its cash position was $110.4 million at the end of 2022. It estimates that this capital combined with the IPO proceeds will be sufficient to fund operations for at least the next 18 months—enough time for the two planned Phase 2 tests of lorundrostat to report preliminary data. Photo by Getty Images 内容来源于网络，如有侵权，请联系删除。

Dive Brief:Mineralys Therapeutics has become the second biotechnology startup in a week to go public, raising $192 million in one of the sectors largest new stock offerings in months.Mineralys sold 12 million shares at $16 apiece, the biggestoffering by total proceeds since May 2022, according to BioPharma Dive data. The company, which is headquartered in Radnor, Penn., will begin trading under the ticker symbol MLYS on Friday on the Nasdaq stock exchange.Mineralys focus is on an experimental drug for difficult-to-treat hypertension. Called MLS-101, it was licensed from Mitsubishi Tanabe Corp. and recently met its goal in a Phase 2 trial.Dive Insight:Mineralys IPO follows closely on the heels of Structure Therapeutics $161 million offering last week.Its Nasdaq debut marks the first time two biotechs have each raised more than $100 million in IPOsin the same month since last May, a reflection of the tough funding environment young drugmakers currently face.Mineralys, like many of the companies that successfully went public in 2022, is built around one primary asset thats already in clinical testing. Amid a market downturn, investor support has grown again for single product-focused biotechs, versus platform companies that require longer runways and often greater funding.In a June 2022 analysis of more than 500 biotechs that have gone public since 2010, seven of the top 10 underperformers then were platform companies, according to consulting and research firm Bay Bridge Bio.Mineralys candidate, MLS-101, is whats known as an aldosterone synthase inhibitor. A hormone released by the kidneys, aldosterone manages blood pressure by controlling levels of sodium and potassium in the blood.Its also been the target of drugmakers for years. High levels of aldosterone are linked to uncontrolled hypertension, when extremely high blood pressure is not adequately treated by other medications.Last fall, the company read out positive data from a Phase 2 study of more than 200 patients, showing that a daily dose of MLS-101 resulted in substantial placebo-adjusted reduction in blood pressure for 24 hours.Other companies, including the recently acquired CinCor Pharma, are currently developing aldosterone synthase inhibitors, while others such as Idorsia Pharmaceuticals are testing drugs for uncontrolled hypertension that work in different ways.Mineralys raised $40 million in a Series A round in 2021, and $118 million in a Series B round in 2022. Its investors include Catalys Pacific, Samsara BioCapital, HBM Healthcare Investments, Ysios Capital and RA Capital Management. The startup is run by Jon Congleton, a former Teva Pharmaceuticals executive and previously CEO of Nivalis Therapeutics. '