Mineralys Therapeutics, Inc.

Greetings and welcome to the Mineralis fourth quarter and full year 2022 earnings call. At this time, all participants are in a listen-only mode. A brief question and answer session will follow the formal presentation. If anyone should require operator assistance during the conference, please press star zero on your telephone keypad. As a reminder, this conference is being recorded. It is now my pleasure to introduce your host, Dan Ferry of LifeSci Advisors. Please go ahead, sir.

Thank you, operator. Good afternoon, everyone. Welcome to our fourth quarter and full year 2022 conference call. Today, after the market closed, we issued a press release providing our fourth quarter and full year 2022 financial results and business updates. A replay of today's call will be available on the investor section of our website approximately one hour after its completion. After our prepared remarks, we will open the call for Q&A. Before we begin, I would like to remind everyone that this conference call and webcast will contain forward-looking statements about the company. Actual results could differ materially from those stated or implied by these forward-looking statements due to risks and uncertainties associated with the company's business. These forward-looking statements are qualified by the cautionary statements contained in today's press release and our SEC filings, including our annual report on Form 10-K and subsequent filings. Please note that these forward-looking statements reflect our opinions only as of today, March 15th. Except as required by law, we specifically disclaim any obligation to update or revise these forward-looking statements in light of new information or future events. I would now like to turn the call over to John Congleton, Chief Executive Officer of Mineralis Therapeutics. John?

Thank you, Dan. Good afternoon, everyone, and welcome to our first corporate update and financial results conference call. I'm joined today by Adam Levy, our Chief Financial Officer and Chief Business Officer, and Dr. David Rodman, our Chief Medical Officer. I'll begin with a brief overview of the business and recent milestones, followed by David, who will discuss our clinical programs, and then Adam will review our fourth quarter and full year financial results before we open up the call for your questions. The past few months have been a truly transformative period for Mineralis. As we announced positive Phase II proof-of-concept data for our product candidate, Larunderostat, our proprietary, orally administered, highly selective aldosterone synthase inhibitor that we are initially developing for the treatment of patients with uncontrolled hypertension or resistant hypertension. As we will discuss in detail later on, these Phase II data support the planned initiation of our pivotal program in 2023. Before we get to the updates on our program, I want to offer a few key points about our target indication, the therapies currently available in the market, and the unmet need among patients failing to achieve their BP goals with current therapies, which should allow you to see why we're so excited about this opportunity and our clinical data today. To start, over 115 million patients in the U.S. have sustained elevated blood pressure or hypertension. And over 30 million hypertensive patients in the United States are unable to achieve their BP goal despite treatment. And within this population, over 10 million patients suffer from resistant hypertension, defined as failing to achieve goal on three or more medications. Furthermore, obesity, particularly when associated with visceral adiposity, is a major cause of hypertension, accounting for 65 to 75% of the risk. Uncontrolled hypertension is a serious medical condition, as patients with hypertension that persists, despite taking two or more medications, have a significantly elevated risk of developing heart disease, stroke, and kidney disease. For example, it is estimated that uncontrolled hypertension patients have a 1.8 times greater mortality risk due to cardiovascular disease and a 2.5 times greater mortality risk due to stroke. Despite numerous options available to treat hypertension, including thiazide diuretics, ACE inhibitors, angiotensin receptor blockers, calcium channel blockers, beta blockers, and mineral corticoid receptor antagonists, the majority of hypertension patients require multiple therapies to achieve their target blood pressure. Also worth noting is that many of these therapies designed to address hypertension were introduced several decades ago. When the incidence of obesity was below 20%, and abnormal aldosterone production affected less than 10% of the U.S. population. As a result, these therapies failed to adequately address the shifting biology of hypertension, particularly in the obese population with a body mass index equal to or greater than 30. Current guidelines, while well thought out, emphasize an empirical approach. In other words, mainly trial and error. While first and second line treatment, often an ACE inhibitor or angiotensin receptor blocker plus thiazide diuretic, have general efficacy, they are often unable to normalize blood pressure. And third-line agents tend to produce only a 6 to 7-millimeter mercury improvement. However, this incremental reduction does not always adequately enable patients to reach their blood pressure goal. Therefore, many patients require three, four, or more antihypertensive agents in an attempt to achieve their target blood pressure. In addition, while hypertension is an asymptomatic disease, many of the currently available treatments have side effects and tolerability issues, which may limit their use. For example, patients taking ACE inhibitors often develop a chronic cough, and men taking spironolactone often develop gynecomastia, otherwise known as breast enlargement. Notwithstanding this significant and growing unmet need, there's been a lack of U.S. FDA-approved novel therapies targeting hypertension, with no new class of antihypertensive treatment approved within the last 15 years. There's also a heavy cost beyond that of the health of the individual patient, as estimates show that hypertension and related health issues resulted in an average economic burden of about $130 billion each year in the United States. This brings me to our late stage clinical candidate, a proprietary, orally administered, highly selective aldosterone synthase inhibitor designed to reduce aldosterone levels by inhibiting the enzyme CYP11B2, which is responsible for producing the hormone. We are targeting aldosterone because abnormally elevated aldosterone levels are a key factor in driving hypertension in approximately 25% of hypertensive patients. Our goal is to emphasize a precision medicine approach in the development of lorundrastat and identify predictors of enhanced response, a toolkit to inform when and how to use lorundrastat in order to help patients achieve their goal blood pressure. We began this journey of bringing targeted treatments to hypertension with our phase two proof of concept study, Target HTN, which was completed last year. Top-line data from this study announced in November 2022 show that we demonstrated the clinically meaningful reduction in systolic blood pressure with 50 milligrams and 100 milligrams once daily dosing. In addition, we pre-specified certain variables to determine if they predicted an enhanced response in subjects. In this pre-specified analysis, we demonstrated that concomitant use of a diuretic yielded a 12.9 millimeter mercury placebo-adjusted reduction in systolic blood pressure with 50 milligrams once daily of lorundrastat. We also demonstrated that a body mass index greater than or equal to 30 predicted an even greater response with 50 milligrams once daily, yielding a 16.7 millimeter mercury placebo-adjusted reduction in systolic blood pressure. Given the rising epidemic of obesity, its correlation to abnormal aldosterone levels, and the risk of uncontrolled hypertension, we believe our Phase II data offer a critical finding that we will further investigate in our pivotal program. In summary, hypertension remains an area of significant unmet need with significant implications to long-term patient health. The clinically meaningful reduction demonstrated in Target HTN with Larunder's death represents a substantial benefit for the millions of patients struggling to achieve their blood pressure goal. At Mineralis, our goal is to develop lorundrastat in a novel, targeted manner with a toolkit to inform enhanced clinical response. Let me now turn the call over to Dr. David Rodman, Chief Medical Officer of Mineralis Therapeutics, who will offer a review of our clinical data and ongoing clinical program for lorundrastat. Dave?