Rhythm Pharmaceuticals, Inc.

Good day and thank you for standing by. Welcome to the Rhythm Pharmaceuticals Q1 2023 Earnings Conference Call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you will need to press star 1 1 on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star 1 1 again. Please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker today, Dave Connolly, Executive Director of Investor Relations and Corporate Communications. Please go ahead.

Thank you, Benny. I'm Dave Connolly here at Rhythm Pharmaceuticals. For those of you participating on the conference call, our slides can be accessed and controlled by going to the Investors section on the Investors page of our website at ir.com. This morning, we issued a press release that provides our first quarter 2023 financial results and a business update, which is available on our website. And as listed on slide two is our agenda. Here with me today in Boston are David Meeker, Chair, Chief Executive Officer and President of Earthen Pharmaceuticals, Jennifer Chen, Executive Vice President, Head of North America, Hunter Smith, our Chief Financial Officer, and Jan Mazzebro, Executive Vice President, Head of International, is on the line joining us from Europe. And I'll remind you that this call contains, on slide three, I'll remind you that this call contains remarks concerning future expectations, plans, and prospects, which constitute forward-looking statements. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed on our most recent annual or quarterly reports on file with the SEC. In addition, any forward-looking statements represents our views only as of today. It should not be relied upon as presenting our views as of any subsequent date. We specifically disclaim any obligation to update such statements. With that, I'll turn the call over to David Meeker, who will begin on slide five.

Thank you, Dave, and thank you all for joining this morning as we record another strong quarter. As we will keep reiterating, this company is built on strong, well-understood biology, that is the impairment in the MC4 pathway, which governs calorie intake, i.e. the hunger, and energy expenditure. A clear unmet medical need in the patients who suffer with these rare diseases and a simple solution. Incivary is a replacement therapy restoring function in that pathway. The near-term value and rhythm resides in our ongoing global launch of Incivri for patients living with EBS and our phase three trial in hypothalamic obesity, which is now up and running. As we grow the organization, we continue to attract outstanding talent when a small company executing a global program working in a challenging space continue to execute. We are well capitalized with funding into 2025, but Incivri revenue is now beginning to make a meaningful contribution to the overall picture. So looking at slide five, these are our three strategic pillars. Commercial launches are off to a strong start. Our conviction in the value we are bringing within Sivri, particularly with regard to the less well-appreciated and less well-understood hyperphagia part of the disease, continues to grow. Obesity is not one disease, it is many diseases. Our educational efforts helping healthcare providers recognize these diseases and their need for a targeted solution are making a difference. Our personalized approach to supporting patients and their healthcare providers is working. We see each patient for who they are, we meet them where they are, and we don't give up. In the U.S., scripts continue to be written by a growing number of physicians, and we are making continued progress in expanding payer approvals, particularly in patients covered by Medicaid, as Jennifer will explain. Internationally, we have launched Incivri for DBS in Germany, the largest European market, following a second exemption from the German Federal Joint Committee, which recognized that Incivri is a therapy for a devastating rare genetic disease and not a lifestyle medication. As Jan will describe, the team is moving, and we look forward to updating on the progress. The H.O. trial has initiated with the first patients treated. We expect a complete enrollment as we have previously guided in Q1 of 2024. We look forward to providing updates on the 12-month data at a medical meeting in Q4. And we are continuing to make progress on our expansion opportunities for the M&A trial enrolling, pediatric trial finishing, the weekly switch study finishing, and Daybreak Part 1 data to be presented later this year. The Shinbento integration has gone extremely well as we work towards candidate selection for the lead indication of congenital hyperinsulinase. We will provide further updates on all of these programs in the fourth quarter. On slide six. Slide six is our biology slide, which we will probably show on every earnings call. And this is to remind you that this is a differentiated pathway, which when impaired requires a targeted solution. These diseases are quite distinct from general obesity, The early onset obesity is severe, and the obesity is lifelong. The common thread across these diseases is hyperphagia, that insatiable pathologic hunger drive that leads to abnormal food-seeking behaviors. On slide 7, you see the two foundational opportunities, BBS and HO, affect meaningful numbers of patients with a BBS prevalence of 4,000 to 5,000 and an HO prevalence of 5,000 to 10,000 in the U.S., with comparable numbers in Europe. The major difference between the BBS and HO opportunity is that the vast majority of HO patients are diagnosed and actively engaged with the healthcare system, specifically the doctors we are working with. The additional opportunities represented in the Phase III M&A trial offer significant potential upside from there. As a reminder, no therapies are approved for HO and no therapies have been shown to consistently work. The GLP-1 question is important. earlier generations of GLP-1 did not show benefit. While we do not have trial data on the newer GLP-1 or combo therapies, anecdotally, as Dr. Abouzahab described on our first HO call last year, she believes 20% or so of HO patients may have some response to GLP-1, and the magnitude of that response might be on the order of 10% or less. These drugs are different. They work through different receptors on different pathways. It makes sense that some patients may have some response to other medications, including GLP-1s, because obesity is a complex disease and more than one factor may be affecting any given patient. What we thought was most noteworthy about the Phase 2 cohort is how consistently supplemented work in those patients who are compliant with a therapeutic dose. The 18 patients had a mean BMI decrease of 14.5% at 16 weeks, associated with meaningful decreases in their hunger scores. The consistency of those results strongly suggests set melanotibes targeting the underlying cause of the disease. As with each of the diseases caused by impairment in the MC4 pathway, it is critical to correct the basic defect before deciding on the need for additional therapy. The obvious and most simple of those interventions is a diet and exercise program, which these patients have universally failed when tried in the presence of an MC4 pathway defect, but find greater success once function in that pathway is restored. And moving to slide eight, we are excited to have our phase three trial underway, but the design is shown here on slide eight. As a reminder, this trial in HO is a double-blind, randomized controlled trial enrolling 120 patients, randomized two-to-one treatment and placebo. Patients will be dose escalated over four to eight weeks and then followed for 52 weeks for the primary endpoint of percent BMI reduction as compared to baselines. It is a challenging time to be running clinical trials, but the team has done a great job working with our CRO, and we expect to have all of our sites up and enrolling by the end of Q3. In slide nine, you can see our pipeline of approved indications and the trials. Overall, we have worked with over 100 clinical sites in 15 countries, which in addition to testing our therapy, creates awareness, builds experience with the therapy, and most importantly, helps build a community of patients and physicians working to improve the lives of patients living with these MC4 pathway diseases. With that, I will turn the call over to Jennifer.