Rhythm Pharmaceuticals, Inc.

Good day and thank you for standing by. Welcome to the Rhythm Pharmaceuticals fourth quarter and full year 2022 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 11 on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star 11 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, Michelle. I'm Dave Connolly. I are here at Rhythm Pharmaceuticals. For those of you participating on the conference call, our slides can be accessed and controlled by going to the investor section on the investors page of our website at ir.rhythmtx.com. And this morning, we issued a press release that provides our fourth quarter and year end 2022 financial results and business update, which is available on our website and as listed on slide two. 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 Rhythm 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 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 represent our views only as of today and should not be relied upon as representing 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, who will begin on slide five.

Thank you, Dave, and good morning, everyone. Thank you for joining the fourth quarter earnings call, and we are going to talk about earnings, which were good, and this week's announced acquisition of Zinvento. However, before we do that, I want to reflect for a moment on this company's journey. It was almost a decade ago when we published the first case reports in the New England Journal of Medicine describing the remarkable effect of stepmelanotide in two patients with palm seed deficiencies. Since then, we have learned so much about the MC4 receptor pathway, the associated genetic deficiencies, the importance of hyperphagia and energy expenditure in the development of obesity. At the same time, we started to learn about what it means to live with one of these rare diseases, complete lack of awareness on the part of the healthcare system, the relative shortage of experts, the almost complete lack of genetic testing, all compounded by a societal and medical bias which confronts the individual and family living with obesity. As the mother of one child with BBS said when asked, how bad can hyperphagia and obesity be when your child may be losing their sight? Her response, people are kind to blind people. So slide five, the challenges of living with a rare disease were further highlighted this week as we mark Rare Disease Day at Rhythm of the Guest Speaker, a mother of two children with BBS who described the incredible challenges of living with the hyperphagia. The severe preoccupation with food and the associated abnormal food-seeking behaviors and how her child and her family's life has been changed since starting in chivalry. And Rare Disease Day reads into Obesity Care Week and World Obesity Day on March 4th, which brings obesity to the forefront as a disease that requires a new way of thinking and new therapeutic options at work. Rhythm is at the center of these awareness events, as we know obesity is not just one disease, but many diseases, some of them rare, and each disease deserves a careful evaluation and the right treatment. Slide six. 2022 is a transformative year for Rhythm as we now embark on our next chapter as an established commercial stage company expanding geographically and now further diversifying our pipeline. The DBS launch, as you will hear from Jennifer and Jan, continues to go extremely well. Since FDA approval in June through the end of the year in the U.S., we have received more than 200 new prescriptions from 125 prescribing physicians with more than 100 patients approved for reimbursement. Our confidence in this opportunity continues to grow. Internationally, Incivry is now available in eight ex-U.S. markets for POMC and LEPR. France also includes BBS through paid early access. The success to date in both regions speaks to the quality of the teams we have. And we're continuing to execute on our strategy to expand the overall opportunity for set melanotype. With strong proof-of-concept data in our Phase II hypothalamic obesity trial in 2022, Phase 3 trial sites are now being initiated, and we have begun screening patients. This year, we'll also have data readouts in our Phase 3 Pediatrics Trial and Phase 3 Switch Study, evaluating the weekly formulation of cefalantide and preliminary data from the open-label Stage 1 portion of the Phase 2 Daybreak Trial. Monday, we were excited to announce the acquisition of Zinvento, a preclinical Dutch company with a suite of drug candidates for congenital hyperinsulinism. which we believe represents an outstanding fit with RILM and our expanded focus looking at rare endocrinology. This fits perfectly with our concentration of pediatric endocrinologists, and we've already heard from some of them how they are excited about this development and look forward to working with us as we develop those compounds. We're targeting being in the clinic in 2024, and as noted, we are well capitalized into 2025, and this inventory acquisition will have no impact on that forecast. Slide seven. So CHI is a disease where the available treatments are suboptimal, both in terms of safety, tolerability, and importantly, effectiveness. The unmet need is clear. I had the opportunity to get to know Claudine Benesendi, the CEO, and Pete Wigernink, the CSO, as one of their scientific advisors. I was incredibly impressed by Claudine's personal story, the thoughtful way she has pursued her mission, and the great progress she and Pete have made in a short period of time. The fit with rhythm was obvious. CHI is a genetic disease with patients presenting during the neonatal period with hypoglycemic episodes, which may trigger seizures, loss of consciousness, and with repetitive insults, brain damage, and death. Biologically, in a normally functioning beta cell, an increase in glucose levels triggers insulin release, and as glucose levels drop, insulin release is suppressed. In CHI, this process malfunctions, and insulin release continues in the presence of low glucose levels, resulting in further lowering of the blood glucose for life-threatening levels. The emergency treatment is dextrose and glucose infusion. We know from patient and family surveys conducted by the International Patient Organization that these hypoglycemic low blood sugar levels are occurring one or more times per day in 25% and one or more times per week in an additional 20% of patients despite being on standard of care. This is an ultra-rare disease with an incidence of approximately 1 in 30,000 individuals in the U.S., EU, and Japan, respectively. Approximately 70 to 80% of these patients need medical treatment. In addition to patients with chronic hyperinsulinism, there's another population of patients potentially twice as large with transient hyperinsulinism in the neonatal period, who we will potentially target as well. We look forward to providing a more in-depth presentation on the science and our development plans later this year. Slide eight. The A3 trial for HO is actively screening patients. This is a double-blind randomized controlled trial of 120 patients randomized two-to-one to set melanotide or placebo. Patients will be dose escalated over eight weeks and then followed for an additional 52 weeks. The primary endpoint is percent change in BMI. We expect it will take six to 12 months to enroll, probably skewing closer to the 12-month time frame. Slide 10, as you know, this is a fundamentally different opportunity for rhythm with an estimated 5,000 to 10,000 patients in the U.S. and the EU, respectively, largely already identified based on their history of injury to the hypothalamus with associated impairment of the MC4 pathway and their need for ongoing hormonal replacement related to pituitary injury. We look forward to providing an update on the patients in the long-term extension before the end of the year and anticipate that will be tied to an abstract presentation at a fall meeting. Slide 11. Multiple trials ongoing. These other programs are progressing well. Both the PEDS and weekly switch trials, as noted, will read out top line data in the second half of this year. We'll provide an initial look at the phase two daybreak open label portion in the second half of this year. And Emanate is enrolling patients in each of its four independent sub-studies. Slide 12. Before I turn it over to Jennifer, we are formally updating our BDS prevalence numbers, which we talked about previously. As we have described, When we look at the identified patient numbers in Europe where the diagnostic rated ahead of the U.S. and extrapolate that to the U.S. population, combined with the frequency of patients with a biallelic pathogenic variant for BDS being identified in our URO testing program and our initial experience with launch, all of this gives us increased confidence that the target population is larger than originally anticipated. It's on the order of 4,000 to 5,000 patients in the U.S. and similarly in Europe. With that, I'll turn it over to Jennifer.