Rhythm Pharmaceuticals, Inc.

Good day and thank you for standing by. Welcome to the Rhythm Pharmaceuticals Q3 2025 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 one, one again. Please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker today, David Connolly, Investor Relations at Rhythm. Please go ahead.

Thank you, Heidi. 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 of our website. This morning, we issued a press release that provides our Q3 financial results and a business update, and that press release is also available on our website. Our agenda is listed on slide two. On the call today are David Meager, our Chairman, Chief Executive Officer and President, Jennifer Lee, Executive Vice President, Head of North America, Hunter Smith, Chief Financial Officer, and Jan Mazzebro, Executive Vice President, Head of International, is on the line joining us from Europe. On slide 3, 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 quarterly reports on file with the SEC. In addition, any forward-looking statements represent our views as of today and should not be relied upon as representing our views as of any subsequent dates. 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. Good morning, everybody. Thank you for joining us this morning. Rhythm delivered strong growth and continued momentum during the third quarter as we prepared a launch in Sivri and acquired hypothalamic obesity pending FDA approval. That is a transformative opportunity for Rhythm. We are finishing strong in 2025, a year in which we delivered robust phase three data with set melanotide and HO, presented outstanding phase two efficacy data with our next gen oral MC4R inhibitor, Bifamelegon, and strengthened our balance sheet with a 189 million equity offering in July. With our PDUFA date next month and additional data readouts coming this quarter and next, we are well positioned to deliver sustained long-term growth. The steady growth in global incivary revenue, driven predominantly by BBS, continued this quarter, with $51.3 million in sales, representing growth of approximately 10% in the number of patients on reimbursed therapy. We have built a strong global foundation for our business with Incivary, the only therapy that addresses the root cause of hyperphagia and the severe obesity of rare MC4R pathway diseases. The teams continue to engage with physicians and prescribers, identify patients, and ensure access to Incivary. Beyond commercial success, we have been executing on the regulatory front as well. For HO, both the FDA and EMEA accepted our regulatory filings this quarter, the EMEA EMA validated our Type 2 marketing authorization request, and the FDA accepted our supplemental NDA filing. The regulatory dialogue has been promising and productive in keeping us on track for a December 20th PDUFA date and potentially European approval in the second half of 2026. Jennifer and Jan will share some details on the quarter, as well as the upcoming launch efforts in the U.S. and the timing in the international regions. We remain on track to report preliminary results from our exploratory phase 2 trial in Prader-Willi syndrome by the end of the year. I have no further updates on today's call, but I will reiterate several of the comments we have made previously. There's a strong biologic rationale as to why MC4R agonism may work in PWS, based to a large extent on the involvement of the MAGL2 gene, where patients with isolated MAGL2 variants have impaired signaling through the MC4R path. We also know PWS is an incredibly complex disease due to defects in many genes and a clinical presentation characterized by obesity, hyperphagia, cognitive delay, and abnormal behaviors. It is this latter aspect of the disease which makes clinical studies particularly difficult. Thus, our rather neutral prediction that we have a 50-50 chance of working. Success will be defined by a BMI percent change with the target being results that would give us confidence we could clear a 5% threshold in BMI decrease at 52 weeks in a phase 3 trial. We are collecting measures of hyperphagia, specifically the HQCT questionnaire in this trial, but I remind you, it is an open-label trial and absent a control group interpretation will be difficult. We are working with one site with a goal of enrolling 10 to 20 patients, followed for six months. Obviously, we will not be reporting out on the full cohort in our end of the year release. I know there will be questions on exact timing. There are practical aspects to that with regard to having as much data entered into the system and quality checked as possible, but we can commit that it will be prior to the Christmas break. One comment before we dive into the findings on slide six is that over my career working on a number of rare diseases, one aspect that is invariably true is that when you get a therapy approved, you have only just begun to learn the full impact of your therapy on that disease. In BBS, for example, we had a clinical data from approximately 50 patients at the time of approval. These MC4 pathway diseases are rare and absolutely fit that mold. The paper, described here on slide six, is a German study that showed six months of set melanotide therapy was associated with clinically meaningful improvements in steatotic liver disease and kidney function. This prospective observational study was conducted at University Hospital Essen in Germany, where 26 patients with BBS, ages six to 52 years, all with metabolic dysfunction associated steatotic liver disease, or MASLD, at baseline. These patients were followed for six months, and after six months of treatment, more than 80% of patients exhibited either resolution of muscle or stabilization at the lowest grade of S1. We know weight loss can improve liver function in patients with obesity, but these changes did not correlate closely with BMI change, raising the possibility that some other aspect of the bone and cortin biology may be mediating these changes. These results were recently published in the Journal of Clinical Endocrinology and Metabolism. On slide seven, our upcoming launch in HO represents an incredibly important milestone for Rhythm. As you heard from Jennifer at our investor event in September, and we'll hear again from her this morning, we have the pieces in place to execute a successful launch. She and her management team have done a great job expanding our existing commercial teams with the hiring of a group of highly experienced and extremely talented individuals who are excited to get started. With an estimated prevalence of 10,000 patients in the United States, this is, as noted, a transformative opportunity for us. The unmet need is significant and clear, and Southland type showed strong efficacy in phase two and three trials. The regulatory dialogue is ongoing, and we appear to be on track for our PDUFA date of December 20th. Obesity week begins this week in Atlanta. Dr. Christian Roth has an oral presentation of the outcome of patients on GLP-1 therapy in our phase three trials. You have seen this data previously, but it will again be an opportunity to highlight the value of correcting the hormonal deficit in alkyl nanosite-stimulating hormone in patients who may not be getting the desired response from other anti-obesity medications. Overall, there is strong buzz in the community and a lot of excitement and rhythm as we near launch. Lastly, slide eight are the upcoming milestones. We covered the first two, norepinephrine aid and potential HO approval, and the preliminary data readout and greater will aid, both likely coming in December. We aim to complete an enrollment of the RM718 weekly phase two study in HO patients during the first quarter of 2026. We will also release top line data from the Japanese cohort from our phase three acquired HO trial in Q1, and we will release top line data from the M&A trial in Q1. We aim to complete enrollment of the congenital HO trial Finally, we will initiate our phase three study with Biv and Melagon and Acquired HO next year. We'll further refine the timing once we've had feedback from the regulators. It's a busy end of the year. With that, I will turn the call over to Jennifer.