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Good day, and thank you for standing by. Welcome to the Rhythm Pharmaceuticals third quarter 2024 earnings conference call. At this time, all participants are on 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, David Connolly, Head of Investor Relations and Corporate Communications. Please go ahead.

Thank you, Shannon. 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, ir.rhythmtx.com. This afternoon, we issued our press release that provides our third quarter 2024 financial results and business updates. And that press release is available on our website. We are coming to you today from San Antonio, the site of Obesity Week, the annual meeting of the Obesity Society. Listed on slide two is our agenda. On the call today are David Meeker, 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 president, head of international, is on the line joining us from Europe. 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 in our most recent annual or quarterly reports on file with the SEC. In addition, any forward-looking statements represent our views as of only 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. So thank you all for joining today. We realize we're probably not the lead story today, November 5th, Election Day, but we are really pleased with both the quarter and the progress we have made in 2024. We recognized at the start of 2024 this would be a year of execution with the highly anticipated readouts coming in 2025. We have executed, and in addition to the expected readouts, we have one unexpected readout, which was presented today at the TOSS meeting, an early look at the real-world data in French hypothalamic obesity patients. I'll say a little more about that shortly. As shown in slide five, we remain focused on our three main value drivers. First, the team continues to drive results through strong execution of our global commercial strategy. Second, we are positioned to expand this patient opportunity to include hypothalamic obesity. and we have increased confidence in the potential for this indication based on the new real world data, efficacy data from the early access program in France. We remain on track to report top line data from our phase three trial and acquired hypothalamic obesity in the first half of 2025. Third, we continue to make progress with our MC4R agonist pipeline with daybreak data presented at the Obesity Society's Obesity Week, demonstrating potential new expansion opportunities and genetic indications. And we continue to progress our next generation MC4R agonist, the weekly RM718, and the oral daily small molecule, Bibimelagon. Study growth continues with incivary revenues for the third quarter coming in at 33.3 million, driven primarily by BBS sales globally. We continue to identify patients, physicians continue to prescribe incivary, and payers are supporting access. We have an experienced rare disease team executing in challenging environments, and of note, We are only two years post-approval in the US and continuing to introduce new markets internationally. It is early in the commercial lifespan of this opportunity. Our clinical programs are progressing as we remain on track to report top line data from the phase three HO trial in the first half of 2025. The dropout rate remains less than 10%. We are targeting full enrollment of the Japanese cohort of patients by year end. Our small molecule program has 50% of the targeted number of patients dosed or in screening. For the RM718 study, we are completing the rat and nonhuman primate toxicology studies, and we'll submit those along with an amendment to allow dosing patients with hypothalamic obesity for more than four weeks to the FDA. We are targeting dosing the first hypothalamic obesity patients with 718 in the first quarter of 2025. We are doing this call, as Dave said, from Obesity Week, and I want to highlight two of our poster presentations. First are the full results from the daybreak trial. This was an ambitious undertaking where we sought to enroll patients with genetic variants in any one of 30 genes, which literature suggested may be linked to the MC4R pathway. On slide six, you can see the design of the two-part trial and the open label part one we reported out last December. Patients who lost 5% or more after 16 weeks were eligible to enter the double-blind randomized withdrawal part two. where patients were randomized two-to-one to either continued setmelanotide therapy or placebo for 24 weeks. On slide seven, you can see the patient demographics. Forty-nine responder patients entered part two, and 39 patients completed this part of the trial. We had equal numbers of adults and pediatric patients. On average, they lived with severe obesity based on their BMI or BMZ measurements. Slide eight shows the summary results with a mean decrease in BMI of 12.4% in the 32 patients on continuous setmelanotide therapy for a total of 40 weeks. And 84% of patients on setmelanotide maintained or further decrease of BMI beyond the initial 5% as opposed to only 29% of patients randomized to placebo during the 24 week stage two of the trial. Overall, we were quite pleased with the results. The trial design worked. The open label trial period identified patients who seemed to be true responders in that those randomized to continued treatment continued to respond, whereas those randomized to placebo mostly regressed towards baseline. On slide nine, you can see the individual spaghetti plots for the four of these genes or gene groups. The blue lines represent set melanotide, whereas the green lines represent the placebo patients. Also note that scales on the graph for each gene are different and were adjusted to accommodate those patients with the greatest decrease in their BMI for that gene group. I won't go through each of the panels, but if you look at the PHIP gene in the upper left, you can see the adult patients on the left and the pediatric patients on the right. In general, those continuing onset melanotide had a good response, whereas the three patients randomized to placebo regained weight. The PHIP gene was the gene with the highest overall percentage of responders, particularly in those who completed part one. The key learnings from this trial are that there are patients who seem to have a clear response to several antitides, suggesting their variant is impairing signaling through the MC4R pathway. The challenge for future development will be identifying those patients with true loss of function variants, recognizing for many of these genes, relatively little work has been done on the different variants leaving most variants classified today as VOOCs, or variants of unknown significance. Our expectation is that we will do additional research on one or more of these genes, but that work will be done with one or both of our second generation programs. Now I want to finish my introductory comments talking about HO. We know there's a significant unmet medical need with no approved therapies, and we believe the prevalence is in the range of five to 10,000 patients in each of the US and Europe, as we've described previously. and we believe there may be similar numbers of patients in Japan. Importantly, unlike BBS, most of these patients are diagnosed and under the care of endocrinologists. We reported out Phase II data in mid-2022 and moved directly to the randomized placebo-controlled 60-week Phase III trial. Both France and Italy, in recognition of this significant unmet medical need, the absence of approved therapies, and the strength of the Phase II data, in an unusual move, have made setmelanotide available through paid early access programs. Patients from France began enrolling late last year and Italian patients are just beginning to receive treatment under the program. Real world data from the initial French patients which was presented today at TOS is shown on slide 10. Eight adult patients with a mean age of 31 who had undergone brain surgery 12 years earlier at the mean age of 19 have been followed for three to six months on setmelanotide. As you can see from the slide, they were severely affected with a mean BMI of 44. On average, these eight adult patients had a mean BMI decrease of 5.6% and 12.8% at one and three months respectively after initiating treatment. Patients have continued to lose weight, with five patients who have reached the six-month time point experiencing a 21.3% on average decrease in their BMI. We see this data as important for multiple reasons. It is the first new data we have presented since the original Phase II readout in 2022. We had relatively few adult patients in the Phase II trial and almost no adults in the long-term extension, leaving us with an important unanswered question. Would adults be less responsive than children who are being treated in closer proximity to the onset of their HO? This data set goes a long way in answering that question. These patients were adults with a mean age of 31, as I said, who are on average 12 years out from the time of their injury. The response to date has been consistent, and that's one of the most remarkable things is the consistency of the response, and robust, further strengthening our conviction in the importance of the MC4R pathway in this disorder, and the potential role semilanotide may play in the management of hypothalamic obesity. So finally on slide 11 is a summary of our upcoming milestones. The PDUPA date for our US and survey label expansion to include patients ages two to up to six years old is December 26th, and Jennifer will touch on that. Based on the progress of initial enrollment and sites opening, we expect to complete enrollment in the 12-patient Japanese cohort of our phase three acquired hypothalamic obesity trial by the end of this year. We also expect to complete enrollment in two of the MNH sub-studies, POMC-PCSK1-HETS and SH2B1 by the end of the year. We do not anticipate being able to achieve full enrollment in the other two sub-studies, LEP-R and SRC1. In the first quarter of 2025, we anticipate we will complete enrollment in the 28-patient phase two trial, evaluating vivameligon, and also in the first quarter begin dosing patients with acquired hypothalamic obesity in part C of our phase one trial with the weekly MC4 agonist, RM718. And as we have said many times, our top line data readout from the pivotal 120 patient cohort in our global phase three trial of set melanotide and acquired hypothalamic obesity is on track for the first half of the year. With that, I'll turn the call over to Jennifer.