Rhythm Pharmaceuticals, Inc.

Good day and thank you for standing by. Welcome to the Rhythm Pharmaceuticals first quarter 2025 earnings conference call. At this time, all participants are in a listen-only mode. Please be advised that today's conference is being recorded. After the speaker's presentation, there will be a question and answer session. To ask a question, please press star 1 1 on your telephone and wait for your name to be announced. To withdraw your question, please press star 1 1 again. I would not like to hand the conference over to your speaker today. David Connolly, Investor Relations at Rhythm.

Thank you, Josh. 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 morning, we issued our press release that provides our Q1 2025 financial results and a business update, and that press release is available on our website. Our agenda is listed on slide two. On the call today are David Meeker, our chairman and 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 and 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 on our most recent annual or 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 displayed any obligation to update such statements. With that, I'll turn the call over to David Meeker, who will begin on slide five.

David Meeker Thank you, Dave. So, good morning, and thank you for joining. So, we're about one month since our call highlighting the topline results from a Phase III trial on acquired hypothalamic obesity. We remain on track for Q3 filing, including having an in-person Type D meeting scheduled with the FDA. I will say the FDA is responsive, and I would characterize our interactions as completely normal. We have reviewed all of the data, which we will present at upcoming meetings. The more we dig into the data, the more convinced we and I are that setmelanotide has the potential to transform the life of both the patient and their families. I will remind you of the top-line data with a little additional color in the next few slides. Commercially, with BBS, we had a very good first quarter. In the U.S., demand, as reflected in vials dispensed to patients, continues to grow. The team, as Jennifer will describe, is making good progress on multiple fronts, addressing the challenges of this complex disease. The growth in demand is obscured this quarter by the inventory shifts, which Hunter will walk you through. The international team continues to execute on its country-by-country BBS launch strategy, and the HO contribution to revenues predominantly from France and Italy continues to grow, supporting our view of the unmet need and the level of interest in set melanotide as such. As we have highlighted, we're looking forward to the Bibimelagon Phase II readout in Q3 and having something to say about the ongoing DWS study, Brader-Willi, and the 718 weekly study in HO by the end of the year. And we remain well-capitalized with a projected cash runway in 2027. On slide six, this is data from a publication by Professor Mueller from Germany, a renowned expert in the field of hypothalamic obesity. It provides some numbers behind what we are learning as we get to know this community and review the data from this trial. The medical complexity and severity that these patients and their families are dealing with is unlike any disease I have worked on in my industry career. There are diseases with higher mortality rates, but very few with higher medical complexity. And you can see that from the numbers on the slide. 3.7 hospitalizations in the first two years after the injury, of which 23% required an ICU admission, 12 visits to their general practitioner, and on average, 20 visits to a specialist. And even more strikingly, the average number of prescriptions written per month is 5.5. The average number of unique medications prescribed in the first two years is 22. and 89% of these patients require three or more therapies for neuroendocrine dysfunction. As the data from this trial shows us, including the exit interviews with patients and caregivers, the untreated hypothalamic obesity with its associated hyperphagia and fatigue represent a significant part of the medical burden they are dealing with. The fact that patients were willing to commit to this 52-week placebo-controlled trial, given the incremental burden of testing and clinic visits, which are part of any trial, speaks to the motivation of this community to find solutions, We at Rhythm are highly motivated to do that. On slide seven, I'll now provide you a little additional color around the results of the phase three study. First, the top line, and it's worth showing again, with a 16.5% reduction in BMI in the set melanotide cohort as opposed to a 3.3% increase in BMI in the placebo group for a placebo-adjusted difference of 19.8%. As we showed you last time, moving to slide eight, there was no difference in effect between patients under 18 and those over 18, but we have broken this out further. So on slide nine, we did stratify patients between three age groups, breaking out the under 18 to those between 12 and 18, and those less than 12. Adults may be a relatively homogeneous population, but there's a big difference between a four-year-old and a 17-year-old. Here you can see the three age cohorts, and remarkably, They are similar again with placebo-adjusted BMI percent changes ranging from 19.2% to 21%. On slide 10, a hallmark of the trials of septal amptide in this disease has been the consistency of response. And as we showed you last call, 80% of the patients lost more than 5%, suggesting some response. As always, the patients of greatest interest, at least to me, are the apparent non-responders. And I gave three patient examples last call of patients who did not reach the 5% but had other data suggesting a response to drug. A more complete summary of that analysis is as follows. There were 17 out of 81 set melanotide-treated patients who were not considered responders by virtue of reaching 5% or more in this analysis. Eight of these patients discontinued treatment prematurely and had their data imputed. Three of these eight patients actually had reductions in BMI greater than or equal to 5% at their last time point assessed, but were counted as non-responders due to the conservative nature of the multiple imputation method, which uses the placebo patient data to generate the imputation values. Of the nine non-responders who did complete the trial, Six of the nine patients either had a response greater than 5% at some point during the trial and or, for the pediatric patients, had a BMI-Z score decrease greater than or equal to 0.2, which is clinically significant. Two of the three patients with no response and no other explanation had drug blood levels consistent with significant noncompliance. So in summary, the consistency we saw in the Phase II trial and the consistency response we're seeing in the real-world French experience is evident here. This further analysis supports the thesis that the biology in this disease is driven by impaired signaling through the MC4R pathway with a consequent deficit in alpha-melanocyte-stimulating hormone. The consistency of the response to setmelanotide we see across this highly heterogeneous and medically complex patient population suggests we are helping to correct a fundamental biologic deficit. On slide 11, I'll remind you of the disposition in this trial. The vast majority of the 143 patients enrolled consisting of 120 in the pivotal cohort, 11 supplemental, and 12 in the Japanese cohort have moved to the open-label extension trial. A total of 120 patients remain on treatment 108 patients who transitioned to the open-label extension, and the 12 Japanese patients who remain in the blinded portion of the study. And importantly, there were no new safety signals related to set melanotype observed, which of course is in line with set melanotype's well-established and well-understood safety profile. Consistent with prior experience, set melanotype is also generally well-tolerated in the study. And on slide 12, which you've seen before, to remind you of the very significant opportunity in acquired HO. The unmet need is there, these patients are accessible, they're diagnosed, and this set melanotide data looks extremely promising. We believe we can make a significant difference in this disease. So with that, I'll turn the call over to Jennifer.