Rhythm Pharmaceuticals, Inc.

Good day and thank you for standing by. Welcome to the Rhythm Pharmaceutical second quarter 2024 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 this session, you will need to press star 11 on your telephone. You will then hear an automated message advising you 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, David Connolly, investor relations and corporate communications. Sir, please go ahead.

Thank you, Michelle. 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 investor section on the investors page of our website, ir.rhythmtx.com. This morning, we issued our press release that provides our second quarter 2024 financial results and business update, and that is available on our website. Listed on slide two is our agenda. On the call are David Meeker, our chairman, chief executive officer and president, Jennifer Lee, 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 on slide three, I'll remind you 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 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. We'll begin on slide five.

Thank you, Dave. We are pleased to report out another strong quarter with continued steady progress on our commercial opportunity, both in North America and internationally, another regulatory milestone with pediatric approval for incivary in patients ages two to younger than six in the EU, and broad progress across our development programs. We remain focused on our three main value drivers shown on slides five and six. In this quarter, we have made advancements in each. First, as noted, the team continues to execute on our global commercial strategy. Second, we remain excited about the hypothalamic obesity and the likelihood of success in our ongoing global phase three trial. And third, we continue to make progress with two new MC4R agonists in phase one and phase two trials. We have completed the Phase 2 Daybreak Trial and the Phase 3 Emanate Trial remains on track to complete enrollment in the two leading cohorts by year-end. Revenues for the quarter were $29.1 million, driven predominantly by BBS. Two years post-approval in the U.S. and with increasing market access in international, what remains most striking to me is the extent to which BBS is a classic rare disease challenge. The obesity and the hunger are there for all to see, but the disease remains relatively invisible to those who are not expert. Two weeks ago, I attended the BBS Foundation International Conference in Minneapolis, the first in-person meeting at this level in more than four years. More than 200 patients and family members attended, along with a number of the expert physicians. One common refrain was, aren't you tired of having to explain to each new doctor that you see what Bartlett-Beetle syndrome is? In the opening session, the head of the foundation charged the attendees with one goal, meet someone they did not know from the community. Of the many challenges facing the rare disease patients and families, which include getting to a diagnosis, finding an expert physician, managing their disease, one of the biggest is simply feeling alone. Rhythm, from the beginning, has not focused on selling a drug. Instead, our focus has been on supporting community development with the goal of having more experts more integrated care centers, and most importantly, more opportunities for patients and their families to interact with other members of the community. That meeting was one big family, and we, as Rhythm, were privileged to be part of it. How does all that relate to revenue growth? You do the right thing for each patient, their family, and the community, and the revenues will follow. In hypothalamic obesity, our ongoing phase three pivotal trial remains on track for a first half readout in 2025, and our enthusiasm remains high. At this point, the first patients enrolled have completed their placebo-controlled portion and are rolling over into the open-label extension. A brief reminder, the pivotal cohort for this trial enrolled 120 patients, randomized 2 to 1, drug to placebo, with the protocol calling for up to 8 weeks for dose titration and 52 weeks on the therapeutic dose. The trial is over-enrolled, dropout rate remains exceedingly low, and the trial is 99% powered to show a 10% placebo-adjusted difference in BMI. Of note, we do not counsel these patients on diet or exercise as a formal part of the trial design. Patients receive only what is standard of care for that institution, recognizing almost all of these patients have tried diet and exercise previously without success. Of interest, approximately 25% of patients enrolled in this trial had tried GLP-1s, and about 10% of enrolled patients entered the trial on active GLP-1 therapy. We did not exclude patients on or with GLP-1 experience from the trial. They were allowed to enroll as long as their weight was stable over the preceding three months. Our overall position on GLP-1 use in this population, informed partly by our engagement with the community, but also by the research many of you have done, is that many patients with HO may have some initial response to GLP-1s, but the percent of patients with sustained benefit will be less than 20%, and the magnitude of that benefit may be 10% or less. In Japan, where we estimate the number of patients with hypothalamic obesity to be 5,000 to 8,000, which is on par with European and United States total patient estimates, despite Japan's overall population being much smaller, we have dosed the first patients in our 12-patient cohort, and we are actively screening patients at four sites in Japan. This Japanese cohort will enable us to seek regulatory approval in Japan with data from these 12 patients plus the pivotal cohort and not affect timing for U.S. and European regulatory submissions. Our two next-generation MC4 agonists designed to avoid the hyperpigmentation that comes with MC1R agonism are advancing on schedule. Last month, we announced dosing of the first patient in our 28-patient Phase II placebo-controlled trial evaluating the oral MC4R agonist, LB54640, in hypothalamic obesity. The phase one study of RM718, our weekly injectable, built offset melanotype, is progressing through the SAD, the single ascending dose, and MAD, multiple ascending dose, portions of the trial in normal healthy volunteers with obesity. We made the decision to add two additional higher dosing cohorts in the SAD portion with the goal of satisfying the regulatory requirements in this early phase study, potentially avoiding the need for a dedicated QTC study, measure of heart rhythm, thereby simplifying the regulatory development path. Finally, we were pleased to receive the expanded marketing authorization for Incivary from the European Commission for patients two to less than six years old with Bartlett-Beetle syndrome or POMC-Lepar deficiency. In the U.S., we completed submission of the supplemental new drug application to the FDA in the second quarter, which keeps us on track for a potential label expansion towards the end of this year. As we have previously highlighted, this approval modestly expands the treatable population But more importantly, it may offer patients fortunate enough to get a diagnosis at an early age potential for better outcomes. Two key takeaways from the phase three trial were, one, patients as young as two can be severely affected, and two, as shown on slide seven, they responded uniformly and well to a treatment with an 18.4% mean reduction in BMI at one year. These are genetic diseases, and the defect is present at birth. Jan will share modeling data, which was presented at the European Congress of Obesity in May, that modeled the impact of early intervention on long-term comorbidities in patients with obesity. Given the potential benefit, why would you not want to start treatment as early as possible? So I now turn the call over to Jennifer to provide the North American update. Jennifer.