Rhythm Pharmaceuticals, Inc.

Good day and thank you for standing by. Welcome to the Rhythm Pharmaceuticals Q2 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 11 on your telephone. You will then hear an automated message advising that your hand is raised. To withdraw your question, please press star 11 again. In the interest of time, please limit yourself to one question. 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, Investor Relations. Please go ahead.

Thank you, Tanya. 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 of our website, ir.rhythmtx.com. This morning, we issued our press release that provides our Q2 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 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 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 disclaim any obligation to update such statements. With that, I'll turn the call over to David Meagher, who will begin on slide five.

Thank you, Dave. Good morning, everybody. Thank you for joining. Today marks the first earnings call where we can truly start mapping the long-term future of RHYTHM. Early startups, beyond the simple struggle to survive, often don't have the luxury of looking longer term. At Rhythm, we have more than survived, and in quarter two, we laid the foundation for significant future growth. I'll briefly review those elements on this call. We had another solid quarter of BVS sales growth. Why is that important? We're now three years post-launch of an extremely promising but very challenging opportunity. Our North American international teams have entered a classic ultra-rare disease community with all the challenges they face from lack of disease awareness, difficulty getting to a diagnosis or finding an expert, through to gaining access to the only approved medication. The projected epidemiology seems right. The patients are benefiting and the healthcare system is working with us. All of that translates to sustainable, steady growth, which is what you are seeing this quarter. We expect BBS will be an important part of these quarterly earnings calls for the next 15 years. In terms of significance, I don't think we have had a more impactful quarter. The phase three readout of set melanotide and acquired hypothalamic obesity and the phase three readout of the first of our two next generation compounds sets us on course for our next phase of growth. Although we previously reported those results, I will briefly review them. They are worth revisiting. We had a productive meeting with the FDA, the first in-person meeting in five years, and we are on track to complete US and European regulatory filings in Q3. we will update you upon acceptance of the filings. Finally, we're very well capitalized following our recent oversubscribed $189 million raise. On slide six, I remind you again of the meaningful opportunities ahead of us. PBS with an estimated 5,000 patients in the US and similar numbers in Europe, acquired Hypothalamic Obesity with 5,000 to 10,000 patients in the US, and as noted, a growing level of competence in the upper range of that number with similar numbers estimated for Europe. The Japan opportunity looks equally promising. Finally, we look forward to the MNATE readout in the first quarter of next year. Importantly, we have the time to fully develop these opportunities. Set melanotide composition of matter patent is up in 2032, but importantly, the formulation patents extend to 2034 in the US. Our next generation compounds will extend that protection to 2040 plus. On slide seven, we wanted to share a little more color as to what the patients are experiencing. 30 patients or their caregivers who participated in our phase three trial of cetlanetide and acquired hypothalamic obesity, participated in a qualitative one-hour interview. These results were presented at ENDO last month. I encourage you to read the representative quotes on the slide. I'm not going to read them. But these individuals who may have been living a relatively normal life prior to their injury, brain tumor in most of these cases, suddenly were confronted with rapid weight gain, increased hunger, a severe preoccupation with food, all accompanied by a lack of control. Once on treatment, they could, as they described it, feel good and find joy in their lives again. On slide eight, you can see that of the 30 patients participating in the interviews, they almost all experienced the increase in hunger, the increase in fatigue, and a decrease in their physical activity. This disease is not about simply adding a few additional kilograms. Moving to slide nine, the set monotide phase three acquired hypothalamic obesity results we reported out in April. We're hugely validating both in terms of the underlying biology. This is a disease driven by impaired MC4R signaling and effect of set melanotide, a functional analog of the endogenous hormone alpha-MSH, which had a consistent and meaningful impact on the primary and key secondary endpoints. As shown here, the placebo-adjusted difference was 19.8% reduction in BMI. Importantly, this result was consistent across all age groups in both male and female patients. We were equally excited to get the results of the Phase II Vivomelagon trial. These were the first results in patients, and we are learning. As shown on slide 10, the placebo cohort gained weight, there was a clear dose response, and the 600-milligram cohort decreased their BMI by more than 9%. On slide 11, as you remember, we made our best attempt to draw an apples-to-apples comparison with the set melanotide data at 12 and 16 weeks from the Phase II and III trials in acquired hypothalamic obesity in patients age 12 and above. As you can see, the patients decreased their BMI by 9.7% and 10.1% at 12 and 16 weeks respectively, as compared to 9.3% for the 600 milligram dose cohort at 14 weeks in an intent to treat analysis. We expect 600 milligrams will be our target dose going into phase three trials. We will request an end of phase two meeting with the FDA and request scientific advice from the CHMP of the EMEA to share the data and gain alignment on the design of the phase three trial and a path to registration. Finally, Al Garfield, our CSO, and I had the privilege of joining Jan in his team at the IMPROVE meeting in Prague. He will describe in greater detail, but it is a unique event focused on MC4R pathway diseases. While the prior meetings were more genetically focused, this meeting had significant discussions about HO and a sharing of some of the early real-world treatment experience in Europe. The fact that approximately 150 physicians from around Europe would attend a Rhythm-sponsored meeting speaks to the quality of the science, which was shared, and the level of trust Jan and his team have built with that community. Finally, slide 13 highlights a number of the upcoming milestones. We remain on track for U.S. and EMEA filings this quarter for set melanotide and HO. Our goal is to disclose preliminary results from the Phase II Prader-Willi trial before the end of the year. We aim to complete enrollment of the 718 weekly phase two study in HO patients in Q1, 2026. We'll also release data, top line data from the Japanese cohort from our phase three alpha acquired HO trial in Q1. And we will release top line data from the Emanate trial in Q1. We aim to complete enrollment of a congenital HO trial in the first half of 2026. And finally, we will initiate our phase three study with Bill Milligan in acquired HO in 2026. And we'll further refine the timing once we have feedback from regulators. With that, I will now turn the call over to Jen.