Rhythm Pharmaceuticals, Inc.

Good day and thank you for standing by. Welcome to the Rhythm for Mechanicals Q2 2021 Earnings Conference Call. At this time, all participants are in 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 the star 1 on your telephone. If you require any further assistance, please press the star 0. I would now like to hand the conference over to your speaker today. David Connolly, Head of Investor Relations and Corporate Communications at Rhythm. Thank you. Please go ahead.

Thank you. Good morning. I'm David Connolly, Head of IR and Corporate Communications here at Rhythm Pharmaceuticals. With me today for our second quarter financial results and business update conference call are David Meeker, Chair, President, and Chief Executive of Rhythm Pharmaceuticals, Maurice Stewart, our Chief Medical Officer, Jennifer Chen, Executive Vice President, Head of North America, Jan Mazzebro, Executive Vice President, Head of International, who is dialing in from Europe this morning, and Hunter Smith, our Chief Financial Officer, who is here in Boston with us. For those of you participating via conference call, the accompanying slides can be accessed and controlled by going to the Events section of the Investors page of our website, ir.rhythmtx.com. This morning, we issued two press releases, one of which provides an update on our comprehensive expansion of clinical development program with five new phase two and three trials planned to evaluate set melanotide in rare genetic diseases of obesity, and a second press release that provides our second quarter financial results and business update. Both press releases are available on our website. On today's call, on slide two, David will provide an overview and some introductory remarks. Murray will provide an update on regulatory and clinical development plans. Jennifer will provide an update on U.S. commercial. Jan will provide an update on international. And Hunter will provide an update on our finances and balance sheet. Lastly, the team will be available to answer questions. On slide three, I'll walk you through our forward-looking statement. I'll remind you that this call will contain 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 factors, including those discussed in our most recent annual report on file with the SEC. In addition, any forward-looking statements represent our views only 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.

Thank you, Dave. And I'd like to offer my welcome to everyone for Rhythm's first quarterly earnings call. Starting on slide five, as Dave highlighted, it's been a highly productive quarter. Not a lot of flashy headlines, but we're really pleased with the significant progress that we've made, and I think you'll hopefully appreciate that, particularly on the clinical development front, which Murray will walk you through. Some of the highlights from the second quarter on the clinical side, again, Many discussions with the FDA and EMEA leading to our current state with a newly named Phase III M&A trial, our newly named Phase II Daybreak Trial, and then the Phase III study in pediatrics, children ages 2 to 6, and then two Phase III trials for our weekly formulation. We've been very encouraged by our first full quarter of NCIVRI availability. We're learning a tremendous amount, which Jennifer will walk you through, and we are making significant strides in building out our infrastructure. We got our European Commission authorization for NCIVRI. We knew this was coming, but an incredibly important milestone nevertheless. And I'm very happy with the indication, the labeled indication that we got. We're approved for the treatment of obesity and the control of hunger. We have hunger in the U.S. label, but in the European label it is included in the indication and, again, signals the importance of that aspect of this disease given the underlying biology. Jan's going to take you through the progress in Europe and outside. We recently announced our agreement with Medicine Pharma to commercialize in Sivri in Israel. Again, he'll go into a little more depth there, but this agreement signals, again, our commitment to go global with this opportunity. The CRIBS collaboration, again recently announced, is an important step, certainly for the BBS community in rhythm as we work to learn more about that opportunity and support that community. I firmly believe in the area of rare diseases. When you get a drug approved, you are truly just at the beginning of understanding that opportunity. By nature, you have very few patients that may have been treated in the clinical development program. So much of that learning does begin at that point in this collaboration. will give us a real opportunity to learn much more about the natural history of this disease. And, of course, we'll continue to track the benefits as patients move on to incivary. And finally, URO, our gene panel that we support and offer to the community, which is the backbone of virtually everything we do, and we provided a updated panel now that extends to 80 genes, and Jennifer will walk you through a little more on that aspect. Turning to slide six, I know many of you on the phone are familiar, of course, with what we do, but I think it's worth reminding people, you know, we're focused on the rare genetic diseases of obesity, which is very distinct from general obesity. Many times they present in a similar fashion, but the underlying drivers and what they're experiencing is different. characterized by early onset severe obesity and the very important aspect of hyperphasia, which is this pathologic hunger associated with persistent and potentially extreme food-seeking behavior and highly impactful in terms of a patient's overall quality of life. It's a genetically defined population by definition, tends to be resistant or refractory to therapies and interventions, including bariatric surgery. and it is associated, again, strictly as a function in many cases of the severity of obesity with all the complications and comorbidities we see in that population. So in essence, this is a life-threatening disease with no approved therapies to date other than the three indications that we were approved, we had approved in November of last year. So moving to slide seven, our focus as we seek to transform the care of patients with rare genetic diseases of obesity is fourfold. The U.S. is our first opportunity to learn and build on the commercial availability of Incivri. That's on track. As we first start, you know, making a drug available, it's always interesting to see how patients, the initial patients do, who go on therapy outside of a clinical development program. And I'll just share one anecdote. One of the first patients to go on therapy was an eight-year-old girl. who experienced a decrease in her BMI at three months. She cleared her reauthorization with her payer. But more importantly, she experienced some of those more subtle things we don't think about. Her glasses started fitting better. Her shoes started fitting better. She had more energy and just an overall general improvement in her quality of life. Again, it's just not to forget, you know, we get focused on the numbers, but some of these more nuanced aspects are what really transform people's lives. Secondly, the clinical development program, and again, I'll leave it to Murray to take you through the details, but that's the backbone of everything we do. The community building, all the educational, the development of experts, of course, patient awareness and testing, all of that will be anchored by our clinical development efforts, which are increasingly robust. Third, we're poised to deliver on our BARTed beetle opportunity with the filing on track, as, again, you will hear in the near term. And we're excited about that opportunity. I mean, that's a, you know, we've highlighted that the first three genes we've been pursuing, that that opportunity will have tens of patients on near term, many more long term. But it's the needle in the haystack, and we'll take a little bit of time to get there. But Barted Beetle is a much better organized community, and the 2,500-plus patients in the U.S. equal or greater numbers, as you'll hear from Jan, outside the U.S. Again, we're focused on that, and that's something that we want to get right. And finally, just as a highlighter, we're excited about progress that Jan is making, I think, outside the U.S. Many U.S. biotechs, small companies, tend to shy away from Europe. It's complex, hard to penetrate. country by country differences that need to be understood. And we're just incredibly fortunate to have someone like Jan with deep experience on leading that effort for us and making the approval, the progress that he has been making. And, you know, just for example, I mean, as we work with payers and one of the most important aspects of his efforts and our efforts as a company are to make sure that the whole community and certainly the payer community part of that understands that these diseases are not obesity. These are rare genetic diseases driven by clear deficits in a pathway in the brain and that they happen to be associated with obesity. And I think Jan's made good progress with that. So turning to the last slide in my section, slide eight, this is a small pipeline cut, if you will. Working from the right side, we have the three genes approved. And I think the message I want to leave here is that we are going very specifically gene by gene. And so the expansion of this opportunity will be as we can get additional genes approved, and that's been our clinical development strategy. So we'll be filing for the BBS and Allstroms. And just one note on Allstroms, as Mary will get to as well, we see clear responders there, but... We have, I think, a good understanding with both regulatory agencies that absolutely we should file and make the case, and I think we have reasonable optimism, but one will not unduly impact the other. They will be looked at basically as independent genetic opportunities. The Phase III trial, again, excited about the five genes we're pushing through the Phase III M&A trial, and then the Daybreak trial is a highly efficient way, I think, of understanding additional genes in that pathway. No way that all 31, of course, are going to respond. I think this will allow us to rapidly, relatively rapidly, begin to sort that group of 31 that we think, based on existing knowledge, tie them strongly to the pathway. But, of course, the ultimate confirmation will come from their response to semilantotype. And as we said, we're committed to the lifecycle management strategies we're adopting. So with that, I'll turn it over to Murray for the clinical and regulatory update.