Rhythm Pharmaceuticals, Inc.

Thank you for standing by and welcome to the Rhythm Pharmaceuticals fourth quarter fiscal year 2021 financial results 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 the session, you'll need to press star 1 on your telephone. As a reminder, today's program may be recorded. I would now like to introduce your host for today's program, David Connolly with Rhythm Pharmaceuticals. Please go ahead.

Thank you, and good morning. I'm Dave Connolly, head of IR and corporate communications here at Rhythm Pharmaceuticals. For those of you participating via conference call, the accompanying slides are available and can be controlled on the events section of the investors section of our website at ir.rhythmtx.com. This morning, we issued a press release that provides fourth quarter and year-end 2021 financial results and a business update, which is also available on our website. as listed on slide two, is our forward-looking statement. And I'll remind you that this call will contain certain 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. And on slide three is a list of today's speakers. We're all here today in Boston. David Meeker, chair, president, and chief executive officers here. Linda Shapiro, our chief medical officer. Yann Mazzebro, our executive vice president, head of international. Connor Schmidt, Chief Financial Officer, and Jennifer Chan is also here for Q&A. She's Executive Vice President, Head of North America. And with that, I'll turn the call over to David.

Thank you, Dave, and good morning, everybody. Thank you for tuning in this morning. So we're really pleased to report out another strong quarter, wrapping up what was an incredibly important year for Rhythm. And today we'll take you through some of the more recent highlights, which are captured on slide five. First and foremost, as we continue our preparations for BBS launch, and hopefully most of you have had a chance to review or see or tune in to our event about two weeks ago, where we heard from Mary Morris, a caregiver, a mother of two children with parted beetle syndrome. And I'll speak a little more about Mary's story in a moment. And we also heard from two of the experts, Dr. Haas and Dr. Conroy, and that That session gave us all, I think, a much stronger sense of both the challenges faced by individuals and families living with BVF, as well as how the experts view this community coming together and the ultimate opportunity for semilantotide. As you know, we heard recently from the FDA requesting some additional analyses. No new data was required, but additional analyses, all of which we felt were good, strong, supportive of the overall file, and perhaps ultimately a better way of looking at the data. So no issue there. But it did come with an additional three-month delay in our PDUFA date, which is now set for June 16th. We also indicated in our recent communication that we made the strategic decision to remove Ahlstrom syndromes from the file in Europe. This was based largely on a calculation that we didn't want to prolong the review in Europe. there was a risk that engaging more around the Alstrom opportunity that might do that. Also strategically, I think as we look at market access opportunities in Europe, it is advantageous to go in a layered way. I think going to the authorities with the combination of BBS and Alstroms made it a little more of a complicated file. So again, from a very strategic standpoint, we decided to withdraw Alstroms at this time from our European application. There's no change to our plans for the U.S. Second, we're going to hear from Jan Masbro today about our international, and I have come to understand, believe, spent time in Europe, that if you can get it right internationally in a rare disease opportunity, and most specifically in Europe, you can pretty much get it right anywhere. It's some of the more challenging healthcare systems in the world, and you'll hear from Jan about exciting progress in that sphere. We're also very pleased with our U.S. commercial experience to date. I'll spend one slide on that, but it's going as predicted and laying the foundation for our PBS launch. And finally, you'll hear from Linda as she takes us through a couple of different programs that we're excited about, meaning they are progressing well. We have a number of milestones met with a number of these trials now underway. And again, she'll speak to that in a little more detail. Next slide, number six. So this is a picture of Mary Morris and her family, her two children, Ashley and Carly. And again, if you have a chance to listen in, what we heard during that session is just the incredible challenges that individuals living with Barted Beetle Syndrome and their families face as they deal not only with obesity, but they deal with the underlying cause, that genetically driven central defect which causes the increased hunger. And, you know, we focus, this is hyperphasia. This is not the hunger that you and I know. And again, when you listen to individuals who are suffering or living with somebody suffering from it, you begin to understand. I don't think we can fully understand if you don't experience yourself, but you begin to understand that this is not what you and I experience when we miss a meal. We heard yesterday at our company-wide meeting from a caregiver, who told the story of her family and their son's challenges of living with Bartlett-Beetle syndrome. It was unique, of course, different in the sense that not completely different individual and family, but the nature of that. She spoke for an hour and literally 55 minutes of the hour was focused on the hyperphagia and the challenges of living with hyperphagia. The consequence, the obesity, the weight gain, the other actors, of course, were important, but what is so striking here is that this is a different disease. These are different diseases from what we see in patients who are living with general obesity. So, again, you can hear more about that if you tune into our session. Slide number seven just highlights, again, the progress or how we think about the frame for our BDS preparations. First is understanding the unmet medical need, which I just spoke to, the importance of the hyperphagia, but Also, the rapid weight gain is severe obesity, which occurs early. And the fact that it occurs early means that the complications of obesity come with it, and they start early. And so the cumulative effect over a lifetime is much greater. The solution, growing confidence in the solution, which is setmelanotide, I think is a targeted therapy addressing the MC4 receptor, lanocortin-4 pathway, which governs hunger and energy expenditure. The story is not completely in the numbers. The numbers are important. The amount of weight loss is important. The scales are important. But as you listen to the stories, you get a much better sense of how, in fact, a drug like set melanotide can change the overall picture. And finally, we spoke about our preparations for launch and feel really good about that. A number of us, we have a highly experienced team here led by Jennifer Chen and a number of people that both she and I have worked with over the years, as well as some new people to us who come from other deeply experienced backgrounds. And that's what it takes, I think, to be successful in a rare disease, are individuals with an entrepreneurial mindset and the ability to problem solve in a customized way. We've made great progress, and I'll speak a little more about that in the next slide, in terms of building this community and helping more and more patients come to diagnosis and, as I said, organize the overall opportunity. So next slide, number eight. Now, we spoke on the call about 350-plus individuals who have been identified. We spoke about the process of identifying those individuals, which consisted of going to physicians where we had a strong understanding that they were caring for an individual with Bartlett-Beetle syndrome. The goal of those visits were to connect in, to validate and confirm that, in fact, they were still following that patient. And so that represents one part of this group, the identified and diagnosed group. We also know that there's a large number of patients out there who are diagnosed today, but may not be actively engaged in the system. That's another opportunity. As we've done genetic testing, the genetic testing, our current panel of 80 genes includes 23 genes for Barded Beetle. And we know the hit rate when you do screen an individual with a history of early onset obesity and hyperthasia for Barded a barded beetle is on the order of 1.5% of those individuals will come back biallelic for a barded beetle gene. Now that doesn't mean that they will meet the diagnosis for barded beetle, but that does create a roadmap to somebody whose probability of having barded beetle may be slightly higher. And so again, falling in this suspected category. And as always in rare disease, by far the largest part of the population is undiagnosed. It is a syndrome. It has advantages in the sense that If you can connect the dots, you have a better chance of making a diagnosis. But you don't connect those dots if you haven't seen one in a reliable way. And you can look at something that's obvious to an expert as a non-expert, and you just miss it. And so as a result, many of these patients are on this prolonged diagnostic odyssey where their ability to get a diagnosis, despite some classic parts of the presentation, they may see five to 10 different positions before somebody puts all it together and says, you may have Bartlett-Beetle syndrome. So we feel good about the 350-plus patients we talked about. The fact that the PDUFA data has been pushed out by three months doesn't change anything. Foundationally, everything remains the same, and we'll continue those efforts and really look forward to June 16th, when we will hopefully be able to move into a commercialization phase. Next slide, number nine. So as I said, we're really pleased with where we are in terms of our initial commercial experience, and we reported 3.2 million patients. in revenues for 2021 with 1.8 million in the last quarter. As or more importantly is what we've learned, logistics are in place, contact and interactions with payers is going well. And the practice, one of the most important things is we bring up our patient services group and we have the opportunity to interact directly with patients who have consented and said they want to be in contact with Rhythm for all the services we can provide. It gives us greater insights into how we can best support this population, both in terms of disease education, what they can expect, the onboarding as they start therapy and what they can expect from therapy, and just, again, general support in the rare disease world that they can't always get from the healthcare system itself. And finally, on slide 10, I just want to remind you all that we announced in December our partnership with RareStone for the opportunity in China. Really excited about that. It's hard to do, maybe not so hard to do the deals. I think it's hard to find the right partner, And as we've interacted over the past two months, our confidence that we've got the right partner in Railstone is growing. We're completely aligned from a cultural standpoint, from a philosophical standpoint. They're highly experienced, having taken a couple of different products through the regulatory process, And they are well on the way with filings related to Rhythm's Opportunity itself. And we're quite hopeful that in that exercise, they will be in a position to be participants in our Phase 3 effort, the M&A trial specifically, and contribute to that. So with that, I'd like to turn it over to Linda Shapiro, our CMO, to take you through our regulatory and clinical update. Linda.