Rhythm Pharmaceuticals, Inc.

Good day and thank you for standing by. Welcome to the Rhythm Pharmaceuticals Q2 2023 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 TAR11 on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press TAR11 again. 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, Executive Director of Investor Relations and Corporate Communication. Please go ahead.

Thank you, Bella. 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 on the investors page of our website at ir.rhythmtx.com. This morning, we issued a press release that provides our second quarter 2023 financial results and a business update, which is available on our website. As listed here on slide two is our agenda. Here with me today in Boston are David Meeker, Chair, Chief Executive Officer and President of Britain Pharmaceuticals, Jennifer Chen, Executive Vice President, Head of North America, Hunter Schmidt, 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 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 FEC. as of any subsequent date. We specifically disclaim any obligation to update such statements. With that, I'll turn the call over to David Meeker, who will begin on slide five.

Thank you, Dave, and good morning. Thank you all for joining today. Q2 was a very good quarter, so we're going to dive into the details behind the quarter in our presentation, but before we do that, let me try to put these results in a larger context. We recognize, and I think all of you recognize, that Rhythm has two main drivers of value creation. BBS commercial execution, and HO clinical development. On top of that, we have a number of additional efforts which offer potential upside that may be significant. The fundamentals, which we have discussed multiple times, are strong. The biology is well understood. Impairment in signaling through the MC4 pathway leads to hyperphagia, that uncontrolled hunger that stems from not getting a signal that you work full, coupled with a decrease in energy expenditure, which all leads to obesity. The community is increasingly recognizing that not all obesity is the same and that patients with impaired signaling through the pathway have a distinct disease which requires a specific approach. Two, the unmet medical need is clear. Treatments for patients with general obesity may have some effect in individual patients. For example, my craving for ice cream may go down on a GLP-1, but I have not addressed the fundamental problem. Impairment in MC4 pathway signaling leads to a decrease in the endogenous hormone alpha-melanocyte-stimulating hormone. Semilanotide is an analog of alpha-MSH. We are a precision medicine that happens to be a hormonal replacement. Why wouldn't you replace the hormone if there were a deficit? Three, our drug works. Approved for multiple genetic diseases and with strong proof-of-concept data and hypothalamic obesity, we are now increasingly seeing the real-world effect. Patients are choosing to go on treatment and are largely staying on treatment. So now to the quarter. We are one year post-approval for BBS in the US. We have discussed each quarter whether we can trend the quarter-on-quarter script numbers, and I'm sure we will again today. The answer will be the same. No, don't trend the quarter-on-quarter numbers. But you can look at a full year now of data and conclude BBS is evolving into a very meaningful rare disease opportunity. The patient community is engaged. The number of doctors writing scripts continues to grow. The payer community is listening and recognizing this is a unique rare disease and not simply an extension of the population of patients living with general obesity. The teams are executing and our confidence is growing. We hope yours is as well. We're making good progress on our phase three study for hypothalamic obesity. We have moved up our timeline for completing enrollment to the end of the year based on good progress getting sites up and going. I wish no one took so many vacations, but the patients are there and waiting. Our six-month long-term extension data show continued reductions in BMI at six months, and we look forward to updating you on the 12-month data in the fall. I will speak briefly about our phase two long-term extension data and a couple of slides. Finally, we have a number of trials reading out in the second half of this year with a daybreak, pediatric, and weekly switch studies. We will highlight these results at an upcoming R&D session in Q4 of this year. And we are excited to introduce you to our next generation program, RM718, which I will discuss in the next slide. So slide six. RM718 is a more specific and potentially more potent molecule. It is MC4R specific in its targeting. It does not hit MC1R and therefore eliminates the hyperpigmentation effect we see with MC1R agonism. And it is a weekly formulation with patent protection out to 2041. are preserving the option of continuing with our current weekly program but we will push out initiation of the weekly study into 2024 when we will make a final decision on our weekly strategy pending further development with 718. our goal quite simply is to develop a better drug which happens to come with a significantly longer patent protection we look forward to providing more details of the upcoming r d day so on slide seven Slide seven is to remind you of the overall opportunity. We started small with POMC and LEPR. BBS and HO represent meaningful rare disease populations with the major advantage being they can be diagnosed more easily. And the HO population, as you know, is largely diagnosed today. On top, a significantly larger world potentially opens up with the M&A trial populations. Moving to slide eight. We remain laser focused on getting our global phase three trial up and running. As previously discussed, the challenge was not patient interest, but clinical trial site bureaucracy. We are breaking through all of that with one third of the sites open and about a quarter of the patients screened. Screening is a good indicator because very few patients screened fail. The physicians have their list of patients, they know the entry criteria, and they invite patients to participate accordingly. Based on our progress to date, we are moving up our targeted enrollment completion date from Q1 2023 On slide nine, we remind you of the six-month data we presented at ENDO, which shows continued BMI reductions over time in the majority of patients. The blue bars represent the 16-week data, and the red bars represent the six-month data. On slide 10, we have the summary of this data. And you can see the mean change for the 11 pediatric patients moving from minus 18% at 16 weeks to minus 22% at six months. The two adults we broke out separately, with one patient moving from minus 14% to minus 21%, and the other patient who has been up and down on her drug dose, regaining as the dose was decreased and losing again as the dose was increased. She has now again lost approximately 10% at six months. So on slide 11, I'll finish my section on this slide, which shows an increasingly robust portfolio of indications which are progressive. More to come later this year on our pediatric program, weekly program, daybreak open label results, and the 12-month data from the HO patients and long-term extension. I'll now turn the call over to Jenna.