Rhythm Pharmaceuticals, Inc.

Good day and thank you for standing by. Welcome to the Rhythm Pharmaceuticals third quarter 2022 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 the session, you need to press star 1-1 on your telephone. 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 and Corporate Communications at Rhythm Pharmaceuticals. Please go ahead.

Thank you, and good morning, everybody. I'm Dave Connolly, IR and Corporate Communications here at Rhythm. For those of you participating via the conference call, our slides can be accessed and controlled by going to the events section on the investors page of our website at ir.rhythmtx.com. This morning, we issued a press release that provides our third quarter financial results and business update, which is available on our website. And as listed on slide two here today with me in Boston for the conference call are David Meeker, Chair, President, Chief Executive Officer, 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 France. With 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 in our most recent annual or quarterly report on file with the SEC. In addition, any forward-looking statements represent our views as only 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, who will begin on slide five.

Thank you, Dave, and good morning, everyone, and thank you for joining our third quarter earnings call. So we had a really strong quarter. Last week, we presented the full phase two hypothalamic obesity data set, and we will review that data briefly on today's call. But the real focus of today is on the progress we are making with our commercial launches in both the U.S. and Europe. BBS is a really good rare disease opportunity, both in terms of the number of patients potentially needing treatment and the syndromic nature of the disease, which facilitates patient identification. The fundamental question has been whether we can get this system to work. We felt good about the early signals in August, and we feel even better about the signals today, as you will hear. On slide five, since BBS approval in June, we have received 120-plus scripts, 80-plus physicians have written prescriptions, and 40-plus patients have been approved for reimbursement. Jennifer will go into some depth on all these. Country-specific launches are happening in Europe, and of course, we received EC authorization for BBS, which was followed in record time with approval for the early access program in France. Jan will provide the international update. In clinical development, we continue to progress our multiple programs with the opportunity for significant label expansion. Slide six. So we had a strong presence at the obesity society meeting with 11 presentations, both our presence at TOS, and improve meeting, which we hosted in Berlin, are good examples of how this should work. In addition to being intensely focused on understanding and meeting the individual patient's needs, we want to lead with the science. We continue to learn more about the genetics, the diseases we are treating, and the impact of semilanotide. In rare diseases, when the first therapy becomes available, there's an acceleration in both the awareness of the disease and disease understanding. We want to be leaders in that effort. At TAS, we presented data showing the sustained effect on BMI reduction in patients with POMC and LEPR deficiencies and body composition data showing that BMI reduction is largely due to the loss of fat mass with relative reservation in body mass. Our genetic testing program continues to support the observation that approximately 5% of patients tested will be positive for a gene where incivary is either approved or the patient would be eligible for the Phase III MNA trials. Slide 7. So now let me briefly review our acquired hypothalamic obesity program. Although the estimated patient population of 5,000 to 10,000 patients may be similar or somewhat larger than the BBS population, the fundamental difference is that these patients are identified, have ongoing engagement with the healthcare system, and for the most part, we believe they are being actively followed by endocrinologists, a primary call point for our current commercial efforts. This is a transformational opportunity for them. So on slide eight, here are the results for all 18 patients, which we announced last week. 16 of 18 met the primary endpoint, decreasing their BMI by 5% or more at 16 weeks. 14 of 18 decreased their BMI by 10% or more at some point during the 16-week trial. Mean BMI decrease was 14.5%. As you can see on the next slide, in addition to the magnitude of the BMI decrease, we think the consistency of the response is quite remarkable. So this is slide nine. So on the waterfall plot last week, we focused on the purple box, highlighting the five patients who had not decreased their BMI by 10% or more at 16 weeks. To remind you, patients in that box were either on track to lose 10% or more when they discontinued the drug due to AEs, the first two patients on the left-hand side of the box. They did lose 10%, but regained when the dose was decreased to allow a slower retitration. That patient has now again lost approximately 10% as the dose has been increased, or they were non-compliant, the last patient on the right. In short, there was only one patient who was compliant and failed to reach 5% at 16 weeks. This was Dr. Ross' patient, who, as we showed, was having rapid weight gain, which continued through the dose escalation period and then reversed course once the therapeutic dose was reached, and since that time has been slowly but steadily losing more weight. Slide 10. 13 of 14 patients reaching their first visit in the long-term extension, that's 29 weeks on therapy, had a mean BMI decrease of 21.1%, and the five patients who reached their second visit decreased their BMI by 26.7%. In summary, we see this data as highly supportive of a strong, consistent, and durable effect in this heterogeneous population of patients with acquired HIV. Slide 11, we had a positive type C meeting with the FDA for our program and acquired hypothalamic obesity. We're pleased to have received breakthrough designation and to have reached alignment on the phase three trial design, which is diagrammed here. We will enroll 120 patients randomized two to one to treatment or placebo with an eight week dose titration period, followed by 52 weeks at their therapeutic dose. The primary endpoint will be the change in BMI at 60 weeks. On slide 12, Here we summarize our multiple ongoing clinical programs, and we look forward to updating you further on those efforts in 2023. And with that, I will turn the call over to Jennifer.