Rhythm Pharmaceuticals Inc to Discuss Preliminary Data from Exploratory Phase 2 PWS Trial Transcript

The following is excerpted from the question-and-answer section of the transcript.

Question: Philip Nadeau - TD Cowen - Analyst : Congrats on the data. David, we wanted to dive into your comments about the Phase 3 trial and the likelihood of success in a bit more detail and kind of have two questions in that vein. So first, could you go into a bit more detail about what you think the primary endpoint of a Phase 3 trial would be? Would it be a change of -- change in mean BMI from baseline with the expectation that, that would hit a 5% hurdle? Or do you think the responder analysis could be the primary endpoint? And then second question, kind of along those lines, I guess, as we look at the data, it does seem like at least in two of the patients, the weight loss was progressive that gets you to that BMI of over 5% by month six and admitting there's mitigating circumstances for the three patients, but it wasn't necessarily progressive in the other three. So how confident are you that the BMI reductions here could be progressive to get you to that 5% level by month 12? And are you thinking maybe in a placebo-adjusted trial, the placebo group would actually increase. So you don't need an absolute reduction of 5% in the patients, but placebo adjusted if you could get there anyway?

Question: Philip Nadeau - TD Cowen - Analyst : That's really helpful. Maybe just one follow-up question. What change in BMI would you expect for an untreated patient similar to the ones that you enrolled in this trial over 12 months? How much is the average?

Question: Philip Nadeau - TD Cowen - Analyst : Perfect. That's very helpful. Congrats again on the data.

Question: Tazeen Ahmad - Bank of America Securities - Analyst : Thanks for the update on PWS. I wanted to get a sense about how you're thinking about the profile of patients you plan to enroll in Phase 3. So just based on the data that you presented today, you've talked about certain caveats about why certain patients may not have had ideal weight loss, for example. So how do you take that information and translate that into entry criteria for your study? And then as it relates to 718, you've chosen to look at it, is it primarily because it doesn't have the hyperpigmentation side effect? Or do you think it could have mechanistically reason to induce more weight loss and maybe more control of hyperphagia than you've seen with setmelanotide? LSEG STREETEVENTS | www.lseg.com | Contact Us consent of LSEG. 'LSEG' and the LSEG logo are registered trademarks of LSEG and its affiliated companies. DECEMBER 11, 2025 / 1:00PM, RYTM.OQ - Rhythm Pharmaceuticals Inc to Discuss Preliminary Data from Exploratory Phase 2 PWS Trial

Question: Tazeen Ahmad - Bank of America Securities - Analyst : Okay. And maybe just a quick follow-up. For PWS, if patients experience hyperpigmentation, do you think that this population is similar to how you described HO or doctors have described HO as that would not be rate limiting?

Question: Michael Yu - Morgan Stanley - Analyst : Congratulations on the early data as well. Maybe just a question among those patients that had lost weight, can you talk about the pattern of weight loss over the treatment period? Was it more choppy? Or was there a general downward trend in those patients? And do you think continuing to treat those patients longer may result in even greater weight loss?

Question: Derek Archila - Wells Fargo Securities LLC - Analyst : Congrats on the update. So just one for David, and one for Dr. Miller. David, I guess, should we assume that the start of this Part D cohort with 718 in Prader-Willi patients implies that Part C and HO is trending positively? And then a question for Dr. Miller is more centered around the Vykat and IMCIVREE combo usage in the trial. It didn't seem like there was much synergy there, but just curious to get your thoughts if there's any things underlying there. And I guess whether or not you see roles for both Vykat and IMCIVREE in your practice?

Question: Dennis Ding - Jefferies LLC - Analyst : Maybe a question on placebo. I know the beloranib data suggests placebo should gain BMI, but there's also a liraglutide study in kids that show placebo reduces BMI. So I wonder how you're thinking about the placebo effect and if there are nuances that we're missing with interpreting the liraglutide data? And then number two, for RM-718, it seems like you're looking at 10 to 50 milligrams weekly. How do those doses correlate with the doses of setmelanotide used here in the Prader-Willi trial? And could there -- could you guys be dosing higher? LSEG STREETEVENTS | www.lseg.com | Contact Us consent of LSEG. 'LSEG' and the LSEG logo are registered trademarks of LSEG and its affiliated companies. DECEMBER 11, 2025 / 1:00PM, RYTM.OQ - Rhythm Pharmaceuticals Inc to Discuss Preliminary Data from Exploratory Phase 2 PWS Trial

Question: Jonathan Wolleben - Citizens JMP Securities LLC - Analyst : Just wondering if you had a chance to look at the PK data and if there's an association between drug levels and the effects you're seeing. And then pivoting to the Phase 3 trial, how do you think about the variability of moving to a multicenter study and kind of losing Dr. Miller's expertise, but perhaps getting less challenging patients at the same time. So how do you account for that moving into a larger multisite study? LSEG STREETEVENTS | www.lseg.com | Contact Us consent of LSEG. 'LSEG' and the LSEG logo are registered trademarks of LSEG and its affiliated companies. DECEMBER 11, 2025 / 1:00PM, RYTM.OQ - Rhythm Pharmaceuticals Inc to Discuss Preliminary Data from Exploratory Phase 2 PWS Trial

Question: Whitney Ijem - Canaccord Genuity - Analyst : It's Angela on for Whitney. Congrats on the data. Just curious, any additional color you can provide on that one patient discontinuation? It sounded like hyperpigmentation was the reason, but was that the only reason? And then can you also confirm what dose they titrated to before discontinuing and like what the -- like the timing around that was?

Question: Whitney Ijem - Canaccord Genuity - Analyst : Got it. And maybe a very quick -- sorry, if I could have a quick follow-up question for Dr. Miller. For the patients who might not be eligible for therapy on a weight basis, so about 60%, would you maybe want to put those patients on setmelanotide for other benefits like giving them more energy to do things or just be happier? Like is there a potential for a broader label here?

Question: Whitney Ijem - Canaccord Genuity - Analyst : Sorry, just for the patients who might not be eligible because they're overweight, would you also potentially want to put those patients on for the other benefits like having more energy to do things and just being happier overall? Is there like just that potential for a broader label down the road?

Question: Thomas J. Smith - Leerink Partners - Analyst : Congrats on the early data. Apologies if I missed this, but could you talk a little bit about the kinetics and the consistency of the hyperphagia improvements in the study and maybe directionally how that's trending out at 6 months and beyond? And then on the Phase 3 plans, could you elaborate a little bit on some of the stratification factors you're considering, whether it's baseline BMI, hyperphagia genotype or some other factors and how you're planning to maximize probability of success there from an enrollment standpoint?

Question: Rohan Mathur - Oppenheimer & Co Inc - Analyst : This is Rohan on for Leland. Just given how debilitating hyperphagia is in this patient population, how are you thinking about the relative importance of showing robust reduction in hyperphagia versus clinically meaningful BMI changes, especially as you're thinking about the pivotal study? And this is maybe more for Dr. Miller. As you think about positioning with Vykat, what kind of patients would you expect to be considered eligible for Vykat and not setmelanotide?

Question: Raghuram Selvaraju - H.C. Wainwright - Analyst : I just wanted to ask about how you folks are looking at the prediabetic space in Prader-Willi syndrome. At what point would you be able to proactively identify patients who wouldn't be considered candidates for Vykat therapy because of the likelihood that the therapy might predispose them towards the development of diabetes. So what we're really looking at is the segment of patients who might not necessarily be formally diagnosed with type 2 diabetes, but who are trending in that direction. And maybe this, in a sense, is also something for the expert to opine on. But I just wanted to see if it would be possible for you to comment on how early in the treatment continuum you might expect a drug like setmelanotide to be deployable.

Question: Raghuram Selvaraju - H.C. Wainwright - Analyst : Yes, that's perfect.

Question: Joseph Stringer - Needham & Company LLC - Analyst : Sorry if I missed this, but just generally, can you describe the types of background meds that patients were on? I know you mentioned ICAT, but others that could potentially affect weight loss such as CLIPS. And then quickly for Dr. Miller, just in general, were the patient baseline characteristics and the corresponding background meds representative with what you would see with PWS patients in your practice?