Rhythm Pharmaceuticals, Inc. Common Stock Wells Fargo 21st Annual Healthcare Conference

Thank you, Derek. Glad to be here.

Yeah. It's a great moment for Rhythm, to be honest, as you highlighted some of the headlines there that have come out. We're into our second quarter of launch on the HO side of the business. Maybe just to back up to frame all of this, where Rhythm is today, we think about three pillars. We have our genetic pillar, which was the basis of the biology here, where we had our first indications, POMC deficiency and the BBS opportunity. BBS, meaningful, growing steadily. HO, an anatomic disruption of the melanocortin-4 receptor pathway, recent approval, first quarter of launch, as I said, that we're into now. Much bigger opportunity, 10,000 patients, and I'm excited about how we've gotten out of the gates there, and we can talk more about that. The third pillar is Prader-Willi, and that's just an enormous unmet need.

It has a lot of favorable characteristics from a rare disease standpoint in terms of a disease that is approachable, meaning, virtually all those patients will be diagnosed at about birth or shortly thereafter. There is a community that they can, if they are given a diagnosis, the family, patient can enter into, get a lot of information. There are experts that are available and centers of excellence and the like. Payers recognize that it is a devastating disease. Survival, 30 years approximately. It is an underappreciated, I think, devastating disease, but the system recognizes it, and that is an opportunity we are going to go after hard. Yeah, it is a really good moment for Rhythm. A lot going on. Excellent.

Yeah. I think the advantages of HO as an indication are one, just remind people, this is acquired hypothalamic obesity. It occurs predominantly in patients who have had a benign tumor in the region of their pituitary and their hypothalamus that can be resected. In the process of treatment, whether that is the surgery or radiation, injury to the hypothalamus can injure this pathway, the melanocortin-4 receptor pathway, and they just have a classic presentation where, from the moment of injury, they have accelerated weight gain, they have this hyperphagia, this increased hunger that they have to live with, and debilitating fatigue, which is often unrecognized as a part of that overall manifestation.

Now, because of the injury to that area of the brain, they invariably injure the pituitary as well, and so they will have a number, one or more, and 80%, 90% of the patients will have one or more hormonal deficiencies, which means almost invariably, they are seen by an endocrinologist. We see this as a classic rare disease, ultra-rare, 10,000 patients in the U.S., but it is concentrated in a specialist, and that makes it entirely approachable. Just to give you an example of how that causes us to think differently, for BBS, we had a sales force of about 16 people recognizing that the BBS patient might be in four or five different specialties. Many of them will be sitting with their primary care. We knew there is no way you can call on all of the doctors who might be seeing a BBS patient.

You're really out there trying to just create a system that has the ability to recognize BBS, and the patients find you as much as you find them. There is some direct identification, but you're really working to just build a system. Contrast that with HO, where you have a specialty, our goal will be to cover that specialty, and we've tiered them, as we've said, and we have 42 reps out there in the field dedicated to HO, with the goal, again, of being able to call on certainly all of the top one to two tiers, which is about half of the 10,000 endocrinologists out there. But we will get to the bigger, we're not going to ignore the other 5,000 because these patients, to a lesser degree, will be sitting in that lower tier as well.

Yeah. I think it's interesting. Obviously, we had centers, so you have your clinical trial centers where they knew about the drug, they had experience with it. We had the conversion of the clinical trial patients, and those scripts were written. Then we have centers, and Jennifer Lee, our head of North America, has highlighted this on a number of calls where 40-plus centers where a disproportionate number of these surgeries are done, and by definition, that's where the incident occurs. Ideally, that patient gets diagnosed shortly thereafter. What we've learned historically is many of them that weren't diagnosed, so they went out through the community. But in terms of early adopters, about 25% of our scripts have come from those centers, so not zero, but it's not 80% of those.

The other thing is of the 400-plus scripts we've talked about, those have been written by about 300 prescribers, so about one script per prescriber. Again, I think what's been encouraging is that it's been very broad based. We had a question today, is there any endocrinologist who said they wouldn't prescribe? The answer is no, but there's not really a reason that in a rare disease where you've got a precision medication, and you've got a firm diagnosis, and that's the only treatment, why wouldn't you treat? Again, I don't see this as an early adopter market as much as just an awareness market.

Yeah. I mean, awareness is a key to script writing.