All right, everyone, I think we'll get started here with the next fireside. Again, my name is Derek Archuleta. I'm one of the Senior Biotech Analysts here at Wells . Very excited to have Rhythm Pharmaceuticals here for our next discussion. We have David Meeker, CEO from the company. David, great to see you. Continuation from our conversation this morning on the breakfast meeting. Maybe just to start out, kind of give us the state of affairs, where we're at with the business. A lot of news flow this year, a lot of exciting stuff. Maybe we can recap that before we get into the Q&A.
Yeah, thanks, Derek. No, it's been obviously a really good year for Rhythm. I think maybe I'd characterize it by, you know, we've tried to follow the science, follow the biology here in the past 12 months. The biology has continued to open up in a really positive way. I'll just give the quick recap. The company back in the early teens, strong proof of concept for this POMC biallelic was just basically said, you know, melanocortin 4 signaling. That's a key part of, you know, for patients affected, driving their obesity, their hyperphagia, and the like. setmelanotide as a precision medicine, analog of the missing hormone, seemed to address that. Very strong early proof of concepts. Then getting Bardet-Biedl syndrome approved back in June of 2022, that was a legitimate opportunity.
I mean, you could build a business around that, classic ultra-rare disease, blocking and tackling, steady as it goes. You wouldn't spend a lot of money on R&D, but you could make a profitable business out of BBS alone. The HO piece of it, which also, we revealed the first data in that summer, that wasn't so obvious to us. We knew that if you knock out that part, if you injure the hypothalamus, then of course you could have a defect in signaling to the pathway, it's gone. It wasn't so clear that the drug would work because maybe you're knocking out the receptors as well and just how it works. The fact that it worked so well and so consistently, again, opened our eyes to a whole other avenue of potential developmental opportunities. Obviously, in the past 12 months, we've had the Phase III data.
A big part of Rhythm, or some of the concern about Rhythm was, you know, setmelanotide, like all drugs, has a, and our composition of matter is up in 2032. One thing that people haven't, I think, fully appreciated, we should try to highlight a little more, is that when you get a drug approved, the FDA puts out guidance in terms of what a generic would have to do. That guidance takes you more or less through the formulation patent. Actually, our formulation patents in the U.S. are up in 2034. We think we might have a pretty good position out through 2034 in the U.S., a little longer in Europe, actually, on just that. The really big opportunities, our big, you know, patent extension part of it was our next gens.
The Bivamelagon, which wasn't so obvious, meaning that many people asked, you know, between 718, our weekly formulation, and the oral small molecule, which do you think is more likely? We always answered that, well, you know, the 718 weekly is probably more likely because it's much closer to setmelanotide. All the preclinical data was kind of almost milligram per milligram looks similar. Whereas biva is, you know, it's a new chemical entity, quite different, oral, you know, different bioavailability, different dosing, et C. Less certain. We were thrilled, needless to say, about the data we saw. I think it just, I think we're getting good MC4 agonism, you know, with all of these, you know, well, Biva certainly, and then set. That's what came out in the HO. Now, you know, as we look ahead, you know, I think Rhythm's really at the beginning.
I know there's a lot of feeling like, "Wow, a lot's been happening. Is this story done?" I don't think so. I mean, we're, there's a lot of just continuing to execute on our current businesses, BBS and, you know, HO. We got it filed in, you know, rapid fashion and credit to the team there. You know, we'll launch HO and, you know, hopefully do a good job with that. When looking ahead, you know, on the genetic side of the equation, we'll keep working these other genes. There's a lot of ground to and work to be done there. On the injury side, the HO side of the equation, there's other, you know, ways the brain gets injured other than with, you know, tumor and surgery and the like. We'll be exploring those. Prader-Willi, of course, you know, that's a tough disease, but I've said 50-50.
You know, I'll stay, continue to say 50-50. I mean, I'm optimistic about the biology there, but very respectful of, you know, the challenges of, you know, successfully developing a drug for that disease.
Got it. All right, lots to cover. Maybe just starting off with the hypothalamic obesity and kind of the opportunities that you see there for setmelanotide. Obviously, like you said, your filing was recently accepted, probably launching early next year. How should we think about the trajectory of that launch relative to some of the other indications, but also, again, like a Prader-Willi, for instance, what does that look like?
Yeah, you know, so again, we're early in learning here. I think, you know, we've got a Bardet-Biedl syndrome experience. Bardet-Biedl, as I said, classic rare disease. That disease, it's classic in the sense that it's not concentrated in any one specialty. Many of the physicians who are writing prescriptions for Bardet-Biedl syndrome are the family practitioner. They're the primary care doctor. They may have one or two patients that they're following. They're not experts. They write the prescription because they know the patient needs to be treated. That's a harder population to get at. The advantage of this HO, many, if not the vast majority of these patients, we believe, are with an endocrinologist. They may not all be diagnosed, interestingly enough.
I think as we get out there and learn a little bit more about this, even in an endocrine specialty, you're managing their pituitary insufficiency, they're presenting with obesity. They maybe had a history of an injury in the past, but you may not connect all those dots right away. Until there's a treatment available, the urgency to connect the dots or the way those things spread to the community and a community gets energized and educated around these things, it's all catalyzed by having a treatment. Hopefully we'll see some of that dynamic coming. Your question was around RAMP. It's concentrated in endo. That's an advantage. Maybe it'll come out a little bit more quickly than BBS in the initial RAMP. The ultimate opportunity, obviously, is significantly larger. You asked about Prader-Willi, the drug, DCCR just approved and a very good launch. There's different dynamics there with Prader-Willi.
One, it's a very well-diagnosed community population. I think most of the patients, if they have it, they know they have it. One. Then two, the behaviors are really challenging. Some of it's violent. If you're a family trying to manage a child with Prader-Willi, your motivation and urgency to treat is extremely high. You can imagine them seeking. Another not insignificant factor is so many drugs have been tested in Prader-Willi. There's been many trials run. That community is very well organized. The roller coaster, we talked about this this morning, but the roller coaster that community has been on with, you know, hopes, you know, a new trial, and then it doesn't work, and then try another trial. They're really primed for just give me something that works. You get a drug approved like VYKAT did, credit to them.
You would fully expect, you know, the quick, you know, quick take-up there. We're not that. There's been very little prior work done in HO other than us. We're earlier on that curve. We're going to be laying that foundation. Expect a more gradual launch there, but it's no diminution of, you know, the overall opportunity here, which is significant.
Can you speak to the overlap between physicians that treat Bardet-Biedl and the other conditions, you know, setmelanotide is already approved for in HO? I guess, if you're thinking that maybe it's more gradual than Prader-Willi, although that's kind of more of a very straight-up launch, I guess. That still means it could be pretty good. I guess, do you, would you expect sort of a bolus effect? Are there people kind of being warehoused and kind of awareness growing, you know, since the Phase III data?
Awareness is growing. I mean, I think we had some, you know, there's a little bit of bolus. It may not have been so apparent with Bardet-Biedl. I mean, there's patients who are out there and talking to a physician and ready to go. We're closer to Bardet-Biedl than we are to Prader-Willi, I think in terms of how this thing will come out of the gates. I think everything we're learning here is reinforcing of our general optimism and bullish view of this whole opportunity. I mean, the size of the population, we talked about five to ten thousand. I think our confidence we're at the higher end of that range is growing and for good reason. You continue to do claims work and the like. A big part of validation of all this is the team's getting out in the field and talking to docs.
That feedback is, you can do the math on a lot of these other exercises. Talking to physicians and getting a sense, the needs there are clearly, and I think there's pretty good energy around it.
I know at Obesity Week last year, we had heard that there's some emerging HO centers. Obviously, Prader-Willi has these and some others that are out there for other rare diseases. Do you think that'll grow? Is that something that, I don't know if you're helping with or kind of circling some different centers in the U.S. and Europe that could really be those centers of excellence around HO?
Yeah, Europe lends itself much more naturally to that. I mean, they have them anyway. In the U.S., Bardet-Biedl, for example, there was one center in the United States. The teams, when we launched or started, that was in a place hard to get to in Wisconsin, amazingly. It was emblematic of the fact that the center developed around a person who was really the grandfather of the whole BBS effort in the U.S. People traveled there to see him, and that became a center of excellence. They formalized it and had a very comprehensive visit, three or four days kind of thing. Since then, the team, we have four or five, at least, other centers now who have taken an interest in BBS and are looking to set up the multidisciplinary part of it. Back to your question about HO, how I think this will happen.
For sure, they're already, because of the nature of this, if your entry point, your source of your injury is the tumor and the surgery, it's likely you're already at a specialized center and then potentially seeing an endocrinologist. Now, how many of those patients then go from that center back to their local endocrinologist? That'll be some, and we don't have a good handle on that, but that's obviously some. They'll need to continue to be seen by an endocrinologist because they almost all have pituitary insufficiency at some level. That's not, the primary care physician tends not to be the one who's directly managing their hormonal deficiencies as a rule. A long story short is, yes, I do think centers will develop.
The other thing that often happens in rare diseases is, if you're a young, developing physician and you're looking at a way to make your career, new opportunities, right? I mean, if you're in cardiology, it may not be so easy to go out and become a big leader in hypertension. That ship sailed. In HO, you can look at this and, the way departments, I've seen this over my career multiple times, the senior person in the department says, well, you set up a small clinic and suddenly you've got a few and you become the expert and you're giving talks and your career is launched on the back of this early opportunity where, because you were in early, everything's news. You get to talk about it and stuff. That's a dynamic that for sure will play.
Gotcha. In terms of the approval in HO, are there any label considerations that we should be thinking about? I know the discussion this morning centered around not only just the weight loss, but potentially getting hyperphagia on the label and what that could do for setmelanotide.
Yeah, that's critical. I mean, we've tried each time. The challenge with getting hyperphagia on the label is not that it doesn't work or we haven't decreased hyperphagia. It's that we haven't made it an inclusion criteria, and that's been a bit of a hiccup from the FDA standpoint just in terms of the way they view rules and the like. Every trial we've done, that's the way the drug works, we reduce hyperphagia. This trial, we have three different measures, all of which robustly hit P-values in terms of reducing, improving on the hyperphagia scores. We'll try again. The indication statement we submitted includes hyperphagia in the indication. I'll give you my optimism here.
I know this division, they're receptive to the fact that the absence of it, given the statute, the Medicare statute, that they don't cover obesity, and that ripples through to some other payers and Medicaid in some cases. Certainly, Medicare, we're not covered. We need to be differentiated. We need something else in there, and hyperphagia, of course, we've shown it. Why can't that be in the indication statement? I'm hopeful. Doesn't mean it's going to happen, but we're going to go at it.
Does it really matter in terms of the opportunity as you see it, or is it more just kind of from the Medicare component?
It's definitely the Medicare component. I think it's helpful. I think we'll do fine without it. We'll do fine. I mean, this is one of those things, oh my God, if we, I mean.
We have a good bull case scenario. It'd be nice to have because you didn't.
It's nice to have. You know, in these things, you don't get to run the opposite experiment. We've done fine with BBS without having it, right? It's not like that's been the end of the world. It'll help.
Gotcha. In terms of some of the pre-commercial work that you're doing with HO, like potentially with payers, how are they resonating with the data? Ultimately, how do you think about the positioning there in terms of reauthorizations and stuff like that? You've seen that with Bardet-Biedl, but is this going to be a cleaner story or is there some sort of pushback that you might see on the payer side?
I think, you know, big advantage, obviously coming on the heels of, you know, POMC and BBS. They know, they understand increasingly the biology. They know this drug. I think it's been, not relative, it's been incredibly smooth so far with BBS up to date. We're coming in with better data. We're coming with a very clear unmet medical need. There's nothing in our early interactions. I don't want to overread that, but nothing in the early interactions which suggests this will be different or we'll have a problem. In terms of reauth, I told you this morning, I think almost all BBS patients who've come up for reauth have been reauthorized. It's not a black and white. For example, if you didn't make a 5% threshold on your weight loss and some of the BBS patients might not have reached that, but you're clearly benefiting.
Hyperphagia's down, behavior's down, you're concentrating better at school, sleeping better, whatever, all the different factors which may be indicated, the physician writes a letter. It tends to get through. It's just a matter, you got to continue to work the system and maybe an additional step. Now the last part is, I don't think, given the way we ran the trial and the results and the like, that there will be a threshold in the label that said you should expect to see X by Y number of months, and then the payers would incorporate that into a reauth plan. I can imagine they might want to reauth, which is just to say, look, we need an attestation, you're still benefiting.
It is more of a subjective versus an objective.
If the doctor's saying, yeah, it feels good, maybe they have to submit some of the data, but there won't necessarily be a number.
Gotcha. Okay. Really just curious what you plan on highlighting at the HO day or the upcoming analyst day. Obviously, you were suggesting that you believe that the HO population might be toward the higher end. I don't know if that's indicative that you'll raise your potential prevalence numbers for HO. What should we be taking away from that event?
Yeah, I mean, we did one with BBS back in spring or early 2022 before we read out the Phase III data for BBS. It's similar. I think Jennifer and her team will share some. First of all, we'll have two experts there. One probably well known to the community, one not so well known, but follows a large population of HO patients. Two different perspectives. Jennifer and her team will talk about what they're learning, and you'll have the experts there, so you get hopefully a good sense of that. We gave some patient numbers in our BBS world. I think we'll try to figure out how we can give you some sense of what we're feeling, a number of docs we've talked to. There are different metrics.
Maybe Jennifer will talk a little bit about the tiering and how we think about dividing or tiering these, the endocrine subspecialists and the like. In terms of the TAM, I don't think we're going to update that then. There's no urgency to do that, number one. I think we've signaled pretty strongly that we're more and more confident that we're at the upper end kind of thing. I think that should hopefully work pretty well for people. We'll see where we go over time. Look for more specifics, how we're going to structure Salesforce kind of thing and go at it.
Gotcha. Maybe shift gears to Prader-Willi, which is a very hot topic, you know, with you guys. Obviously, you know, with Soleno and the DCCR launch, you know, you're revisiting this with setmelanotide. You've discussed kind of the earlier trial, you know, not being run well. Maybe just, you know, provide some context again, why you're revisiting it, what was kind of, you know, maybe messy about that original trial and, you know, how you think you guys have maybe remedied that with the ongoing trial.
Yeah, the original trial was run back in 2018, 2019, because, I mean, the biology is, you know, pretty well established. Of the, you know, 20 + genes that are maybe affected in a Prader-Willi patient, two of those genes impact this pathway, the melanocortin 4 pathway. We know that that is part of Prader-Willi biology. It's just not the only thing. If you were to fix that, you're still left with all this other stuff. It's all the other stuff, which potentially makes it hard to study or hard to see a positive result. I'll come back to that in a minute. They ran, they end up saying it's the team that predated our current management team, but they ran a study. It was a convoluted study in the sense that it was crossing patients over every two weeks.
That was done with good reason because when we had run our original POMC Phase III study, it was an open-label study. Ten or 11 patients were put on treatment, and then they were blinded, in a blinded way, randomly placed on a placebo drug for two to four weeks. What happened was when they went on their placebo period, their appetite came right back. They started gaining weight. It was literally a switch, which is basically how our biology works, right? I mean, we signal on and off this throughout the day when we eat and then we don't eat. It made total sense. They designed a study which would capture that, you know, two weeks on and off with the hope that they could see this kind of pretty dramatic shifts in short periods of time. I think the reality is, again, Prader-Willi, it doesn't shift like that.
Even if you're changing some of the feelings, you may still have hardwired behaviors that are, you know, making it harder to see. Long story short, they were studying, because we were earlier in development, much lower doses. The study was absolutely negative from a technical sense. However, if you looked at, you know, the four patients who happened, because of the way, you know, the crossovers went, who happened to be on 2.5 mg for eight weeks consecutively, three out of the four trended down under 5%, but definitely trended down, one trended up. It's not like you'd bet your house on that, but it was definitely something that said, okay, we came away, I came away from that looking at saying, this isn't telling us it doesn't work. We just had a negative study, and there's a kernel of hope here that, you know, maybe.
We decided to go and do an open-label study for six months. Make sure to take hopefully duration minimum six, six- 12 will go. If they're still benefiting, they'll continue on, of course. Let's go higher on the dose because we don't want to get to the end of the study and go, I wonder if we, you know, got a little higher way there. Our currently approved dose is 3 mg. This trial goes up to 5 mg. I think, you know, and we know it's safe to go up to 5 mg, so there's no risk there. Hopefully, I think that, and that should be plenty. If it doesn't work at 5 mg, I think, you know, we can say we're done. We decided to work with one center, Dr. Miller's site at the University of Florida, and she's a renowned expert in the field.
The advantage of, in an open-label study, a small number of patients, the advantage of working with somebody who really understands their patients is critical. I mean, if you're an investigator and you just see the patient in clinic every month, but you don't follow that patient, they're not your patient, you don't know what's going on at home, you don't know the parents, you don't know, I mean, there's all these other elements. She knows those parents, and she knows the families. It will be very helpful. You know, how will we interpret it? The goal is 5%. That's the goal. It's not GLP-1 weight loss. It's not HO weight loss. It's 5%. That is what's required by the current policy guidance from the FDA for obesity meds. In general obesity, that's been kind of, you know, in the past because of GLP-1 results.
In a disease where nothing works, 5% is, it's associated with improvements in comorbidities, it's, you know, et cetera, et cetera. 5% is the goal. If we can become convinced that we can run a trial, a Phase III trial, and hit that 5%, we'll go forward. We're not going to show you a bunch of open-label data and a P-value. There's no P-value coming out of this. We'll show you a bar chart and try to give you some color behind individual patients, which hopefully working with Dr. Miller, we've come to understand. If some patient looks good, why do we think they look good? If some patient doesn't look so good, maybe there's a reason. Do we understand why that is? We'll try to explain where we netted out, in terms of do we think this supports going forward or not?
Maybe we just let we're going to treat some more patients.
Yeah, I mean, do you think it's more about like the average or median weight loss? Or is it kind of going back to a lot of your prior trials, looking at the responder rate? What percent of patients are getting that 5% threshold? You know, if it's 30%, 50%, whatever percent, that's kind of the driver to move forward.
Consistency is incredibly important. Obviously in HO, we had a remarkable consistency. Back to your responder rate point, that's it. Again, I'm coupling it with, it's not, I don't have, we don't have a number like, you know, we got to see 50% responder rate greater than 5% to go forward. We have to understand what happened in every patient and say, with that context, do we think we can hit in a Phase III?
Yeah.
If that makes a difference, right?
I guess the other question, obviously with Prader-Willi, is kind of the heterogeneity in this population. These patients also are coming on a lot of background therapies, including VYKAT, you know, in the trial. I guess, you know, how do you kind of hope to control some of that, that those issues, you know, with the, again, notorious for Prader-Willi trial?
Yeah, so they're on a lot of meds. You take that first HO patients, as we talked about. I mean, they're on one to two pages of meds. HO patients are about as complex as any patient I've ever worked with in my career. I think complexity itself is okay. This drug, think about this drug, it's not pharmacologic intervention in that, you know, you're taking a normal situation and then distorting it to try to get some benefit. You're taking a deficit, a hormonal deficit, and arguably bringing that back up to normal. That coexists more naturally, if you will, with a complex medical background because you're just restoring normal physiology. It's not like you've got multiple pharmacologic interventions and now you add another pharmacologic intervention and you don't know how that's all going to interact.
This is just filling the tank up, get it, you know, get you back to normal. I think it's okay in terms of the complexity. In terms of VYKAT, they're allowed in this open-label because we're interested. The mechanisms are different. They don't, you know, work through the melanocortin 4 pathway specifically. We'll see. Curious.
I guess the last question on this is just in terms of, you know, you're focused on weight loss. Obviously, VYKAT approved on hyperphagia. Again, would you intend to kind of go through that, you know, again, more of a weight loss kind of strategy in a Phase III? Does that change the division where you would get approved? I think the idea would be if you're losing weight, you'd probably see something on hyperphagia. How do you reconcile all that?
Just that way. I think, you know, so A, I don't think the world needs necessarily another hyperphagia drug. I know there's multiple companies that are pursuing that, A, because the door is open there in a sense. The way our drug works, if we get weight loss, we will get hyperphagia. I mean, it just has to, number one. Two, weight loss will be our primary, which means that we will go through the same division. So diabetes metabolism. The companies, including Soleno, who went through the psychiatry division, was because that, you know, their primary was hyperphagia. It was a questionnaire. We will have, as our secondaries, if we run a trial, measures of hyperphagia, including HQ-CT. Hopefully we can include some other ones because we know, everybody knows that that's still a, you know, it's the gold standard, but it's not the greatest tool.
It has challenges as well. Anyway, we'll collect very similar to what we did in HO, similar to what we did in BBS. You know, these different measures of, you know, both weight and hunger.
Gotcha. Okay. Maybe you're shifting gears to the kind of second-gen molecule. So Bivamelagon, obviously you reported positive data there for the oral. Also, 718, we'll get some data. I guess, yeah, how do you think about, you know, future development strategies there? I know you kind of talked about HO, obviously. Again, which one, where, and also, you know, if let's say Prader-Willi hits, would you be bringing setmelanotide forward or one of these other agents?
Yeah, so for Bivamelagon, now we have positive data. We'll go into Phase III as soon as we can for HO. 718, we'll finish this, hopefully confirm that it works in HO, and then we'll take that into HO. The goal will be to develop both of those in HO. The question becomes, do you develop one, for sure develop one of the two in BBS and POMC, including LEPR. Do you do both? Maybe. I think that's a question, and you know, what's the urgency there? That's certainly part of a strategic question. What we've said is we'll do all new development work with one or both of the next gens. The only wrinkle to that is, in fact, Prader-Willi.
The reason for that is that, you know, if we felt confident in the results we were seeing with setmelanotide, the reason you would go forward with setmelanotide is there's a time advantage. You'd have a supplemental NDA. You've got a strong safety package already. I mean, you know, there's things that allow a slightly more rapid development period than if you move with one of the two new chemical entities. We're going to have to do, we will want to do the new next gens sooner or later. Because, again, Prader-Willi, you know, HO is a big opportunity. Prader-Willi is equally transformative for any company, Rhythm included, of course. If we get, you know, positive signals and feel good about it, then we're going to do a robust development plan for that.
The variable, which to be determined, is would we do set first or just, you know, wait to see what happens with 718 and then Bivamelagon?
What should we be expecting for 718? I know a lot of the preclinical data and you've modeled it off of setmelanotide. Where's the biggest variable in terms of what you're looking at from the Phase I in the HO patients? Not necessarily what could go wrong, but what are we looking for that could be different?
Yeah, the one thing that's different is the PK profile. By definition, it's not a daily, it's a weekly. We had an earlier version of setmelanotide weekly. We did a small trial in patients who were already stable on their existing setmelanotide, crossed them over. That weekly formulation looked fine there. There was a little bit of noise around it, but that data was too small. The biggest variable for us going into the 718 study is not, is 718 a good agonist? It's a good agonist. We're confident in that. It's safe. It seemed to be safe in the normal volunteers. The biggest question is, is that PK profile going to get us a similar kind of result?
Gotcha. I mean, I guess you usually, I mean, obviously you did SAD, MAD. Are you still looking at multiple doses in the HO patients? Can you just remind us how that's set up?
Yeah, because it's so close to undosing, and again, we talked about this this morning in another session, in rare diseases, you rarely get to, because you just don't have the patient numbers to precisely define the dose. You know, in big indications, you do a lot of dose work, and you can be very specific about it, you know, what quote unquote dose you're using. Here, what we're looking for is a dose range that seems to be safe and get us our therapeutic effect. For setmelanotide, that 1 mg- 3 mg dose range served us incredibly well. We're going to, for example, develop Bivamelagon now that we have the Phase II data in exactly the same way. 200 mg, we had a couple of patients who seemed to respond, but in general, 400 mg and 600 mg were better than 200 mg.
We'll have a dose range where you dose escalate from 200 mg to 600 mg with the option to stop or dose down if you can't tolerate it or you seem to be doing fine. We're going to develop a range. Back to 718, we're not having, there's only one dose. There's only one dose, and that meaning that it's a dose range. We'll be looking, starting at 10 mg and going up to 40 mg, not that milligrams matter here. That's the concept behind it.
Patients will march up. We'll see how they do, hopefully confirm the dose range, and then we'll go to Phase III.
Gotcha. I know in some of the preclinical models, like the data looked even a little bit, a smidge better sometimes than, you know, setmelanotide. I mean, is there a chance there that that, you know, could come through in the HO patients as well? I guess obviously from a safety perspective, you believe this to have, you know, hopefully less hyperpigmentation or no hyperpigmentation. I guess how are you kind of looking at the overall profile?
Yeah, it'll still be what it is. I'm not so, from a milligram, I don't care, to be honest. I mean, we went higher in our normal volunteer to give us the freedom to go higher. We can go up to 50 milligrams, for example, on this, just again, just trying to build in the flexibility. You don't know what you don't know. On hyperpigmentation, incredibly reassured by the Biva data. 718 is more specific for the MC4 over MC1. I'm more confident that we'll do well with RM-718, even than with BIVA. I think hopefully that's taken care of the data.
Gotcha. Maybe just kind of bigger picture, you know, MC4 receptor agonists in general and the opportunities. Like, you know, you have MNH also, you've got some of these other basket trials that you've kind of looked at in the past. Like, where do you think, you know, beyond, obviously everyone's very focused on Prader-Willi right now, but, you know, beyond that, like, where do you think the other opportunities lie and, you know, where do you, like, I guess, or more of like, when will you kind of really have more focus on some of these other indications that can broaden out, you know, kind of the franchise?
Yeah, I think there's a lot of things that are really interesting about this. I'll just throw out a few small things. There's a genetic pillar. All the work on the different genes, as we've said, the key to getting at that part of our opportunity is being able to find who has true loss of function. There's a big group there, and we've made some good progress, and hopefully we can come out in the next year or so and talk about which genes we might pursue based on now having a better understanding of loss of function, number one. Two, there are some other syndromes which are really tough. We actually have some early work being done by investigators, investigator-initiated trials looking at ROHHAD, this rapid-onset obesity, hypoventilation, and autonomic dysfunction.
It's horrible, incredibly rare, but those kinds of opportunities are interesting because they teach us about what else this can do, MC4. There are some early papers that are coming out that raise some question about respiratory drive. I mean, we know we interact with the autonomic nervous system. Again, don't take this to the bank because there's no place to go yet, but the biology is there, meaning that there's more here than just a satiety signal. I think part of Rhythm's future will be getting to continue to try to work at that. On the anatomical side of the equation, obviously we have congenital forms of hypothalamic obesity, and we'll work on that.
All right. David, thank you so much for joining us. Everyone in the audience, thank you again.