I'll turn it to you to provide a brief overview of the company.
Sure. So, Rhythm is a company that's focused on developing has developed therapy for the melanocortin-4 pathway, and this is a pathway that's in the hypothalamus. It governs our hunger and our energy expenditure, so basically keeps us in balance if everything is working well. There's a population of patients, many genetically based, if you will, who have an impairment in their pathway due to an abnormal genetic finding. And, our initial approvals for the company for this drug, setmelanotide, brand name Imcivree, is for two very rare indications, POMC and leptin receptor. Like I said, those are ultra, ultra-rare, and were approved in 2020, and we actually didn't put a sales force in the field.
Following that, we got approval for another more common rare disease, Bardet-Biedl syndrome, and launched that in 2022, and are 2 years in launch and pretty excited about where that's going. And then I think what's gotten a lot of focus and attention to the company or brought a lot to the company is hypothalamic obesity, where we presented phase II data also in 2022, which showed in an entity where the biology had not been well understood and essentially nothing worked, setmelanotide did. And setmelanotide, because it's a precision medicine that basically only works by interacting with the MC4 receptor, tells us that to get that kind of response in hypothalamic obesity, that must be fundamental to the underlying biology. So, that program, we'll talk more about that as we go through the morning here-
Yeah.
But is well underway. Teeing me up nicely for hypothalamic obesity. So maybe just, set the stage for us in terms of the like, where we are with the development of Imcivree and HO. Yeah. So phase II trial completed, that was about an 18-patient trial. We read that out in mid-2022. We've now, the phase III trial is fully enrolled. We finished enrolling that at the end of January of this year. 131 patients dosed. We will read that trial out in the first half of 2025, when the first, 120 patients get to their endpoint. The one wrinkle we introduced more recently, a very positive wrinkle, is that we had very positive interactions with the Japanese authorities and-
They, Japan's evolving. I think, just their overall regulatory approach, they, they would like Japan, I think, to be a little more user-friendly in the sense that it's easier to develop drugs there, so the drugs get to the Japanese population in a more timely way, whereas historically, they've lagged just because it's harder. So we had very positive interactions, and, we agreed with them that we, by adding 12 patients to our current running phase III trial t hat would support an approval in Japan, but we will not delay the filing in the US and Europe to complete that part of it.
Okay.
There'll basically be 2 closes down there. HO trial's running well. 100%.
Okay, great. You mentioned that the Imcivree working in HO is Somewhat of an empirical finding. So maybe talk to us now that we've seen that, what the rationale is for targeting MC4R in this space?
Yeah, it's. You know, rare diseases in general, I think, one of the challenges, of the many challenges rare diseases face, is that when there's no treatments, there's little research, little reason. You may have a few people around the world who are paying attention to an entity, but, once you have a treatment and there's a reason to diagnose and people start paying attention, then the information really explodes and, a lot of progress is made around the disease. So in this case, you know, somewhat surprising result with Imcivree setmelanotide, that it works so well. And what was striking about that result was that it wasn't. We did well on the arms race of % decrease in BMI, which everybody's focused on.
Yeah.
Right? We, you know, had 14% or so at the 16-week mark and 25% at the 12-month mark. But that's not, in my mind, what was most impressive. What was most impressive is essentially every single patient who took the drug responded. So the consistency of the response, I think, really tells us that this pathway is core fundamental to, patients with hypothalamic obesity.
Correct. You do have the phase III study that you referenced. It's ongoing, with data probably early next year. Walk us through the parameters of what you're evaluating in that study, how many patients, what are the endpoints, how long is it? All of these things.
So, when we first interacted with the FDA, we felt that the results from the phase II were quite strong and would support a relatively small trial. Where that discussion ended up was they wanted a slightly larger trial to build out the safety database, so we ended up being vastly overpowered, with, like, 99% power to show a 10% difference in the primary endpoint, which is % change in BMI. But it's 120 patients total, will support this filing. It's a 12-year study plus the 2-month, 8-week dose escalation period, so, 60 weeks in total. Like I said, fully enrolled, and we'll read out first half of next year.
Perfect. And then how does the trial compare to the phase II with respect to the inclusion criteria, background meds, or any of the other endpoints that are going to be evaluated?
So these are complicated patients, I hadn't explained. So the way you develop hypothalamic obesity is, the part of the world we're pursuing right now are those who've had an injury to their hypothalamus, and that most often occurs, in patients who have a tumor in their, in between their pituitary and their hypothalamus. And that tumor, as it grows, can grow into the hypothalamus and injure the hypothalamus. And then if you go to surgery, that's another way you get injury to the hypothalamus. So these are all, you know, patients who have had that injury. So, bottom line is, what's felt to happen is that that injury leads to this deficit in this MC4R pathway and the like.
Your question was about how the trial and what, you know, patients, you know, what's the difference between our phase 2 and our phase 3? They're complicated patients because of this background. Almost all of them have pituitary insufficiency, which means that they are on, hormonal replacement for thyroid growth hormone and the like. A long list of medications, they may have seizure disorders, there may be other things that are associated with this brain injury that they've had. So they're complicated, and the drug worked consistently. So the approach we took to our phase three was we did not limit the entry criteria.
Yeah.
I mean, it's pretty minimal. In fact, we expanded the age group that was eligible from 6 years down to 4 years, 'cause we know these tumors occur at younger ages and the like.
Okay, and then background GLP, I think, is a question that people often ask me. So are they allowed in the study? How does that compare to the phase 2? How do you think about implications of their use?
Yeah. I mean, the GLPs have been a major point of interest of many people looking at Rhythm for a long time since they came out. They're obviously amazing drugs. I think what. We're getting more and more comfortable across all the patient populations we treat, that the MC4 pathway, it's distinct. And all weight loss is, you know, not created equal. So, the drugs work differently. The diseases they're addressing are, are different, which is not to say you can't have some effect as you cross over, but, but no, I think. So in terms of how we handled the GLPs for the trial, the GLPs are allowed. All you have to do is to be stable. Your weight has to be stable for three months before coming in. We have looked at the percentage of patients, so probably, you know, a quarter of the patients had tried GLPs previously before they entered the trial. I think at our latest and best count, a little over 10% of the patients are on GLP in the trial.
Okay Maybe you can contextualize and spend a bit more time on this conversation, because I know one of the questions is: why not just use GLPs here? So we've seen how some early data around how GLPs behave in this population. Maybe you could expand on that. How do they work? How well? How often are they used?
Yeah, I mean, the history of GLPs, the earlier generations, Exenatide, for example, one of the first generations, has been studied, and the only double-blind randomized controlled trial, that was 40 patients total. Exenatide showed no effect, so that first generation did not. Liraglutide has been out since 2014, so there are no drug shortages. It's been around for a long time. And this is a relatively desperate population. So if Liraglutide worked, arguably, everybody would be on it. I mean, they're seeking and willing to try anything. There are case reports out there, small case series of promising some degree of weight loss, some with Liraglutide. But again, as I said, it clearly was not fixing the problem. So then you get to the more recent generation, Semaglutide and Tirzepatide, the two most ones that are approved.
Much more limited data, but mechanistically, they're the same. So, again, we're still working with a small series of case reports, and again, it's in the promising category. What a couple of the KOLs have said, Dr. Bouzahzah, who was one of our phase 2 investigators, I mean, she estimated, not counted, estimated that approximately 20% of patients, HO patients, may have some response to GLPs, and magnitude, that magnitude will be 10% or less. Dr. Miller, another one of our investigators from the University of Florida at our R&D day in December, you know, highlighted the fact that one side effect of the GLPs is really tough. So it's tough to manage this drug in that population. The other thing she said, "You will get some weight loss, but that weight loss over the period of a year, you lose the benefit, and they, they've regained it again.
So I'm gonna summarize by how we think about GLPs in our space is we gain weight for different reasons, and if you have a deficit in your MC4R pathway, I mean, enough of alpha melanocyte-stimulating hormone, which is the hormone at the end of this signaling pathway, hunger and hyperphagia. If you replace that deficit, you restore essentially more normal physiology and a more normal relationship with food. The GLPs work through another pathway which is a part of the brain. But, so your level of ice cream may go down, but if you haven't corrected your deficit, you're still gonna be struggling with this hyperphagia. This constant lack of satiety signal that is present for those who are suffering with an MC4 pathway deficit.
Okay. So how should we think about the market opportunity for Imcivree in this indication? And in particular-
Okay
how does HO compare to some of the other indications you've explored the drug in, in the past?
Yeah, I mean, we've estimated in the U.S., and we'll use U.S. numbers here, that there's 5,000-10,000. And that number, I think, is a... or that range, it's a broad range, but it's, it's pretty robust in the sense that it's built off, the tumor registries. And so craniopharyngiomas is the most common cause of these, the tumors, that these benign pediatric tumors, as a rule, and about 50% of the patients who have the tumor and go to surgery develop HO. So you can do the math on that, you get to a 5,000-10,000 number.
Yeah.
We think there's similar numbers in Europe. Again, for... There's a little better organization in Europe, which again, I think supports that concept that there's about 5-10 thousand. So Bardet-Biedl syndrome, we think there's about 4-5 thousand patients in the U.S. The numbers aren't so different. What's fundamentally different about HO as compared to BBS is, BBS is the classic rare disease where you just have to keep doing the work. You know, there's not a big pool of patients. There wasn't a community, as I said, no treatment, no reason to diagnose. So a lot of these patients are lost in the system. You have to find them, bring them in, educate the doctors and do that work, and it's a slow and steady world.
which is why we've been so emphatic about the fact that, you know, that growth, slow and steady. It's gonna grow, and it's gonna grow for a long time.... HO is fundamentally different, and it's fundamentally different because these patients, to a large extent, and we're increasingly learning, maybe there's a still a significant undiagnosed population there. They had their surgery, they know something fundamentally changed, meaning before they went into surgery, otherwise healthy, normal kid in that sense. They come out of surgery, with this injury, with this hyperphagia and explosive growth
weight gain. So that group's relatively well diagnosed, they tend to sit with experts. Bardet-Biedl syndrome, after they're diagnosed by an expert, because there'd been nothing to do, they get sent back to their primary care. So a lot of them are sitting with their primary care physicians. HO patients, because the vast majority, percent plus, have some degree of pituitary insufficiency, they're sitting with an endocrinologist which is the world of physicians that we again, a very different dynamic as we get into this striking effect, at least it seems to be coming out of the phase 2 study.
So I think finding the patients seems to be a bit easier, but one of the other things that came up, I think at the R&D Day, was just, like, motivation, both by patients and physicians, to seek therapy and, you know, stay on treatment. Maybe you could talk a little more about that.
Yeah, I mean, I think universally, I'd say the outreach from physicians was striking in the sense that that outreach just signals the fact that they have been desperate here. You know, despite all their other challenges, their pituitary insufficiency, the fact that they have this brain tumor, this satiety problem, like hyperphagia, and the rapid, rapid weight gain that they have is incredibly disrupting to their overall quality of life.
Okay.
So.
So as you think about the infrastructure that you would need to build out and kind of all the things you'd have to do to support a launch in HO, how should we think about kind of like the SG&A spend and infrastructure build that will be required on the back of likely positive data next year?
Yeah, I think, you know, we're. We do guide, you know, on our OpEx, you know, on a yearly basis, and we have this year. So, we're pretty well built out, certainly in the U.S., on the sales and marketing side. Now, and a lot of that's leverageable for HO.
Mm-hmm.
Obviously, we'll add resources. The way we scale, I'm using the U.S. now as a very specific example, it's very much a function of patient numbers. So our patient support programs, there's a ratio and-
Mm-hmm
... you know, as you get more patients on, you build out your patient support program. In terms of the sales force, they're calling on exactly the same people. Now, it's a bigger opportunity, so for sure we'll add some. We have another team internally who's doing some work to support the enrollment in our phase 3 trial for EMANATE. So as that, the genetic testing group, as that winds down, we'll, you know, leverage that group to do some work.
Okay.
So I'm not expecting a significant, you know, ramp in spending on the U.S. side. Internationally, we'll ramp as we, we'll ramp it, as we get approval. We basically, you know, as we get market access and the like, we'll build out a country. You know, we know we have early access for HO in France, and that country is coming on. And so, yeah, you'll see more of a ramp in Europe, but it'll be similar to the kind of steady, you know, growth that we're seeing now.
Yeah.
Long answer is, not a lot of overall increase in SG&A to execute.
Yeah. Last year, you announced a next-generation MC4R agonist called RM-718 at this stage. Maybe you could share some of the key kind of differences between those two assets with respect to MC1R, for example, and the dosing paradigm.
Yeah, I mean, there's two drivers for our weekly program. One is a daily chronic injectable is not a great option if you can obviously make it a weekly, so huge from a tolerability standpoint, that was a huge lever. Second is our current drug does hit MC1R receptor, and that is on the melanocytes, and so it causes hyperpigmentation, which has not been a huge problem for the vast majority of patients. About 5% of patients discontinue because of hyperpigmentation, but it, it's not great. So you know, obviously, we had a desire to eliminate it. So the RM-718 was very much designed to preserve all the good that we see in setmelanotide. It was built off of what we know about setmelanotide.
Setmelanotide is an 8 amino acid cyclic peptide; this is a 7 amino acid cyclic peptide. What you wanted to preserve was you wanted to preserve the activity, the satiety benefit, and the subsequent weight loss, and not have any of the side effects, which are the cardiovascular side effects and the like, which have plagued other attempts to develop drugs in the MC4R pathway. So, long story short, the RM-718 program does that, but it's more specific. We eliminated the MC1 activity, so it's vastly—its agonism for MC4 is, you know, 100-fold, hundreds-fold higher-
Mm
... than for MC1.
Okay. You've highlighted some preclinical data, which I think is relatively de-risking for the product. Maybe you could expand on the confidence that you have from that preclinical data as you enter the clinic with 718.
Yeah, I mean, we ran multiple, you know, rodent models, which have the limitations, but we know the effect of that setmelanotide had on that model. We're obviously looking to recreate it with RM-718. And then the second part of it is to, you know, prove in those preclinical models that you don't have a cardiovascular signal. And so we do that through a non-human primate study, and we did that, and it performed very well. So I think we have exactly the profile that we want. The goal of our development programs, early development programs, are obviously to prove that it's safe in humans. We're in the normal volunteer part, but also to get a good sense for dose. That, that'll be a key aspect.
Okay. So maybe you could help us understand the development path from here for 718, and particularly, like the efficiencies you think you can get, given your prior experience.
So the huge advantage of hypothalamic obesity is that it's such a sensitive model. And so when we were developing setmelanotide, we didn't know that it would work in HO, and some of these other models were more challenging. So we're starting in HO. If it doesn't work in HO, we're done.
Mm-hmm.
That's the gift, if you will, of that opportunity or that specific indication. So we'll do the current normal volunteer part, single and multiple administration. That's being done in patients with obesity. So MC4 does not work in patients with general obesity, but it does have a signal.
Mm-hmm.
Meaning that you will lose 2%-3% of weight over a relatively short period of time.
Sure.
So we'll be looking for that. Again, just to reconfirm that, you know, that's. And we're going to talk in a moment about the oral and they did see 2%-3%
Sure
So that was all reassuring. So for RM-718, we'll do the normal volunteer part, and then we have a part C of that study, which is in hypothalamic obesity patients, and that'll be open label.
Okay.
That, again, hopefully will be fully enrolled and completed by first half of next year. So, and again, what I'm hoping, we hope is that the phase 3 trial will be done. That's locked. That timeline is locked in the first half of next year, and that both the HO, the RM-718 program and the daily oral program also complete their phase 2-like work in the first half of next year.
Okay, great. One of the benefits is also on patent, so just remind us what the patent extension is here?
Yeah. So the setmelanotide's composition of matter is through 2032. We have methods patents go well beyond that, the late 2030s. But the advantage of both RM-718 and the small molecules, that they both have composition of matter, depending on patent term extension, 2040+.
Okay.
So it gives us a very long runway here to fully develop this MC4 pathway opportunity, and we think there's a lot of work to do.
Awesome. You've talked about it a couple of times, so now let's transition to the oral. You acquired this oral MC4 agonist earlier in the year. So talk to us about the impetus behind that deal.
Yeah, we've been following LG Chem, as anybody who's on our space had when they first put out their preclinical data, which was interesting. So we had a long engagement of, you know, probably over a year of dialogue, trying to figure out what made sense, and got to a very good place for both companies at the end of the day. So what we are excited about with the small molecule, they did a very robust preclinical program. Ran more rodent models than we had run internally, so we felt confident there, and they'd also shown that they didn't have the cardiovascular signal. So those were the two major issues we wanted to.
Sure.
The phase 1 study, as I indicated, they had the expected efficacy, biologic signal of this 2%-3% weight loss. Then really importantly is the tolerability, and numbers are still, you know, relatively small. We'll, we'll, we'll see how we do as we get into patients, but it looks very tolerable from a GI. I mean, they have the same on-target effects. So the GI, the nausea, a little bit of vomiting, a little bit of diarrhea, those are on-target effects of MC4 agonism. Expect to see those. They didn't have anything else, at least in the... so far, that is that unexpected, you know, your drug has a problem kind of issue.
Okay. Walk us through the development strategy then for this program, and when we could see next updates.
So HO, we'll be running a classic phase 2 study, which will be a 3-arm, 3 doses and a placebo. So 4-arm, placebo-controlled study that 16 weeks, and again, we will be starting imminently here in the second half, and with the goal of having that fully enrolled and done by the first half of next year.
Okay. Maybe then, we've talked about all of the assets within this franchise. So how do you think about the fit, where you've got obviously Imcivree up front, you've got the weekly, you've got the oral, these two programs in development? Like, how do you think about where each of the assets fits within a broader franchise?
Yeah. Yeah, I think one of the really exciting things is ultimately a broader franchise. I mean, I think this MC4 pathway is involved in more places than people realize today than we realize today, so we'll continue to explore that. The plan for further development work, so for both the weekly and the oral, we will take it into HO. Assuming it works, it'll go immediately into phase three, hopefully for the oral and for the weekly and the oral in HO. And we will, in parallel then, look at getting it developed and approved in BBS, and for the two very rare POMC and LEPR homozygous indications that we had originally. So we'll do everything we've done with setmelanotide so far.
Okay.
And then any new developmental work, phase 3 work from here on forward, will be done with one or both of the two. We won't do any more phase 3 work with setmelanotide-
Okay
since the future is obviously the next generation, molecules.
Okay. Maybe we'll talk a little bit about BBS then. Obviously, ongoing commercial launch. We've now got about two years of the launch behind us. So what have you learned about the BBS market during that time, and how has it informed your expectations of kind of the peak opportunity here?
Yeah, it's been very reinforcing. I mean, I think, as we've said many times, I you know, really thrilled. I'm excited about where we are with BBS. This was... Just didn't know how it was gonna play when we launched, you know, two years ago. Would we get reimbursed, in the way we wanted? Would we be able to find these patients? We updated our epidemiology numbers, you know, once we were six months or so in, based on everything we were learning. So I think the opportunity is robust. Those numbers, you know, 4,000-5,000 patients in the U.S., probably similar numbers in Europe, are good numbers. I think that the vast majority, or majority, maybe not vast, majority of those patients are undiagnosed.
So again, like this kind of opportunity, the work that you need to do is to create the awareness, get people looking, give them a reason to diagnose, and you start to drive that number up. What's been encouraging quarter-over-quarter is we continue to find them, and that's again, what gives us a lot of comfort in the epidemiology. So, it's rare, but it's not, you know, that, you know, impossible to find kind of rare. In terms of response, extremely rewarding in terms of, you know, the patient response
the overall community response, and it's, it's, you know, the stories, what's probably most striking about the stories is that in quieting down the hyperphagia, these patients are getting, and their families, are getting their life back. That's the most consistent part, and then the weight loss is variable. The weight loss, some lose a tremendous amount of weight, some lose not so much, but almost everybody is having this quieting down of this hyperphagia that's allowing them to You know, really, you know, participate in life in a different way.
How would you say the physician awareness and the patient awareness of Imcivree as an option for this patient population has evolved over time, and what do you expect to come from here?
Yeah, it grows. I mean, it's rare diseases, and so a lot of the work that we do as a company, both directly and indirectly, so you know, in 2024, you have a lot more tools than you did a decade ago. Non-personal promotion, you can target your promotion and your messaging to people who are searching and interested and the like. One of the things we've done from the beginning, and it tends to continue to be very fruitful, is these patients have other problems. So you know, 80% are legally blind by the time they're 18.
That means they're seeing an ophthalmologist, and so you can get into the ophthalmologist community and try to understand who's being diagnosed with the classic BBS retinitis pigmentosa. Some of those ophthalmologists are doing genetic screening, and so these are other avenues you can tap into to, you know, begin to figure out, you know, who's been diagnosed or who, who should or be ultimately diagnosed.
Okay. I think there's been more than something like 700 patients with written prescriptions, kind of over time, but not all of these are still on drug or, you know, got kind of reimbursed. And so talk to us about the translation from patient identification and a script getting written to actual revenues.
Yeah. Yeah, I think, I mean, it's a journey. And we've talked about from the time, you know, it's 3 to 6 months on average, you know, in terms of, you know, how long it takes for people to ultimately get from their script to getting their drug. That time has been moving up as we've, you know, gotten better at it, and we've got coverage. So if you break it down, on the payer side, we've done incredibly well. So we're, you know, 80+% on the 85% on Medicaid-covered lives, and this population is disproportionately Medicaid. It's about 45%, which is a little higher than the U.S. population. So, you know, we've got very good coverage there.
There's still, you know, a couple of states that we're struggling with. Medicare does not cover, so if you're a Medicare patient, and some of these patients are of our, you know, 20%ish patients who are on free drug, about half of that patient population group is in the Medicare group. So those patients will go immediately to that. Once you're on drug, you know, the. We've talked about a discontinuation rate of about 20%-30% of the patients discontinue, and that's, I think, a function, and we spent a little bit of time in the last earnings call to break that out for people. It basically falls in two groups.
There's drug-related issues, for example, the hyperpigmentation, so about 5% of patients stop because of that, and that's a very solid number, not increasing, and just... You know, so it's not huge, but it's, for those patients, that's a real issue, and, they would benefit if they could stay on drug. And so fixing that with our next generation, of course, is good. But then the other bucket, which is non-drug related, and just, that's just a plethora of, you know, reasons that these patients, they have, you know, other organs involved. Bardet-Biedl's a very tough disease on the families. It's a significant Medicaid population, so, you know, social, financial issues that may be, you know, challenging, and so taking a, a chronic daily injectable for that group, group is tough.
So those are all things that we've really made, I think, a lot of progress in terms of supporting the community, our patient education managers. Every patient who gets a script, who consents, which is 90% plus, is assigned a patient education manager, and they are in regular contact with the patient, particularly early on. We maintain that contact, and so, you know, patients that do discontinue, we don't lose that contact.
Yeah.
We continue to work with them and the like. So it's a comprehensive... We try to, you know, surround sound as best we can to support this, the patient and the community as a whole.
Okay. You've also got the launch underway in Europe now. I guess, how should we think about the adoption curve in that region, and what should we expect in terms of contribution over the near to intermediate term?
Yeah, I mean, the slow and steady, I mean, again, it's a similar, for different reasons, the dynamic's slightly different-
Yeah
but it's still classic ultra-rare disease, which is, again, you'll... You know, we have, as each country comes on, you know, Germany's on, it's well, you know, established now and running. Germany is a little bit more like the U.S. in terms of being more decentralized. We have, you know, a few more larger centers than we did in the U.S. to start with, but, but it's still quite decentralized. So that's very much a U.S. dynamic as we get better education, bring on new experts, work with the patient community, slow and steady, it'll grow. You know, the other countries, again, they have a little more center of excellence driven, but again, you know, Europe, for example, you get approval in Spain and Italy at a national level.
On reimbursement, you still have to work through regional and local pharmacy budgets. These are things that just, you know, they dampen down a little bit, the rate at which patients will come on. But it will be slow and steady. In Europe, you know, from the beginning, we've been thinking globally. It's a very important part of our overall strategy. They're about 20%-25% of our revenues. I think that's not a bad ratio.
Yeah
to think about as we go forward.
Perfect. Beyond the two indications, we've talked, HO and BBS, you also have some work going on in the EMANATE study and Daybreak study you referenced earlier. Maybe just briefly talk to us about the strategy there.
So EMANATE, those are 4 genes that we had positive results on in a phase 2 study. So the goal there is to have at least 2 of the cohorts fully enrolled by the end of this year, and then, you know, we'll go from there. I think the other 2 cohorts, we'll, we'll see how we're doing, but we may just declare victory on that, but at least 2. Daybreak, we're waiting to read out the phase 2 study here in the second half of the year, or part 2 of that phase 2 study. The bar is high. I mean, we won't rush into a phase 3 study there. There's definitely some genes of interest, and, you know, we'll look to try to understand them as best we can, but the bar is pretty high to rush into a phase 3.
Okay. How do you think about how these trials could expand the market opportunity overall for the franchise?
Yeah, I think, you know, this is the part of Rhythm that is probably underappreciated. There's clearly, as we're already demonstrating, multiple genetic defects that can lead to an impaired pathway, where an MC4 agonist, such as setmelanotide, would be beneficial. You know, there may be other areas of where the MC4 pathway-- I think this is, you know, the space that once you have a tool-- Go back to what I said in the beginning. Once you have a tool that allows people to start asking the question, looking a little more closely, a reason to care begins to open up. So I think there's a lot of white space there.
Okay. So as you think about 2024 and, like, the... what you would view as a commercial success for the year, how do you think about that? And then what—how does it set you on a path to, I think you've talked about $200 million in terms of peak sales in BBS? Yeah, I mean, we, you know, so again, I won't guide to 2024, but you know, what we have said on the BBS opportunity is, you know, what's the probability we can get 1,000 patients on drug? And I think that's high, you know. And at a $250,000-$300,000, you know, per patient kind of opportunity, that's the $250 million-$300 million, U.S. alone.
Then you bring international on top of that. So I think BBS, over time, and time meaning, you know, a number of years, is easily a $300-$500 million kind of opportunity. HO is a multiple of that. Very different.
Maybe last question from me is, you think about cash runway. Obviously, you just did some financing. What is the update in terms of cash runway, and how do you think about capital sources from here?
Yeah. So we did in this convertible, and that was very specifically designed to replace the money that we spent to acquire the LG Chem asset. We did that plus some, and so that now gives us a runway well into 2026. I think we feel really good. Obviously, you know, how the longer term is very much gonna be revenue dependent. I think our revenue story will continue to, you know, emerge as a very positive part of this equation. That gets us well past HO, you know, the readout and the like. So again, that's where we go from there, we'll see. But,
Yeah. Obviously, a convert most recently, but, like, as you think about sources of capital, anything you'd highlight in terms of preferences?
No, I think, Hunter-
Should I get Hunter on screen?
CFO, has been very disciplined here. I mean, the nice thing is we have options. I mean, we're not, you know, backed into a corner. I mean, the equity is reasonably strong. I think it has a lot of upside potential. I think, you know, you can start to tap into other, you know, potential sources of...
Yeah
you know, capital, given the stage we're at as a company, so.
Great. Well, that wraps it up for me. Thank you so much, David-
Thank you
for joining us today, and we'll see you all later.
Thanks.
Thanks, guys.