Rhythm Pharmaceuticals, Inc. (RYTM) Earnings Call Transcript & Summary

[Audio Gap] team from Rhythm for joining us today. We have the CEO, David Meeker, very much appreciate you joining us this morning, and thanks to everyone else joining us at the Goldman Sachs Global Healthcare Conference. Maybe we'll start with an overview because I think that's always nice to level set. So with that, 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 a 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 it basically keeps us in balance if everything is working well. There's a population of patients, many genetically backed, 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, for 2 very rare indications POMC and leptin receptor. Like I said, those are 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 the 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 has 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, but it's well underway.

Teeing me up nicely for hypothalamic obesity. So maybe just set the stage for us in terms of the -- where we are with the development of IMCIVREE in HO?

Yes. 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. This year, 131 patients dosed. We will read that trial out in the first half of '25 when the first 120 patients get to their end point. The one wrinkle we introduced more recently, a very positive wrinkle is that we had very positive interactions with the Japanese authorities, and the Japan is evolving. I think just their overall regulatory approach. 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 have very positive interactions, and we agreed with them that we -- by adding 12 patients to our current running Phase III trial that will support an approval in Japan, but we will not delay the filing in the U.S. and Europe to complete that part of it. So there'll basically be 2 closes out there. So HO trial is running well.

Okay. Great. You mentioned that the IMCIVREE working in HO is somewhat of an empirical finding, so maybe you talk to us now that we've seen that what the rationale is for targeting MC4R in the space.

Yes. It's rare diseases in general. I think one of the challenges of the many challenges rare disease space is that when there's no treatment, 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, 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 percent decrease in BMI, which everybody is focused on, right? 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 it's a -- we -- when we first interacted with the FDA, we had -- 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, we're like 99% powered to show a 10% difference in the primary endpoint, which is a 1% change in BMI. But it's 120 patients total, we'll 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 compared 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 that most often occurs in patients who have a tumor and they're 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 patients who have had that injury. So bottom line is what's felt to happen is that, that injury leads to the deficit in this MC4R pathway. Your question was about how the trial and what patients -- what's the difference between our Phase II and our Phase III. They're complicated patients because of this background. Almost all of them have pituitary sufficiency, which means that they are on hormone replacement for thyroid growth hormone and the like, a long list of medications. They may have seizure disorders, maybe 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 III was we did not limit the entry criteria. I mean, it's pretty minimal. And in fact, we expanded the age group that was eligible from 6 years down to 4 years because we know these tumors occur at younger ages and the like.

Okay. And then back on GLPs, I think it's a question that people often ask me, so are they allowed in the study? How does that compare to the Phase II? How do you think about implications of their use?

Yes. 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 we're getting more and more comfortable across all the patient populations we treat that the MC4 pathway is distinct and all weight losses not created equal. So the drugs work differently. The diseases they're addressing are different, which is not to say you can't have some effect as you cross over, but no, I think -- so in terms of how we handle 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 3 months before coming in. We have looked at the percentage of patients. So probably 1/4 of the patients had tried GLPs previously before they enter the trial. And I think at our latest and best count, a little over 10% of the patients are ongoing 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?

Yes. I mean the history of GLPs, the earlier generations, exenatide, for example, the first generation has been studied in 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, a small case series of promising some degree of weight loss 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 2 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. Well, a couple of the KOLs have said Dr. Abuzzahab, who is one of our Phase II investigators, I mean she's 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 highlighted the fact that [indiscernible] side effect of the GLPs is really tough. So it's tough to manage this drug in that population. And 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've regained it again. So I'm going to 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, [indiscernible] 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 our [indiscernible] brain, but so you may [indiscernible] level of [ ice cream ] go down, but if you haven't corrected your deficit, you're still going to 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, how does HO compare to some of the other indications you've explored the drug in the past?

Yes. I mean, we've estimated in the U.S. and we'll use U.S. numbers here that there's 5,000 to 10,000. And that number, I think, is those -- that range, it's a broad range, but 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 -- benign pediatric tumors as a rule. And about 50% of the patients who have tumor and go to surgery develop HO. So you can do the math on that, you get to 5,000 to 10,000 number. We think there are similar numbers in Europe. Again, for -- there's a little better organization in Europe, which again, I think, supports that concept, but there's about 5,000 to 10,000. So Bardet-Biedl syndrome, we think there's about 4,000 to 5,000 patients in the U.S. So the numbers aren't so different. What's fundamentally different about HO as [ apparent ] to BBS is, BBS is the classic rare disease where you just have to keep doing the work. 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, that growth is slow and steady. It's going to grow, and it's going to 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 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 in weight gain. So that group relatively well diagnosed. They tend to sit with experts, Bardet-Biedl syndrome may -- after they're diagnosed by an expert because there had 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 [indiscernible] plus have some degree of pituitary insufficiency. They're sitting with an endocrinologist, which is the world of physicians that we [indiscernible] different dynamic as we get into this. Striking effect at least that seems to be coming out of the Phase II study.

So finding the patient 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 stay on treatment. Maybe you could talk a little more about that.

Yes. I mean I think universally, I'd say the outreach from physicians [indiscernible] striking in the sense that outreach just signals the fact that they have been [indiscernible] desperate here. This has a -- despite all their other challenges, their pituitary insufficiency, the fact that they had this brain tumor, this satiety problem [ lack ] hyperphagia and the rapid, rapid weight gain that they have is incredibly disrupting to their overall quality of life.

So as you think about the infrastructure that you would need to build out and kind of all the things you 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?

Yes. I think we're -- we do guide on our OpEx 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 is leverageable for HO. And so we'll -- obviously, we'll add resources. The way we scale, I'm using the U.S. now is a very specific example. It's very much a function of patient numbers. So our patient support programs, there's a ratio. And 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 is doing some work to support the enrollment in our Phase III trial for EMANATE. So is that the genetic testing group, as that winds down, we'll leverage that group to do some work. So I'm not expecting a significant ramp in spending on the U.S. side. Internationally, we'll ramp as -- we'll ramp it as we get approval. We basically -- as we get market access and the like, we'll build out a country. We know we have early access for HO in France, and that country is coming on. And so, yes, you'll see more of a ramp in Europe, but it will be similar to the kind of steady growth that we're seeing now. So the long answer is not a lot of overall increase in SG&A to execute here.

Yes. Last year, you announced a next-generation MC4R agonist called RM718 at this stage. Maybe you could share some of the key kind of differences between those 2 assets with respect to MC1R, for example, the dosing paradigm.

Yes. I mean there's 2 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 MC1 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's not great. And so obviously, we had a desire to eliminate it. So the 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 an 8-amino acid cyclic peptide. This is 7-amino acid cyclic peptide. And 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 718 program does that, but it's more specific. We eliminated the MC1 activity. So it's vastly -- it's agonism for MC4 is hundredfold -- hundreds of folds higher than for MC1.

Okay. You've highlighted some preclinical data, which I think is relatively derisking for the product. Maybe you could expand on the confidence that you have from that preclinical data as you enter the clinic with 718.

Yes. I mean we ran multiple rodent models, which have the limitations, but we know the effect of setmelanotide had in that model. We're obviously looking to recreate it with 718 and then the second part of it is to prove in those preclinical models that you don't have a cardiovascular signal. And so you 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 preclinical -- 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 they got a good sense for dose, and that will be a key aspect.

Okay. So maybe you could help us understand the development path from here for 718, in particular, 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. That's the gift, if you will, of that opportunity for 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, meaning that you will lose 2% to 3% of weight over a relatively short period of time. So we'll be looking for that. Again, just to reconfirm that that's -- we're going to talk in a moment about the oral, and they did see 2% to 3% in that. So that was all reassuring. So for 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 will be open label. And that, again, hopefully, will be fully enrolled and completed by first half of next year. So as we get -- what I'm hoping, we hope is that the Phase III trial will be done. That's locked, that time line is locked in the first half of next year and that both the HO, the 718 program and the daily oral program also complete their Phase II like work in the first half of next year.

Okay. Great. One of the benefits is also on patents. So just remind us what the patent extension is here.

Yes. So the setmelanotide composition matters through 2032. We have methods patents go well beyond that the way 2030, but the advantage of both 718 and the small molecules that they both have composition of matter, depending on patent term extension, 2040 plus. 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.

Yes. 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. And so we had a long engagement of 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're 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've also shown that they didn't have the cardiovascular signal. So those were the 2 major issues we wanted to... The Phase I study, as I indicated, they had the expected efficacy biologic signal of this 2% to 3% weight loss. And then really importantly is the tolerability. And numbers are still relatively small. We will see how we do as we get into patients. But it looks very tolerable from a GI and they have the same on-target effect. So the GI, the nausea, a little bit of vomiting, a little bit of diarrhea, those are on-target effects of MC4 agonism. So expect to see those, but they didn't have anything else, at least in the -- so far that is that unexpected 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 update.

So HO -- so they'll be running a classic day now us running a classic Phase II study, which will be a 3-arm, 3 doses and a placebo, so 4-arm placebo-controlled study that 16 weeks and again, we'll 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 talked about all of the assets within this franchise. So how do you think about the fit where you've got, obviously, IMCIVREE upfront. You've got the weekly, you've got the oral, these 2 programs in development? Like how do you think about where each of the asset fits within a broader franchise?

Yes. Yes, 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 and people realize today and 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 will go immediately into Phase III, hopefully, for the oral -- for the weekly and the oral and HO, and we will, in parallel, then look at getting it developed and approved in BBS and for the 2 very rare POMC and LEPR homozygous indications that we had originally. So we'll do everything we've done with setmelanotide so far. And then any new development work, Phase III work from here on forward will be done with one or both of the two. We won't do any more Phase III work with setmelanotide since the future is obviously the next-generation molecules.

Okay. Maybe we'll talk a little bit about BBS and obviously, ongoing commercial launch. We've now got about 2 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 kind of the peak opportunity here?

Yes. It's been very reinforcing. I mean, I think, as we said many times, really thrilled. I'm excited about where we are with BBS. This was -- I just didn't know how it was going to play. When we launched 2 years ago, would we get reimbursed in the way we wanted, we'd be able to find these patients and we updated our epidemiology numbers once we were 6 months or so in based on everything we were learning. So I think the opportunity is robust. Those numbers, 4,000 to 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 diagnosed and you start to drive that number up. What's been encouraging quarter-on-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 that impossible to find kind of rare. In terms of response, extremely rewarding in terms of the patient response, the overall community response. And it's -- the stories are -- 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. And 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 really participate in life in a different way.

And 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?

Yes, it grows. I mean, it's -- again, it's rare diseases. And so a lot of the work that we do as a company, both directly and indirectly. So in 2024, you have a lot more tools than you did a decade ago. Nonpersonal 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 continues to be very fruitful is these patients have other problems. So 80% lose are legally blind by the time they're 18. And 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, they're doing genetic screening. And so these are other avenues you can tap into to begin to figure out who's been diagnosed or who should 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 got kind of reimbursed. And so talk to us about the translation from patient identification and a script getting written to actual revenues?

Yes. Yes. I think -- I mean, it's a journey, and we've talked about from the time, it's 3 to -- 3 months on average in terms of 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 gotten better at it, we've got coverage. So if you break it down, on the payer side, we've done incredibly well. So we're 80-plus percent 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 we've got very good coverage there. There's still a couple of states that we are struggling with. Medicare does not cover. So if you're a Medicare patient and some of these patients are and of our 20%-ish patients who are on free drug, about half of that patient population group is on the Medicare group, so those patients will go immediately to that. Once you're on drug, the -- we've talked about a discontinuation rate of about 20% to 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 that break that out for people. It basically falls in 2 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, 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 nondrug-related. And that's just a plethora of reasons that these patients, they have other organs involved, Bardet-Biedl is a very tough disease on the families, significant Medicaid population, so social, financial issues that may be challenging. And so taking a chronic daily injectable for that 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 can sense, which is 90% plus is assigned a patient education manager and they are in regular contact with the patient, particularly early on. And we maintain that contact. And so patients that do discontinue, we don't lose that contact. We continue to work with them and the like. So it's a comprehensive. We try to surround sound as best we can to support this -- the patient and the community as a whole.

Okay. You've also had 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?

Yes. I mean the slow and steady. I mean, again, it's a similar -- for different reasons, the dynamic is slightly different, but it's still -- it's classic ultra-rare disease, which is, again, we have -- as each country comes on, Germany is on, it's well established now and running. Germany is a little bit more like the U.S. in terms of being more decentralized. We have a few more larger centers than we did in the U.S. to start with. 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 will grow. The other countries, again, they have a little more center of excellence driven. But again, 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. So these are things that just -- they dampened down a little bit the rate at which patients will come on, but it will be slow and steady. In Europe, from the beginning, we've been thinking globally. It's a very important part of our overall strategy. They are about 20%, 25% of our revenues that's not a bad ratio to think about as we go forward.

Perfect. Beyond the 2 indications we've talked HO and BBS, you also have some work going on in the EMANATE study and DAYBREAK study 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 II study. So the goal there is to have at least 2 of the cohorts fully enrolled by the end of this year. And then we'll go from there. I think the other 2 cohorts, 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 II study here in the second half of the year -- part 2 of that Phase II study. The bar is high. I mean we won't rush into a Phase III study there. There's definitely some genes of interest, and we'll look to try to understand them as best we can, but the bar is pretty high to rush into a Phase III.

How do you think about how these trials could expand to the market opportunity overall for the franchise?

Yes. I think 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. There may be other areas of -- where the MC4 pathway. I think this is 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 the care begins to open up. So I think there's a lot of wide space there.

Okay. So as you think about 2024 and like what you would view a commercial success for the year, how do you think about that? And then how does it set you on a path to -- I think you've talked about a couple of hundred million in terms of peak sales in BBS.

Yes. I mean -- so again, I won't guide to 2024, but what we have said on the BBS opportunity is what's the probability we can get 1,000 patients on drug. And I think that's high and at a $250,000, $300,000 per patient kind of opportunity, that's the $250 million, $300 million U.S. alone and then you bring international on top of that. So I think BBS over time and time meaning a number of years, is easily a $300 million to $500 million kind of opportunity. HO is a multiple of that.

Maybe last question for me. As 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?

Yes. So we did in this convert, 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, how the longer term is very much going to be revenue dependent. I think our revenue story will continue to emerge as a very positive part of this equation. That gets us well past HO, the readout the like, so again, that's where we go from there, we'll see, but...

Yes. Obviously, convert most recently, but like as you think about sources of capital, anything you'd highlight in terms of preferences?

No. I think, Hunter, CFO, has been very disciplined here. And I mean the nice thing is we have options. I mean we're not backed into a corner. I mean, the equity is reasonably strong. I think it has a lot of upside potential. I think you can start to tap into other potential sources of capital given the stage we're at as a company.

Great. Well, that wraps it up for me. Thank you so much, David, for joining us today and we'll see you all later. Thanks, guys.