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

And thanks to everyone joining us here and on the phone as well as David Meeker, the CEO for Rhythm Pharmaceuticals. Thanks for joining us this morning. Perhaps we could get started just with a brief overview of the company, with a particular focus on what you see as key value drivers over the next, let's call it, 12 to 24 months.

Yes. Thank you, Corinne. Great to be here. So Rhythm Pharmaceuticals, we're working on a -- we have a precision therapy for a defect in the melanocortin-4 pathway, which is the pathway in our hypothalamus, which governs our food intake and our energy expenditure. So when we eat a meal, we got signaling from the gut to the brain that says you're full. It shouldn't be hungry anymore. You should stop eating and your energy expenditure should go up. Conversely, if you haven't eaten, that signaling occurs and it drives this feeling, a lack of [ society ] hunger and your energy expenditure has decreased. So what we have, setmelanotide, the endogenous ligand is this alpha melanocyte stimulating hormone in patients who have an impairment in this pathway have decreased or absent levels of melanocyte stimulating hormone, and we -- a replacement therapy. So it's at 1 level, very simply hormonal replacement for the different indications that might be affected.

Great. So maybe we'll start with the Bardet-Biedl syndrome program. You launched nearly a year ago now. And what have you learned about the BBS market over that time period? And how does it shape your expectations for the opportunity set in this indication?

Yes. I didn't fully answer your prior question, which is what are the value drivers. So 1 of the 2 value drivers is Bardet-Biedl. The other is hypothalamic obesity, which we'll be talking about shortly here. But Bardet-Biedl syndrome, so our very first indications, which were POMC and leptin receptor impairments, deficiencies, mutations, if you will. Very rare. Tens of patients and really a proof of concept. We didn't put a sales force in the field, but we did make the drug available, got it priced and the like learned a lot. But Bardet-Biedl syndrome is a legitimate opportunity from a pure market standpoint, we think there's 4,000 to 5,000 patients with Bardet-Biedl syndrome in the U.S. By our estimates is probably 1,000 or so plus probably in our universe diagnosed. But there's a significant number as with all rare diseases that are not diagnosed. And what you're trying to do as a company is not just get some patients on therapy, but to build a community that has the ability to recognize, diagnose and care for these. And when you get that working and you know it's working when -- it's not just that we, as a company, are finding patients helping that happen but increasingly, the community, the patients themselves are finding us. And that tells you, again, you've built something sustainable. So 1 year in, when we started, again, you could look at this and say, wow, you're going to have a rare disease, orphan disease with commensurate pricing for treatment for obesity. How is that going to work? The reality is we've been recognized very clearly, this is a classic rare disease with all the challenges, but also the positives associated with the rare disease. And what's happened is doctor writing scripts, a large number of doctors, 175 have written scripts so far. The number of scripts written, 300 last, has well outperformed what we would have -- I think personally had expected where we'd be at this point in time. And probably the most challenging and least certain part of this was the system going to pay for it. And could we get through? About half of our patients are covered in a commercially insured space. About less than 10% of Medicare, which does not cover any "obesity drug" just by statute. But Medicaid is the balance. And Medicaid can be challenging in many cases and certainly for a rare disease. But I think we've been amazingly successful to be honest, right now in terms of where we are, and we can break that out further. But the bottom line is year-end, almost a year in and feel remarkably good about progress made.

Yes. We'll get to that in a second. But I'd say you have, as you mentioned, 300 patients with written prescriptions at the end of the first quarter, that compares to the 375 you had talked about a year ago as knowing that we're out there. I guess with that context in mind, how should we think about the cadence of new patient growth from here?

Yes. A lot questions about this. Again, we updated -- we gave that number, as you said, a year ago, February, actually. We haven't updated it since because it's inherently a softer number. That was the number we put out before launch, so we didn't have other metrics, and we wanted to give the world a sense of how things are emerging. But no, we are continuing to find patients. We're continuing to find patients. And the way I would think about that is it's a starting point. Here's a couple of other numbers, which may help. So the CRIBBS registry, which is the one registry in the United States, of which 80% of the people in that registry are less than the age of 18, and patients don't die when they reach 18, of course. We have, for sure, there's some overlap of the world we know, but not 100% overlap. So there's 600 there. There's the 350 that we talked about, maybe some overlap. And in the past year, because we have continued to make good progress in building the community, we have continued, as you'd expect, to find patients. So a long answer to say, this is not falling off a cliff. We don't expect it to fall off the cliff. I expect a slow, steady ramp going forward. And based on my history working in other rare genetic diseases that have good basic fundamentals, I would expect this to go on for a number of years.

Great. You mentioned reimbursement, of the 140 patients that weren't reimbursed within that 300 at the -- as of the last quarter, what portion do you expect to ultimately get on to pay drug? And how do you think about the stickier population that may never get a paid product?

Yes. So we have, again, as many companies, we have a free drug patient assistance program. About 20%-ish patients are in that. We move them to the free drug when we've exhausted what we think are the near-term opportunities get reimbursed. So Medicare is not reimbursed. That's a little less than 10%. All of those patients immediately go to free drug. The balance of that is a mix of commercial plans and it's the small self-insured commercial plans because we've done extremely well, but a church-based plan, the school, teachers-based plan, they just can't handle rare disease drugs in general. And then the other part of it is, of course, Medicaid and what we described about Medicaid is as of today or as of our last earnings call, 75% of the Medicaid lives, covered lives are either covered by a statute, about half, which approves it or there's no statute in place, but we're very regularly and successfully getting patients through that. The balance, the 25%, there's about 10% of that covered lives where we think it's Red-Red, meaning the prospect of getting approved is low and sort of exhausted. There's a tough states, if you will and then the other 15%, we just haven't had a patient in front of. So your question was back to the 140, how many patients do we think ultimately will come on. I'd go back to about 20% of that world may end up on free drug but once the -- and the others I expect to get approved. Once they're on free drug, you don't give up. You're continuing to work, and it's already started to happen in our world. Again, in my past experience, it was not uncommon. Remarkably, you can, things open up. I know today is not a no tomorrow. Patients get other insurance, which allows them to be switched over. So we expect that patient assistant world to be somewhat dynamic. Patients coming in and going off.

Yes. That's helpful. Maybe in terms of compliance, what are you seeing now with patients, some of which have been on for quite a while.

So compliance, again, hard to measure. You don't always have 100 great insight into that, but 90% plus of the patients who are on drug consent into Rhythm to allow Rhythm to speak to them. And as with most rare disease companies, the special sauce, if you will, a critical aspect of this is your patient support program, and we scale that aggressively. We've increased the number of individuals there. But every patient on drug gets assigned a patient education manager. That patient education manager works very closely with the patient. And we have a particularly early on and part of the reason our discontinuation rate has been so low is that from a side effect standpoint, that patient education manager is preparing the patient, this is what you'd expect. This is how long you expect it to last, it will go away. You can tolerate, if you're really challenged, why don't you talk to your doctor, maybe decrease the dose a little bit, stay a little longer on the lower dose, and we increase it. And so the ability of the patient support services group to help patients get through that is extremely high. Second is that level of communication also tells you how you're doing on compliance. And our compliance based on that anecdotal or more informal readout is extremely high. And not a surprise in the sense that this is a treatment where the impact on the patient's hyperphagia, of the severe pathologic hunger and for Bardet-Biedl, there's the obesity of the weight gain, which is problematic, and the system tends to focus disproportionately on that. But what we've really come to appreciate is the suffering is largely, if not the majority of it is related to this uncontrolled hunger. And it's different from the cravings that a lot of people feel are like ice cream or whatever. This is a failure to recognize you're full. So you've eaten a meal, you're not satiated. You're continuing to feel like I'm not full. I have to keep eating and my energy expenditure is low. And I'm just dominated by that feeling. And so if you can quiet that feeling, that translates to a remarkable improvement, not only in their life, but their family's life, sibling's life. I mean many, many aspects, and that's probably going to get better.

Understood. You're also in the early days of launch in parts of Europe. Perhaps the start, you can characterize what the European market looks like compared to the U.S. market.

So historically, and certainly today, Europe are, again, single-payer health care systems. They have centers of excellence much set up, much more reliably than the U.S. does. Physicians refer their patients into these centers of excellence. The U.S. tends not to refer so easily. So it's a much better system. More patients are diagnosed, genetic testing are more universally available. There's more experts and greater levels of awareness. So again, all of that as your starting point is much more robust one. Two, the challenges we know in Europe is getting reimbursed. The health technology assessments are much more challenging than they are in the U.S. to the extent they even exist in the U.S. And so being successful there means country by country, you've got to make your case. We have incredibly senior experienced group of individuals leading our European organization and if there's one thing not surprisingly that correlates with success there, it's the level of experience of your team. And I think what -- so far, top 5 markets, we've gotten our first POMC LEPR original genetic, through and reimbursed in all of those top 5 markets. We're working our way through Bardet-Biedl syndrome now. In Germany, as we talked about and publicized, we got the first ever exception for the treatment of obesity drug. They're viewed as lifestyle management drugs, which are not reimbursed but what they came to understand through, again, a concerted effort with the patients and expert physicians and the like is, this was a rare disease with a very specific treatment back to replacing a missing hormone and the like. And so we got the exception, and we got it originally for POMC. We got it again from Bardet-Biedl. So what should you expect? A long answer to the -- for the European piece of this, Germany will be the first significant contributor that is basically just underway. So the second half of '23, you'll see that, that will be the most significant contributor to the European revenues. On top of that, what we have today is we have the first -- the more -- the POMC and leptin receptor group of patients, which is a smaller number but more diagnosed in Europe for the reasons I said. They've come on early access programs in France, early access programs in Italy. U.K. has just approved and the like. And so those -- that will be a small contributor and then the BBS launch in Europe as a whole will become more meaningful in 2024.

Okay. That's helpful. I guess maybe double-clicking on a couple of those countries. France, for example, has allowed for some early access programs. When do you expect to formalize reimbursement in that country?

So anticipating again, we know how these things play out, but based on history and how things going out in the second half of 2024.

Okay. And as you think about, obviously, there's some structural differences. What about physician priorities or how they think about treating this patient population?

I think reception overall has been very good. In the earlier access programs, you -- patients get put on through centers of excellence. So often, these are physicians have been part of the trials. They understand the drug well. Again, conviction is high. The barriers there are just the logistics, the administrative patients have to be referred to those centers and not -- they may be at another center, but there's only a national center or 2 that -- which is the case in France that are governing or making these early access decisions for each patient. But overall, again, it tends to be a more knowledgeable group than the U.S. where U.S., in our original group of patients treated for BBS, we talked about 25% of the physicians who are not physicians we've been in regular contact with, with written scripts. These are not necessarily experts. I mean these are often, I'd say the majority of those are probably primary care physicians, where their patients, either they or their patient, they came together and said, look, I want to give this a try and Rhythm then steps in and help them through that process.

Okay. Great. Recognizing that you haven't given formal guidance, how do you think about what a successful outcome looks like for the BBS launch, let's say, on a 1-year view as well maybe an out-year view?

On a 1-year view, so we're coming up on 1 year, if you asked me a year ago where I thought we'd be today, I wouldn't be here. So -- and I just won at a level of relief that it's working the way we had hoped and expected. But beyond that, I think also incredibly positive about the reception at the payroll level, the desire of the patients getting treatment. We've had almost no, maybe 1 or 2 max patients who have discontinued for "lack of efficacy". So back to again, you run these relatively small trials, rare disease trials. You know a small amount at the moment your drug is approved, you really begin to learn when you get out in the marketplace. And so at year-end, what we're learning, like I said, reassuring. I mean, these patients, they're benefiting, they're benefiting in a range of ways, not just weight loss.

Yes. Great. Maybe switching gears here a little bit to the hypothalamic obesity indication. First, let's just level set, what is hypothalamic obesity? And can you give us a sense for that market?

So hypothalamic obesity, again, was an entity that's defined by damage to the hypothalamus, classically it occurs in these children, mostly children, but can be adults who develop these benign tumors, but the location of that tumor is right between the pituitary and hypothalamus. They are treated most usually by resection and/or radiotherapy. And about half of the patients who have these benign tumors and that their treatment end up with this hypothalamic obesity and what -- it's an observation, a description. It's the coming out of surgery and the like, they explode off of their growth chart. So an otherwise normal child would somewhere be well above the 95th percentile for weight in a very rapid period of time. So that's the classic presentation. The understanding of why was not well understood, what was driving this. Multiple things have been tried -- literally everything has been tried. It's a relatively desperate group in terms of the unmet medical need and what their -- what challenges they and their families are living with. And when we started out with setmelanotide, MC4R pathway, obviously, we recognize the pathways in the hypothalamus. It's likely to be damaged. But concern was certainly myself, if you're damaging the pathway, but maybe aren't you damaging and losing the receptors as well. So how would the drug work? And what was quite striking was we had this amazingly consistent response across the 18 patients that we studied in Phase II. And so we had a good level of response, remarkable in that sense. But the consistency, I think, was really -- that consistency tells us, I think, that we're getting at the underlying biology here.

Yes, great. Maybe we can go a little further on that. You mentioned there was a successful study last year. How many patients? What did you evaluate? And what did you see?

So it was open label, 18-patient trial. And interestingly, again, we -- it started out and roll very slowly with a lot of skepticism in the community. I think trial fatigue at one level. Other things hadn't worked and not wanting to be disappointed again. So once the first 2, 3 patients began to have a response, we got a buzz in the community and then enrolled the balance of the 18 patients in about a quarter, it went very, very quickly. So that's how these small rare disease communities work when something begins to work. The endpoints, bridges classic, I mean we looked at weight, the BMI, look at BMI z, which is -- BMI is not a great -- that's a calculation that corrects for your height and weight. And one of the challenges maybe just for rare disease trials in general is you don't get to be picky. You need to take whoever you can to enroll the patients. So they tend to be highly heterogeneous. And in this world, we're mixing adults and kids. And so when you're looking at weight as an endpoint and in adults and kids, obviously, the kids are growing, so they should be gaining weight, at least not BMI, which corrects for height, corrects to a certain extent, but there's additional more sophisticated corrections, which we also measured called BMI z or the 95th percentile of the 95th -- the percentile of the 95th percentile. Bottom line is all of these are trying to understand the relationship of your weight to your growth curve and how far you are off of that. So all of those things improve quite dramatically on average across the group. And as I said, virtually every patient have a significant response.

Great. Maybe you can also contextualize that versus some of the other things that have been tried, particularly the GLP because I know people often ask why wouldn't a patient just use a GLP?

Yes. Yes. I mean, as we said, I mean, GLPs are amazing drugs. The difference is we're working on a very specific pathway here, and we have a precision medicine that is targeted directly to the MC4 receptor, the GLPs are working, I would call in other areas of the brain, other circuits, and they're not replacing anything. They're trying to manipulate basic normal physiology. So that's number one. Two, groups have been tried in hypothalamic obesity, the earlier generations, so exenatide and liraglutide. Exenatide is the only one that's had a 40-patient randomized controlled trial, did not work. Anecdotally, semaglutide, clearly a better drug than the earlier generations. There are anecdotal cases and including among our investigators, where patients have responded to the GLP-1s, asking one of our lead investigators, how do you think about that? She has one patient doing well on a GLP. Her thought was that about 20% of the patients may have some response to a GLP and that the magnitude of that response would be about 10% or less. Pressure tested that with other investigators, and they think that's probably about right, if anything, a little bit high. And if you think about where the GLPs work, the GLP also work in the hypothalamus. So one of the reasons you are may not be getting universal effect with the GLP is because of that, depending on the damage and the like and what's affected. Why does our drug work? And the hypothesis is that not only we may be working through whatever residual opportunity there is in the hypothalamic part of it, but the receptors -- these MC4 receptors are outside the hypothalamud, in the spinal cord and the brain stem, interacting with the autonomic nervous system, the sympathetic nervous system, specifically is one which impacts the energy expenditure. So I think a lot of the consistency in effect is being mediated by the energy expenditure side of the equation.

That's helpful. In terms of magnitude, obviously, you talked about the consistency of response. What did you see with respect to magnitude of response?

So 14% to 15%, which averaged in a 1 patient who was completely noncompliant and gained weight. And we also -- when we presented that data, the first time about a year ago, the 16-week data, the way we presented it was basically, all the patients who hit in the waterfall plot who hit 10% or more, and then there was 5 patients that did not hit 10% or more at the 16 weeks and walk through each one of the file, making the case that they either hit it and then regressed a little bit or they weren't -- 2 patients stopped because of adverse events, but they were on track to lose 10% or more. And then we have 1 patient completely noncompliant. And there was only 1 of the 18 who was compliant and lost 2.7%. That patient had a reversal, their very steep trajectory and has continued just to lose gradually over time. And as we update the data with the 12-month data by the end of the year, I think people will hopefully be reassured by the fact that even that patient who is the 1 patient who didn't hit the 10% is having a very clear response.

Yes. Maybe we can spend a bit of time on the 12-month data coming later this year. What should we look for in that? And how many patients will still be on drug?

Yes. So 14 patients enter the long-term extension. So we'll update that. 1 of the patients who enter the long-term extension that actually did not get dosed in the long-term extension was immediately lost to follow-up. That patient did regain all of their weight. We subsequently refound them. And they've been re-entered and so you'll get an update on that, but that patient won't have the 12-month data, but the other should have the 12-month data.

And what do you expect to see with respect to weight loss space in some of the other programs?

Yes. So these are -- this is a slightly different setting, obviously, than patients who have a genetic driver for their underlying obesity and hyperphagia and they've lived with it by definition for a lifetime. These are individuals who may have been on the normal part of the curve, less than 50% of their overall growth curve. And to the extent we're reversing something, and we basically almost saw it in the 16-week period. I mean you're getting some of these kids back to where they're back on the normal curve. Now you don't want them to keep losing weight there. So what you should expect to see is that they don't continue to lose weight. In fact, you want them to start gaining weight as they grow. So again, I hope that we're able to show as we get all this data in and it's not all in is that there is a return towards normality, not that all patients will get to normal, but the potential you could get to normal, certainly for some part of that population is clearly there. So again, long story short, you should see a continuing deepening or a meaningful -- or plateauing at a meaningful level is what I hope we can show.

Great. You recently initiated a Phase III study in this indication. What can you share related to the trial design? And any change differences between that and the Phase II?

A larger number of patients. So it's 120 patients, randomized 2:1 to placebo. First 18 patients was open label, of course. It's a full 52 weeks plus the 8-week titration, so 60 weeks in total, which is the regulatory blueprint for these. There's just no field negotiation around that. We're well over powered. People have asked us about that. I mean we're 99% plus power to show a 10% difference between treated and placebo. So it's not an efficacy question. The goal or desire of the regulators is really to have a full year of safety data which, again, although this is an approved drug, which was the case we made and therefore, it's already got the CLO safe and efficacious and the indications, we haven't had a robust full year control population in our prior studies. So there was a strong desire to get that. So that's it. And the endpoints are the same ones we looked at before in terms of the variety of weight measures. We'll have a hunger score, a variety of quality of life scores, again, which we've gotten better at assessing. We've gotten better. I think I have a better questionnaire and capture the changes in hunger. So hopefully, we'll see that. And the one thing which is novel, and we are interested in, these kids, the way it's described -- otherwise normal kids go to -- have developed a tumor, they go to surgery and they come out literally not wanting to do anything. So energy level is quite low. And anecdotally, in our open-label trial, the physicians and families are describing more energy. And the question is, okay, well, great, you lost a little bit of weight, maybe you're feeling better and doing more. But what they're saying is no, no, they think they're really feeling more energy. So we're going to try to capture that with an active graph, which just measures by definition, activity. But I think that's an exploratory endpoint. But to be honest with you, it's one of the more interesting parts of it. And I really hope we can see something there.

Yes. Any updates on pace of enrollment?

So no update. What we've said is that we expect to have this fully enrolled by the first quarter of next year. We have -- sites are up and running. And the other 2 pieces of color we've given, which have continued to be confirmed is the drag on this whole process is getting the site open. It's -- and there, we're just -- we're competing with all trials running at a site. It's not just an obesity trial, for example, it's any trial, oncology or otherwise, it has to go through IRBs, has to go through contracting. Sites that are coming out of COVID are still under resourced and is challenging. So that's the drag. From a patient standpoint, all the sites that we have enlisted have multiple patients, many of them double-digit patients on their list. The screen failure rate, very -- even very early on is extremely low, which is what we'd expect, meaning when they're generating their list of patients of who they think might be eligible, they know these patients. They know the entry criteria. And so again, that's pretty reassuring that the numbers of patients that are telling us, I think, are there and are going to be eligible. So I think once the sites open, it should move. But the variable is getting the sites open.

Great. Before we move on to [indiscernible], I guess in terms of the market opportunity or the commercial opportunity there, what are some of the key differences? And can you frame out the size of that addressable market?

Yes. So the Bardet-Biedl market, we think in the U.S. is on the order of 4,000 to 5,000, feel really good about that number. HO is 5,000 to 10,000 is our best estimate. But fundamentally, what's different and the reason I think a lot of people, including ourselves, were excited about this opportunity is it's a very different population than the Bardet-Biedl world where many of those patients are undiagnosed. This world, they know who they are, for the most part, they have their tumor. They went to surgery. They know something radically changed. So arguably, a large percentage of that 5,000 to 10,000 is diagnosed. And then secondly, because they also injure the pituitary, you -- many of them, 80% plus have some level of pituitary insufficiency meaning they require another hormone replacement in their thyroid, their cortisol for renals and the like. And so that means they need active management by an endocrinologist, and they're not lost in the system. So all of that says that 5,000 to 10,000 is highly approachable. And so when we think about BBS, which we think about as a very robust ultrarare but sustainable opportunity, [ HO ] is a multiple of that.

Okay. Helpful. Beyond these 2 indications, you have a number of other genetic obesity studies ongoing. Maybe just give us a brief overview and particularly like what you expect to provide updates on in the near term.

Yes. So the 2 other major efforts are: one, is M&A which is a Phase III trial, looking at 4 different genes, the heterozygote form of our POMC and LEPR and 2 other genes, which we had positive data in a Phase II basket study. Those are actively enrolling. Just there are year-long trials as well. So we expect those will read out in 2025. The other trial, which is the DAYBREAK study, which is an exploratory study design to efficiently, hopefully, sort through about 30 genes that were linked to the pathway and we've already scaled down significantly. So the trial is doing exactly what we wanted. We scaled down genes where we saw no early response in the open-label portion and then those that were just too small and weren't enrolling. So we stopped looking for those. So we look to report out, hopefully, before the end of the year, on 5 plus or minus of those genes that we think might be -- not the all interesting, but 5 of we've got enough data to be able to say something meaningful about what we've learned.

What criteria will you be using to evaluate whether you want to move forward with those populations? And I guess depending they all hit it, are you prepared to fund all of those?

Yes. So again, we have probably more that we can, could do and then we can afford to do, if you will. So that's part of your question. The [indiscernible] go forward, we'll compare everything. So Alstrom syndrome, for example, which was part of our original Bardet-Biedl. We had a very clear signal in the pediatric population. So they would be on the table in comparison of whatever we learn from the DAYBREAK and we'll look at those opportunities, which are the most meaningful, most approachable variety of criteria. What would we take forward? I'm not -- I can't envision us taking forward something that just barely clears the 5% part of this. So we'd expect a higher bar there. But if you look at the totality of the evidence, and then we'll have to pick and choose because for sure, we won't be able to do everything.

Great. Another study that you have ongoing is a weekly formulation of IMCIVREE. Maybe first, just touch on what the importance is of that formulation to the overall portfolio.

So weekly is incredibly important. We are very focused on getting that done and approved. So most specifically, just practically, it's from an IP issue. So setmelanotide's IP goes till 2032, composition of matter. The weekly extends us to 2038. So from that standpoint, I don't think, to be honest with you, this world needs a daily and a weekly injection. So if we get the weekly, you can imagine that the daily might gradually phase that out, so it wouldn't be available. So IP extension is a critical part of this. There's no question that weekly is a better option just from a convenience standpoint. But interestingly, I don't feel like we've left a lot of patients on the sideline with the daily, and we're not getting that feedback. It's not 100%, but it's been quite small. So the urgency to get this approved, it's to get it done comfortably before 2032, but it's not like we have to get it at all costs in a short period of time.

Great. And so I guess to that point, what is the development path for weekly formulation? And where are you in that process?

So we have 2 studies. One is a switch study, which is -- will be mostly just looking at the pharmacokinetics and tolerability of the drug. So we'll have that information by the end of the year. That's fully enrolled and running. But the second piece, which is necessary based on discussions with FDA and EMEA is a de novo study in Bardet-Biedl. So with a control group, that would run outside the U.S. What's been holding that up, and we've been pushing that out. And largely, to be honest with you, are related to the availability of our auto-injector, which is the key part of that presentation. We're running the SWITCH study without it, but it's a slightly larger gauge needle because it's a viscous solution. So once we get a firm handle and a time line for that auto-injector, then we'll lock in the start point for weekly de novo.

Understood. Maybe in our final minutes here. Could you touch on the cash runway and then perhaps how you think about versus the funding?

So we finished the first quarter were just under $300 million in overall cash. We've guided Hunter Smith, our CFO, has to about $200 million to $220 million in spend for the year. And our cash runway, just under $300 million extends us into 2025. And what -- the variables there as we look at our cash needs and how we think about the balance of that time is pleased with the revenue and how that's growing. And so obviously, the better we do there, that decreases overall cash need. We see our spending approaching a relative peak here because it's largely driven by R&D. We've built out our U.S. commercial infrastructure and we don't expect to spend a lot more incrementally there. We will gradually in Europe and in the pay-as-you-go way. We don't get ahead of that. So it's really an R&D piece, and that R&D spend will come down as these Phase III trials move past their early start-up in full enrollment place. So long story short, our burn rate -- cash burn rate should decrease progressively as we move closer to 2025. And then our options for funding, obviously, you can always go to the equity markets. We did a capital royalty structure which has a sales milestone based incremental tranche that we can take, which we haven't drawn yet. That's $25 million. And beyond that, that's a group they are open to potentially extending as one option in addition to equity markets. But I think our focus right now is really just managing our burn and driving our revenue, which will make that cash need as small as possible.

Absolutely. Great. Well, thanks for joining us today, and thanks to all of you who joined us both in person and online.

Thank you.