Ladies and gentlemen, thank you for standing by, and welcome to the Rhythm Pharmaceuticals First Quarter 2026 Earnings Conference Call. At this time, all participants are in a listen-only mode. After the speakers' presentation, there will be a question and answer session. Please be advised that today's conference is being recorded. I would like now to turn the conference over to David Connolly. Please go ahead.
Thank you, Michelle. I'm David Connolly here at Rhythm Pharmaceuticals. For those of you participating on the conference call, our slides can be accessed and controlled by going to the investor section of our website, ir.rhythmtx.com. This morning, we issued our press release that provides first quarter 2026 financial results and a business update, and that press release is available on our website. Our agenda is listed on Slide 2. On the call today are David Meeker, Chairman, Chief Executive Officer, and President; Jennifer Lee, Executive Vice President, Head of North America; Hunter Smith, Chief Financial Officer; and Yann Mazabraud, Executive Vice President, Head of International, is on the line joining us from Europe. On Slide 3, I'll remind you that this call contains remarks concerning future expectations, plans, and prospects which constitute forward-looking statements.
Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in our most recent annual or quarterly reports on file with the SEC. Any forward-looking statements represent our views as of today and should not be relied upon as representing our views as of any subsequent dates. We specifically disclaim any obligation to update such statements. I'll turn the call over to David Meeker, who will begin on Slide 5.
Thank you, David Connolly. Good morning, and thank you for joining. We had another good quarter. Now, before we dive into some of the more recent events, I do wanna highlight the ongoing progress in our base business, predominantly BBS. Revenues for the quarter were $60 million. As we would expect with an ultra-rare disease, awareness of the disease continues to grow, leading to more patients diagnosed, more potential candidates for therapy. We have learned much through this initial launch, and we continue to adapt and optimize use of available data to connect with the right healthcare providers who may have a BBS patient. There is still more long-term opportunity to unlock with BBS. With the FDA approval of IMCIVREE for acquired HO on our PDUFA date and European marketing authorization, which came early, we have expanded our focus.
As with the BBS launch, our plan will be to share a view of the early launch metrics with a goal of giving you a sense of how it is working with the usual caveat that it is extremely early. That said, we are pleased with a strong start with more than 150 start forms to date and a good reception at the payer level. Jennifer will provide more details. Slide 6 is to remind you again of the significant opportunity in HO with an estimated prevalence of 10,000 patients in the U.S. and Europe and 5,000-8,000 patients in Japan. With a much more concentrated call point than BBS, this is a meaningfully larger opportunity. Japan is positioned to be the second-largest opportunity for HO behind the U.S.
As we have shared, we have been extremely appreciative of the highly collaborative, encouraging nature of our interactions with the Japanese Regulatory Authority, the PMDA. All Japanese patients have completed the 12-month trial, 8 patients on treatment and 4 on placebo. 1 patient discontinued early secondary to hyperpigmentation. Slide 7 shows the BMI change as compared to the values for the full 142 patients. As you can see from the results, the results were similar to the full cohort. The placebo-adjusted differences were slightly less, mostly due or due in part, at least to the fact that the placebo group did not gain weight in the same way their Western counterparts did. Although the numbers are small, this may reflect the cultural differences with a more obesity-prone environment in the West.
The team has moved rapidly to complete the filing, putting us in the position of an anticipated approval before the end of the year. The Japanese team is fully in place, and Yann will talk more about the opportunity and the organizational build. Finally, as we have previously shared, we look forward to a number of milestones this year. Pending late-breaking abstract acceptance, our goal is to share Dr. Miller's six-month data in PWS at the ENDO meeting in June. Similar to what was presented in December, we would expect to share BMI data, HQ-CT data, and DEXA scan data for those patients who have completed the scans. We anticipate sharing RM-718 data mid-year, and we are targeting the Q2 earnings call, at which time we would share the Part C results in HO and potentially the available data in PWS.
CMC work and bioequivalent studies for the new formulation are underway with a goal of being in a position to start the phase III trial with bivamelagon in HO by the end of 2026. I will now turn the call over to Jennifer.
Thank you, David. I'm gonna be starting today on slide 10. It is an exciting time for Rhythm with the acquired HO approval and our U.S. commercial launch is off to a strong start. The early reception has been positive. Physicians are prescribing IMCIVREE for patients with acquired HO. Payers, especially those with experience through BBS, have begun approving reimbursement, and we have patients with acquired HO who have started therapy. IMCIVREE was first approved in 2020 for POMC and LEPR, and we launched in 2022 for Bardet-Biedl syndrome. BBS is an ultra-rare disease with an estimated prevalence of 5,000 in the U.S.
Disease awareness and diagnosis rates were low at the time of launch. Over the last 3 years, we helped build an active community of engaged physicians who support the earlier identification and treatment of patients, and we have worked to expand reimbursement of IMCIVREE. In doing so, we delivered steady, consistent growth over the last 3 years. It wasn't always easy, but we've learned from the challenges along the way and laid a solid foundation for future launches, including our recent one in acquired hypothalamic obesity. For BBS, in the first quarter of 2026, we had steady growth in prescriptions. Similar to Q1 last year, we had patients that transitioned to new insurance plans, leading to a temporary increase in patients provided free drug through our Bridge program.
As of mid-April, we had transitioned most of these patients back to reimbursed therapy, and we are seeing steady growth in commercial patients. Now moving to the acquired HO opportunity, which we estimate is approximately twice the size of BBS at 10,000 patients. We've grown our commercial organization to extend our reach in this larger opportunity, going from 16 sales reps for BBS to a total of 42 sales reps deployed across the country. We have similarly scaled our patient services team as well. The FDA approval on March 19th and the broad label, which goes beyond tumor and tumor treatment-related HO to include other injuries that may lead to acquired HO, has opened the doors for our team to engage with more physicians.
Our teams continue engagement with HCPs around the causes of acquired HO, the role of MC4R pathway, and the compelling efficacy data and the product profile of IMCIVREE. This has resulted in the identification of more acquired HO patients, and we've seen steady progress of patients moving to diagnosis from suspected as physicians gain a better understanding of this unique disease and its causes. Next slide. The initial response from patients and the physician community reflects a high unmet need for treatment for acquired HO. We have received more than 150 start forms in the six weeks since approval. Of these start forms, approximately 40 are for clinical trial patients. During the first six weeks of launch, there have been approximately 110 unique prescribers for acquired HO, of which about 80% are new prescribers of IMCIVREE.
To date, the large majority of prescribers have written one script for an acquired HO patient. In these early days of launch, approximately 80% of prescribers are endos, along with some pediatricians and primary care physicians. We're seeing encouraging receptivity among payers too. Having approval in place enables us to get back in front of payers to continue education around acquired HO and IMCIVREE for this new indication. Our prior education that led to IMCIVREE coverage for BBS has facilitated our discussions with payers and supported their understanding of acquired HO as an MC4R pathway disease. We are pleased to see initial approvals for reimbursement for acquired HO prescriptions during this early phase of launch, but we continue to expect it will take approximately 3-9 months from approval for HO-specific IMCIVREE policies to be established.
The early launch indicators are highly encouraging, reinforcing our confidence in the long-term potential of IMCIVREE in hypothalamic obesity. We look forward to updating you on our progress. With that, let me hand it over to Yann.
Thank you, Jennifer. I will begin on slide 13. We are very excited about the HO opportunity in the international region as we achieved significant milestones on our path towards bringing IMCIVREE to more patients. Just last week, the European Commission granted marketing authorization for IMCIVREE for the treatment of obesity and control of hunger in patients 4 years old and older with acquired hypothalamic obesity due to hypothalamic injury or impairment. Our dialogue with European regulators was very constructive and efficient, resulting in the EMA's positive CHMP opinion coming sooner than we originally expected, with marketing authorization following just 1 month later, despite this process typically taking 2 months.
This is a tremendous achievement and the result of years of work and collaboration between Rhythm and our investigators, the European HO experts, and the regulatory authorities, all of whom focused on bringing the first-ever therapy specifically approved for patients with HO. With an estimated prevalence of approximately 10,000 patients in Europe, this is a meaningful opportunity, and we have a very experienced market access team that will lead us through country-level negotiations with launches anticipated to begin in 2027. Similar to the process we previously followed for our approved indications of POMC/LEPR and BBS, we have begun efforts to seek an exemption from the German Federal Joint Committee, the G-BA, from its exclusion list that prohibits reimbursement for lifestyle drugs, such as drugs indicated for smoking cessation and general obesity.
The CHMP opinion enabled us to begin this process, which can take 6-9 months, putting us on track for a launch in Germany in 2027. In addition, the key local reimbursement dossier are finalized, and we will begin negotiations in France, Italy, Spain, and other countries. For the U.K., we leverage our E.U. submission through the International Recognition Procedures, IRP, to seek authorization from the Medicines and Healthcare products Regulatory Agency or MHRA. This was already submitted last week based on the positive CHMP opinion. Of course, there is already much enthusiasm in Europe, as we have seen with the reimbursed early access programs for HO in France and Italy, which account for a meaningful portion of patients on reimbursed therapy in the international region.
These early access programs have enabled many of the leading physicians in France and Italy to begin patients on setmelanotide, gain experience with the drug, and see the benefit in patients. The French AP1 program, in particular, has generated real world efficacy results for publication, adding to the body of evidence supporting setmelanotide therapy for HO. Next week, at the European Congress of Endocrinology in Prague, French physicians will present real world data from more than 60 patients with HO on setmelanotide in the early access program, including a cohort on therapy for up to 12 months. Next slide. We are also rapidly advancing towards achieving anticipated marketing authorization and commercialization in Japan.
With an estimated 5,000-8,000 patients with acquired hypothalamic obesity in Japan, where the prevalence and incidence rates are higher on a per capita basis than Europe and the U.S., the unmet need for an effective therapy is quite pronounced. There has been strong KOL support since we first disclosed our phase II data in HO. Our commitment to quickly bringing IMCIVREE to Japanese patients in need has enabled positive and open dialogue with Japanese regulators. We now have almost 50 employees in Japan. We've begun executing on our pre-launch tactics focused on disease awareness, including face-to-face interactions, webinars and symposia, and patient identifications. These activities provide us with a strong understanding of the disease landscape and position us well to begin pricing negotiations upon approval. Just last month in Japan, I joined the team for a series of meetings with KOLs and Japanese government officials.
In addition to the excitement for the potential impact setmelanotide will have on these patients, these KOLs and officials told us they were very appreciative of the speed and urgency with which we entered Japan. Of particular note, our team has moved fast, potentially securing approval in Japan less than a year from the U.S. approval, when many companies wait years or partner with someone else to pursue approval. As we announced today, the PMDA has accepted and is reviewing our NDA filing for IMCIVREE for acquired hypothalamic obesity. Japanese regulators do not publish or announce a timeline for approval as it is done in the U.S. and Europe, but we anticipate approval and launch by the end of 2026. Slide 15. Lastly, Q1 2026 was another strong quarter for the international region.
We saw double-digit percent growth in patients on reimbursed therapy throughout the region, which includes more than 25 countries where IMCIVREE is available through national reimbursement or named patient sales. BBS was a primary driver of growth from Q4 2025 to Q1 2026, with the early access programs in France and Italy for HO contribute meaningfully. Since IMCIVREE was first authorized in Europe for POMC and LEPR in 2021, we have built a very strong foundation with positive and collaborative relationships in place with many experts and market access officials. This experience will serve us well with HO. With that, I will turn it over to Hunter.
Thank you, Yann. I begin on slide 17. Rhythm is well capitalized and off to a strong start of what promises to be a transformational 2026. The initial phase of the U.S. launch in acquired HO is quite encouraging, and we're excited about the significant ongoing progress in the international region as well. We had a solid first quarter of 2026 with $60.1 million in global net revenues from sales of IMCIVREE, which represents 5% sequential growth over Q4 2025. During the first quarter, 61% of revenue was generated in the United States, with the remainder generated outside the U.S., reflecting continued strong performance across those geographies. Globally, we saw continued growth in patients on reimbursed therapy with an 8% increase over the prior quarter, driven primarily by BBS.
On slide 18, I'll walk through the revenue quarter-over-quarter as revenue increased from $57 million in Q4 2025 to $60 million in Q1 2026. First, the U.S. While the number of patients on reimbursed therapy in the U.S. increased from the end of Q4 to the end of Q1, the specialty pharmacy inventory increase of approximately $1.8 million in Q4 had the effect of pulling sales forward, which affected U.S. revenue during the quarter. Separately, during Q1, shipments to our SP and dispenses to patients were pretty balanced. Specialty pharmacy inventory changes during the quarter did not have a significant impact on revenue.
In addition, as we saw last year during the 1st quarter, and as Jennifer mentioned, a number of patients transitioned insurance plans in the new year, and as a result, they received free drug from our bridging program for some or much of the quarter. Due to the strong collaborative efforts of our patient support teams working closely with patients, payers, and HCPs, the number of patients on bridge therapy has since returned to Q4 levels. Revenue outside the U.S. increased from $18.3 million to $23.2 million in Q1, reflecting a 27% sequential quarter-over-quarter increase. This growth was driven by increased sales volumes in Germany and France, as well as certain named patient sales markets, particularly Saudi Arabia and Greece.
As we have said previously, some of these named patient sales markets order with longer lead times, which can result in more variable quarterly revenue growth. On slide 19 is the financial snapshot of the first quarter of 2026 results compared to the first quarter of 2025. Gross to net for U.S. sales in Q1 was 84%, which is consistent with recent quarters. Cost of goods sold in this quarter was 11.9% of product revenue within our normal range and primarily driven by cost of materials from royalty payments on setmelanotide in connection with higher product revenue during the quarter. As a percentage of product revenue, COGS can vary quarter to quarter based on changes in inventory balances and manufacturing activity.
R&D expenses were $41.7 million for the first quarter of 2026, compared to $37 million in the same period last year. Sequentially, R&D expenses were flat compared to the fourth quarter of 2025. During the quarter, an increase in headcount or related costs was offset by a decrease in clinical trial costs and costs related to chemistry, manufacturing and controls or CMC work. The year-over-year increase is primarily attributable to an increase in headcount-related costs. SG&A expenses were $63.6 million for the first quarter of 2026, compared to $39.1 million in the prior year period. Sequentially, SG&A expenses increased by $6.1 million or approximately 11% compared to the fourth quarter of 2025.
The change in SG&A expenses primarily reflected higher headcount-related costs, including stock-based compensation and marketing activities in support of the anticipated launch of IMCIVREE in acquired hypothalamic obesity. Weighted average common shares outstanding were 68 million in Q1. Cash used in operations was approximately $44.2 million during the quarter. GAAP EPS for the first quarter of 2026 was a net loss per basic and diluted share of $0.83, including $0.02 per share from accrued dividends on convertible preferred stock of $1.1 million. We ended the first quarter with approximately $341 million in cash equivalents and certain term investments, which we continue to expect will be sufficient to fund planned operations for at least 24 months. Lastly, for me on Slide 20, there is further detail on operating expenses for the first quarter and our full year operating expense guidance.
For the first quarter, operating expenses of approximately $105.3 million included $23.1 million of stock-based compensation. Non-GAAP operating expenses for Q1 were $82.2 million. We expect this to increase on a quarterly basis throughout 2026 due to investments in CMC supporting RM-718, increased spending on clinical trials, increased spending on clinical supply of bivamelagon ahead of our planned phase III trial in hypothalamic obesity, and the ongoing build-out of our team in Japan and preclinical work associated with our CHI program.
Our guidance is unchanged as we anticipate approximately $385 million-$415 million in non-GAAP operating expenses in FY 2026, comprised of non-GAAP R&D of approximately $197 million-$213 million, and non-GAAP SG&A expenses of approximately $188 million-$202 million. With that, I'll turn the call back over to Dave.
Thanks, Hunter. In closing, I hope it's clear why we're excited about building the next phase of Rhythm. We see three clear pillars supporting this phase. Work is continuing on the genetic causes MC4R pathway impairment. That work is focused on improving our understanding of the specific genetic variants to better clarify those variants which have true loss of function. Those patients would be the focus of our next trials, which will be done with one of our next-generation therapies. That work will continue through 2026. The second pillar, as we have focused on today, is Hypothalamic obesity, either due to injury or hypothalamic dysfunction due to failure of the hypothalamus to develop normally. The third pillar is Prader-Willi syndrome, an extremely complicated disease with a huge unmet need where we believe the MC4R pathway plays an important role.
We are aggressively pursuing our lifecycle management strategy with the next-generation therapies, and we are building out our early research function focused on a small number of programs, which includes our program for CHI. With that, we can now open the call for Q&A.
Thank you. We do ask that you please limit to 1 question. The first question will come from Phil Nadeau with TD Cowen.
Good morning. Thanks for taking our question and congrats on the HO launch. The question is on those patient start forms and patient identification. I think the last number you gave was for number of patients identified was approximately 2,000, but you've said you've identified more since. Any update to that number today? Of the patient start forms you've received, how many were from that patient pool versus how many were newly discovered patients since launch? Thank you.
Jennifer Lee?
Sure. We've continued to make progress. We had a tiered list of groups that our sales reps were out targeting just in terms of disease education. We've continued to make inroads in terms of penetrating that list. As I outlined, the 2,000 number has continued to increase even since that September date. It's not a number that we are updating moving forward as we're focusing more on metrics, including start forms. Many of those start forms that we received, if you take a look at them, have come from the list of physicians that we educated prior to approval.
I would say that overall, the vast majority of these start forms were from physicians that our field teams had some type of engagement with prior to approval.
That's very helpful. Thank you.
Thanks, Phil. Thank you. The next question's come from Paul Matteis with Stifel. Your line's open.
Great. Good morning. Congrats on the early launch progress. Taking a step back, it feels like with a number of rare disease launches lately, the street just debates whether early success is a bolus or linear and sustainable. It looks like outside of the patients who are converted from clinical trials, you're adding around 20-ish a week. Do you feel like that's a cadence based on your visibility and conversations with physicians that, you know, could be sustainable for 2026? Or if not, how are you thinking about the kinetics? Thanks so much.
Sure. I would say, like, overall, we were very pleased just in terms of the early, first six weeks, just in terms of how we were progressing. As you mentioned, we did have 40 of those RXs coming from trial conversions, and our teams continue to work with our clinical teams, just in terms of pulling those forward. I would say that from the trial conversion piece, you know, the remaining patients really are going to be based on the last visit that is actually set. We continue to work through those in the next quarter and so moving forward. In terms of additional patients beyond the trial conversion, you know, you talked about bolus.
I would say that in any launch, as expected, there's gonna be physicians who are quite activated just in terms of waiting for approval. We had some that had proactively reached out to their patients upon approval to let them know about the availability of therapy. The vast majority of the patients, or the physicians, are waiting to have those conversations with their patients as they come in for their regularly scheduled visits. That will flow through on a, I would say, more of a steady pace, moving forward. We still have a lot of opportunity in terms of education, as we move forward into the launch.
Did I answer your question, Paul?
Yep. Thanks very much.
Thank you. The next question's gonna come from Derek Archila with Wells Fargo. Your line's open.
Hey, good morning, and thanks for taking the question. Congrats on the progress here. Yeah, just had a question on the 110 prescribers. I guess, what's the makeup of these physicians? Are these mostly in centers of excellence or are these more one-off? Thanks.
In terms of the prescribers, one, I will say that we were very happy to see that there is a nice breadth of physicians with patients that have been activated just in terms of interest to prescribe IMCIVREE for their patients. That's something that we will continue to focus on as we move forward as there were, you know, many physicians on our targeted list with potential patients. To date, I would say that the vast majority, similar to other rare diseases, you know, of these physicians have written one script for their patients. I would also say that there's still opportunity that remains with some of these physicians just in terms of having additional patients within their practice.
That is, you know, aligned with sort of the flow that I outlined in terms of those patients coming in so that that physician can have that ongoing dialogue regarding diagnosis as well as IMCIVREE potential. Relating to the concentration within the centers of excellence, in the past, we have outlined that we are focused in terms of these 42 priority accounts. However, I would say that our list follows also the patients that we have identified in the claims and the physicians who actually have these patients potentially that are HO patients. That breadth goes beyond these priority accounts, and we have received definitely scripts that are outside of these priority accounts as well.
Thanks, Jennifer.
Sure.
Thank you.
Thank you.
The next question's gonna come from Dennis Ting with Jefferies. Your line is open.
Hi. Thanks for taking my question, and congrats on the quarter. We're trying to get a sense of underlying demand here. For the doctors who have prescribed IMCIVREE to an HO patient, what's primarily been the gating factor preventing them from prescribing it to their second or third patient? Is it, you know, is it doctors getting comfortable with the product profile and reimbursements? It seems like the vast majority of them are new to IMCIVREE, or perhaps it's just the timing of patient visits. Thanks.
I would say that the primary gating factors are, could be two pieces. The primary one is the pace and the schedule just in terms of those patients coming in to have that dialogue around IMCIVREE. That is, you know, really pre-planned just in terms of what that normal visit may look like for that patient. I think the other factor is, as we also continued with our education with HCPs, there were some patients that may have come top of mind or had already been diagnosed, but through our education, they also had several aha moments just in terms of other patients that they suspected may also have HO.
Going back in terms of our breadth, we were very pleased in terms of the label that we got upon approval that was broader than just brain tumor and brain tumor management-related, you know, causes of HO. There's still opportunity just in terms of educating about the other, you know, potential causes of HO and getting those patients also to a diagnosis.
Perfect. Thank you.
Next question.
Next question comes from Corinne Johnson with Goldman Sachs. Your line's open.
Maybe you could just quantify a bit more the reimbursement dynamics here for these HO patients that are getting on therapy and translate that to how we should think about maybe net price per patient as this becomes a bigger portion of contribution to revenue. Thanks.
Yeah. Yeah. Jennifer Lee, just the reimbursement. A little bit of sense for the mix of payers here, and then I think Corinne's getting at the, you know, Medicaid, of course, would have a discount and the like.
Sure. We are very early in the launch, with both, you know, just in terms of understanding what that payer mix will look like. I, you know, and with that said, what we have seen is we've received scripts from basically all different payer types. I would say that just from the access perspective moving forward, you know, I think there was a lot of benefit just in terms of the education that we had done with the BBS and, you know, the payers who have experience with BBS, also understanding that this is very different than general obesity. Once again, very pleased in terms of the fact that we did, and already do have patients who have been approved for reimbursement this early in the process.
You know, the caveat here is that in terms of actually having those policies in place, I reiterate that, you know, expectation continues to be approximately, you know, 3 to 9 months from approval. We're gonna continue to monitor what that payer mix looks like, as we move forward and update in future calls.
Thanks.
Thank you.
Thank you.
The next question will come from Michael Utz with Morgan Stanley. Your line's open.
Good morning. Thanks for taking the question, and congrats on the launch as well. Maybe just a follow-up on the HO launch, just in terms of the greater than 150 start forms. Maybe if you can compare that to your internal expectations at the beginning of the launch. Secondly, just how should we think about converting those patients to revenues? Just given it sounds like you're having sort of good traction with payers, you know, early on here. Thanks.
I would say that overall, just in terms of the start forms that we've received, we were really pleased with, one, the speed, just in terms of working and all the work had been done with planning for those clinical trial conversions. Once again, the number that we were able to convert to actually having a commercial Rx, was great just in terms of that collaborative effort to get to that point. In terms of the other Rx's that we've received, I think that, you know, it is a strong start right now. We still feel like there's a lot of opportunity that remains just in terms of physicians that we've spoken with that may potentially have a patient, who will have that conversation as we move forward.
We do expect to see a steady growth throughout the year just in terms of the Rx's we receive moving forward. From the payer dynamic piece, I would say that in terms of the approvals, if we also compare with BBS, well, one, the expectation in terms of these Rx's being denied up front because there isn't a specific HO policy in place this early just in terms of launch, that did happen. However, like with the appropriate information that was provided, you know, we were seeing with some of these payers a quicker approval timeline than we did in the initial BBS launch.
I think that was a positive dynamic that we did see.
Very helpful. Thank you.
Thank you.
Thanks.
The next question is gonna come from Seamus Fernandez with Guggenheim. Your line's open.
Great. Thanks for the question. There's gonna be some updates on PWS, you know, soon. Just wanted to get a better sense of what you believe the sort of clinical value add of setmelanotide in this space, or at least targeting MC4R can be in this space. Is it going to be exclusively on weight loss without much benefit on satiety? Is it both weight loss and satiety benefits that are a possibility? Just trying to get a better sense of what you see the overall kind of PWS target product profile that you're seeking in this setting and what we're likely to learn with the six-month data versus a potential update on the second quarter results conference call, which may be incremental to the presentation in that setting. Thanks.
No, thanks, Seamus. Just to be clear, for the 718 data, that Prader-Willi data, whatever we have, and hopefully we'll have something that we can comment on at that point, that'll be extremely early in a much smaller number of patients. The most informative data set that's coming is Dr. Miller's data set, which we'll put out at ENDO. Our expectation is really just based on the biology here, right? Which is MC4. So one, as I said in my opening comments there, I mean, we're quite convinced that this MC4R pathway is an important part of the biology in Prader-Willi. It's not the only thing. Correcting this does not fix or help us, you know, correct a Prader-Willi patient's disease, it can have a, we believe, a significant impact.
And that biology is it's a satiety signal. You, you decrease hunger and, you know, we think an accompanying, you know, decrease in their hyperphagia symptoms, which are the behaviors that are driven by that severe hunger and increases energy expenditure. The net of that will be, you know, a decrease in their overall weight. We also know, and we highlighted this on our December call when we released the early data from Dr. Miller's trial. There's other reasons these patients eat, and we've talked about the obsessive compulsive disorder part of this and the like. You know, those are confounding elements of a very complicated disease.
Specifically with regard to, you know, what we would hope, it would be both a reduction in their hyperphagia symptoms and a decrease in their weight.
Thank you.
Thank you. Our next question will come from Samantha Semenkow with Citi. Your line's open.
Hi. Good morning. Thanks very much for taking the question and congratulations on the early HO launch. I have one on Japan. Given the large potential market for HO in Japan, this is a bit in your prepared remarks, but could you elaborate more on some of the feedback you've received from Japanese KOLs on the impact IMCIVREE could have in this population? Pending the approval there later this year, how should we think about the trajectory of that launch in Japan relative to the early start we've seen thus far in the U.S. for HO? Thanks very much.
Yeah. Yann, did you get that? KOL reactions to-
Yeah.
Yep.
Yes. Thank you for the question. First of all, as I said in my remarks, I was in Japan a few weeks ago, and I have met with many of the Japanese KOL and many of the investigators of the trial. First, I think everybody in Japan is really concerned about the disease because of the significant prevalence. 2, they saw firsthand the results on their patients, so they are already believers in the efficacy of the drug. The 3rd aspect is that we have engaged with them extremely early on. It's more than 3 years that we have interacted with them, and they have been part of publications and they have worked with us on a lot of data.
There is almost already a long-lasting relationship with them. That's the third aspect. The third aspect in terms of trajectories is still difficult to. First, I will not compare the U.S. and Japan. A bit difficult to forecast. We have good results so far in terms of patient identification. We have identified 151 tier 1 hospital with the highest volume of brain tumor surgeries, and those hospitals are currently being visited by the Japanese field force. Again, I will not give a number, but we think that we have a significant amount of Japanese patients who will start the treatment in 2027 following the launch.
Perfect. Thanks, Yann. Next question.
Thank you. The next question will come from Joseph Stringer with Needham & Company. Your line's open.
Hi. Good morning. Thanks for taking our questions. You mentioned the 150 START forms in the first 6 weeks of the HO launch, 40 or so from clinical trial. How does this number of START forms compare to the first 6 weeks of the BBS launch, is this a fair comp at this point? Our second question is on the patients, the 150 patients associated with these START forms. How many of these are tumor injury related patients and those who have had surgery? Just curious, given the broad label, what you're seeing in terms of a diverse patient pool, perhaps outside of the more common tumor-related cause. Thank you.
Yeah. Thanks, Joey. Maybe I'll make a comment on the BBS and then Jennifer can comment on the mix of the tumors versus that. You know, is BBS a good comp? I mean, it's a rare disease. I think there's some, you know, fundamental differences here, which we've highlighted, just in terms of how the HO population, A, it's larger, but B, also being concentrated in the Endo. There is a difference there. I'm not sure it's the best. That said, this is a steeper launch. I mean, where the rate of START forms in the first 6 weeks is higher than we had in BBS. I'll make a few comments once we finish all the questions about maybe how to put all this together.
I think, you know, what you're hearing is, yeah, we're really pleased with 150. Yes, it is a more rapid, you know, start than we had with BBS. On the tumor side.
Sure. I'll echo the point that David made just in terms of the difference between the number of start forms in the first six weeks of the HO launch versus the BBS launch. The piece though that I don't exactly remember is the number of trial conversions on the BBS side, where that study had a much smaller number of total patients that were in the U.S. in that BBS study. You know, definitely even with that said, a higher number of Rx's on this launch versus the BBS one. In terms of the backgrounds of the patients, you know, the vast majority of these patients are with tumor or tumor treatment-related backgrounds. However, our indication is broader, and it covers things like stroke or TBI or inflammation.
We have received Rx's from patients with these backgrounds as well. I think that, you know, to date, of the physicians who are aware of acquired hypothalamic obesity, I think their thinking is more around the tumor-based background. There's still a lot of opportunity in terms of even educating physicians holistically in terms of the various other backgrounds that may lead to acquired hypothalamic obesity moving forward as well.
Thanks. Next question.
Okay, our last question is gonna come from Lisa Walter with RBC Capital. Your line's open.
Good morning. Thanks for taking our question. Maybe just one on Prader-Willi syndrome. I'm just curious how important you think it is for ex-U.S. approval to have both hyperphagia and weight loss on the label. I think with VYKAT XR, we saw that the EMA perhaps did not want to approve VYKAT XR given some of the choosing endpoints. Just curious how you are thinking about Prader-Willi syndrome trial design here for success, both in the U.S. and ex-U.S.
Thanks for the question. I think, one just on, back to the mechanism of this drug and this pathway. The satiety signal, we reduce hunger. We've shown that consistently across all of our trials. We haven't, you know, for some trial design reasons, have had some challenges getting that into the U.S. label, but we have gotten it into the European label. The European label, it is indicated for the reduction of hunger, in our different diseases that we're studying. As I said before, our expectation is that we will seek a label that has both a hyperphagia reduction, with the expectation that we would get that worldwide, globally, certainly in the three major regions that we've talked about today, and a reduction in weight/BMI.
Thank you. I would now like to turn the call back over to David Meeker for closing remarks.
Thanks everybody for tuning in. I hope and I, you know, thanks for your patience here. I realize everybody would like the specific numbers and the ability to provide guidance. As we've said with BBS, and as we all know, you know, launches are, you know, enormously challenging to forecast, and rare disease launches are even more difficult. You know, with that famous caveat that it is early, what you're hearing is we're pleased. We're really pleased with the start here. I think this is a strong start, one. We're very happy about the breadth of prescribers that Jennifer highlighted. This is not a launch where we've got, you know, two or three believers and, you know, they're writing a bunch of scripts. This is where it's very broad.
The dynamic, that question was raised and as Jennifer highlighted, I think the good news about the dynamic is, there's been some reasonable sense of urgency. I was at the Pediatric Endocrine Society meeting over the weekend in San Francisco. I don't know, I've been around a lot of rare disease type meetings, and rare diseases tend to get lost in these larger meetings. That wasn't a huge meeting.
I have to say, I was struck by the level of awareness, the number of endos, endocrinologists, pediatric endocrinologists in this case, with awareness, you know, tremendous amount of excitement and just, you know, really struggling with what they can do for their patients and excited about, you know, at least now that there's something to do. All of those dynamics again are, you know, very much in the positive category here. We look forward to updating you. You know, that'll be on our Q2 call, but pretty excited about where we are out of the gates. Thanks, all.
Thank you. This concludes today's conference call, and thank you for your participating, and you may now disconnect.