Rhythm Pharmaceuticals (NASDAQ:RYTM) released second-quarter financial results and hosted an earnings call on Tuesday. Read the complete transcript below.
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Summary
Rhythm Pharmaceuticals reported a strong second quarter 2026, with global net product sales of IMCIVREE totaling $71.3 million, marking a 19% sequential growth.
The company launched IMCIVREE for acquired hypothalamic obesity (HO) in the U.S., receiving over 400 start forms from approximately 300 prescribers in the first 14 weeks post-FDA approval.
Encouraging preliminary data from the Phase 2 trial of RM718 showed potential for clinically meaningful BMI reductions in patients with acquired HO, with a favorable tolerability profile.
Rhythm Pharmaceuticals anticipates IMCIVREE approval and launch in Japan by the end of 2026, with plans to begin pricing discussions post-approval.
The company updated its annual operating expense guidance to $363-$397 million for 2026, reflecting a shift in R&D expenses related to RM718 and bivamelagon from late 2026 to early 2027.
Full Transcript
OPERATOR
Good day and thank you for standing by. Welcome to the Rhythm Pharmaceuticals second quarter 2026 earnings conference call. At this time all participants are in a listen-only mode. After the speaker's presentation, there will be a question-and-answer session. To ask a question during the session, you will need to press star 11 on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star 11 again.
Please be advised that today's conference is being recorded. I would now like to hand the conference over to your first speaker today, Dave Connolly, Investor Relations at Rhythm Pharmaceuticals. Please go ahead.
Dave Connolly, Investor Relations
Thank you, Dede. I'm Dave 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 investors section of our website, ir.rhythmtx.com. This morning we issued our press release that provides our Q2 2026 financial results and a business update, and that press release is available on our website. We also released data for RM718's Phase 2 trial in acquired hypothalamic obesity.
Our agenda today is listed on slide 2. On the call are David Meeker, our Chairman, Chief Executive Officer and President; Jennifer Lee, Executive Vice President, Head of North America; Hunter Smith, Chief Financial Officer; and Jan Massabro, Executive Vice President, Head of International, is on the line joining us from Europe. On slide 3, I'll remind you 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. In addition, 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.
With that, I'll turn the call over to David Meeker, who will begin on slide 5.
David Meeker, Chair, President and CEO
Good morning and thank you for joining us. We have a lot to share today, headlined by a strong start to the U.S. launch of IMCIVREE for acquired hypothalamic obesity, reinforcing our conviction that HO represents a meaningful long opportunity for Rhythm. Progress during the quarter wasn't limited to our commercial business. In June we presented positive six-month data in Prader-Willi syndrome at ENDO showing setmelanotide achieved clinically meaningful BMI and BMI Z-score reductions, reductions in fat mass and preservation of lean mass, and improvements in hyperphagia and anxiety measures.
These data confirm the mechanistic rationale that MC4 agonism plays a key role in the pathology of PWS and demonstrated the positive impact IMCIVREE can have in this difficult-to-treat patient population. We look forward to updating you on a path forward for PWS in the next few months, which brings us to our pipeline. We believe our next-generation MC4R agonists have the potential to bring meaningful new treatment options to patients living with rare neuroendocrine diseases, and today we announce encouraging results to demonstrate RM718, our weekly MC4R agonist, has the potential to deliver clinically meaningful BMI reductions in patients with acquired hypothalamic obesity with efficacy comparable to what we've demonstrated with setmelanotide and bivamelagon, and importantly a favorable tolerability profile with no reports of generalized hyperpigmentation. But first let me comment on the IMCIVREE launch in HO. This is a unique, severe, rare disease marked by accelerated and sustained weight gain caused by a brain tumor and/or its treatment or other brain injury to the hypothalamus that impairs the MC4R pathway.
Acquired HO is clearly distinct from general obesity and remains underdiagnosed and under-recognized. With an estimated 10,000 patients in the U.S., a similar number in Europe and between 5,000 and 8,000 patients in Japan, this represents a significant global opportunity. In July, results from the Phase 3 HO TRANSCEND trial were published in the New England Journal of Medicine by lead author Dr. Jennifer Miller and senior author Dr. Christian Roth, two of the world's leading experts in HO.
In addition, as shown on slide 6, the New England Journal of Medicine published an accompanying editorial with its Science Behind the Study feature authored by Professor Sadaf Farooqi, one of the world's leading experts in MC4R pathway diseases. Articles like this in the New England Journal of Medicine, 10 years after the POMC deficiency New England Journal of Medicine article that put Rhythm on the map, raise visibility of a historically under-recognized disease among clinicians, researchers and payers and further establish setmelanotide as a clinically meaningful advancement for patients.
The awareness that there is an effective therapy for a rare disease increases the urgency on all parts of the healthcare system. Getting to a diagnosis matters when there's a precision medicine available. The New England Journal of Medicine article follows on the heels of the FDA approval on March 19th of this year. Throughout 2025 and 2026, our teams have been in the field focused on disease awareness and patient identification, engaging endocrinologists to deepen understanding of acquired HO and the connection between hypothalamic injury and the disruption of the MC4R pathway.
Our HO launch builds on this engagement and a successful commercial effort in B—an opportunity that continues to grow. Rhythm now has a mature rare disease commercial platform built on four years of commercial success and established relationships across physicians, payers and patient communities. We're off to a promising start with this next phase of growth, with strong demand from patients and families, a broad and growing prescriber base, and a positive reception from payers.
We are encouraged with the first 14 weeks of the U.S. launch. Since approval on March 19th, we have received more than 400 start forms from approximately 300 prescribers. Jennifer will provide additional color on the U.S. launch. Jan will detail the next steps toward anticipated approval and launch in Japan this year and country-level launches in Europe next year. We are mindful that it is early days; however, the first launch-quarter performance reinforces our conviction that HO represents a long-term, durable and sustainable opportunity for Rhythm.
Now I want to briefly review preliminary data from the open-label Phase 2 Part C trial of RM718, our weekly MC4 agonist in acquired HO. RM718 is one of the two next-generation MC4 agonists that have the potential to improve on the hyperpigmentation and convenience of setmelanotide. The weight loss efficacy for each of these three assets has been remarkably consistent. We believe these preliminary results are encouraging and meaningful, de-risk RM718 as a development candidate going forward.
Beginning on slide 8 we show the patient disposition and patient demographics. Eleven patients were enrolled and eight patients remain on active therapy. Seven patients have reached 16 weeks, and that is the data we are sharing here. Two patients discontinued because of AEs during the first four weeks of treatment: one patient stopped because of injection-site reactions, and a second patient discontinued secondary to ongoing nausea which could not be controlled even with dose reductions.
A third patient completed the 16-week trial period and later withdrew from long-term extension for personal reasons. Two additional patients have yet to reach the 16-week time point. Patients in the trial were 12 years of age or older with a mean BMI of 40.1. Per protocol, doses were escalated to 40 as tolerated. The mean BMI change of 11.6% for the seven patients who have reached week 16 is shown on slide 9. As you can see on slide 10, these results compare favorably with setmelanotide and bivamelagon results at a similar time point in patients with acquired HO, and the pooled analysis of patients with HO in the Phase 2 and Phase 3 setmelanotide trials. The week 16 BMI reduction was 10.1% for bivamelagon at the 600 milligram dose. Mean BMI reduction for seven patients at week 14 was 10.1%, and slide 11 shows a continued deepening of the effect in four patients with 28 weeks or more of treatment. As shown on slide 12, RM718 was generally well tolerated, with the most common adverse events being injection-site reactions and nausea. Importantly, we have observed no generalized hyperpigmentation with either bivamelagon or RM718, which you would expect to see with MC1R agonism.
Overall, these results validate our conviction that RM718 has the potential to be a viable treatment option for rare MC4R pathway diseases. Both RM718 and bivamelagon have been shown to affect BMI reductions comparable to setmelanotide in patients with acquired HO, and both have greater specificity for the MC4 receptor without generalized hyperpigmentation. Importantly, the patent protection for both RM718 and Biva goes past 2040. We believe today's data further de-risks our ability to build a durable franchise of MC4R agonists.
Enrollment of PWS patients in Part D of this open-label trial will complete by the end of the year with a goal of enrolling 10 to 15 patients. As I mentioned, we are moving closer to a decision on a potential path forward for PWS with setmelanotide, bivamelagon or RM718 all viable options. As a reminder, we are aiming to initiate the Phase 3 trial of bivamelagon NAPRNH over the end of this year, which is listed among the upcoming milestones on slide 13.
The first patients enrolled will be patients 12 and older as we finalize CMC work for the oral dissolvable tablets in the first quarter of next year. With that, I'll turn the call over to Jennifer and then Jan to provide more color on our strong commercial progress during the quarter.
Jennifer Lee, Executive Vice President, Head of North America
Thank you, David. I'll begin on slide 15. I'm pleased to provide an update on the U.S. launch of IMCIVREE for acquired hypothalamic obesity. This was the first full quarter of launch plus one additional week following FDA approval on March 19th. While we remain very early in the launch, we have seen strong demand, broad and expanding prescriber engagement and activation, and positive early payer experience supporting access. Overall, the early indicators are encouraging and reinforce our conviction in the long-term opportunity for acquired hypothalamic obesity.
On slide 16, I'll start with the patient-level metrics. In the 14 weeks between FDA approval on March 19 and June 30, we received more than 400 start forms for acquired hypothalamic obesity. This includes 66 start forms for converted trial patients, accounting for almost all the U.S. trial patients. The age distribution for these patients is evenly split between patients 21 and younger and those 22 and older, with 21% of prescriptions for patients ages 4 to 11, 18% for patients 12 to 17, and 12% for patients 18 to 21.
Care for acquired HO patients tends to be more coordinated in the pediatric setting, and this contributes toward higher rates of recognition and diagnosis. As a result, pediatric patients make up a larger share of our early IMCIVREE patients. We expect this to evolve over time and to have a higher contribution for adults in the future. Among these early prescriptions we see a broad mix of both incident and prevalent patients. Based off an internal analysis of a portion of prescriptions received, approximately 15% of patients suffered the injury resulting in their acquired HO within the last two years.
The majority of start forms are from prevalent patients living with HO for more than two years, with approximately 50% of patients having their injury occur more than 10 years ago. These early dynamics are encouraging and demonstrate meaningful demand across a broad range of patients. On slide 17 are provider-level metrics for the acquired HO launch. We are seeing broad activation and engagement of healthcare providers between approval and the end of the second quarter.
We have approximately 300 unique prescribers for acquired HO. Approximately 20% of these physicians have prescribed IMCIVREE for more than one patient with acquired HO. In line with our view that this is primarily a specialty opportunity, the majority of prescribers are endocrinologists, with adult and pediatric endocrinologists accounting for 43% and 37% of prescribers, respectively. We are encouraged by the early activation levels of our priority accounts and top prescriber targets.
We've made solid progress in penetrating our priority accounts with 65% activated by the end of June and almost 25% of prescriptions coming from these accounts. On to slide 18 and our progress with payers. The early payer experience has been positive and supportive of access, a reflection that payers recognize the severity of acquired HO and, similar to BBS, understand the distinction from general obesity and the benefit of IMCIVREE. While we still work to gain access for prescriptions received since approval, we are encouraged by the number of initial approvals that came in at the prior authorization stage during this first quarter of launch, many through payers without a specific acquired HO policy for IMCIVREE yet in place. By the end of Q2, we secured positive policies for HO covering approximately 25% of Medicaid covered lives and 35% of commercial covered lives. In line with our expectations, we expect additional policies to become established within three to nine months post approval, or by the end of this year. The strength and consistency across the early launch metrics give us confidence this opportunity will continue to build over time, reinforcing our long-term conviction in the acquired HO opportunity and our belief that IMCIVREE can become the standard of care for these patients. Moving to slide 19. While we are encouraged by the progress in the HO launch, we also feel there remains opportunity for growth in BBS. We recently supported the publication of a new evidence-based, consensus-driven diagnostic algorithm designed to help physicians identify and diagnose patients with BBS earlier in their disease journey in a population that has historically been very difficult to diagnose. We believe this is an important step toward enabling more BBS patients to get to a timely diagnosis and appropriate care.
Lastly, on slide 20, we are also evolving our North America commercial organization to ensure acquired HO and BBS each receive dedicated focus to maximize their ability to help patients. With the acquired HO launch now underway, we have made a transition to focus our 42 territory managers exclusively on HO. We modified our field team structure so we now have a new territory manager group dedicated to BBS, with plans to grow this to 10 TMs. This reflects our long-term commitment to patients living with BBS.
These changes allow us to pursue both opportunities with dedicated teams, ensuring focused execution in acquired HO while continuing to build upon the strong foundation we have established in BBS. Now let me hand it over to Jan.
Jan Massabro (Executive Vice President, Head of International)
Thank you, Jennifer. Our strong international commercial performance continued during the second quarter as the number of patients on IMCIVREE continues to grow either through national reimbursements or inpatient settings, and we have also made significant progress in Europe and Japan towards our goal of bringing IMCIVREE to patients with acquired hypothalamic obesity. Slide 22: We are entering the final stages in the regulatory process towards approval and launch in Japan.
We anticipate IMCIVREE approval for acquired HO and launch in Japan by year end 2026. Following the PMDA review, we anticipate marketing authorization from the Japan Ministry of Health, Labour and Welfare, or MHLW. Once we receive marketing authorization, we would begin pricing discussions with the Japan National Health Insurance Authority, and this process can take two to three months. With this timeline, we will anticipate commercial launch in Japan in the fourth quarter.
With approximately 5,000 to 8,000 patients living with acquired hypothalamic obesity in Japan, which is a higher per capita prevalence than the United States or Europe, Japan represents a meaningful opportunity. Our team in Japan is in place, actively engaging with a community of experts, patients and caregivers. Similar to the approach Jennifer's team took in the U.S., we are engaging with the treatment community to identify potential patients ahead of launch.
We will share more details about Japan on our next quarterly conference call. Next slide. Turning to commercialization of IMCIVREE for acquired HO in Europe: In May, the European Commission granted marketing authorization for IMCIVREE for the treatment of obesity and control of hunger in patients 4 years of age and older with acquired hypothalamic obesity due to hypothalamic injury or impairment. We have a very experienced team in place working through country-level processes to secure market access and reimbursement, which we have successfully done in the past years for POMC, LEPR, BBS and the pediatric label expansion in Germany.
We anticipate launching in the first half of 2027. We are encouraged by the initial engagement in the process to secure an exemption from the German Federal Joint Committee, or G-BA, Annex 2 exclusion list. The G-BA Annex 2 exclusion list prohibits reimbursement for lifestyle drugs such as drugs indicated for smoking cessation and general obesity. We are confident in our ability to secure an exemption enabling reimbursement for acquired HO, as we have done before for all our previous indications.
We are making progress towards market access elsewhere in Europe. We have submitted the dossiers to begin pricing discussions in France, in the UK, in Italy, in Spain and in the Netherlands, with launches in each country anticipated in 2027 following Germany. With an estimated prevalence of approximately 10,000 patients in Europe, it is a meaningful opportunity, and our early access programs in France and in Italy have enabled many of the leading physicians to gain experience with setmelanotide and see the benefit in patients living with HO.
In May, we presented approximately a dozen posters at the European Congress of Endocrinology and at the European Congress on Obesity. Next month, at the 2026 European Society for Pediatric Endocrinology meeting, we have had three abstracts accepted for oral presentations and three accepted for poster presentations, and there are two additional non–Rhythm-sponsored presentations that will highlight findings in patients living with BBS from Germany and the UK.
We have approximately 75 abstracts, both originals and encores, submitted and presented and/or slated for presentation this year in European and Japanese medical congresses, giving us an unparalleled level of engagement with the international experts and healthcare providers. With that I will turn it over to Hunter.
Hunter Smith, Chief Financial Officer
Thank you, Jan. I will begin on slide 25. We exited the second quarter in a solid financial position and are encouraged by our strong initial launch execution in acquired HO in the US. At the same time, we continue to make meaningful progress with BBS in the US and internationally, underscoring the strength of our business and the opportunity we see for continued growth. We had a strong second quarter of 2026. Global net product sales of IMCIVREE totaled $71.3 million, which represents 19% sequential growth over Q1.
During the second quarter, $51 million, or 72%, of product revenue was generated in the United States. Globally, we saw continued growth in patients on reimbursed therapy with an increase of greater than 20% over the prior quarter, primarily driven by the acquired HO launch and continued growth in BBS in the US, as well as ex-US growth in BBS and our HO early access programs. On slide 26, I'll walk you through the quarter-over-quarter revenue change.
With revenue increasing from $60.1 million in Q1 2026 to $71.3 million in Q2, we saw $11.3 million in revenue growth attributable to increased product demand in the US. A bit more than half of this increase came from the strong start in the US launch for acquired HO, where a percentage of our early scripts converted to starts at the prior auth stage. As Jennifer mentioned previously, BBS had a strong quarter as well with higher demand growth and strong compliance compared to what we have experienced in other recent quarters.
GTN improved somewhat in the quarter to 86%, providing additional support to Q2 revenue. With the anticipated increase in demand for IMCIVREE following FDA approval for acquired HO, product shipments to Rhythm Specialty Pharmacy exceeded patient dispensings by approximately $2.9 million, providing a modest benefit to revenue in the quarter. Inventory at PANTHERx Specialty Pharmacy increased slightly to 20 days as of June 30. International revenue decreased from $23.2 million to $20.3 million in Q2, even though we saw a steady increase in the number of patients on reimbursed therapy.
The decrease in revenue was mainly attributable to a $3.8 million retrospective charge associated with the French contribution mechanism, which levies a charge on pharmaceutical companies when reimbursed drug sales industry-wide exceed specified statutory thresholds. $2.3 million of this $3.8 million charge was related to 2025 revenue. Excluding this impact, our international business remains strong as evidenced by the continued growth in patients on therapy during the quarter.
On slide 27 is a financial snapshot of Q2 2026 results compared to the second quarter of 2025. Cost of goods sold this quarter was 12.5% of product revenue, within our normal range, and primarily driven by cost of materials and royalty payments on setmelanotide in connection with higher net product revenue during the quarter. As a percentage of product revenue, COGS varies quarter to quarter based on changes in inventory balances and manufacturing activity, and this quarter increased slightly because of that.
R&D expenses were $43.4 million for the second quarter of 2026 compared to $42.3 million in the same period last year. Sequentially, R&D expenses increased $1.7 million compared to the first quarter of 2026. This sequential quarter-over-quarter increase was due to increased spending on bivamelagon clinical trials and preclinical work associated with our congenital hyperinsulinism program. These were partially offset by lower headcount-related costs.
The year-over-year increase is primarily attributable to an increase in headcount-related costs, increased costs related to genetic testing and preclinical work, and the increase partially offset by reduced costs associated with RM718 development and clinical supply. SG&A expenses were $67.4 million for the second quarter of 2026 compared to $45.9 million in the prior period. Sequentially, SG&A expenses increased by $3.8 million, or approximately 6%, compared to the first quarter of 2026.
The increase was primarily driven by higher personnel-related costs to support our expanding commercial operations. Weighted average common shares outstanding were 68.6 million for Q2 2026. GAAP EPS for the second quarter of 2026 was a net loss per basic and diluted share of $0.73, including $0.02 per share from accrued dividends on convertible preferred stock of $1.1 million. Cash used in operations was approximately $9 million during the quarter.
We ended the second quarter with approximately $331 million in cash, cash equivalents, and short-term investments, which we continue to expect will be sufficient to fund planned operations for at least 24 months. Lastly for me, on slide 28 there is further detail on our operating expenses for the second quarter and our full-year operating expense guidance. For the second quarter, operating expenses of approximately $110.9 million included $26.1 million of stock-based compensation.
Looking ahead to the second half of this year, we are updating our annual OpEx guidance. We now anticipate approximately $363 million to $397 million non-GAAP operating expenses for 2026, comprised of non-GAAP R&D expenses of $175 million to $195 million and non-GAAP SG&A expenses of $188 million to $202 million. SG&A guidance remains unchanged, while the midpoint of our R&D expense guidance has been reduced by $20 million, as the timing of certain CMC activities related to RM718 and bivamelagon has shifted from late 2026 to early 2027.
We do not expect these changes to affect overall timelines for ongoing or planned clinical development work with either asset. And with that, I'll turn the call back over to David.
David Meeker, Chair, President and CEO
Thank you, Hunter, and we'll open it up now for Q&A.
OPERATOR
Thank you. As a reminder, to ask a question, please press star 11 on your telephone and wait for your name to be announced. To withdraw your question, please press star 11 again. In the interest of time, we ask that you please limit yourself to one question. Please stand by while we compile the Q&A roster. And our first question comes from Tazeen Ahmad of Bank of America. Your line is open.
Tazeen Ahmad, Analyst at Bank of America
Hi, good morning. Thanks for taking my question, and congrats on a good quarter. It's early, but can I ask what type of expectations you have around discontinuation rates? Presumably you're not seeing any, but if you are, can you just give us any color on why those might be happening? On a go-forward basis, what do you think over time discontinuation rate from setmelanotide could be for the HO, and thanks.
Jennifer Lee, Executive Vice President, Head of North America
Thanks, Tazeen. So it is really early in the launch to articulate color really in terms of the discontinuation rate expected. I would say one thing, though. In the past we have outlined that the global discontinuation rate for the BBS patients was around 30%. And holistically there are differences just in terms of what our data has shown in the BBS patient population versus the HO population in terms of the strength of efficacy that may make that discontinuation rate lower in this particular population.
There are also different factors of the HO population that we're experiencing in terms of the ease of injections and such that may also overall make the ongoing discontinuation rate for this patient population a bit less than the BBS patient population. And that was also seen in the clinical studies, like when you compare the BBS clinical studies versus the HO clinical study and compare the discontinuation rates there. So it's one thing that we're definitely going to be monitoring.
There's a huge focus on as an internal organization and we'll continue to monitor that moving forward. Thank you.
OPERATOR
And our next question comes from Phil Nadeau of TD Cowen. Your line is open.
Phil Nadeau, Analyst at TD Cowen
Good morning, congratulations on the strong progress. Question on the HO launch: seems to be going really well. Based on our math, if you back out the clinical-trial patients, you're doing about 110 patient start forms per month. We're curious to get your thoughts on whether you think that's sustainable for the next couple quarters. Is there any sign of an early launch bolus, or do you expect a more even trajectory to patient starts?
Jennifer Lee, Executive Vice President, Head of North America
Thank you. So overall, in terms of the start-forms experience in the first quarter plus the one week since approval, we're really happy in terms of what we're seeing with the Rx's coming in. As you mentioned, there's a one-time event in terms of the clinical-trial patients, and if you take that out, I would say that in any launch there may be some patients who were really anxiously waiting in terms of getting that onto therapy upon approval. With that said, I think all of the launch metrics that we have been really monitoring strengthen our belief holistically in terms of this long-term opportunity for sustained, ongoing growth in the HO opportunity.
As I outlined, the Rx's are really coming from a good breadth of prescribers versus being localized in terms of just a few writing the vast majority of these Rx's. We're also seeing a lot of different things around the patients and the background from an age perspective, disease severity, incident versus prevalent patients, which really point to the breadth in terms of patients within the HO indication that are really interested in getting onto this therapy.
And even with the Rx's that we have received, there are still physicians who have additional patients under their care that they have not yet Rx'd. So overall, a lot of opportunity still remains. I would say that with that said, there are some considerations in terms of the speed of the uptake, which I've said in the past as well. These are really very, very busy endo offices. They have long wait times for their patients that can also impact our ability to get in in terms of having the ongoing discussion.
But our teams are very persistent from that perspective. But that can take some time just in terms of being able to continue the dialogue with these HCPs. The other piece is that all these patients are not yet diagnosed. So it takes some time after we're in there to educate the physician, for that patient to come in and be educated and further evaluated by the HCP before they can have that IMCIVREE discussion. And it's a new drug on the market, so some of the physicians, even with more than one patient, they want to experience IMCIVREE before prescribing to all of their patients at once.
So once again there's so much opportunity that remains. We feel very confident in terms of the ongoing trajectory, but there are some considerations as well.
David Meeker, Chair, President and CEO
And Phil, as you know, we don't guide toward the future here, but everything that Jennifer just outlined I think speaks strongly to the fact that although there may have been a little bit of pent-up urgency, there was no bolus in this thing. We feel really good about all these metrics and how they speak to the future.
Phil Nadeau, Analyst at TD Cowen
That's very helpful. Thank you. Congrats again.
OPERATOR
Thank you. And our next question comes from Derek Archila of Wells Fargo. Your line is open.
Derek Archila, Analyst at Wells Fargo
Hey, good morning, and thanks for taking the questions. Congrats on the updates and the progress here. So I know you highlighted greater than 400 start forms against, I think, a 2,000 number for identified HO patients, so implying about 20% penetration into that pool in 14 weeks. So I guess, should we be thinking that number of identified patients is materially larger now? Thanks.
Jennifer Lee, Executive Vice President, Head of North America
Yeah, thanks, Derek. We provided that number back in September, and we have not updated that number. We have been ongoing since that time educating additional physicians within our target list, and we still have a ways to go in terms of penetrating the full list. So that number, in terms of both the suspected or diagnosed HO patient population, is continuing to grow. Thank you.
OPERATOR
And our next question comes from Paul Matteis of Stifel. Please go ahead.
Paul Matteis, Analyst at Stifel
Good morning. Congrats on the quarter and thanks for taking my question. I was wondering if you could comment on what you're seeing as it relates to either concomitant use with GLP-1s, or whether there are physicians, or many physicians, who are looking to try a GLP-1 before IMCIVREE. And then I know it's really early on the payer side, but are you seeing any payers put in a GLP-1 step edit? Thanks so much for access.
Jennifer Lee, Executive Vice President, Head of North America
Thank you. Sure. Let me start with the last one. We are pleased in terms of the progress that is being made around the HO-specific policies. Of the ones that we have in place, there is no step edit requirement in terms of needing to try a GLP-1 before IMCIVREE, which is also something that we're pleased overall with. It's pretty much aligned with our label in terms of background patients relating to GLP-1 use. In the HO patients, of the ones that have been prescribed IMCIVREE, we are experiencing that, you know, this patient population was one that was seeking treatment.
So about 50% of our IMCIVREE-prescribed HO patients had prior or current experience on GLP-1. But currently there's about 25% of the patients that are still on a GLP-1. And when I outline that, it's not known in terms of if it's for diabetes versus for the obesity indication, but about 25% of the patient population is on GLP-1. I would say that that is also in a time where IMCIVREE wasn't available; there wasn't a specific treatment to treat their underlying condition.
So as we move forward, it'll be available for these patients. And that means, through the metrics that I just outlined, 50% of these patients were never on a GLP-1 but still interested in getting on IMCIVREE after understanding that there was a treatment available for their specific condition.
David Meeker, Chair, President and CEO
Yeah. And, Paul, just to add a little bit, you remember from the clinical trial, we had also about 25% of the patients, 30 out of the 120 in the original cohort, who either had a prior experience or were actively on GLP-1s in the trial. They came in, met all the criteria for entry, and then had a virtually identical response to IMCIVREE as the others. So I think, you know, as Jennifer said, it's really, I think, quite instructive the extent to which a high percent of these patients have been on GLP-1s or continue on GLP-1s.
She said, speaking to the unmet need here, but it's not addressing the unmet need here. They're coming over to IMCIVREE. So, yeah, I think that overall experience has been really reinforcing that a precision medicine here is the right way to go for this patient population.
Paul Matteis, Analyst at Stifel
Excellent, thank you.
OPERATOR
Thank you. And our next question comes from Dennis Ding of Jefferies. Your line is open.
Dennis Ding, Analyst at Jefferies
Hi, good morning. Thanks for taking my question. I have a broader question for David. So there's been some investor questions around biotech M&A that came out of the AstraZeneca and Bristol merger speculation. So I'm curious, given Rhythm is obviously a leader in the rare disease space, and David, you're on the board of several biotech companies, how would you characterize pharma M&A appetite recently? Obviously, without going into specific discussions, but do you have any general comments on what pharma is excited about?
But also at the same time, if they think premiums may be getting harder to justify given the broader move in the XBI? And then as a quick follow-up, the territory manager split, 42 for HO and 10 for BBS — did that get implemented already, or when will that happen? And do you actually expect an acceleration in HO adds in the second half? Thanks so much.
David Meeker, Chair, President and CEO
Yeah, so thanks, Dennis. I think, let me take that briefly on the biotech M&A. And this is completely unrelated to Rhythm, as you've heard here. We feel really good about where we are and Rhythm's ability to grow as a company and platform and a product and expanding pipeline here. So we're watching like everybody else. I am. I think that was a bit of a surprise coming over the weekend, and we'll see if anything happens there and how it might shake up.
But I think the larger landscape here — pharma, with many, many acquisitions over the first half of the year — just speaks to the way our healthcare ecosystem works. We've got a strong and robust early biotech community that's creating value, and we have a pharmaceutical community and some mid-size caps who are looking everywhere to expand their pipeline. So I expect it to continue. I don't see this having a big dampening effect if it were to go forward.
But yeah, it's clearly, you know, a noteworthy event here. So with that, I'll turn it over.
Jennifer Lee, Executive Vice President, Head of North America
Relating to the question around the TM split, this was already implemented, so we already have split the teams into two. I would say that one of the guiding factors around this decision-making point was we really feel strongly that there's an opportunity in both BBS and HO. I would say the vast majority of the time spent by the 42 territory managers, when it was combined under their care, was already focused on HO. So we just wanted to make sure that we had the right amount of focus also in terms of unlocking the BBS opportunity and being able to get those patients to a diagnosis and treatment as well.
Dennis Ding, Analyst at Jefferies
Perfect. Thank you.
OPERATOR
Thank you. And our next question comes from Mike Ulls of Morgan Stanley. Your line is open.
Mike Ulls, Analyst at Morgan Stanley
Good morning. Thanks for taking the question and congratulations on the strong quarter and 718 data as well. Maybe just a question on 718: now that you have your early HO data there and it seems to be trending in line with your other assets, maybe you can talk about early thoughts on read-through to PWS data and remind us when that data is coming. Thanks.
David Meeker, Chair, President and CEO
Yeah, thanks, Mike. So yeah, we're really pleased with the 718 data. Remind everybody, all of you have asked me multiple times between these different assets, which one do we think was most likely to be successful — this was before we had the Bivamelagon data — and I was handicapped that 718 probably had the higher chance of being successful. And we had the very good data on Bivamelagon, so that was great. But I think this data validates the original hypothesis, which is 718 was built off of setmelanotide, and lots of similarities there, with a major difference being, one, the weekly formulation, but second, importantly, the greater specificity for MC4R, so we really don't have the hypopigmentation. And I'll just note: when you run these clinical trials and you ask them to report, as was the case with Bivamelagon, there were a few patients in both of these trials where localized, quote-unquote, increased pigmentation, under intense scrutiny, was observed. We've tried to get closer on the Bivamelagon side; I don't have quite as much detail in the 718, but to me I don't hear anything in these reports that suggests, to be honest, that this is necessarily drug-related, or if it is, it just highlights the fact that, you know, maybe around a nevus or something — melanocytic nevus — you might get a little more darkening. But again, it's all been super supportive of the fact that these two drugs don't have anywhere near the same level of pigmentation change. Read-through to PWS: yeah, it's very early. Again, as we said, we'll complete enrollment by the end of the year. We'll look for an opportunity to update. We've been asked before, will we wait for the results of those Prader-Willi data to make a final decision on which asset will go forward?
The answer is no, meaning that that decision-making is being driven much more around, to be honest, some of the CMC issues and timing of availability of these different formulations and drug supply. Right. If we do everything with one asset, that'll put a little more pressure on its supply; if we spread it around, so again, there's a number of things we'll take into consideration over the next few months which will get us in a position to make that decision.
But we're not waiting in terms of our planning — protocols are being drafted and we're working to be in a position, once we have that information to make that decision, we'll be ready to go.
Mike Ulls, Analyst at Morgan Stanley
Thanks and congrats again.
OPERATOR
Thank you. And our next question comes from Seamus Fernandez of Guggenheim Securities. Your line is open.
Seamus Fernandez, Analyst at Guggenheim Securities
Thanks for the question. So just two on my end, hoping you guys could provide us a little bit more color on developments in Japan and how we're likely to see a rollout of HO emerge in Japan, and the pace at which that could play through — just a very different market and would be interesting to get a better understanding of how you see that market evolving as it comes forward. And then just a second question, David: I think there's still a little bit of confusion on this daily versus weekly discussion as it relates to PWS.
Just trying to get a better understanding of where you're likely to come out on that and if there are critical decisions that need to be made along those lines. Or do you feel like there's an opportunity that's robust enough in PWS to actually warrant advancing both Bivamelagon and 718 to offer choice to that patient population? Thanks.
David Meeker, Chair, President and CEO
Let me just quickly on Japan, and then I'll let Jan make a comment. So we, as John indicated, will do a deeper dive on the Japan opportunity on our next earnings call. He laid out the timeline in terms of the process we're going through in terms of regulatory review, and then we get into pricing negotiations, all of which we expect to put us in a position to launch by the end of the year. But Jan, I don't know if there's any additional color you want to add to your comments.
Jan Massabro (Executive Vice President, Head of International)
No. Maybe two, three things. Thank you for the question. So first, as you've heard, we plan to launch before the end of the year. Two, the prevalence is meaningful. Three, in terms of efficiency in Japan, we can leverage claims data, hospitals data. Like in the US, we have a strong team in place for many months and a field medical affairs team in place for now six months. And we also have, which is very important in Japan, the support of the scientific committee, the support of leading experts.
And as you may remember, we had a few sites for the HO Phase 3 in Japan, which did help a lot, both in terms of drug understanding, adoption, and also interaction with the regulators. And maybe a last thing with the regulators and the payers: I've been myself in Japan a few weeks ago; I've met with some senior executives of the MHLW, and what was really clear is that they value a lot the speed with which Rhythm has tackled the problem, which is an important one for them, and the drug lag/drug loss issue, which is, as you know, a meaningful one for Japan.
So we are very optimistic in terms of what we can achieve there.
Seamus Fernandez, Analyst at Guggenheim Securities
Great. Thanks, John.
David Meeker, Chair, President and CEO
And then with regard to the daily/weekly question, I realize this all got triggered, I think, by Dr. Miller's comments on our June conference call where she was strongly in favor of a daily for PWS patients who like their routine. So obviously we'll take that into consideration as we make final decisions. I'm not sure in the Prader-Willi community, given how complicated this disease is, that we'll get one single opinion, and we'll obviously, you know, get some opinions from some other experts as well.
So, yes, that'll be considered. It's not the overwhelming factor that'll, you know, cause us to pick one over the other. And then last part of your question is, could we envision developing both in Prader-Willi? Absolutely. I think, you know, for both HO and Prader-Willi, very significant opportunities — maybe even a comparable magnitude, depending how you cut them. Yeah, we'd want patients to have that choice. So you can very much imagine that we would get it done, but maybe not in parallel.
Leave it there.
Seamus Fernandez, Analyst at Guggenheim Securities
Great, thank you.
OPERATOR
Thank you. And our next question comes from John Wolloban of Citizens. Your line is open.
UNKNOWN Analyst
Hey, thanks for taking the question, a couple for me. I might have missed this, Jen, but I think last update you said time to paid/approval was about 60 to 90 days. And I was wondering if there was an update there. And then can you remind us how many priority accounts you guys have? And with 25% of prescriptions coming from those as of now, do you expect that to accelerate in the near term or will that take a little bit more time? Sorry, Jen. So the first question was just around the time to approval. 60 to 90 days. What's your sense about where it is now?
Jan Massabro (Executive Vice President, Head of International)
Oh, yes, we are expecting the feedback from the... Sorry. Actually, apologies. That was for Jennifer. No, no, it was good. I was looking to be updated on the Japan schedule here, but no, no, it's good.
Jennifer Lee, Executive Vice President, Head of North America
Okay, sorry. 60–90 days. I thought it was surprising. So from the time to approval standpoint, I would say that holistically, on average, we expect that time to approval to continue to get better. I would say that overall, when we take a look at BBS where the payers had very little understanding of diseases impacting the MC4 pathway, little understanding in terms of the differentiation from general obesity, there was a lot of education that we've had to do on the payer side to really educate them on this piece and on Imcivree, and that helped a lot.
Even pre-approval, as we move forward with the pre-approval discussions with the payers, that is leading to approvals that are quicker than what we experienced, at least in those early approvals to date, than what we experienced with BBS. With that said, we have a lot more impending that we're still working towards, and we're also working to make sure that we get HO-specific policies in place with the payers as we move forward into the year as well.
So that was the question in terms of the time to approval. The priority accounts—so these are the accounts that for the most part are where patients with brain tumors go for holistic management of their tumors, pre-surgery management as well as post-surgery and management in terms of any type of hypothalamic dysfunction. So there's around 43 across the nation that our teams have identified and are working towards. And it's where likely the incident but also the near-term prevalent type of patient population remains for a couple years after the surgery or procedure to maintain appropriate care.
From there they go on to other sites outside of these centers for treatment. So overall these are very centralized just in terms of patient populations. And the 25% is aligned with what we have seen in claims as to identified patients that may be HO, because within these accounts we have identified or estimated about 33% of the HO patients are within these centers. So we are going after both physicians within these centers as well as outside, and we're going to continue to make sure that the patients are diagnosed and put onto therapy moving forward.
UNKNOWN Analyst
That makes sense. Thanks.
Jennifer Lee, Executive Vice President, Head of North America
Thank you.
OPERATOR
And as a reminder, please limit yourself to one question in the interest of time. Our next question comes from Whitney E. Gem of Canaccord. Your line is open.
Whitney E. Gem, Analyst at Canaccord
Hey guys, congrats on the quarter. Sorry if I missed this, but you talked about 80% of prescribers being endocrinologists. What are the other 20%? And are those doctors that you're proactively targeting, or are they just kind of coming to you because they have the patients? Thanks.
Jennifer Lee, Executive Vice President, Head of North America
So the backgrounds of the other 20% are primarily primary care as well as pediatricians. In terms of our target list, we provide the teams also physicians who may have a patient that have backgrounds in terms of potential obesity management holistically, which may include primary care physicians that are ABOM certified, for example. So the backgrounds in terms of the physicians are endocrinologists primarily, but also supplemented with these physicians that have interest in obesity medicine overall.
OPERATOR
Thank you. And our next question comes from Samantha Simakal of Citi. Your line is open.
Samantha Simakal, Analyst at Citi
Hi, good morning. Thanks very much for taking the question. I just have a follow-up on one that was just asked about 75% of scripts that are outside of your priority targets. Can you speak to the type of physician that is writing scripts and how we should think about the growth among that segment going forward? Thanks very much.
Jennifer Lee, Executive Vice President, Head of North America
So outside the priority accounts, the backgrounds are very similar just in terms of the focus in terms of endocrinologists as well as physicians with backgrounds in terms of obesity medicine that have been tagged as potentially having HO patients. For follow-up for our teams, we go where the patients lead us to in terms of the targets that we have. So there's patients within the priority accounts, there's patients outside the priority accounts, there's the access issues.
So when our teams have a list and they can have an in, in terms of being able to engage with the physician, that is where they will go in terms of having the discussion. But we've outlined the priority accounts being a key focus because it would enable patients to not leave without an appropriate diagnosis of HO and would prevent sort of the broader bleed into the community centers moving forward. So we have an ability to really change the paradigm just in terms of how these patient populations are treated.
But, you know, we go where we can have a discussion with physicians who have the patient.
David Meeker, Chair, President and CEO
And if you think about how our healthcare system works, for any complex medical problem, you're perhaps more likely to be seen at an academic center of excellence. You're there, you get your problem managed. And as Jennifer said, these are the chronic management of these patients. They have a lifelong need for pituitary hormone replacement. They will have a lifelong need for management of their hypothalamic obesity. Then they go back to a local endocrinologist, obviously closer to home, somebody they may know better. So as Jennifer said, we'll try to reach all of those patients. But yeah, there's a natural flow here.
OPERATOR
Thank you. And our next question comes from Lisa Walter of RBC Capital Markets. Your line is open.
Lisa Walter, Analyst at RBC Capital Markets
Oh, good morning. Thanks for taking our question, and congrats on the quarter. Maybe just another one on RM718. Given the early but positive results shared today, just curious: what are the next steps? Could you perhaps run a basket study across HO and Bardet-Biedl, maybe some of the other indications, to accelerate the path to approval and perhaps gain a label eventually similar to Imcivree? Any color here would be helpful. Thanks so much.
David Meeker, Chair, President and CEO
Yeah, thanks, Lisa. So one, the development path will be at this point indication by indication. We had feedback earlier on—and we'll perhaps go back at some point, I don't think we're there yet—that the regulators, FDA specifically, were not ready to entertain something like an MC4R pathway label, which might argue you have the ability to treat anybody where you can document there's a pathway label. So given that, we'll be going indication by indication.
Two, our plan will be for all of our currently approved indications—so the POMC and leptin receptor biallelic, the BBS population—we will get one of our two next-generation molecules into those populations and get the indication. We may not develop both molecules in all of those indications; they're smaller. But as I said in my earlier response, for the large indications—HO and Prader-Willi specifically—we very much may entertain developing both of the molecules.
OPERATOR
Thank you. And our next question comes from Priyanka Grover of J.P. Morgan. Your line is open.
Priyanka Grover, Analyst at J.P. Morgan
Thanks so much for taking our question, and congrats on the quarter. So we just have a question about Europe. Aside from the one-time revenue recognition charge in France, were there any other factors to think about for Europe? In the past quarters, Europe has been a strong growth driver for Rhythm Pharmaceuticals. So curious how you're thinking about Europe going forward, especially with acquired HO launch in 2027. Thanks.
Jan Massabro (Executive Vice President, Head of International)
Yes, thank you for the question. So maybe a few words about the HO launch in 2027. First, we are encouraged by what we have seen in France and Italy in terms of diagnosis and willingness to treat. As you know, we have named-patient sales in place for more than one year in those two countries, so we have observed the conviction, the growing conviction among the treating community. Another very positive aspect is that we will leverage most, if not all, the same centers of excellence and prescribers that we already have for POMC and BBS.
But we also have new medical specialties to explore, as Jennifer also mentioned in the U.S. So we feel good. We also know very well the payers, because we have spoken with them for many years, and these are the same teams across Europe, and they know the drug very well and they know the drug benefits very well. So with all that and other aspects, we feel good.
Priyanka Grover, Analyst at J.P. Morgan
Thank you.
OPERATOR
Next question. And our next question comes from Thomas Smith of Lyric Partners. Your line is open. Thomas, your line is open.
Thomas Smith, Analyst at Lyric Partners
Hey, good morning. Sorry about that. Thanks for taking our questions, and let me add my congrats on the strong quarter and the nice 718 data here. Just on 718, wondering if you could expand a little bit on the comments regarding the dose escalation in the study. How many of these initial HO patients are getting up to the target dose? And then just on the tolerability profile, could you provide a little bit more color on the injection site reactions and how those compare to the Imcivree experience?
Thanks so much.
David Meeker, Chair, President and CEO
Sure. So the vast majority got to the 40 milligrams, as I indicated. We had the one patient who actually didn't get much above 10 or 20 milligrams—they might have reached 20 milligrams weekly—but we're having, and we saw this in our earlier development program with setmelanotide, where there was a small percentage of patients who just were extraordinarily sensitive in terms of their GI side effects. And again, I think that's part of the background of this disease.
But aside from that, everybody basically got to the 40 milligrams. The injection site reactions/reactions slash the way the drug works—this is a weekly formulation. The formulation itself is somewhat viscous. And the mechanism, essentially you inject and you get a nodule in the subcutaneous tissue under the skin, and then the drug disperses from there. So that's how it's delivered. The nodule is present. And I think in the case of the patient who wasn't thrilled with the injections, part of it was, you know, didn't like the nodules per se.
And the other thing is we also were delivering this drug without the autoinjector, and so it has to be pushed in by hand. And the autoinjector we know for a fact will make a significant difference, I think, in terms of the ease and also probably the patient experience. So that's what for the most part is being referenced when they reported the injection site reaction—the formation of this nodule, which is just part of how the drug's delivered.
OPERATOR
Thank you. And our next question comes from Joseph Stringer of Needham and Company. Your line is open.
Joseph Stringer, Analyst at Needham & Company
Hi, good morning. Thank you so much for taking our questions. Question on the early-stage pipeline: you have a CHI program in preclinical development. Can you provide any updates there? And more broadly, any updated thoughts on pipeline expansion beyond the MC4R assets?
David Meeker, Chair, President and CEO
Yeah, thanks, Roy. So CHI we've been working on for a while here, as you know, and we look forward to updating you. As I've said before, and I'll say it again, we're actually making good progress there. We're, you know, we look forward to an update. We're not prepared to give one today, but we are making good progress. And as Hunter highlighted, you know, we're beginning to increase our spend there. So, you know, we're moving deeper into the developmental program.
So we'll talk more about that. We're excited about that program. I think we have a unique approach to addressing that disease, but more to come there, I think, you know, in terms of other approaches here, we'll continue to think about the biology around the MC4R pathway, signaling through the receptor and the like. Like every company, we entertain other approaches to these diseases, and we're doing some of that. We're not at a point now where we're in a position to talk about that, but we'll look at that.
And then, you know, externally, we got this question, you know, would you consider going outside? And I think our answer continues to be, we feel really good about the opportunities in front of us, the pipeline and a product strategy we've been pursuing. And there's many indications, including our whole genetic pillar, if you will, which we will absolutely come back to and work our way through there. And as we look at some things, biomarkers, for example, we're continuing to try to understand how we can better understand and refine the patient population most likely to respond in terms of that genetic population.
So that's going to be our focus. That said, we'll remain opportunistic. We're obviously in a stronger position in terms of our balance sheet and in their position as a company. So we'd be not averse to doing something that made sense, but we're not specifically looking to do something.
OPERATOR
Thank you. And our last question comes from Ram Savaraju of H.C. Wainwright. Your line is open.
Ram Savaraju, Analyst at H.C. Wainwright
Thanks so much for taking our question. Just with respect to Prader-Willi syndrome, given the extended history so far with at least one approved drug in that condition and greater familiarity overall with that target indication, can you share with us any additional information at this time regarding market segmentation, analysis and what you anticipate to be the key patient population within the Prader-Willi syndrome community that you might focus on for your products?
Thank you.
David Meeker, Chair, President and CEO
Yeah, thanks. I think so. One, as we've indicated on our prior calls, our initial developmental indication, as other companies in the space have done, following the Soleno approval would be for hyperphagia—makes total sense. There's a very clear, I think, template for how that trial can, should be done. Our mechanism, as we said, we started with a very clear focus on both hunger, hyperphagia and BMI/weight change. Because our drug signaling through this receptor gives you a satiety signal, increases energy expenditure.
And we always believed if we got a weight change, BMI decrease, we would of course get, achieve that end by, you know, in some way decreasing caloric intake, decreasing the hunger slash hyperphagia. So long story short is we'll continue to pursue that paradigm. I think in terms of market segmentation, no, I think it's way too early. I think this is an extremely complex disease. You all know it as well as we do or maybe better, some of you. It's remarkably heterogeneous, but they share a lot of common features.
Currently approved therapies have some limitations. We know that. I don't think there's likely to be a one-drug solution to Prader-Willi. So obviously we included patients who are on Victoza in our current trial that Dr. Miller's running. So combination therapy is another strategy that I'm sure the community [is] looking at and will be thinking about as we go through our developmental plans and the like. But no, I think our goal is to serve the Prader-Willi population writ large, recognizing that the clinical trials may need to be more targeted to run that successful trial.
Ram Savaraju, Analyst at H.C. Wainwright
Thank you.
OPERATOR
Thank you. This concludes our question and answer session. I'd like to turn it back to David Meeker for closing remarks.
David Meeker, Chair, President and CEO
Great. Well, thanks, everybody, for tuning in in August, as you heard. Incredibly excited, I'll say, about our start here. I mean, we've been working on HO for a number of years and now to be at a point where we're actually getting the drug to patients and we're seeing a community that's embracing it and responding, you know, well to their initial experience is, like I said, it's very exciting for us. Lots more to come and, you know, hopefully we've outlined some of that.
We'll have more discussions going forward, but we look forward to our next update, the Q3 call. Thanks all.
OPERATOR
This concludes today's conference call. Thank you for participating and you may now disconnect.
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