Rhythm Pharmaceuticals Inc
NASDAQ:RYTM
Earnings Call Analysis
Q2-2023 Analysis
Rhythm Pharmaceuticals Inc
Our story begins with a tale of tenacity and innovation, woven by a company passionately striving to improve the lives of individuals with rare genetic disorders of obesity. A testament to its commitment is the remarkable progress seen since June 16, 2022. Within a year, the firm has garnered over 425 prescriptions for Bardet-Biedl Syndrome (BBS) with more than 125 of these coming in the second quarter of 2023 alone.
Charting new territory, the company proudly expanded to Germany and France, offering their groundbreaking treatment for POMC/LEPR and BBS, and is mapping further expansion with expected launches in Italy and Spain, among other countries. Despite the conservative mindset towards new drugs in Germany, the organization triumphantly initiated its German operations in April 2023 and has since seen encouraging prescription growth. Their efforts to educate physicians and support patients have been vital to their success, making a significant impact in a relatively short period.
In the EU4 and UK regions, the company has identified an estimated prevalence of up to 2,500 patients with biallelic POMC/LEPR and a formidable 4,000 to 5,000 patients with BBS, with Germany alone accounting for roughly 1,200 of those BBS cases. This significant potential patient base fuels the organization’s drive to increase awareness and treatment availability.
In a striking jump from the previous year, the company reported $19.2 million in net product revenue for Q2 2023. This marks an incredible 68% increase from the prior quarter, largely attributed to an influx in reimbursed BBS patients in the United States. They've also managed their inventory carefully, reaching more normalized levels, and improved their U.S. sales gross-to-net percentage to 85%.
The cost of goods sold in Q2 represented 12% of net product revenue, showing a minute decrease year-over-year. Meanwhile, R&D expenses came down by $4.4 million from the previous quarter, totaling $33.5 million for Q2 2023. SG&A expenses rose year-over-year to $30 million for Q2 2023, encompassing increased marketing spend and stock compensation. Despite these cost pressures, the non-GAAP operating expense guidance for 2023 remains steady at $220 million, excluding non-cash impacts from stock-based compensation.
While German conservatism may slow initial growth, the company is confident in building steady, solid growth in the long run, drawing from their experience in successfully penetrating the U.S. market. Supported by robust data and a clearer understanding of epidemiology, the organization's optimism for its planned market penetrations is at an all-time high.
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Good day, and thank you for standing by. Welcome to the Rhythm Pharmaceuticals Q2 2023 Earnings Conference Call. [Operator Instructions] Please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker today, Dave Connolly, Executive Director of Investor Relations and Corporate Communications.
Thank you, Bella. 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 on the Investors' page of our website at ir.rhythmtx.com. This morning, we issued a press release that provides our second quarter 2023 financial results and a business update, which is available on our website. As listed on Slide 2 is our agenda. Here with me today in Boston are David Meeker, Chair, Chief Executive Officer and President of Rhythm Pharmaceuticals; Jennifer Chien, Executive Vice President, Head of North America; Hunter Smith, our Chief Financial Officer; and Yann Mazabraud, Executive Vice President, Head of International is on the line joining us from Europe. And 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. In addition, any forward-looking statements represents our views only 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.
Thank you, Dave, and good morning. Thank you all for joining today. Q2 was a very good quarter. So we're going to dive into the details behind the quarter in our presentation. But before we do that, let me try to put these results in a larger context. We recognize and we think all of you recognize that Rhythm has 2 main drivers of value creation; BBS commercial execution and HO clinical development. On top of that, we have a number of additional efforts which offer potential upside that may be significant. The fundamentals, which we have discussed multiple times are strong. The biology is well understood. Impairment and signaling through the MC4 pathway leads to hyperphagia, that uncontrolled hunger that stems from not getting a signal that you worked full, coupled with a decrease in energy expenditure, which all leads to obesity. The community is increasingly recognizing that not all obesity is the same and that patients with impaired signaling through the pathway have a distinct disease which requires a specific approach. Two, the unmet medical need is clear. Treatments for patients with general obesity may have some affected individual patients. For example, my craving for ice cream may go down on a GLP-1, but I have not addressed the fundamental problem. Impairment in MC4 pathway signaling leads to a decrease in the endogenous hormone, alpha melanocyte-stimulating hormone. Setmelanotide is an analogue of alpha MSH. We are a precision medicine that happens to be a hormonal replacement. Why wouldn't you replace the hormone if there were a deficit. Three, our drug works. Approved for multiple genetic diseases and with strong proof-of-concept data in hypothalamic obesity, we are now increasingly seeing the real-world effect. Patients are choosing to go on treatment and are largely staying on treatment. So now to the quarter. We are 1 year post approval for BBS in the U.S. We have discussed each quarter whether we can trend the quarter-on-quarter script numbers, and I'm sure we will again today. The answer will be the same, no, don't trend the quarter-on-quarter numbers. But you can look at a full year now of data and conclude BBS is evolving into a very meaningful rare disease opportunity. The patient community is engaged, the number of doctors writing scripts continues to grow, the payer community is listening and recognizing this is a unique rare disease and not simply an extension of the population of patients living with general obesity. The teams are executing and our confidence is growing. We hope yours is as well. We're making good progress on our Phase 3 study for hypothalamic obesity. We have moved up our timeline for completing enrollment to the end of the year based on good progress getting sites up and going. I wish no one took some vacations, but the patients are there and waiting. Our 6-month long-term extension data show continued reductions in BMI at 6 months and we look forward to updating you on the 12-month data in the fall. I will speak briefly about our Phase 2 long-term extension data in a couple of slides. Finally, we have a number of trials reading out in the second half of this year with the DAYBREAK, pediatric and weekly switch studies. We will highlight these results at an upcoming R&D session in Q4 of this year. And we are excited to introduce you to our next generation program, RM-718, which I will discuss in the next slide. So Slide 6. RM-718 is a more specific and potentially more potent molecule. It is MC4R specific in its targeting. It does not hit MC1R, and therefore, eliminate hyperpigmentation effect we see with MC1R agonism. And it is a weekly formulation with patent protection out to 2041. We are preserving the option of continuing with our current weekly program, but we will push out initiation of the weekly study into 2024 when we will make a final decision on our weekly strategy pending further development with 718. Our goal quite simply is to develop a better drug, which happens to come with a significantly longer patent protection. We look forward to providing more details at the upcoming R&D Day. So on Slide 7. Slide 7 is to remind you of the overall opportunity. We started small with POMC and LEPR. BBS and HO represent meaningful rare disease populations with the major advantage being they can be diagnosed more easily. And the HO population, as you know, is largely diagnosed today. On top, a significantly larger world potentially opens up with the EMANATE trial populations. Moving to Slide 8. We remain laser-focused on getting our global Phase 3 trial up and running. As previously discussed, the challenge was not patient interest, but clinical trial site bureaucracy. We are breaking through all of that with 1/3 of the sites open and about 1/4 of the patients screened. Screening is a good indicator because very few patients screen fail. The physicians have their list of patients, they know the entry criteria and they invite patients to participate accordingly. Based on our progress to date, we are moving up our targeted enrollment completion date from Q1 2024 to the end of this year. On Slide 9, we remind you of the 6-month data we presented at ENDO, which shows continued BMI reductions over time in the majority of patients. The blue bars represent the 16-week data and the red bars represents a 6-month data. On Slide 10, we have the summary of this data. And you can see the mean change for the 11 pediatric patients moving from minus 18% at 16 weeks to minus 22% at 6 months. The 2 adults we broke out separately with 1 patient moving from minus 14% to minus 21% and the other patient who has been upping down on our drug dose regaining as the dose was decreased and losing again as the dose was increased. She has now again lost approximately 10% at 6 months. So on Slide 11, I'll finish my section on this slide, which shows an increasingly robust portfolio of indications which are progressing. More to come later this year on our pediatric program, weekly program, DAYBREAK open label results and the 12-month data from the HO patients in the long-term extension. I'll now turn the call over to Jennifer.
Thank you, David. We are now 1 year into our BBS commercial launch for IMCIVREE, which was approved by FDA in June 2022. We are very pleased with how the launch has progressed and I am proud of the team for all we have accomplished. And most importantly, IMCIVREE is now making a positive impact on the lives of hundreds of patients and families in the United States. Now beginning here on Slide 13. Throughout the year since launch, we have heard from many patients with BBS who have benefited from IMCIVREE therapy. Just last week, we hosted in our office a patient summit to formally launch our Patient Ambassador program. We welcomed 8 patients and/or their caregivers, all who are active participants in our live or virtual speaker programs, designed to continue building the BBS community and offer peer-to-peer support. Hearing and learning from other patients with BBS or their caregivers can be tremendously powerful as each patient and family is on their own journey with BBS and IMCIVREE therapy. On this slide, you see a picture of Kathryn, who is diagnosed with BBS when she was 6 years old and struggled throughout her teens and early 20s with hyperphagia, that pathological hunger that leads to abnormal food-seeking behaviors and severe obesity. She tells us how she was hungry all day long and snuck food every night. Now at age 28, having been on IMCIVREE since last September, that hunger no longer, through her words, consumes her energy and she is able to enjoy life more. She learned about IMCIVREE through our digital non-personal promotion efforts, attended one of our programs to learn about IMCIVREE and began participating in our InTune Patient Support Service program. Almost 1 year in, she tells us how she is sleeping better, able to focus more and participate in a number of activities and is currently writing a book about her experiences. She is a remarkable young woman, a truly inspiring and powerful advocate and we are very grateful to her and others who continue to share their stories and voices. Next slide. Our experienced teams continue to execute at a high level and we couldn't be more pleased by all the progress we have made throughout this first year of launch. We are seeing strong continued demand for IMCIVREE, the first and only approved precision medicine for BBS patients with hyperphagia and severe obesity. Throughout the launch from June 16, 2022 through the end of the second quarter of 2023, we now have received more than 425 new BBS prescriptions, which includes robust growth through the second quarter where we received more than 125 prescriptions. In addition, more than 250 physicians have written prescriptions. And we have received approval for reimbursement for more than 250 prescriptions. We continue to identify more BBS patients and work to speed diagnosis. Physicians continue to recognize the benefits of IMCIVREE and prescribe it for their patients. Additional patients continue to initiate and maintain on IMCIVREE. And payers see the value and differentiation of IMCIVREE as they approve reimbursement. Moving to the next slide with some details on physicians who are writing IMCIVREE prescription. The specialty breakdown remains consistent with what we have reported at the end of the first quarter of this year. Launch to date, endocrinology, both pediatric and adult, remained a top specialty at a combined 45% since launch. Pediatricians and general or primary care combined come in at just under 40%. Also, the portion of new-to-Rhythm prescribers or physicians our territory managers had not previously called on directly prior to prescription, accounts for about 26% of our prescriber base. This continues to give us confidence in our non-personal promotion efforts as an effective supplement to our field team by educating a broader physician and patient population. Lastly, on prescribers. Since launch, more than 25% of them have written 2 or more prescriptions, which is a growing percentage of repeat prescribers. This is our goal to have greater breadth and prescribers over time as well as more and more HCPs who identify additional patients and prescribe because they see the value of IMCIVREE for their patients through their own experiences. Next slide. On access and reimbursement, last quarter, we shared a similar slide showing the breakdown of states where we had success on IMCIVREE Medicaid coverage as well as those we have not had successful based on covered lives. I'm pleased to report that we have seen incremental improvement in gaining access over the last quarter. According to Medicaid, there are approximately 85 million of individuals enrolled in Medicaid in all 50 states plus Puerto Rico and the District of Columbia. Launch to date, approximately 80% of Medicaid covered lives are in states with a positive IMCIVREE policy in place or in a state where we have been able to get at least one positive coverage decision in the absence of an IMCIVREE policy. The remaining 20% of Medicaid lives represents a mix of states in which we either have not yet had a prescription for IMCIVREE that would trigger a coverage decision or we are still working to secure access for a prescription, or finally, where we have not been successful in gaining access through the appeals process. This marks a 5% shift in our favor over last quarter where we reported a 75%-25% breakdown. Additionally, the payer mix for BBS does remain consistent as almost 90% of prescriptions since launch fall under commercial or Medicaid plan. The average timeframe for approval is approximately 1 to 3 months with some tails extending out several months, consistent with our previous report. Overall, we are pleased with achievements to date in securing approvals. Next slide. Here are some details on patients with BBS with prescriptions and on drug. Adults now account for approximately 54% of prescriptions received since launch. This speaks to an opportunity identified upfront. In the CRIBBS Registry, we knew approximately 80% of participants were 18 years of age or younger, which is not representative of the age distribution of the overall BBS population. We believe many older patients may have been lost to follow-up or lost in the system. So we put plans in place to find them through non-personal promotion, educational webinars, engagement with the BBS Foundation and more. Kathryn, the women on my opening slide today is a prime example of this. She found us with a little digital help after IMCIVREE was approved. Lastly, on access, and this becomes more important as we look ahead to coming quarters, is our reauthorization rate. While the majority of the reauthorization decisions are made at 12 months on therapy, some plants do have 3 or 6-month reauthorization requirements. We are very pleased to report that launch to date, we have seen 50 reauthorization approvals with only 1 patient who did not meet criteria. This was a patient who was not compliant on medication. Next slide is my final slide on patient identification. With our bolstered confidence in the need for a targeted therapy like IMCIVREE and the benefit it can provide, we remain focused on educating the community to find already diagnosed patients, while expediting the identification of individuals with BBS who do not yet have a diagnosis. Our efforts over the last several quarters have shown to be effective and we continue our engagement with all key stakeholders along with our overall community building efforts. We are excited about our progress over the last year and the opportunities we have ahead of us. With that, I'll hand it over to Yann.
Thank you, Jennifer, and good morning. Slide 20. I will start with a reminder, Europe is a key market for rare diseases for Rhythm. As we have spoken before, European countries typically are better organized for rare diseases and more centralized in their approach to care than the United States with single payer healthcare systems, government-funded genetic testing, more established networks of experts and referral patterns, multiple centers of excellence and patient advocacy group. Even though these diseases are quite rare, the opportunity is meaningful for us in both POMC, LEPR deficiencies and Bardet-Biedl syndrome. In the EU4 plus U.K., we estimate the prevalence for Biallelic POMC and LEPR to be between 600 and 2,500 patients and we have identified approximately 100 patients being cared for in these countries. For Bardet-Biedl Syndrome, our estimated prevalence in the EU4 plus U.K. is 4,000 to 5,000 patients, which is a prevalence similar to the U.S. And we have already more than 1,500 patients identified in this country. With our growing international team, we remain focused on identifying more patients and continuing to collaborate with country-level authorities and centers of excellence to gain reimbursement and access for these patients. Next slide. Overall, on a global level, IMCIVREE is now available in more than 10 countries outside the United States. We are now approved and available for both POMC, LEPR and BBS in Germany. In France, we are available for the same indications under a paid early access program. We also have full coverage for IMCIVREE for POMC and LEPR in England, Italy and the Netherlands. And we are advancing with pricing negotiation for BBS in the U.K., Italy, Spain and the Netherlands, with BBS launches planned in Italy and Spain for this year and in 2024 in the U.K. and in the Netherlands. We also have achieved named patient sales in Spain, Austria, Turkey, United Arab Emirates and early access in Argentina. And we have initiated reimbursement processes in Belgium and the Nordic countries. Next slide. Lastly, an update on our launch for BBS in Germany where the G-BA, which is the German Federal Joint Committee, did recognize the fact that IMCIVREE is a precision medicine, did exclude IMCIVREE with an unanimous vote from its lifestyle exemption list and made it eligible for full reimbursement by the statutory health insurances for the patients with BBS and POMC, PCSK1 and LEPR deficiencies. Our launch in Germany, which kicked off in late April 2023, is off to a strong start. And our focus remains on collaborating with leading experts to educate the physician community on the MC4 pathway and overcome the typical German physicians conservative mentality when it comes to new drugs. Patient identification also is a key focus. We estimate that the prevalence for BBS in Germany is approximately 1,200 patients. We believe that there are about 800 patients diagnosed. And of those 800, we have identified physicians caring for more than 250 of them and we are focused on identifying more. Our physician engagement and MC4 pathway education efforts are focused initially on major university hospitals across the country. And we have already received many prescriptions from several of them. Lastly, similar to the Rhythm InTune Patient Support program in the United States, we have a new patient support program in Germany called Rhythm@Home. This program is tailored to each patient, designed to educate patients and caregivers to set expectations for IMCIVREE and to maintain adherence. With that, I will turn the call over to Hunter.
Thank you, Yann. With robust demand for IMCIVREE the United States and our growing international business, our focus remains on building long-term value for our shareholders through excellence in execution alongside a strong commitment to financial discipline. Here on Slide 24 are the highlights of the Q2 P&L. Rhythm recorded $19.2 million in net product revenue in second quarter versus $2.3 million during the same quarter last year, an increase of $16.9 million. We received FDA approval for BBS on June 16 last year at the tail end of Q2, so that quarter preceded the BBS launch. On a sequential quarterly basis, product revenue increased by approximately $7.8 million or 68% over the first quarter. The primary driver of this growth was the increase in reimbursed BBS patients on IMCIVREE therapy in the United States. In addition, inventory at our specialty pharma partner increased, both due to the larger number of patients on therapy and an increase in days on hand. Days on hand ended Q1 at a lower than normal level of 5 days and ended Q2 at a more normalized level of 12 days. This impact contributed $1.6 million to Q2 revenue. Gross to net for U.S. sales improved slightly quarter-over-quarter to 85% versus 83% in the first quarter. Growth in international sales contributed approximately $0.8 million to quarter-over-quarter increase. While the German launch began late in the quarter, we began to have more of an impact in future quarters. Cost of goods sold during the first quarter was $2.2 million or approximately 12% of net product revenue, representing a slight decrease versus Q2 '22 as well as versus the first quarter of this year. Cost of sales consisted primarily of product costs, our 5% royalty to Ipsen under our original licensing agreement for setmelanotide as well as amortization of previously capitalized sales-based milestone payments. R&D expenses were $33.5 million for the second quarter of 2023. This compares to $31.5 million during Q2 '22. Compared to $37.9 million in the first quarter of this year, there was a decrease of $4.4 million. Most of this decrease was driven by the $5.7 million in one-time costs and fees associated with the Xinvento acquisition recognized in the first quarter. There also was a decrease of $2.8 million associated with the reduction in CMC expenses given the shift to commercial product. These decreases were partially offset by increased clinical trial expenses of $1.8 million and expenses of $1.3 million related to our RM-718 program. SG&A expenses were $30 million for the second quarter this year versus $22.3 million for the second quarter of '22. On a sequential basis, SG&A increased by $5.4 million versus Q1 '23. This increase was primarily due to an increase of $2.4 million in U.S. marketing spend as well as $1.9 million increase in stock compensation. For the second quarter, common shares outstanding were 56.7 million and quarterly net loss per share was $0.82. Turning to Slide 25. We closed the second quarter of 2023 well capitalized with $278.0 million pro forma cash on hand. This amount includes the anticipated net proceeds of $24.4 million from the third and final tranche of our healthcare -- of our royalty financing agreement with Healthcare Royalty Partners. This cash on hand is sufficient to fund all planned activities into 2025. On the $19.2 million in reported revenue, 86% of revenues were generated from sales of IMCIVREE in the United States, a slight increase from the 83% of net revenues in Q1. International sales growth continues to be robust, albeit from a stronger -- smaller base than the growth rate of IMCIVREE sales in the U.S. Of note, none of our international markets had full reimbursement for BBS throughout Q2. Germany's first full quarter of launch is Q3. Q2 operating expenses included total stock-based compensation of $8.9 million as compared to $6.4 million in the first quarter of '23. The quarter-over-quarter increase is primarily due to recognition of stock-based compensation associated with company performance awards. Finally, our non-GAAP operating expense guidance for 2023, which we initiated last quarter, remains unchanged to $220 million. This guidance excludes the non-cash impact of stock-based compensation. With that, I'll turn the call back over to David.
Thank you, Hunter. And as you hopefully have heard, we're really excited about the progress we're making. Slide 27 highlights that we have a lot coming up, and we look forward to updating you on those events in subsequent calls. And our last slide, 28, is simply a reminder of our strategic priorities, which remain unchanged, and we will continue to focus on execution. With that, we'll open the call up for Q&A.
[Operator Instructions] And our first question comes from the line of Divya Rao with TD Cowen.
I'm Divya on for Phil. Just 2 from us. One on DAYBREAK. Could you provide any color on the scope of the presentation that's coming in the second half? Maybe like, how many cohorts that you expect to present and also patients per cohort?
So DAYBREAK, as I'm going to repeat what I said earlier, this will only be the open label results. The blinded randomized withdrawal portion is ongoing. What I anticipate is we'll report out on a -- probably on the order of 4 to 5 different genes. And again, not all of those genes necessarily will be ones where we've seen a positive result. We'll report out on those where we think we've got enough data to conclude either it's working or not working at some level. The number of patients per gene cohort, again, it's highly variable, as you might expect in this kind of basket trial. Again, I would like to think we'll be in the range of 10 plus or minus patients for the genes that we report out.
That's helpful. And then just one more question from us. In terms of the number -- in terms of the patients who have yet to be reimbursed, how many of those are on the free drug program in BBS?
Jennifer?
So we do have a free drug program available for patients. To be eligible for the free drug, they have to go through several steps in terms of the reimbursement process. To date, the number of patients who are on a free drug still remains at approximately 20% of scripts.
And how do you expect that to change in the long term? Do they have to be relatively consistent?
So we have made incremental progress just in terms of securing access for IMCIVREE, as outlined in terms of the Medicaid portion. And that is a work that is ongoing in terms of going payer-by-payer to educate them and differentiate a patient population as well as IMCIVREE. And we have seen success on that and we're not going to give up in terms of those efforts overall. Approximately 10% of the scripts are Medicare patients where we do not have access. And while we are still investigating potential options in terms of opening up access for those patients, that would be a longer term type of ongoing dialogue with CMS and such. And I would say that in terms of commercial patients, the ones that are on our free drug program, similar to other rare disease therapies, there are -- our coverage from large commercial plans is quite good in terms of reimbursement. It's the smaller, really small, self-insured plans that I think in general rare diseases may have difficulty gaining reimbursement for the cost of therapy.
Your next question comes from the line of Derek Archila with Wells Fargo.
Congrats on the progress. Just first question from us, just any updates on the overall discontinuation rates you're seeing with IMCIVREE, I guess, across all indications, but maybe Bardet-Biedl specifically? And then secondly, I know the amount of sales currently OUS is small and growing, but I guess, how should we think about the sales ramp in Germany now that you're there? And just curious like is that going to mimic the U.S. or should it be -- or should we think about it differently?
Jennifer, discons?
Overall, we're very pleased with the discon rate, which is now approximately 10% of patients who have started therapy. There was an incredible amount of cross-functional team effort just in terms of really getting patients through the initial titration stage and then through the initial nausea vomiting, and we have had very, very low discons from that perspective. And I think that there are a variety of different reasons that patients do discon, some due to AEs, others for other personal reasons, and we continue to monitor those patients. And some of these patients may be interested in getting back on therapy as their situations may evolve over time as well.
Great. And Yann, do you want to comment on the expected German ramp or how you think about that?
Sure. We had a strong start in Germany with a very experienced team in the field. A bit difficult to project the next quarters. What I can tell you is that, first, we did had many prescriptions from several major centers and it will continue. The second thing is that, back to your question, we don't expect a fast ramp up as we had in the U.S. because of the German conservative mindset. But for sure, we have all the signals that will -- that are telling us that we will build a solid growth on the long run.
And your next question comes from the line of Corinne Jenkins with Goldman Sachs.
Maybe a couple from me. First, just how quickly post an IND can you move forward with that weekly formulation you announced today? And should we look for you guys to move directly into Phase 3 studies with that asset?
So again, the timing on how quickly you move after filing an IND is dependent on regulatory input of course. So all we're communicating today is we're filing the IND. And we will obviously meet with the regulators and get further input. The strategy for developing the drug, again, all we'll say today is that we will start with a Phase 1/2 type of effort, which will be initially in healthy volunteers. I think we have a big advantage here in that having developed setmelanotide and understanding the populations we're studying and what needs to be done to successfully get a drug through for these indications. So we'll leverage that learning as we go forward. But step 1 is pretty conventional with a Phase 1.
Okay. And then in terms of the epidemiology, just overall, what portion of patients would be expected to be adults with BBS versus children or pediatric population?
Maybe I'll take that. I think these are the things we know. One is, if you look at the CRIBBS Registry in the U.S. on the order of 80% plus of those individuals were pediatric. That doesn't mean that 80% of the patients are pediatric. It just means that of those patients who stay engaged with the registry, often probably with the help of their families, they're disproportionately peds. That's number one. Number two, we have been focused disproportionately on the pediatric call point, if you will. So that also would skew us to perhaps finding more peds. What's been really encouraging -- maybe the last thing before I get to encouraging part is that, these patients, they don't die. They may die early, the mortality. We don't have good, good data on overall life expectancy here, but they certainly don't die necessarily at a young age. And therefore, there's no reason not to expect a significant number of patients who are now adults. And if you look at the population and distribution overall, a 1/4 peds, 3/4 adults. What's really encouraging about the information that Jennifer presented is that we are penetrating to a significant degree of that adult population. They're finding us. They want to go on therapy and they're staying on therapy.
Your next question comes from the line of Dae Gon Ha with Stifel.
Congrats from us as well on a strong quarter. Just looking at the overall strategy as you continue to roll out BBS in the U.S., I guess, how much more confidence do you now have towards the estimated prevalence on BBS that you initially projected some a couple of months ago that was realized up? And I guess, given the strong ramp up this quarter, I guess, how are you kind of projecting the rest of the year? You mentioned no quarter-over-quarter trend line drawing, but there seems to be a little bit of an inflection this quarter. So does that portend anything in your view or any color on that would be great? And then in terms of the HO trial timeline, recognizing there's approximately 1/3 that you've activated right now. Is the 1/3 still out of the 35? Do you still anticipate 35 to be activated or do you think you can kind of muster with maybe 2/3 of that 35 to satisfy your overall 120?
Yes. Maybe I'll take the last question first just. So on the number of sites, I think the number of sites we'll probably end up opening given the strong patient interest and the like, it is the full 35. So we expect it will be somewhat less than 30. So that's the answer to that. And Jennifer?
Just relating to the projections for the rest of the year, what I would just saying right now is that, we are extremely excited about the opportunity and feel that there is still a lot of room just in terms of growth for this product. And just the feedback we're receiving in terms of patients benefiting on therapy, just gives us so much more energy in terms of really moving forward with finding these patients. We have been pleased overall in terms of the targeted ways that we have identified patients and feel like there's still a lot more that we can do there in addition to the breadth as well as what I outlined in terms of the depth of physicians writing more than 1 script because of the conviction they have around the drug itself. I will say though that things take time in rare disease. It takes time for patients to go and see their physicians. It takes time for some of these physicians and patients to have that conviction to initiate therapy. I mean, some of these scripts that we saw come in, it was many, many months of interaction and education that our TMs had before that script actually came through. And even like physicians who are now educated, it will take time for the patients to come in so that they can actually suspect and then test and get patients to an accurate diagnosis. So overall, like I said, it's rare disease. It really is dependent in terms of what happens within that quarter. But we are very, very happy in terms of what we've achieved and we have a lot more to do.
Yes. And Dae Gon, I think maybe just to amplify one short thing on Jennifer's answer there is, the overall prevalence numbers, all those things that Jennifer highlighted and the progress we've made to date, it does, not surprisingly, increase our confidence in the overall epidemiology, this 4,000 to 5,000. And we're learning more and more, much, much more than we did of course when we first launched. So confidence there is extremely high. And that's our biggest [indiscernible] The quarter-on-quarter piece, again, the nature of rare diseases, which is why we keep reiterating this, it is going to be variable. It will be up. It will be down I mean. But that's not what we hope you're looking at. We hope what you're looking at is a slightly longer view. Again, we've got a 1-year view here. Now our confidence that this is going to continue to grow meaningfully over the next subsequent quarters is very high.
And your next question comes from the line of Michael Higgins with Ladenburg Thalmann.
I'll share my congrats on the continued success with the launch of BBS enrollment progress in HO. DAYBREAK is one of the bigger drivers here this back half. You've got a lot of things going on, of course, but I just wanted to poke in a bit somewhat of a follow-up from a previous question to understand what we are to be looking for. I assume it's some efficacy readings, whether that's BMI, BMI Z-scores, hyperphagia scores. We're curious if we're going to see this as an overall means, any patient-specific data? And also your decision to advance specific genetic patient types, does it matter by the prevalence of that specific patient type?
Yes, Michael. So more to come. I think what we will put out -- so the data cuts we're looking at now are still rough and not final one, so caveat. 2, we'll determine how best to present the data, again, at individuals. I mean, if there's a small number of patients in a specific cohort, we'll probably present those specific. And for those where we have a slightly larger number, maybe we'll mean those. But that's again to be determined. I think the decision-making around what we might do next depends on the strength of the data, #1. What we would consider for sure, as you indicated is, A, how robust is the response; and 2, how prevalent is that routine. If we have one -- we have a gene where we've only been able to find a small handful of patients even though the gene itself looks potentially interesting, we may not feel we have the ability to recruit and actually run a trial just given that small prevalence. So we'll take all that into consideration. I do want to remind everybody that the bar for taking things forward is high. So I anticipate taking this forward because we see a signal, we want to have some confidence that it's robust and that we can execute on the trial and relative to all the other things that we have to do. You heard about the 718 program today. We're going to be incredibly focused on pushing that forward as well.
Just one follow-up here and really one for you, David, is given the state of the markets here slightly improving, but still assets are relatively cheap. I wanted to get your sense for -- in your appetite for expanding the pipeline. Obviously, you've got 718 going forward, you've got Xinvento activity. But curious to hear your appetite for expanding the pipeline?
Yes. Again, answer will be the same at this point. Very, very high bar to do anything. We are not actively looking, but we will be opportunistic in the sense that if -- in our engagement with the world outside, if things are of particular interest, we see a real opportunity to add value, then of course, we would look. But basically, we're just very focused on executing on these near-term value drivers and we'll continue to assess other opportunities as they might arise. But no specific focus on additional acquisitions.
Your next question comes from the line of Joseph Stringer with Needham & Co.
Just curious, what percent of patients on IMCIVREE have titrated back down to the lower daily dose or down either to the 1 mg or the 2 mg dose? And how has that evolved over time?
Yes. BBS in the U.S. is probably our best shot at that. Jennifer?
So overall, in terms of the doses, the majority of these patients are getting to the target 3 mg dose. I will say that just in terms of the percentages that you break down, the different segments, whether adults versus pediatric patients, there is a slightly higher percentage of adults that get to the 3 mg. It may be also because there's basically one titration step from 2 to 3 to get to the next dose of adults. But overall, even within each of the segments, the majority of the patients are getting to the 3 mg dose. And we want them to also be able to work with their physicians to take the time to titrate appropriately so that they can manage through and maintain on drug and receive a benefit.
Your next question comes from the line of Jeffrey Hung with Morgan Stanley.
This is Michael Reid on for Jeff Hung. Congrats on the quarter. Can I just ask for a little bit more color on the previous comment for the 1 to 3 months period for translating scripts to sales. You had said that there was a tailwind for some patients that it could extend that several months. What factors come into play there and what makes those patients more likely to have a longer process?
So the reasons just in terms of the length of time to gain reimbursement is not always relating to the payer itself. Sometimes it's just also delayed in terms of HCP side from a process standpoint, whether they're working through multiple patients and doing things a bit sequentially or for other reasons. With that said, I mean, we have definitely gotten approvals even within those groups of tailwinds of patients and the patient support group as well as our access group and our TMs on ground really continued to be persistent in terms of working that process through.
Okay. That's very helpful. And then maybe just a follow-up, maybe more of a housekeeping question. You reiterated guidance on OpEx. And it seems like for SG&A, it would have to somewhat lower in the second half to stay within guidance. How should we be thinking about expenses in second half, particularly SG&A given the launches happening in EU?
Sure. Good question. And we certainly have factored that in. I think there are a variety of factors that are -- it can be a bit lumpy within SG&A, particularly in the compensation area. So we're quite comfortable that we will still be on track to meet our guidance.
Congrats again on the quarter.
[Operator Instructions] And we have a follow-up question here from Michael Higgins from Ladenburg Thalmann.
Just a follow-up here on 718. Obviously, it's early, IND is not cleared yet, but just looking further down the road as to how this would be developed given your experience with setmelanotide, of course. It's fair to assume the control arm is different, but how do you expect to run 718? Would that be up against setmelanotide, considering it's approved now? And then after the healthy volunteers are tested, assuming positive of course, would you -- is it fair to assume you'd open up a broad basket study with all the patient types you've tested and possibly additional patients?
Michael, all good questions. I don't have the answers today. I mean, those are things we'll think about. Number of choices, you've highlighted some of them about how you develop an asset such as this. But first step, again, there's not much to negotiate there. We'll just get through that. And while we're doing that, we'll evaluate the points that you've highlighted in those -- as I said, those are good questions in terms of strategy.
And I see no further questions at this time. I will now turn the call back over to David Meeker.
Thank you. Thank you all for turning in on the early day of August here. And as you hopefully have heard today, a really good quarter. A lot of momentum here in Rhythm and very much look forward to the next earnings call and updating you further on the progress that we can make. Thank you.
This concludes today's conference call. Thank you for your participation. You may now disconnect.