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spk09: Good day and thank you for standing by. Welcome to the Rhythm Pharmaceuticals Q2 2023 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 TAR11 on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press TAR11 again. 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 Communication. Please go ahead.
spk04: 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 here on slide two is our agenda. Here with me today in Boston are David Meeker, Chair, Chief Executive Officer and President of Britain Pharmaceuticals, Jennifer Chen, Executive Vice President, Head of North America, Hunter Schmidt, our Chief Financial Officer, and Jan Mazzebro, Executive Vice President, Head of International, is on the line joining us from Europe. And on slide three, 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 on our most recent annual or quarterly reports on file with the FEC. as of any subsequent date. 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 five.
spk02: 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 I think all of you recognize, that Rhythm has two 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 in signaling through the MC4 pathway leads to hyperphagia, that uncontrolled hunger that stems from not getting a signal that you work 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 effect in 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. Semilanotide is an analog 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 and 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 one year post-approval for BBS in the US. 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 three 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 so many vacations, but the patients are there and waiting. Our six-month long-term extension data show continued reductions in BMI at six months, and we look forward to updating you on the 12-month data in the fall. I will speak briefly about our phase two long-term extension data and a couple of slides. Finally, we have a number of trials reading out in the second half of this year with a 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, RM718, which I will discuss in the next slide. So slide six. RM718 is a more specific and potentially more potent molecule. It is MC4R specific in its targeting. It does not hit MC1R and therefore eliminates the hyperpigmentation effect we see with MC1R agonism. And it is a weekly formulation with patent protection out to 2041. 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 of the upcoming r d day so on slide seven Slide seven 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 M&A trial populations. Moving to slide eight. We remain laser focused on getting our global phase three 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 one third of the sites open and about a quarter of the patients screened. Screening is a good indicator because very few patients screened 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 2023 On slide nine, we remind you of the six-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 represent the six-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 six months. The two adults we broke out separately, with one patient moving from minus 14% to minus 21%, and the other patient who has been up and down on her drug dose, regaining as the dose was decreased and losing again as the dose was increased. She has now again lost approximately 10% at six months. So on slide 11, I'll finish my section on this slide, which shows an increasingly robust portfolio of indications which are progressive. 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 and long-term extension. I'll now turn the call over to Jenna.
spk10: Thank you, David. We are now one year into our BBS commercial launch for MCFRI, 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, Incivry 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 Incivry therapy. Just last week, we hosted in our office a patient summit to formally launch our patient ambassador program. We welcomed eight 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 emcevery therapy. On this slide, you see a picture of Catherine. who was diagnosed with BBS when she was six 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 antifree since last September, that hunger no longer, through her words, consumes her energy. and she is able to enjoy life more. She learned about MCIVRI through our digital non-personal promotion efforts, attended one of our programs to learn about MCIVRI, and began participating in our Intune patient support service program. Almost one 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 MCIF rates. 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 Incivry and prescribe it for their patients. Additional patients continue to initiate and maintain on Incivry. And payers see the value and differentiation of Insivri as they approve reimbursement. Moving to the next slide with some details on physicians who are writing Insivri prescriptions. 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 two or more prescriptions, which is a growing percentage of repeat prescribers. This is our goal to have greater breadth in prescribers over time, as well as more and more ACPs who identify additional patients and prescribe because they see the value of MCI 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've had success on MCI 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 gating access over the last quarter. According to Medicaid, there are approximately 85 million individuals enrolled in Medicaid in all 50 states, plus Puerto Rico and the District of Columbia. Laws to date, approximately 80% of Medicaid-covered lives are in states with a positive and slippery 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 MCIVRI policy. The remaining 20% of Medicaid lives represents a mix of states in which we either have not yet had a prescription for MCIVRI 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 BVS does remain consistent, as almost 90% of prescriptions since launch fall under commercial or Medicaid plans. The average time frame for approval is approximately one to three months, with some tails extending out several months, consistent with our previous reports. Overall, we are pleased with achievements to date and securing approval. Next slide. Here are some details on patients with BBS with prescriptions and on drugs. Adults now account for approximately 54% of prescriptions received since launch. This speaks to an opportunity identified up front. In the CRWS 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 believed 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 promotions, educational webinars, engagement with the BBS Foundation, and more. Catherine, the woman on my opening slide today, is a prime example of this. She found us with a little digital help after MCFRI 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 plans do have three or six-month reauthorization requirements. We are very pleased to report that, launched to date, we have seen 50 reauthorization approvals with only one 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 MCFRI 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.
spk00: Thank you, Jennifer, and good morning. Slide 20, I will start with a reminder. Europe is a key market for rare diseases and for rhythm. As we have spoken of 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 groups. Even though these diseases are quite rare, the opportunity is meaningful for us in both POMC-LiPAR deficiencies and barbiviral syndrome. In the EU4 plus UK, we estimate the prevalence for biallelic POMC and LiPAR to be between 600 and 2,500 patients. and we have identified approximately 100 patients being cared for in these countries. For Barbie-Biddle syndrome, our estimated prevalence in the EU4 plus UK is 4,000 to 5,000 patients, which is a prevalence similar to the US, 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, MCIVERY is now available in more than 10 countries outside the United States. We are now approved and available for both POMC and LIPAR and BBS in Germany. In France, we are available for these same indications under a paid early access program. We also have full coverage for MCIVERY for POMC and LIPAR in England, Italy, and the Netherlands. And we are advancing with pricing negotiation for BBS in the UK, Italy, Spain, and the Netherlands with BBS launches planned in Italy and Spain for this year and in 2024 in the UK and in the Netherlands. We also have achieved in Spain, Austria, Turkey, United Arab Emirates, and early access in Argentina. And we have initiated reimbursement processes in Belgium and the Nordic country. Next slide. Lastly, an update on our launch for BBS in Germany, where the GBA, which is the German Federal Joint Committee, did recognize the fact that Emsiviri is a precision medicine, did exclude Emsiviri with an anonymous 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 lipar deficiency. 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 GMC4 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 at Home, This program is tailored to each patient, designed to educate patients and caregivers to set expectations for MCV and to maintain adherence. With that, I will turn the call over to Hunter.
spk01: Thank you, Jan. With robust demand for MCV in 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 the 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 16th 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 MCV 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 under Q1 at a lower than normal level of five days and ended Q2 at a more normalized level of 12 days. This impact contributed $1.6 million to Q2 revenue. Growth 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, it 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 due to Ipsen under our original licensing agreement for St. Melanotide, 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 2022. 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 Shinto 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 Q123. This increase was primarily due to an increase of $2.4 million in U.S. marketing spend, as well as a $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 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 MCVRI 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 smaller base than the growth rate of MCVRI 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 2023. 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 at $220 million. This guidance excludes the non-cash impact of stock-based compensation. With that, I'll turn the call back over to David.
spk02: 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 and 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.
spk09: As a reminder, to ask a question, please press TAR11 on your telephone and wait for your name to be announced. To withdraw your question, please press TAR11 again. Please limit your questions to one and one follow-up only. Thank you. Please stand by while we compile the Q&A roster. And our first question comes from the line of Divya Rau with T.D. Cohen. Your line is now open.
spk08: Good morning, guys. Thanks for taking our question. I'm Divya on first. So just two 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?
spk02: Yeah, I think to be. So the 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 four to five different genes. 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.
spk08: 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 BVS?
spk02: Jennifer?
spk10: 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 Scripps.
spk08: And how do you expect that to change in the long term? to be relatively consistent?
spk10: So we have made incremental progress just in terms of securing access for MCFRI as outlined in terms of the Medicaid portion. And that is a work that is ongoing in terms of going pair by pair to educate them and differentiate our patient population as well as MCFRI. And we have seen success on that, and we're not going to give up in terms of those efforts overall. You know, approximately 10% of the scripts are Medicare patients where we do not have access. 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, you know, our coverage from large commercial plans is quite good in terms of reimbursement. It's the smaller, you know, really small self-insured plans that, you know, I think in general rare diseases may have difficulty gaining reimbursement for, you know, the cost of therapy.
spk08: Got it. Thank you so much.
spk02: Thank you, David. Next question.
spk09: Your next question comes from the line of Derek Archula with Wells Fargo. Your line is now open.
spk03: Hey, good morning, and thanks for taking the questions. Congrats on the progress. Just first question from us, just any updates on the overall discontinuation rates you're seeing within Sivri? I guess across all indications, but maybe barred beetle specifically. And then secondly, I know, you 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 I'm just curious, like, is that going to mimic the U.S., or should we think about it differently? Thanks.
spk02: Yep. Jennifer, discounts?
spk10: Overall, we're very pleased with the discount 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 getting patients through the initial titration stage and 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, you know, as they're situations may evolve over time as well.
spk02: Great. And Jan, you want to comment on the expected German ramp or how you think about that?
spk00: Sure, sure. Thank you. 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 add many prescriptions from several major centers and it will continue. The second thing is that, back to your questions, 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 are telling us that we will build a solid growth on the long run.
spk03: Perfect.
spk02: Thank you. Next question.
spk09: One moment. And your next question comes from the line of Corrine Jenkins with Goldman Sachs. Her line is now open.
spk06: Good morning, everyone. 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 three studies with that asset?
spk02: 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 one, two 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 one is pretty conventional with a phase one drug.
spk06: 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 populations?
spk02: I'll take that. I think... These are the things we know. One is if you look at the CRIBS 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 then the last thing before I get to the 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 distribution overall, a quarter peds, three-quarter adults, some What's really encouraging about the information that Jennifer presented is that we are penetrating to a significant degree that adult population. They're finding us. They want to go on therapy, and they're staying on therapy.
spk06: Great. Thank you.
spk12: Next question.
spk09: Your next question comes from the line of Diagon Hall with Stiefel. Your line is now open.
spk05: Great. Thanks very much for taking our questions and 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 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 a third that you've activated right now, is the one-third still out of the 35? Do you still anticipate 35 to be activated, or do you think you can kind of muster with maybe two-thirds of that 35 to satisfy your overall 120. Thanks so much.
spk02: Maybe I'll take the last question first. So on the number of sites, I think the number of sites will probably end up opening given the strong patient interest and the like in the full 35, so we expect it will be somewhat less than 30. So that's the answer to that. And Jennifer?
spk10: Just relating to the projections for the rest of the year, what I was 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 one 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 physician. 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 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, we're a 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. Great.
spk02: Yeah, and Dagon, 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. There's 4,000 to 5,000. Again, we're learning more and more, you know, much, much more than we did, of course, when we first launched. So confidence there is extremely high. And, you know, not to, you know, over beat this course too much, it's the quarter and quarter piece, you know, Again, the nature of rare diseases, which is why we keep reiterating this, it is going to be variable. It'll be up, it'll be down. 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 one-year view here. And our confidence that this is going to continue to grow meaningfully over the next subsequent quarters is very high.
spk05: Sounds good.
spk02: Congrats.
spk12: Thanks.
spk09: And your next question comes from the line of Michael Higgins with Leidenberg Coleman. Your line is now open.
spk13: Thanks, Amber. Good morning, guys. Thanks for taking the questions, and I'll share my congrats on the continued success with the launch of BBS enrollment progress in HO. Daybreak's one of the bigger drivers here, this back half. You've got a lot of things going on, of course, but just wanted to poke in a bit. somewhat of a follow-up from a previous question, 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? Thanks.
spk02: Yeah, Michael, so more to come. I think, you know, what we will put out, so the data cuts, you know, we're looking at now are still rough and not final, one, so caveat. Two, we'll determine how best to present the data. Again, as I said, 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, number one. What we would consider for sure, as you indicated, is A, how robust is the response, and two, how prevalent is that particular gene? If we have one, if 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, you know, run a trial just given a small prevalence. So we'll take all that into consideration. I do want, you know, to remind everybody that the bar for taking things forward is high. So I anticipate taking things forward just because we see a signal. We'll 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. And, you know, you heard about the 718 program today. We're going to be incredibly focused on pushing that forward as well.
spk12: Next question. Yes, you are still on. Sorry.
spk02: Is there another question?
spk12: Operator? Yes.
spk09: We can hear Michael. I can hear Michael.
spk02: Oh, we can't. We can't hear Michael.
spk13: Michael, you're still there? Okay, there you go. We got you. Oh, there we go.
spk02: Sorry about that, guys. We got you.
spk13: Don't worry. 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 and your appetite for expanding the pipeline for Obviously, you've got 718 going forward. You've got some Bento activity. But curious to hear your appetite for expanding the pipeline. Thanks. Yeah.
spk02: Again, the 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 and 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 then we'll continue to assess other opportunities as they might arise, but no specific focus on additional acquisitions. I appreciate that. Thanks again. Thank you. Next question.
spk09: Your next question calls to the line of Joseph Traer with Dido Mancoa. Your line is now open.
spk07: Hi, good morning. Thanks for taking our question. Just curious, what percent of patients on NCVRI have titrated back down to the lower daily dose, so down either to the one meg or the two meg dose? And how has that evolved over time? Yeah.
spk02: BBS in the US is probably our best shot at that. Jennifer?
spk10: So overall, in terms of the doses, The majority of these patients are getting to the target three-mig 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 three-mig. It may be also because there's basically one titration step from two to three to get to the max dose of adults, but Overall, even within each of the segments, the majority of the patients are getting to the three-week 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 the benefits.
spk07: Great. Thanks for the additional color, and thanks for taking our question.
spk12: Thanks, Joye.
spk02: Next question.
spk09: Your next question comes from the line of Jeffrey Hung. With Morgan Stanley, your line is now open.
spk11: Hi, this is Michael Riad on for Jeff Hung. Thank you for taking our questions and congrats on the quarter. Can I just ask for a little bit more color on a previous comment for the one to three month period for translating scripts to sales? You had said that there was a tail end for some patients that it could extend out several months. What factors come into play there and what makes those patients more likely to have a longer process? Thanks.
spk10: So, you know, 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 delays in terms of the ACP 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 tail end patients and the patient support group as well as our access group and our TMS on ground really continue to be persistent in terms of working that process through.
spk11: Okay. Thank you. 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 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?
spk01: Sure, good question. And we certainly have factored that in. I think there are a variety of factors that 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.
spk11: Thank you very much. And congrats again on the quarter. Great. Thanks, Michael.
spk09: Again, to ask a question, please press star 1-1 on your telephone and wait for your name to be announced. And we have a follow-up question here from Michael Higgins. Thanks, Alberta. Can you hear me, guys?
spk13: Yes. Fantastic. Just to 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 St. Melanotide, 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 St. Melanotide, 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?
spk02: Michael, all good questions. Don't have the answers today. I mean, those are things we'll think about. A 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 if you highlight it. As I said, those are good questions in terms of strategies.
spk13: Appreciate it. Thanks, guys. Thank you, Michael.
spk09: And I see no further questions at this time. I will now turn the call back over to David Meeker.
spk02: Great. Thank you. Thank you all for turning in on the early day of August here. And we, 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 earning call and updating you further on the progress we can make. Thank you.
spk09: This concludes today's conference call. Thank you for your participation. You may now disconnect.
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