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 speakers' presentation, there will be a question-and-answer session. [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. Please go ahead.

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 Web site 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 Web site. As listed here 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 presenting our views 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 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 think all of your 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 and signaling through the MC4 pathway leads to hyperphagia. That uncontrolled hunger that stems from not getting a signal that you were 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 GLP1, 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 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 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…

Thank you, David. We are now one 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 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 in IMCIVREE therapy. On this slide, you see a picture of Kathryn who was diagnosed as 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 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 effort, attended one of our programs to learn about IMCIVREE and began participating in our InTune patient support service program. Almost one year in, she tells us how she is sleeping better, able…

Thank you, Jennifer, and good morning. Slide 20, we start with a reminder. Europe is a key market for rare diseases [indiscernible]. 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 and 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 or LEPR deficiencies and Bardet-Biedl syndrome. In the EU4 plus UK, we estimate the prevalence for biallelic POMC/LEPR to be between 600 and 2,500 patients, and we have identified approximately one of the patients being cared for in these countries. For Bardet-Biedl syndrome, our estimated prevalence in the EU4 plus UK 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 more investment and access for these patients. Next slide. Overall, we're a global leader in IMCIVREE now available in more than 10 countries outside the United States. We are now approved and available for both [indiscernible] and BBS in Germany. In France, we are available for the same indications under paid early access program. We also have full coverage for IMCIVREE for [indiscernible] in England, Italy and the Netherlands. And we are dancing 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…

Thank you, Yann. With robust demand for IMCIVREE in the United States and our growing international business, our focus remains on building long-term value for our shareholders through excellence and 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 77.8 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 five days and then in 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 product costs, our 5% royalty to Ipsen under our original licensing agreement for setmelanotide as well…

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. Your line is now open.

Good morning, guys. Thanks for taking our question. I'm Divya on for Phil. Just two footmarks, 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 you expect to present and also patients per cohort?

Yes. Thanks, Divya. So the DAYBREAK -- 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 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.

That's helpful. And then just one more question from us. 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 you expect 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 pair by pair to educate them and differentiate our 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.

Got it. Thank you so much.

Thank you, Divya. Next question.

Your next question comes from the line off Derek Archila with Wells Fargo. Your line is now open.

Good morning. 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 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 we think about it differently? Thanks.

Jennifer?

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 patients through the initial titration stage and through the initial nausea, vomiting, and we have had very, very low discounts from that perspective. And I think that there are a variety of different reasons that patients do discount, some due to an ease, 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, you want to comment on the expected German ramp or how you think about that?

Sure. Thank you. We had a strong start in Germany with a very experienced team in the field. It's 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, which will continue. The second thing is that back to your questions, we don't expect a fast ramp up as we have in the U.S. because of the German conservative mindset. But for sure, we are all signals that are telling us that we will build a solid growth on the long run.

All right. Thank you.

Next question.

One moment. And your next question comes from the line of Corinne Jenkins with Goldman Sachs. Your line is now open.

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 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. And 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 1 coverage.

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?

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, their disproportion 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 mainly as 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, 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.

Great. Thank you.

Next question.

Your next question comes from the line of Dae Gon Ha with Stifel. Your line is now open.

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 some couple of months ago that was realized up? And I guess given this 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 is 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.

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 getting 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 will just say right now is that we are extremely excited about the opportunity and feel that there's 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 death 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. Some of these scripts that we saw come in, it was many, many months of interaction and education that our TMs [ph] 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.

Great.

And 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. Again, we're learning more and more. We know much, much more than we did, of course, when we first launched, so confidence there is extremely high. And that's an over beat this horse [ph] said too much. The quarter-on-quarter piece, given 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.

Sounds good. Congrats.

Thanks.

Thanks. And your next question comes from the line of Michael Higgins with Ladenburg Thalmann. Your line is now open.

Thanks. 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 is one of the bigger drivers here this back half. You 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, and understand what we are to be looking for. I assume at 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.

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. Two, we'll determine how best to present the data. Again, individuals, if there's a small number of patients in a specific cohort, we will 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? 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, it 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 just because we see a signal, we want to have some confidence that it's robust, and we can execute on the trial and relative to all the other things that we have to do. And you heard about the 718 program today. We're going to be incredibly focused on pushing that forward as well. Next question?

Yes, you are still on.

Sorry, is there another question or --? Operator?

Yes. We can hear Michael. I can hear Michael.

We can't hear Michael. Michael, are you still there? There we go. We got you.

Just one follow up here. And really once the new data 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? Thanks.

Yes. 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 our engagement with the world outside of 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 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.

Your next question comes from the line of Joseph Stringer with Needham & Co. Your line is now open.

Hi. Good morning. Thanks for taking our questions. Just curious, what percent of patients on IMCIVREE have titrated back down to the lower daily dose, 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 remake 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 the benefit.

Great. Thanks for the additional color and thanks for taking my question.

Thanks. Next question?

Your next question comes from the line of Jeffrey Hung with Morgan Stanley. Your line is now open.

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 months 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.

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 delays 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, we have definitely gotten approvals, even within those groups of tail end patients in the patient support group as well as our access group, energy on some ground really continue to be persistent in terms of working that process through.

Okay. Thank you. That's very helpful. And then maybe just a follow up, maybe more of a housekeeping question. Your 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?

Very 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.

Thank you very much and congrats again on the quarter.

Great. Thanks, Michael.

[Operator Instructions]. And we have a follow-up question here from Michael Higgins from Ladenburg Thalmann.

Thanks, operator. Can you hear me guys?

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 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, it's something positive, of course, would you -- is it fair to assume you would open up a broad basket study with all the patient types you've tested and possibly additional patients?

Michael, all good questions. Don't have the answers today. Those are things we'll think about. The number of choices, you've highlighted some of them about how you develop an asset that says this. But first step again is there's not much to negotiate there. We'll just get through that. And while we're doing that, we'll evaluate the tests that you've highlighted. As I said, those are good questions in terms of stress.

I appreciate it. Thanks, guys.

Thank you, Michael.

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 joining in. Early day of August here and we as you hopefully you've 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 we can make. Thank you.

This concludes today's conference call. Thank you for your participation. You may now disconnect.