Rhythm Pharmaceuticals, Inc. (RYTM) Earnings Call Transcript & Summary

Good morning, ladies and gentlemen, and welcome to the Rhythm Pharmaceuticals Conference Call to discuss the FDA approval of IMCIVREE. [Operator Instructions] As a reminder, this conference might be recorded. I would now like to turn the call over to your host, Mr. David Connolly, Investor Relations and Corporate Communications. Sir?

Thank you, and thank you to everyone for joining us this morning to discuss the FDA's approval of IMCIVREE, setmelanotide, for chronic weight management in patients with obesity due to POMC, PCSK1 or LEPR deficiency. Please note the press release issued earlier today and presentation we're using for this conference call are available online on the Investors & Media section of our website, rhythmtx.com. Before we begin -- turning to Slide 2. Before we begin, I'd like to remind everybody that there will be forward-looking statements made on this call. Actual events or results could differ materially from those expressed or implied by any forward-looking statements such as final risk of -- as a result of various risks, uncertainties and other factors, including those set forth in the Risk Factors section of our annual report on Forms 10-K or 10-Q or any other filings that we make with the SEC in the future. In addition, any forward-looking statements made on this call represent our views only as of today and should not be relied upon as representing our views as of any subsequent date. We specifically disclaim any obligation to update or revise any forward-looking statements. Turning to Slide 3. On today's call are Dr. David Meeker, Chair, CEO and President of Rhythm Pharmaceuticals; Dr. Murray Stewart, our Chief Medical Officer; and Jennifer Chien, our Vice President and Head of North America -- Executive Vice President and Head of North America. Also, Hunter Smith, our Chief Financial Officer, is with us and available during the Q&A section. Now I'll turn the call over to David.

Thank you, Dave. So thanks to all of you for joining us today and allowing us to interrupt what for many, I'm sure, is a Thanksgiving break. The approval of IMCIVREE or setmelanotide for chronic weight management in patients with early onset obesity due to POMC, PCSK1 or LEPR deficiency is a major milestone for Rhythm, and it's an exciting moment for patients and families who have been living with the early onset severe obesity and the insatiable hunger caused by these deficiencies. So we look forward to sharing some of these -- some of the detail and implications of that approval with you today. So obesity, as we all know, is a common problem. What's often lost is that a subset of these individuals have a genetic defect driving their obesity. Invariably, they present to the physician, they're told to eat less, exercise more. Parents are often shamed, and this, of course, is not the optimal treatment paradigm that we would aspire to. And as the development program for IMCIVREE has shown, lives can be changed by addressing the underlying genetic defect. So we're very helpful -- very hopeful that today's approval, coupled with our broader effort to diagnose patients with these rare genetic deficiencies, will deepen our understanding of obesity and change that current paradigm of care. As with any disease where we deepen our understanding of the genetics and underlying biology, treatment can and should be individualized, and that door is opening for patients with early onset obesity due to POMC, LEPR, PCSK1 deficiency (sic) [ PCSK1 and LEPR deficiency ] today. On today's call, we'll hear from our Chief Medical Officer, Murray Stewart, and the newest member of our leadership team, Jennifer Chien, EVP and Head of North America. Hunter Smith, our Chief Financial Officer, is with us and available for Q&A. So I'd like to start with this first slide, Slide #5, and to many of you have seen this slide. This is a slide we like to use when we want to frame Rhythm and highlight the things we hope people remember about Rhythm. And it starts right with the title, and that in the title, we make -- we emphasize the fact that this is not a drug for a common obesity. We're not pursuing common obesity. This is all about treating a rare genetic disease that manifests with this severe early onset obesity. And the 3 buckets in the middle, these are the 3 milestones. The first milestone, which we hit today, and we'll come back to that in a minute. The second milestone and critical step on our journey is the better understanding and hopefully ultimate approval for 2 subsequent indications, Bardet-Biedl syndrome and Alström syndrome. And we look forward to reporting out our Phase III results from that development program at the turn of the year. As we said, that's a -- it's a larger community. More patients have been identified. It's -- those patients are more easily diagnosed because of the syndromic nature, and therefore, represents them a more meaningful opportunity at the start. And then the third bucket, this third milestone, which is perhaps some, at the end of the day, the most important piece, which is really understanding all of the genes, which are associated with this MC4 pathway, and that might, in fact, patients with mutations or in those genes might, in fact, benefit from setmelanotide and MC4R agonist. So going back to the first bucket, our milestone from today on this validation step, FDA approval. So the regulatory approval derisks the overall program. So that's huge. It validates the biology, showing that an MC4R agonist can restore function of an impaired pathway. And it gives us some, to be honest, greater confidence that the next step on our journey, which will be this Phase III readout of BBS and Alström syndrome at the turn of the year, will be positive. So in summary, today marks the beginning, not the end of a journey, for a therapy, which we believe may benefit many genes in this patient -- in this pathway and, of course, many, many patients with those genetic defects. And we'd like to think of setmelanotide is that classic pipeline and a drug. So let's now move more specifically to today's approval. So IMCIVREE is now approved. It's now the first FDA-approved therapy specifically indicated for chronic weight management in adult and pediatric patients, 6 years of age and older with early onset obesity due to POMC, PCSK1 and LEPR deficiency and confirmed by genetic testing. These obesities are all ultra-rare diseases caused by genetic variants that impair the melanocortin-4 receptor or MC4R pathway, which is responsible for regulating hunger, energy expenditure and body weight. People with these genetic deficiencies struggle with extreme insatiable hunger beginning at a young age, resulting in the early onset severe obesity and attendant comorbidities. So before we jump to the specifics of today's announcement and details on the label and our plans to make IMCIVREE available to patients, I do want to thank and congratulate the Rhythm team, many of whom I know are on the call today, for your dedication and hard work getting us to this point. This has been a long journey. It's just the beginning, but certainly a lot to celebrate here, and thank you. I also want to thank the FDA. I have to say, our experience with the FDA at a very difficult time there has been extraordinary. They partner with us all along the way to make sure that they could bring this in on time. And again, we're hugely appreciative of the roles they have played in partnering with us. I want to thank the investigators and their clinical staff and that there are clinical sites around the world who -- again, clinical trial work is never easy, clinical trial work in the area of rare disease can be particularly challenged and people never gave up and lost their focus. And finally, and most importantly, I want to thank the patients and the families who participated in and continue to participate in our clinical trials. Obviously, we can't do it without you. And getting it right is all about working in partnership with you. So with that, I'll ask Murray Stewart, our Chief Medical Officer, to provide some additional color on today's approval. Murray?

Great. Thank you, David. I'd also I'd like to echo my thanks to the patients, families and investigators for their dedication to the clinical trials and helping get IMCIVREE approved. As Dave said, the FDA were really very helpful with good clear lines of communication and that enabled us to get approval on time as the PDUFA date was today. So prior to IMCIVREE, individuals living with obesity due to POMC, PCSK1 or leptin receptor deficiency had no approved therapeutic options with little effect of interventions to manage their weight and their hunger. And it's really good that we're pleased to deliver our first in class medicine, which has demonstrated to specifically significant reductions in weight and hunger as well from acceptable safety and tolerability profile. On Slide 8, before we share with you the data on IMCIVREE, which led to the approval, I wanted to speak a bit about the MC4 pathway and provide an overview of the 3 genes named in the indication statement. So as you can see here, the MC4 receptors in the brain are involved in the regulation of hunger, satiety and energy expenditure. And the 3 genes, POMC, PCSK1, leptin are upstream of the MC4 receptor. And we know in patients with obesity due to these genes, it results in insufficient activation of the actual MC4 receptor. With IMCIVREE or setmelanotide point here comes in, it establishes the MC4 receptor pathway activity. And this is what enables patients to have reduced hunger and weight loss through decreased calorie intake and increased energy expenditure. On Slide 9, I'll take you through data from Phase III, which led to the approval. What you can see on the left is the graph of the weight loss over time in the POMC and PCSK1 patients. And at the 10 patients involved, 8 or 80% of the patients achieved greater than 10% weight loss at 52 weeks. What's interesting to notice in the placebo withdrawal period, in a 4-week period, there was a 5-kilogram gain in weight, which then reversed when patients went back on therapy. On the right, you can see the leptin receptor deficient patients. And out of the 11 patients enrolled, 5 of the 11 patients, 45% got to 10% weight loss at the end of the year. And again, what you can see is the steady declines in weight over time. When they go on placebo withdrawal, they gain weight and then go back to lose more weight. The weight loss is progressive over time. And if the drug is stopped, you can see the gain in weight. Our long-term data and supplemental data also support IMCIVREE's efficiency in weight loss and hunger reductions over the long term. We enrolled 4 supplemental patients with POMC and 4 supplemental patients with leptin receptor deficiency, and all 8 lost more than 10% at 52 weeks on therapy. Next slide. Slide 10, is the effect of IMCIVREE on hunger. The label does include significant discussions and presentation of the positive Phase III data from both studies, detailing the effect of IMCIVREE on hunger and weight loss. This table shows the worst hunger scores. We look at hunger in different ways. But here is the worst hunger scores in the last 24 hours. And in the POMC patients using a Likert scale of 0 to 10, patients had a median value of 7.9. And after 1-year's treatment, that dropped to a median value of 5.5. In the leptin receptor study, the median value was 7. And after 52 weeks, it was down to 4. And what's important to note as with the weight loss, if you stop the therapy and the placebo, hunger went up. You go back on the drug and hunger goes down. Very consistent with the mechanism and the evidence of IMCIVREE affecting the receptor. Now we'll go into a bit more detail about the label itself on Slide 11. So we're very pleased with the label. The label does include -- makes it very clear who IMCIVREE is for. So first one, IMCIVREE's indicated for chronic weight management in adults and children, 6 years and older. With genetically confirmed variants in the POMC, PCSK1, leptin receptor genes and these are the variants that according to ACMG are interpreted as pathogenic, likely pathogenic or of those variants of uncertainty. It's important to note that IMCIVREE is not indicated for patients with other genetic conditions or for the general obese population. There are no contraindications or black box warnings, but there are warnings related to disturbances in sexual arousal, depression, suicidal ideation and darkening of pre-existing nevi. Our next slide, it goes into a little bit more detail, Slide 12, about the dosing schedule. The dosing schedule, as expected, gives physicians flexibility with adults starting at 2 milligrams and up to 2 weeks increasing to 3 milligrams. Pediatric patients begin at 1 milligram and go up to 2 milligrams. If they need to get more weight loss, they can go up to 3 milligrams if this is tolerated. Physicians are encouraged to evaluate weight loss after 12 to 6 weeks on therapy, and this is consistent with our trial design and actually is very reflective of what would happen in real-world practice. Slide 13 shows our adverse events. IMCIVREE has been generally well tolerated and the safety profile has been remarkably consistent across the complete development program. The label lists all the adverse events reported over the course of the 2 52-week trials. And as you can see, the most common adverse events are localized injections site reactions, skin hyperpigmentation and nausea, the commonly reported ails. Of that that we treated greater than 440 patients with IMCIVREE throughout the clinical program, and many have been on therapy now for 2, 3 and a small number in 4 years. Now it's my pleasure to turn the call over to Jennifer and introduce many of you to her for the first time. Jennifer?

Thank you, Murray, and thank you, David. It's certainly been an exciting time for me to join the company. And for the past 2 weeks, I've experienced the energy and focus of an organization committed to transforming the care of individuals living with rare genetic diseases of obesity and bringing them this much-needed therapy. I'm thrilled to be here with David, Murray and the rest of the Rhythm team on the achievement of this important milestone. And as you heard from David earlier, working together with them on the many future milestones that lie ahead. Now moving to Slide 15. As an organization, we are moving forward with urgency because the unmet needs for patients and families with severe genetic forms of obesity and insatiable hunger are quite real and cannot be understated. We have a few quotes here from patient interviews conducted by our clinical teams during trials, which echo similar sentiments heard throughout the interviews. Starting with the quote on the left, "It became overwhelming. Planning meals, limiting access to food, instilling self-worth and confidence." And on the right, "We've worked so hard at trying to manage this condition. We've done everything, and we still feel powerless." What resonates is the impact of these diseases not only on the lives of patients but the lives of caretakers as well. The time commitment dedicated to planning very regimented meals and the energy invested to manage the disease is not insignificant. Nothing has worked. All their lives they have suffered with an insatiable hunger that feels like pain, which is very different than normal hunger signals. Now there is something we believe will work for them. Beyond the data Murray shared, we have heard from patients on therapy, and it's truly heartening, knowing IMCIVREE provides these individuals with hope. Moving to Slide 16. I'd like to share some details on how we plan to get IMCIVREE to these patients. Given the ultra rarity of POMC, PCSK1 and LEPR deficiency obesity, coupled with the fact that genetic sequencing related to obesity is still limited, we have decided to make IMCIVREE commercially available to identified patients in the U.S. without a commercial sales force. We expect IMCIVREE to be commercially available in the U.S. in the first quarter of 2021. Our immediate focus is on ensuring a positive experience for patients, caregivers and prescribing physicians, and delivering on that promise with an efficient scalable model. This is not a traditional launch, and we don't expect a traditional launch curve. Our prevalence estimates are 100 to 500 for POMC, PCSK1 and 500 to 2,000 for LEPR. And the current diagnosis rate is low. It's important to note that when we consider, we've had nearly 30 POMC, PCSK1, LEPR patients in our trials. The vast majority of them have been ex U.S. Also, all in, we may have identified upwards of 20 U.S. patients today, but some of them are younger than 6, the indicated age for therapy. In the first 2 years, we anticipate 10 of U.S. patients on commercial drugs. We do expect that number to grow over time, but it will be a slow ramp. Increasing awareness and diagnosis is crucial to our ability to find patients eligible for treatment. Since 2019, we have been working to implement a new paradigm for diagnosing rare genetic diseases of obesity. Our medical affairs field force is comprised of 11 medical science liaisons and 8 disease education liaisons in the U.S., and we have 8 disease education liaisons in the field in Europe. We have engaged with hundreds of health care providers as well as the community and respective medical, scientific and advocacy organizations to further disease awareness, educate on early onset obesity and hunger as hallmark characteristics of these conditions. And to also gain key insights into helping support these indications. Education is step one. Testing is next. To support genetic testing, we have launched Uncovering Rare Obesity, which has expanded access to genetic testing beyond academic centers into community physician practices in the United States. We already are seeing increased demand for genetic testing and a strong response from physicians, giving us confidence that our program will help us efficiently identify patients in the U.S. Our vision is that longer term, genetic testing will become standard of care for all people presenting with early onset severe obesity, and this will enable better care overall regardless of whether or not a particular patient is eligible for treatment with IMCIVREE. On the patient advocacy front, we are strengthening our relationships with existing groups, such as the Bardet-Biedl Syndrome Foundation and Alström Syndrome International, and we are laying the groundwork for new advocacy efforts for rare genetic diseases of obesity where none have existed. For eligible patients, we are focused on ensuring these patients have access to IMCIVREE. We will achieve this through our internal team's efforts in partnership with our specialty pharmacy who will serve as the primary point of contact for patients and health care providers. We are committed to providing comprehensive patient support offerings and will provide additional details on our patient support program when IMCIVREE becomes commercially available. Much of these activities also lay the groundwork for future potential launches while ensuring ongoing seamless support to patients within our current approval. With that, I'll turn the call over to David.

Thank you, Jennifer. I have to say we're thrilled that Jennifer joined us recently to lead our efforts in North America and co-lead the global integrated commercial strategies in close collaboration with Yann Mazabraud, who also recently joined us as EVP, Head of International. I had the privilege of working with both Jennifer and Yann for a number of years at Sanofi Genzyme and previously at Genzyme, and both bring deep experience working across a number of rare diseases, and they both share a foundational commitment to serving patients and building these communities. Now I want to address one last point relative to our commercial plan, and that's pricing. The therapy will be priced at $330 per milligram for an adult at the recommended dose of 3 milligrams per day, that translates to an approximate annualized cost of $360,000. If we take into account patients in the 6 to 12 age group who may receive a smaller dose, the dose titration period for each patient, which is 2 weeks, and an expected compliance rate, which, of course, we know will be less than 100%, we estimate that the blended annualized cost per patient may be in the range of $290,000 to $300,000 per patient per year. So how do we get to that price? In over 25 years in this industry, much of it working in rare diseases, I've come to appreciate a number of things. First, the pricing of any drug product, but particularly a product serving a rare disease population to reflect the unmet medical needs, the value the therapy affords and the size of the population to be treated. Second, specifically for a rare disease, pricing is very much a function of rarity. The orphan disease legislation in the United States defined an orphan disease as a population of 200,000 or fewer patients. A population in the 100,000 to 200,000 range is a very different population than a population of 100 to 5,000 patients, for example. And pricing should reflect that difference. Simply put, you don't get an orphan disease price when we get an orphan designation. It truly is a function of rarity. So IMCIVREE will serve a population of patients who suffer from a severe disease, as you've heard. I mean POMC, LEPR and PCSK1 deficiency (sic) [ PCSK1 or LEPR deficiency ] is not a choice. It's a consequence of their genetics, these individuals have an insatiable hunger drive, abnormal food-focused behaviors and may develop the physical comorbidities related to severe obesity, including diabetes, liver and cardiovascular disease. On top of that, many patients must deal with the psychological impact and the family stress associated with living with this disease. A healthy diet and exercise are not a cure for genetically disrupted MC4R pathway, and that requires genetic testing to find the problem and specific therapy to treat it. As you heard through Murray's presentation and comments Jennifer shared from patients, we believe we have a therapy that does just that. IMCIVREE, initially, will serve a population that we estimate in the tens of patients in the U.S. with POMC, PCSK1 or LEPR deficiency obesity, but that will grow over time. With Bardet-Biedl and Alström syndrome assuming Phase III and regulatory success, we could serve a patient population with an estimated prevalence, plus or minus 2,000 patients in the U.S. and more numbers ex U.S. Both of those groups keep us at that ultra orphan end of the spectrum. So in short, in setting this price, we did not want it to be a barrier to access, but recognized it needed to reflect the rarity of the population and the challenge that Rhythm and the community is facing to ensure these patients can be diagnosed and receive appropriate care. We also fully recognize that no health care system in the world is perfect, and patients do fall through the cracks. And as a company, Rhythm is committed to the best of our ability to working with these patients to get them the treatment they need. So with that, I'd like to go to Slide 18 and finish with this slide and looking ahead to the future. So Rhythm's journey to get here from licensing setmelanotide from Ipsen, submitting an NDA, securing breakthrough orphan drug and prime designations and seeing remarkable clinical data at each step of the way has been supported by these same efforts of community building, education and awareness and patient advocacy relations, all done just on a smaller scale. And now with this approval from the FDA, and our MAA being reviewed in Europe, we are looking ahead to what's next. So first, we have several additional value drivers, as I highlighted in my opening, on the near-term horizon with upcoming milestones, top line data from the pivotal cohort in Phase III BBS and Alström trial at the turn of the year; updated data from the HETs, SH2B1 and SRC1 cohorts in our Phase II exploratory Basket Study and an update on our genetic sequencing data early in 2021. And of course, the first commercial availability of IMCIVREE. So additionally, along with the approval of IMCIVREE, we are very pleased to have received a rare pediatric disease priority review voucher, or PRV. This voucher is an incentive to encourage the development of new drugs and biologics for the prevention and treatment of rare pediatric disorders, and we can use this voucher to receive priority review on one of our own future marketing applications that would otherwise be a standard review or we can transfer the voucher to another company as a source of nondilutive financing. So taken together, we're concluding 2020 and entering 2021 in a position of tremendous strength. We received our first FDA approval, not a small milestone for any company. We are weeks away from our next Phase III data readout, which has potential, if successful, to set us up for a supplemental NDA filing for BBS and Alström in 2021. And importantly, we're advancing a broad increasingly derisked clinical program and additional indications. We look forward to updating you further as we continue our efforts to transform the care of patients with rare genetic disorders of obesity. So operator, I'd now like to open up the call for questions.

[Operator Instructions] We have our first question from Phil Nadeau from Cowen & Company.

Congratulations on the FDA approval. It's impressive, given the environment that we're in. A couple of questions from us. First, just on the commercial launch in the first quarter of next year, what do you need to complete before that launch can get underway? Are the medical affairs professionals all on board? Do they need to be hired? And kind of what else needs to happen?

Yes. Thanks, Phil. So let me -- I'll lead off and then let Jennifer complete here. So just on the CMC side, we have the packaging, labeling part of this, and we are working out of Europe and working with third-party vendors there. So we'll -- and needless to say, I think Europe has had a little bit of pressure from the COVID situation. So that's a first critical step. From -- otherwise, organizational infrastructure, Jennifer, do you want to comment on some of the additional plans in place to be prepared here?

Sure. As I mentioned, we already have a medical field force that's in place with the MSLs as well as the disease education liaison. We do not have plans to supplement this with any additions of a commercial sales team just based off of the size of the patient population. And we definitely are moving forward just in terms of having a comprehensive patient support program that will be in place for commercial availability.

Great. That's very helpful. And then second, just on a couple of the warnings. First, on the suicidal ideation, I didn't recall that being a side effect in any of the trials. Did I -- did we miss that? Or is that simply a cause effect whenever you have some mention of depression or depressed mood for a compound?

Yes. Good question. Murray?

Yes. So I mean, this background population does have depression and suicidal ideation. There were 2 SEs of depression and 1 SE of suicidal ideation that we shared, and we shared a detailed poster in the toss. They were not thought to be drug-related or no evidence of worsening of that. The letter clearly relates this to all compounds in the class rather than this necessarily being specific to IMCIVREE.

Got it. That's helpful. And then second is on the -- sorry, go ahead.

No, no. I just want to say, I mean, kind of the challenges are working sometimes with these small trial data sets, and you can't always rule out some of these things. So there are observations in the trial, as Murray said.

Okay. Perfect. And then the second question is just on the benzyl alcohol preservative. What ages does that limit? Clearly, your label is only down to age 6 currently, but would that prevent you from getting an extension to younger patients eventually? Or is that really truly just something that pertains to infants.

Yes. Murray?

Yes. And so that does pertain to infants. It's really a problem called the gasping syndrome that's been identified in neonates. So we're confident we can get the -- the next stage is to get down to 2 to 5. I mean, with the genetic obesity, it really starts manifesting when -- after breast feeding when you start getting to the 2 to 5-year olds. So we wouldn't really envisage going to neonates anyway. But I think as in any compound, as benzyl alcohol, given is a risk for neonates, that's clearly why is in the label, but it won't restrict us going to 2 to 5.

Perfect. That's very helpful. Congratulations again.

Okay. Thank you.

Next question is from the line of Derek Archila from Stifel.

Great. Congrats, guys. So just 3 from us. So first, there's some language in the label around uncertain variants in a run-in period. So I was just curious if you can talk about whether this is something that the FDA asked for or you proposed? And how this might lead through to a potential Phase III Basket Study? That's my first question. The last 2 would be in terms of pricing. You talked about the U.S. pricing and the blended there. How should we think about from a model perspective for EU pricing? And then lastly, how long do you think it will take for patients in the U.S. to eventually go from study drug to paid drugs?

Yes. Okay. So Murray, do you want to take the first question? 2 parts there, one is on the implications of the VUS, and the second is some thoughts on the run-in period.

Yes. So this was done in collaboration with the FDA. We actually have been using ACMG in our clinical trials. Categories are pathogenic, likely pathogenic and VUS benign. We had 1 patient in the POMC who was benign and didn't respond and that is consistent with what we thought because they don't really have a vein that's causing a problem. They shouldn't get the drug, and that's what it says in the label. Regarding the VUS, it's an interesting category. And sometimes you could say, well, if you're not certain, should you get the drug? In our clinical trials, we did have people who had a combination of pathogenic in one allele and a VUS in other allele. And we recommended that we will include VUS in the label and the FDA agreed with us on that. That's also pertinent to the fact that if it was significant, you should see the weight loss in the trial period of 12 to 16 weeks, and this is very consistent with our trials, a good pattern. So I think it certainly makes sense to follow the ACMG guidelines, the pathogenic, likely pathogen and VUS. And I think it will help us moving forward with our clinical trials to the other point in that we have a clear way to look at patients in terms of their variants and a way to move forward with clinical assessment.

Thank you, Murray. So Derek, I think on the -- your second question on pricing, the EU pricing, we are still doing "pricing research" in Europe. As you know, Europe is a -- not the United States of Europe. And so you have the country-by-country assessment, and there will be different conclusions per country. We do expect the price in Europe to be less. I think it would be unusual if it was anything but that. That said, it's critical again for both approaching any health care system in the world, U.S. or elsewhere, that people understand and see this as a treatment for a rare genetic disease and a treatment for simple common obesity or a lifestyle drug. And I think we've made good progress on that. There's more to do. But it's a long way of saying, I don't have an answer for you on the EU and I can't give you a number for your -- for the model, so to speak. But we do expect it to be less, but I also -- I think we have growing confidence that it will be a product that reflects both the value and the rarity of the drug. So more to come on that. And then your last question, which was just how long from study drug to paid drug, and maybe I'll let -- Jennifer, you want to comment on -- just some thoughts on that? We're early, but you may have some thoughts.

Sure. So this is one of those cross-team collaborative discussions that's ongoing with the commercial, clinical and medical teams. The first priority is to make sure that there's absolutely no gap in terms of treatment as the patients are transitioned over. So we are thinking through and discussing the optimal timing in terms of scheduling of the last patient visit. Also taking into consideration that early on in terms of approval, it takes a bit of time or can take a bit of time for a benefit verification. So those discussions are active and ongoing, and we are putting together plans.

Great. Congrats again.

Thank you. Next question?

Next is from the line of David Lebowitz from Morgan Stanley.

My first question is on -- and congratulations on the approval. My first question is on reimbursement from the payers. Historically, they obviously have not been terribly amenable about reimbursing for obesity drugs. But clearly, these are for different types of obesities. What have those discussions been like to this point?

Yes. Thanks, David. Jennifer, do you want to comment?

Sure. So we have had insights from the payers through various different points, including payer-focused market research, payer adboards as well as discussions with individual payers. Our dialogues have been positive and that they also recognize that this is not general obesity. It is genetic diseases that are actually caused by mutations. That segment -- out of that patient population and segment their need for therapies in a different way. Also, they understand the sizes of the patient populations as well. So the discussions have been positive and aligned in terms of the -- also the pricing that David has outlined.

And as far as not actually implementing a traditional sales force at this point, it's understandable given the small population. Could you just run us through how that process actually would work in going from the patient to the doctor, getting the patient drugs?

Yes, Jennifer?

So the discussions with the physicians, just in terms of awareness about IMCIVREE could potentially based off of the size of the patients that have been identified, be an opportunity for our commercial marketing team to also be able to engage in those discussions versus having many different sales reps on the ground right now. So there's opportunities even without a traditional sales force to be able to have the discussions in terms of -- as patients are potentially identified, and there's physicians who are interested in learning more, they can either have that dialogue with somebody within our commercial team or call in and proactively ask questions around products that can be handled by our med info line as well.

Yes, thanks. And David, I might just add to build a little bit on Jennifer's comments. One of the key aspects and the reason we don't have a sales force today, as you said, one very, very small population that we're pursuing, knocking on doors does not work. And the most important thing we can do from a commercial effort standpoint is to focus on building the education, getting physicians confronted with a patient with early onset obesity and an abnormal hunger drive to be thinking this is not usual obesity, and they should be thinking genetics. So the #1 effort here is to get people thinking and testing. And if they test, then we're more than halfway there in the sense that having gotten back a result that indicates that they have a mutation in a gene, in this case, POMC, PCSK1 or LEPR, that would make them eligible for potential treatment. This becomes this virtual circle, right, where they had a positive hit. There's something to be done. There's a reason to test. And so they start testing more and so they then find us. And as Jennifer said, we can service that commercial effort with, call it, an inside sales effort very efficiently. But the #1 thing that's going to drive the number of patients in these 3 genes is the broader effort to develop this MC4R pathway indication for the drug.

We have our next question from the line of Tazeen Ahmad from Bank of America.