Q4 2023 Rhythm Pharmaceuticals Inc Earnings Call

Okay.

Operator: Ladies and gentlemen, thank you for standing by. Welcome to Rhythm Pharmaceuticals' fourth quarter and full year 2023 earnings conference call. At this time, all participants are in the listen-only mode.

Speaker Change: Ladies and gentlemen, thank you for standing by welcome to rhythm Pharmaceuticals fourth quarter and full year 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.

Operator: After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you will need to press star 11 on your telephone. You will then hear an automated message advising that your hand is raised.

Speaker Change: To ask a question during the session you will need to press star one on your telephone.

Speaker Change: Didn't hear an automated message of bites in your hand, just raised to withdraw your question. Please press star one one again please be advised that today's conference is being recorded I would like now to turn the conference over to David Connolly Investor Relations and corporate Communications. Please go ahead.

Operator: To withdraw your question, please press star 11 again. Please be advised that today's conference is being recorded. I would like now to turn the conference over to David Connolly, Investor Relations and Corporate Communications. Please go ahead.

Speaker Change: Yes.

David Connolly: Thank you, Michelle. I'm Dave Connolly here at Rhythm Pharmaceuticals. For those of you participating in the call... Our slides can be accessed and controlled by going to the Investors section on the Investors page of our website, ir.rhythmtx.com. This morning, we issued a press release that provides our fourth quarter and year-end 2023 financial results and a business update, which is available on our website. As listed on slide two is our agenda. Here with me today in Boston are David Meeker, Chair, Chief Executive Officer, and President of Rhythm Pharmaceuticals; Jennifer Lee, Executive Vice President, Head of North America; Hunter Smith, our Chief Financial Officer; and Jan Mazabro, 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.

David Connolly: Thank you Michele I'm, Dave currently here at rhythm Pharmaceuticals for those of you participating on the conference.

David Connolly: The slides can be accessed in control by going to the investors section on the investors page of our website IR dot rhythm TX Dot com.

David Connolly: This morning, we issued a press release that provides our fourth quarter and year end 2023 financial results and a business update which is available on our website.

Speaker Change: Listed on slide two is our agenda here with me today in Boston are David Meeker Chair, Chief Executive Officer, and President of Rhythm Pharmaceuticals, Jennifer Li Executive Vice President head of North America Hunter Smith, our Chief Financial Officer, and Jan Madsen, <unk> Executive Vice President and head of International is on the line joining us from Europe.

Speaker Change: 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 in our most recent annual or quarterly <unk>.

David Connolly: Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in our most recent annual or quarterly reports on file with the SEC. In addition, any forward-looking statements represent our views as of only today and should not be relied upon as representing our views as of any subsequent dates. We specifically disclaim any obligation to update such statements.

Speaker Change: <unk> on file with the SEC. In addition, any forward looking statements represent our views as of only today and should not be relied upon as representing our views as of any subsequent dates we specifically disclaim any obligation to update such statements with that I'll turn the call over to David Meeker, who will begin on slide five.

David Connolly: With that, I'll turn the call over to David Meeker, who will begin on slide four. Thank you, Dave. Good morning, everyone.

David P. Meeker: Thank you Dave Good morning, everyone and thank you for joining the call.

David P. Meeker: And thank you for joining the call. So 2023 was truly a transformational year for Rhythm, commercially, developmentally, financially, and strategically, as we have expanded potential indications for Next Generation Pharmacy. 2024 will be a year focused on execution, setting up an exciting year of milestone achievements in 2025. So on slide five, we've got the three boxes which highlight the important aspects of Rhythm. And on the first box, HO remains the cornerstone of Rhythm value.

David P. Meeker: So 2023 was truly a transformational year for rhythm commercially developmentally financially and strategically as we have expanded potential indications.

David P. Meeker: Next generation products.

David P. Meeker: 2024 will be a year focused on execution setting up an exciting year of milestone achievements in 2025.

David P. Meeker: So on slide five we've got three buckets boxes, which highlight the important aspects of rhythm.

David P. Meeker: <unk> box.

David P. Meeker: <unk> remains the cornerstone of rhythm value, we finished the year, having over enrolled our phase III trial now with all 120 patients and the primary analysis cohort dosed.

David P. Meeker: We finished the year having over-enrolled our phase three trial, now with all 120 patients in the primary analysis cohort dosed, and these 120 will form the basis of the US and EMA filings, keeping us firmly on track for the first half 2025 top line readout. Execution in that trial remains strong with a high level of site and patient engagement. We're excited also to announce that today we have concluded extremely constructive interactions with the Japan Regulatory Authority, the PMDA, which will allow us to include 12 Japanese patients in the phase three trial without requiring an independent study in Japanese patients. Japan is continuing to evolve its regulatory process to further facilitate the development of innovative medications for the Japanese population.

David P. Meeker: This $1 20 will form the basis of the U S and EMA filings keeping us firmly on track for first half of 2025 top line readout execution in that trial remains strong with a high level of site and patient engagement.

David P. Meeker: We're excited also to announce that today, we have concluded extremely constructive interactions with the Japan regulatory authority, the <unk>, which will allow us to include 12 Japanese patients in the phase III trial without requiring an independent study in Japanese patients, Japan is continuing to evolve the regulatory process to further facilitate the.

David P. Meeker: <unk> innovative bit innovative medications for the Japanese population and they were highly motivated to ensure that the Japan patients would be able to participate in the call.

David P. Meeker: And they were highly motivated to ensure that the Japanese patients would be able to participate in the call, in the phase three trial. We were joined in our interactions by one of the leading experts in Japan, who helped them understand the severe unmet medical need and the potential benefits of cephalanotide. What's particularly interesting about Japan Opportunity is that the prevalence of HO is two times higher than in the U.S., with our initial epidemiology work suggesting there are 5,000 to 8,000 patients, which is about the same number as in the U.S., albeit with a population a little more than half the size of the U.S.

David P. Meeker: Phase III trial, we were joined in our interactions by one of the leading experts in Japan will help them understand the severe unmet medical need and the potential benefit out separately Monotype.

David P. Meeker: What's particularly interesting about Japan opportunity is that the prevalence of <unk> is two times higher than in the U S. With our initial epidemiology work, suggesting there are five to 8000 patients which is about the same number as in the U S, albeit with a population of little more than half the size of the U S. So this opportunity plays forward.

David P. Meeker: So if this opportunity plays out as we think it will, the Japan opportunity could become the second most valuable part of the overall Rhythm portfolio behind the USHO opportunity. So Jan will expand more on that epidemiology and our plans going forward. Second, we made great progress advancing several programs. Both our newly acquired daily small molecule from LG Chem and our weekly formulation 718 are progressing well. I'll comment further on those in a couple of slides.

David P. Meeker: As we think it will the Japan opportunity could become the second most valuable part of the overall rhythm portfolio behind the U S. H O opportunity, so Jan will expand more on that epidemiology and our plans going forward.

David P. Meeker: Second we made great progress advancing several programs both our newly acquired daily small molecule from LG Chem and our weekly formulation seven eight are progressing well I'll comment further on those in a couple of slides with regard to the pediatric program I will show again to slide you've seen before reminding you of the strength of that data in.

David P. Meeker: With regard to the pediatric program, I will show you two slides you've seen before, reminding you of the strength of that data and why we think it is so important. We have filed, as previously reported, to expand the use of insurgery to patients between the ages of two and five in the US, sorry, in the EU, and we'll file in the US in the first half. Third, we had another solid quarter commercially with $24.2 million in revenue, over 100 new prescriptions, and more than 70 approvals for reimbursement. We are excited about our recent reimbursement approvals for BBS in Spain and Italy. And with those two approvals, Incivory is now available commercially in 14 countries, including the U.S. and Canada. However, revenues in the quarter were impacted by a change in policy made by a single Medicaid program in one state in response to a disproportionately high volume of prescriptions.

David P. Meeker: Why do we think it is so important we have filed as previously reported to expand the use of <unk> to patients between the ages of two and five in the U S. Sorry in the EU and will file in the U S. In the first half of this year.

David P. Meeker: Third we had another solid quarter commercially with $24 2 million in revenue over 100, new prescriptions and more than 70 approvals reimbursement. We are excited about our recent reimbursement approvals for Bbs in Spain, and Italy, and with those two approvals and Sebree is now available commercially in 14 countries, including the U S and Canada.

David P. Meeker: Revenues in the quarter were impacted by a change in policy made by a single Medicaid program in one state in response to a disproportionately high volume of prescriptions. The state has a favorable policy in place and continues to cover patients, but is now requiring a higher level of documentation than previously required for example, if a.

David P. Meeker: The state has a favorable policy in place and continues to cover patients, but it is now requiring a higher level of documentation than previously required. For example, if a patient has eye findings consistent with the diagnosis of BBS, they will now require an ophthalmology consult to confirm the diagnosis, whereas previously it was simply the attestation of the prescribing physician. With this change in policy, 30 patients came off coverage early in the quarter and were transitioned to our bridge program, which is a free drug program provided while we work through coverage. There is no read-through to any other Medicaid program as this situation is unique to a specific demographic in this state with a higher prevalence of BBS patients who came on to treatment early.

David P. Meeker: Patient has I findings are consistent with the diagnosis of Bbs. They will now require an ophthalmology console to confirm the diagnosis, whereas previously it was simply the attestation of the prescribing physician with this change in policy 30 patients came off coverage early in the quarter and were transitioned to our bridge program, which is a free drug.

David P. Meeker: Program provided while we work through coverage issues.

David P. Meeker: There is no read through to any other Medicaid program. As this situation is unique to a specific demographic in this state with a higher prevalence of Bbs patients who came on to treatment early.

David P. Meeker: The impact of 30 patients coming off reimbursed treatment early in the quarter and going on to the BRIDGE program was about 2 million. Importantly, despite this dip in U.S. patient numbers at the start of the quarter, the remainder of the U.S. story continues to grow as expected, and we finished the quarter in a very good place. Jennifer will, of course, provide more color in her section.

David P. Meeker: The impact of 30 patients coming off reimbursed treatment early in the quarter and going onto the bridge program was about $2 million.

David P. Meeker: Importantly, despite this dip in U S patient numbers at the start of the quarter. The remainder of the U S story continues to grow as expected and we finished the quarter in a very good place and Jennifer will of course provide more color in her section.

David P. Meeker: So moving to slide six. So a little more on Japan. Typically, Japanese regulatory authorities require PK studies to be conducted in Japanese subjects in advance of testing and investigational therapy in patients. However, following extremely constructive discussions with Japan's Pharmaceutical Medical Device Agency, or the PMDA, we have agreed on a plan to enroll 12 Japanese patients into our current phase 3 trial. We will collect PK data in those 12 patients, and there will be no requirement to perform an independent study in Japanese subjects. Importantly, as I said, the additional cohort of Japanese patients and the timing for them to be added to and complete the study will have no impact on our timelines to complete the pivotal cohort, get to top line data, and submit our filings.

David P. Meeker: So moving to slide six.

David P. Meeker: So we're more in Japan.

David P. Meeker: Typically Japanese regulatory authorities require PK studies to be conducted in Japanese subjects in advance of testing an investigational therapy in patients. However, following extremely constructive discussions with Japan's pharmaceutical and medical device agency or the <unk>. We have agreed on a plan to enroll 12 Japanese patients into our current phase III trial.

David P. Meeker: We will collect PK data in those 12 patients and there'll be no requirement to perform an independent study in Japanese subjects.

David P. Meeker: Accordingly.

David P. Meeker: As said the additional cohort of Japanese patients and the timing for them to be added to and complete the study will have no impact on our timelines to complete the pivotal cohort get to top line data and submit our filings in the United States and Europe, specifically, we will file in the U S and EU on the results from the first 120 patients who finished the trial the rim.

David P. Meeker: Meaning patients the approximately 10 plus patients who are part of the over enrolled patient group outside of Japan, and the 12 Japanese patients will be part of a second close which will be used to support Japanese approval and we will of course seek orphan drug designation in Japan in parallel.

David P. Meeker: Specifically, we will file in the US and EU on the results from the first 120 patients who finished the trial. The remaining patients, the approximately 10 plus patients who are part of the over-enrolled patients, will be outside of Japan, and the 12 Japanese patients will be part of a second study, which will be used to support Japanese approval. And we will, of course, seek orphan drug designation in Japan and Paraguay. So on slide seven, this is just to remind you of our phase three trial design for HO, which you all know well. The phase three trials involve patients aged four years and older with hypothalamic obesity, randomized two to one to set melanotype therapy or placebo for a total of 60 weeks, which includes up to eight weeks for dose titration. The primary endpoint for this trial is the mean percent change of BMI from baseline after approximately 52 weeks on a therapeutic regimen of set melanotype compared with placebo.

David P. Meeker: So on slide seven this is just to remind you of our phase III trial design for HR, which you all know well.

David P. Meeker: The phase II trials enrolled patients aged four years and older with hypothalamic obesity randomized two to one to set monotype therapy or placebo for a total of 60 weeks, which includes up to eight weeks for dose titration. The primary endpoint for this trial. The mean percent change of BMI from baseline after approximately 52 weeks on a therapeutic regimen of step Atlanta time compared with placebo.

David P. Meeker: So we are 99 as we told you before at 99, 5% powered to achieve a 10 point differential between the therapeutic arm and placebo given our 12 month data showing consistent response across all patient to adhere to their prescribed therapy in the consistent safety profile separately and other indications we are quite confident in the outcome.

David P. Meeker: On slide eight speak a moment about LG <unk> molecule, we're particularly excited about the acquisition of the global rights for <unk> 641, Yes, we will be working on a name for that which we announced early in January we believe this drug candidate could provide patients with an important new treatment option and could be an important long term.

David P. Meeker: We are 99, as I told you before, 99.5% power to achieve a 10 point differential between the therapeutic arm and placebo. And given our 12 month data showing consistent response across all patients who adhere to the prescribed therapy and the consistent safety profile, set melanotype, and other indications, we are quite confident in the outcome. On slide 8, I'll speak for a moment about LG Chem's molecule.

David P. Meeker: <unk> value driver for our company LG Chem, a highly regarded company with deep chemistry, and early translational experience and expertise has developed an oral drug candidate that based on the early clinical data generated to date suggests they have identified a specific therapy for <unk> four are diseases that will not result in hyperpigmentation.

David P. Meeker: <unk> have associated cardiovascular side effects, we have had a highly collaborative working interaction with the <unk> team as we move to transfer full responsibility for the program to rhythm we anticipate the transfer it to be largely complete within three months of signing and remain on track for that in the meantime, we are jointly progressing the two trials with the primary focus being.

David P. Meeker: We're particularly excited about the acquisition of the global rights for LB54640 and the S., which we announced early in January. We believe this drug candidate could provide patients with an important new treatment option and could be an important long-term value driver for our company. LG Chem, a highly regarded company with deep chemistry and early translational experience and expertise, has developed an oral drug candidate that, based on the early clinical data generated to date, suggests they have identified a specific therapy for MC4R diseases that will not result in hyperpigmentation or have associated cardiovascular side effects.

David P. Meeker: On site initiation of the signal trial for Hypothermic obesity, a parallel focus will be undeveloped a pediatric formulation, which will allow us to move to treating the younger patients who as we know for both <unk> and the genetic causes of emcee for Patrick seasons are in need of treatment.

David P. Meeker: On slide nine a little more about the molecule EB 540 641. As previously described we were impressed by the robust preclinical package and by the data in their phase one study in healthy volunteers with obesity, which showed the expected dose dependent decrease in BMI at four weeks importantly, they did not see hyperpigmentation or any cardiovascular signal, which is <unk>.

David P. Meeker: We have had a highly collaborative working interaction with the LG team as we move to transfer full responsibility for the program to Rhythm. We anticipate the transfer to be largely complete within three months of signing and remain on track. In the meantime, we are jointly progressing the two trials, with the primary focus being on site initiation of the signal trial for hypothalamic obesity. A parallel focus will be on developing a pediatric formulation, which will allow us to move to treating younger patients who, as we know, for both HO and the genetic causes of MC4 pathogenesis are in need of treatment. On slide nine, a little more about the molecule LB54640.

David P. Meeker: System with the preclinical work.

David P. Meeker: Slide 10 shows the design of the signal trial, a phase 228 patient open label trial, sorry, Zeebo controlled trial to evaluate.

David P. Meeker: The molecule in patients with hyperkalemia obesity. The trial is designed to evaluate safety tolerability pharmacokinetics weight loss efficacy with an efficacy endpoint of mean percent change in BMI from baseline of 14 weeks. The trial has four arms three different dose groups and placebo and would be followed by an open label extension period of up to 52 weeks.

David P. Meeker: This is very similar to the exception of the placebo control to the trial. We ran originally with several Antitype NHL. We are fortunate to have a models such as <unk>, which appears to be quite sensitive to the effects of an empty for our agonist. So our expectation is that this relatively small trial will give us good insight into the efficacy safety.

David P. Meeker: As previously described, we were impressed by the robust preclinical package and by the data in their phase one study in healthy volunteers with obesity, which showed the expected dose-dependent decrease in BMI at four weeks. Importantly, they did not see hyperpigmentation or any cardiovascular signal, which is consistent with their preclinical work. Slide 10 shows the design of the signal trial, a phase two, 28 patient open-label trial, sorry, placebo-controlled trial to evaluate the molecule in patients with hypothalamic obesity. The trial is designed to evaluate safety, tolerability, pharmacokinetics, and weight loss efficacy, with an efficacy endpoint of mean percent change in BMI from baseline at 14 weeks. The trial is four arms, three different dose groups in placebo, and would be followed by an open-label extension period of up to 52 weeks. This is very similar to the exception of the placebo control to the trial we ran originally with sepmal antibody in HL. We are fortunate to have a model such as HL that appears to be quite sensitive to the effects of an MC4R agonist.

David P. Meeker: And importantly, the dose range, which we will look to develop as the program advances.

David P. Meeker: On slide 11, the 71 eight weekly program as I highlighted in my intro is advancing well. The IND is filed we reflected our CRM and are looking to dose our first patients in the first half of this year and I can tell you that we are aiming to have those first patients dosed in March here, we're committing to the first half of this year as a reminder, we will begin.

David P. Meeker: <unk> with single and multiple ascending dose cohorts and normal volunteer patients with obesity, followed by a part C, which one will H O patients followed for 28 days those patients will be eligible to enter into a long term extension study once we complete our chronic toxicity studies, which are required to support longer dosing and dose chronic toxicity studies are.

David P. Meeker: Ongoing and running in parallel now.

David P. Meeker: On Slide 12, my last two slides I wanted to revisit the data in pediatric patients. We showed at R&D day in December I find these results quite remarkable for a couple of reasons. One is that despite the extremely young age patients between the ages of two and five with either policy led by deficiency or BV as they were severely effect that you're not sure.

David P. Meeker: So our expectation is that this relatively small trial will give us good insight into the efficacy, safety, and importantly, the dose range, which we will look to develop as the program advances. On slide 11, the 718 weekly program, as I highlighted in my intro, is advancing well. The IND is filed.

David P. Meeker: Not be a surprise given the genetic cause of the disease, which means in most cases. It has been present since birth. Despite this severity we know from multiple anecdotes. These patients are not being recognized as having an underlying disease and in the worst cases. The parents have blamed for their inability to control their child's food intake as you can see on this slide.

David P. Meeker: Patients responded extremely well to treatment with a mean decrease in weight of more than 18% at one year.

David P. Meeker: Slide 13, I think this is where the real story lies in the individual results, which show a waterfall plot of the individual results for the 12 patients two takeaways the Y axis shows the BMI Z score, which is basically the number of standard deviation. The child is away from normal the graph shows the.

David P. Meeker: We have selected our CRO and are looking to dose our first patients in the first half of this year. And I can tell you that we are aiming to have those first patients dosed in March here. We're committing to the first half of this year.

David P. Meeker: As a reminder, we will begin conventionally with single and then multiple ascending dose cohorts in normal volunteer patients with obesity, followed by Part C, which will enroll HO patients and follow them for 28 days. Those patients will be eligible to enter into a long-term extension study once we complete our chronic toxicity studies, which are required to support longer dosing, and those chronic toxicity studies are ongoing and running in parallel. Now, on slide 12, and on my last two slides, I want to revisit the data in pediatric patients we showed at our R&D day in December. I find these results quite remarkable for a couple of reasons.

David P. Meeker: <unk> <unk> score with treatment for the first two groups starting from left to right pumps are on the left hand side of the graph. These children are experiencing a five to seven point decrease in their BMI Z scores from a starting point as high as 12. It is important to remember a BMI Z score change.

David P. Meeker: Greater than 0.2 is considered clinically meaningful the Bbs patients who are not quite as severely affected still showed a 1% to two point decrease the only two patients who did not have a meaningful highly meaningful change in their BMI Z score was one patient who has lost to follow up early in the trial and a second patient who is noncompliant with.

David P. Meeker: The medications.

David P. Meeker: Expanding the label to children to and above will not open up a significant additional market opportunity. It will add incrementally of course, but it will reinforce the importance of thinking about genetic causes when confronted with early onset obesity that will remind people. The cumulative morbidity begins early in the earlier you intervene with specific there'll be the better your chances.

David P. Meeker: One is that despite their extremely young age, patients between the ages of 2 and 5, with either POMC, lepidodeficiency, or BBS, were severely affected. That should not be a surprise given the genetic cause of the disease, which means in most cases it has been present since birth. Despite the severity, we know from multiple anecdotes, these patients are not being recognized as having an underlying disease, and in the worst cases, the parents are blamed for their inability to control their child's food intake.

David P. Meeker: Modify the long term outcomes and third it reinforces the safety of the medication and then it can be given and should be given to children as young as two if clinically indicated.

David P. Meeker: So as I said, we filed for our European label expansion and we look forward to filing in the U S. In Q3 of 2004 with that I'll turn the call over to Jennifer.

Thank you David.

We continue to see solid commercial execution this quarter with new prescriptions prescribers and reimbursement.

David P. Meeker: As you can see on this slide, patients responded extremely well to treatment with a mean decrease in weight of more than 18% at one year. On slide 13, I think this is where the real story lies in the individual results, which show a waterfall plot of the individual results for the 12 patients. Two takeaways. The y-axis shows the BMI Z-score, which is basically the number of standard deviations the child is away from normal.

Beginning on slide 15, we remain pleased with the growth and consistent good man from Jefferies.

David P. Meeker: In June of 2022.

Jennifer Li: <unk> fourth quarter, and our first full calendar year.

Jennifer Li: We continue to see gains in the depth and breadth of prescribers and positive reauthorization decision.

Jennifer Li: During the fourth quarter of 2023, we received more than 100 days.

David P. Meeker: The graph shows the change in BMI Z-score with treatment. For the first two groups, starting from left to right, palm view, and left bar on the left-hand side of the graph, these children are experiencing a 5 to 7 point decrease in their BMI Z-scores from a starting point as high as 12. It is important to remember a BMI Z-score, changes greater than 0.2, is considered clinically meaningful. The BBS patients were not quite as severely affected, but they still showed a one to two point. The only two patients who did not have a meaningful, highly meaningful change in their BMI Z-score were one patient who was lost to follow-up early in the trial and a second patient who was non-compliant with the medication. Thus, expanding the label to children two and above will not open up a significant additional market opportunity.

Jennifer Li: More than 70 approval for reimbursement from payers.

Jennifer Li: As David mentioned earlier these positive trends were offset by a challenge associated with one pair.

Jennifer Li: One state Medicaid because of a higher than expected volume of prescriptions for Bbs patients, which was above the estimated prevalence of bvs had requested additional documentation to support the diagnosis for previously approved and reimbursed patients.

Jennifer Li: And then meantime separate cap rates for these patients.

Jennifer Li: So are these patients do not have any gasoline treatment within reach.

Jennifer Li: We transitioned 30 patients to free drug program.

Jennifer Li: Program F.

Jennifer Li: During Q4, the total number of reimbursed patients.

Jennifer Li: Alone, where we exited Q3.

David P. Meeker: It will add incrementally, of course, but it will reinforce the importance of thinking about genetic causes when confronted with early-onset obesity. It will remind people that cumulative morbidity begins early, and the earlier you intervene with a specific therapy, the better your chance to modify the long-term outcomes. And third, it reinforces the safety of the medication and that it can be given and should be given to children as young as two, if clinically indicated. So, as I said, we filed for our European label expansion, and we look forward to filing in the U.S. 4. With that, I'll turn the call over to you.

Jennifer Li: This event with limited to one state where there appears to be a high prevalence of Bbs patients, making this a unique situation. We are working with this Medicaid program and prescribers cancer patients diagnosed with Bbs continued to receive access to therapy.

Jennifer Li: It is important to note that this state Medicaid still has a policy in place to cover and CFA.

Jennifer Li: Going back to the 70 of peripheral turned the corner, we are seeing these come through faster and with fewer appeal than in prior quarters.

Jennifer Li: Over 70% of approvals for reimbursement during the quarter came at the time of prior authorization or sooner.

Arlinda Anna Lee: Thank you, David. We continue to see solid commercial execution this quarter with new prescriptions, prescribers, and reimbursements. Beginning on slide 15, we remain pleased with the growth and consistent demand for Sivri since launching in June of 2022, marking six full quarters and our first full calendar year. In addition, we continue to see gains in the depth and breadth of prescribers and positive reauthorization decisions. During the fourth quarter of 2023, we received more than 100 new prescriptions and more than 70 approvals for reimbursement from payers. However, as David mentioned earlier, these positive trends were offset by a challenge associated with one pair.

Jennifer Li: Trend that has shown incremental improvement each quarter since launch.

Jennifer Li: Hi.

Jennifer Li: More than half of its every prescriptions for Bbs continues to come from adult patient accounting for 59% of Bbs prescription blocks today.

Jennifer Li: This is a positive trend as we believe many adult Bbs patients who may have H AD of participating in the annual survey of the Cribbs registry or were lost to receiving specific care for Bbs are re engaging with their health care providers.

Jennifer Li: As we've discussed this is typical in rare disease, where the first approved therapy for disease raises awareness and paves the way for a re engagement of the broader diagnosed patient population.

Arlinda Anna Lee: One state Medicaid, because of a higher than expected volume of prescriptions for BBS patients, which was above their estimated prevalence of BBS, had requested additional documentation to support the diagnosis for previously approved and reimbursed patients. In the meantime, coverage for these patients was rescinded. To ensure these patients did not have any gaps in treatment for emphysema, we transitioned 30 patients to free drugs through our bridge program. Therefore, during Q4, the total number of reimbursed patients dipped below where we exited Q3. This event was limited to one state, where there appears to be a high prevalence of BBS patients, making this a unique situation. We are working with this Medicaid program and prescribers to ensure patients diagnosed with BBS continue to receive access to MCBRI therapy.

Jennifer Li: Next slide.

Jennifer Li: We see continued progress with additional first time prescribers as well as Rick <unk>.

Jennifer Li: First of all fibers, while their breakdown by specialty remains consistent.

Jennifer Li: Adult and pediatric endocrinologists account for 45% of prescribers blocks today.

Jennifer Li: Consistent with once a day metrics reported during the last few quarters.

Jennifer Li: New to random person fiber or physicians, our territory managers had not previously called bank prior to the prescription being received.

Jennifer Li: Consistent at 28% of all prescribers.

Jennifer Li: We are pleased to see the source of growth continue as we find new prescribers through our non personal promotion efforts.

Jennifer Li: In addition, first time prescribers or those who wrote their first in February scrap has stayed very consistent.

Jennifer Li: I think 48, new prescribers per quarter in 2023 and in Q4, we were consistent with this at 46 first time writers.

Arlinda Anna Lee: It is important to note that this state Medicaid still has a policy in place to cover MCIV rates. Going back to the 70 approvals in the quarter, we are seeing these come through faster and with fewer appeals than in prior quarters. Additionally, over 70 percent of approvals for reimbursement during the quarter came at the time of prior authorization or sooner, a trend that has shown incremental improvement each quarter since launch. Next slide.

Jennifer Li: And we are seeing incremental increases and the depth of prescribers.

Jennifer Li: 30% of prescribers to date have written two or more prescriptions, which marks an increase from prior quarters.

Jennifer Li: Prescribers are seeing their patients benefit from it separate and they remain interested prescribed for additional Bbs patients identified.

Jennifer Li: Next slide.

Arlinda Anna Lee: More than half of incivory prescriptions for BBS continue to come from adult patients, accounting for 59% of BBS prescriptions launched to date. This is a positive trend as we believe many adult BBS patients who may have aged out of participating in the annual surveys of the CRIBS registry or were lost to receiving specific care for BBS are re-engaging with their healthcare providers. As we've discussed, this is typical of rare diseases where the first approved therapy for a disease raises awareness and pays for the re-engagement of the broader diagnosed patient population. Next slide.

Jennifer Li: Overall, the payer mix for Bbs remains consistent with almost 90% of prescriptions since launch following under a commercial or Medicaid plan, we continue to see incremental improvement carrying access and reimbursement with regards to overall coverage by state Medicaid programs.

Jennifer Li: As we've done in recent quarters, we look at Medicaid coverage measure their covered lives.

Jennifer Li: We introduced this concept at the end of the first quarter. When we reported that approximately 75% of Medicaid covered lives or in states with either a positive in every policy or in a state where we had been able to gain positive coverage and at least one instance in the absence of an <unk> policy.

Arlinda Anna Lee: We see continued progress with additional first-time prescribers, as well as repeat prescribers, while the breakdown by specialty remains consistent. Adult and pediatric endocrinologists account for 45 percent of prescribers launched to date, consistent with launch-to-date metrics reported during the last few quarters. New prescribers to Rhythm or physicians or territory managers had not previously called on prior to the prescription being received remains consistent at 28% of all prescribers. We are pleased to see this source of growth continue as we find new prescribers through our non-personal promotion efforts. In addition, first-time prescribers, or those who wrote their first MCIVory script, have stayed very consistent, averaging 48 new prescribers per quarter in 2023. And in Q4, we were consistent with this at 46 first-time writers.

The remaining 25% of Medicaid lives were in states, where we either had not yet had a prescription firms Jeffrey.

Jennifer Li: We were still working to secure access for a prescription are finally, where we had not been successful in gaining access through the appeals process.

Jennifer Li: In Q2, and Q3 this breakdown shifted to 80 20 and.

Jennifer Li: At the end of this quarter. It was 80 515.

Jennifer Li: Within this 85% we have stronger coverage firms Jeffrey as we have increased the number of states with a specific and separate policy in place.

Jennifer Li: This site.

Jennifer Li: Lastly, we are seeing strong success and reauthorization at the vast majority of Riyadh have been approved this is indicative of patients benefiting from its every therapy as well as payors recognizing these benefits.

Arlinda Anna Lee: And we are seeing incremental increases in the depth of prescribers. 30% of prescribers launched to date have written two or more prescriptions, which marks an increase from prior quarters. Prescribers are seeing their patients benefit from Incivry, and they remain interested in prescribing for additional BBS patients identified. Next slide.

Jennifer Li: Launch to date, we've had 110 a profile for reauthorization for continued in February therapy.

Jennifer Li: Most of these come at the one year on therapy time point, but there are few pairs, whose policies call for reauthorization decision at three or six months.

Arlinda Anna Lee: Overall, the pair mix for BBS remains consistent, with almost 90% of prescriptions since launch falling under a commercial or Medicaid plan. We continue to see incremental improvement in securing access and reimbursement with regard to overall coverage by state Medicaid programs. As we've done in recent quarters, we look at Medicaid coverage measured through covered lives. We introduced this concept at the end of the first quarter when we reported that approximately 75% of Medicaid-covered lives were in states with either a positive MCIVory policy or in a state where we had been able to gain positive coverage in at least one instance in the absence of an MCIVory policy. The remaining 25% of Medicaid lives were in states where we either had not yet had a prescription for MSIFRI, or we were still working to secure access to a prescription, or, finally, where we had not been successful in gaining access through the appeals process. In Q2 and Q3, this breakdown shifted to 80-20, and at the end of this quarter, it was 85-15.

Jennifer Li: As of the end of the fourth quarter, we only had 10 denials since launch and six of these denials have been approved therapies and we are working to get the remaining four as well.

Jennifer Li: Overall, the fourth quarter and the first full year of Bbs commercialization has been strong we will continue focusing our efforts on expediting diagnosis of Bbs patients and supporting access James Jeffrey with that let me hand, it over to Jan.

Jan Madsen: Thank you Jennifer.

Jan Madsen: 2023 was a very successful year for the international organization.

Jan Madsen: With the Bbs launch in Germany.

Jan Madsen: EMEA approval early access program in France for Hypokalemia.

Jan Madsen: Many commercial patients in new countries and all the work that led to our recent announcements, but reimbursement for bvs in Spain.

Jan Madsen: We are looking forward to a strong year in 2024 as well as we are beginning of the year announcing you'll developments within Japan.

Jan Madsen: Slide 21.

Jan Madsen: Giovanni will become a very important market for us.

Jan Madsen: Without prepayments for hypothetical visiting Japan is two to three times the prevalence rates.

Jan Madsen: In the United States and Europe.

Jan Madsen: Through our discussion with local key expense is a Japanese pediatric neurosurgery, so safety data from the Japanese brain tumor registry and also a high level. What's before claims that are these analyses. It has been confirmed that there is a much higher prevalence of <unk> hundred one in Japan with a sim cwiklinski of ability to be resilient.

Arlinda Anna Lee: Within this 85%, we have stronger coverage for MCIVRI as we have increased the number of states with a specific MCIVRI policy in place. Next slide. Lastly, we are seeing strong success in reauthorization, as a vast majority of REopts have been approved. This is indicative of patients benefiting from emissivity therapy, as well as payers recognizing these benefits. Launched to date, we've had 110 approvals for reauthorizations for continued emphysema therapy. Most of these come at the one-year-on-therapy time point, but there are a few pairs whose policies call for reauthorization decisions at three or six months. As of the end of the fourth quarter, we've only had 10 denials since launch, and six of these denials have been approved through appeal, and we are working to get the remaining four approved as well. Overall, the fourth quarter and the first full year of BBS commercialization have been strong. We will continue focusing our efforts on expediting diagnosis of BBS patients and supporting access to MCIFRI. With that, I will hand it over to Jan.

Jan Madsen: U S and in Europe and.

And we believe that there are between 5000 8000 patients with hyperkalemia Kobe city living in Japan.

Jan Madsen: There are more than 100 kilos per total of treatments and sales in Japan that care for patients with <unk> and also brain tumor that may cause hypokalemia.

Jan Madsen: Building the relationship with the center will be key to our strategy and we have already started to do it.

Jan Madsen: In addition, Japan like many European countries is a single payer system with an established history of recognizing rare disease and dedicating the resources carefully.

Jan Madsen: Japan is still not just it couldnt be Michelle by GDP and as David already say that in the long term, we believe that it will become the second most important markets for a reason.

Jan Madsen: The United States.

Jan Madsen: In exploring this exciting opportunity we consider multiple avenues to advance submitted I think in Japan, we made the decision to move forward with a direct presence and we.

Jan Madsen: Was that resemble truly become a global rare neuroendocrine disease company able to leverage our footprint in Japan for future opportunities.

Jan Madsen: Next slide.

Jan Madsen: Our work in Japan is off to a strong start.

Jan Madsen: <unk> is a Japanese PMD, we had the benefit of when leading Japanese expert I put that <unk> was able to emphasize the amendments.

Jan Madsen: And that clinical need in Japan, and the relevance of <unk> in Japanese patients directly phase.

Jan Madsen: <unk> III priority.

Jan Madsen: Just last week, we held our first reasons consoled symposium in <unk> city during the yearly Congress of the Japanese Society for hypothalamic pituitary tumor cells and it was a very successful one.

Jan Mazabro: Thank you, Jennifer. 2023 was a very successful year for the international organization, with the BBS launch in Germany, the pre-EME approval, an early access program in France for hypothalamic obesity, many commercial patients in new countries, and all the work that led up to our recent announcements about reimbursement for BBS in Spain and Italy. We're looking forward to a strong year in 2024 as well, as we begin the year by announcing our development strategy in Japan, slide 21. Japan will become a very important market for us. The per capita prevalence for hypothalamic obesity in Japan is two to three times higher than the prevalence rate in the United States and Europe. Through our discussion with local key experts, with the Japanese Pediatric Neurosurgery Society, data from the Japanese Brain Tumor Registry, and also a high-level hospital claims database analysis, it has been confirmed that there is a much higher prevalence of craniopharyngioma in Japan, with the same frequency of obesity development as in the U.S. and in Europe.

Jan Madsen: Slide 23.

Jan Madsen: Meanwhile, our launch in Germany is progressing well meeting our expectations with approximately 250 patients living with UBS already identified.

Jan Madsen: And importantly, a subset of approximately 800 patients diagnosed with <unk> in Germany.

Jan Madsen: <unk> remains focused on engaging with physicians caring for patients and with the many centers where they are treated.

Jan Madsen: We are expanding the number of treatment centers and not just because we are engaging with those.

Jan Madsen: And those that we have more than nine months into the loans. We have received prescriptions from 15 treatments until which are all within a large and very well structured and Resourced University hospitals.

Jan Madsen: In addition, our.

Jan Madsen: A reason at home services program through which we provide efficient so thoughtful each patient in the county.

Jan Madsen: Been quite successful.

Jan Madsen: <unk> sits treatments expectation with physicians and all feels very tailored services to patients with for example in home visits when needed and since December Prefilled syringes have been available for both Bbs and <unk> patients.

Jan Madsen: Next slide.

Jan Madsen: We also recently announced that we achieved reimbursement for <unk> in Spain and Italy.

Jan Madsen: We received a positive reimbursement decision for Bbs two weeks ago, and we're starting to launch in theory. We believe that there are approximately 200 patients diagnosed and identified on that and those are careful non physician.

Jan Mazabro: And we believe that there are between 5,000 and 8,000 patients with hypothalamic obesity living in Japan. There are more than 100 key hospitals or treatment centers in Japan that care for patients with craniopharyngiomas and other brain tumors that may cause hypothermic abilities. Building relationships with this center will be key to our strategy, and we have already started to do so. In addition, Japan, like many European countries, is a single-payer system with an established history of recognizing rare diseases and dedicating the resources to care for them. Japan is the third largest economy measured by GDP, and as David already said, in the long term, we believe that it will become the second most important market for Rhythm behind the United States.

Jan Madsen: Our team in Italy has focused on engaging with physicians and hospitals and medical centers in 21 states.

Jan Madsen: With all of the country.

Spain, the recently announced positive reimbursement decision <unk>, Bbs and <unk> pump patients.

Jan Madsen: Approximately 100 patients with Bbs identified and now they are.

Jan Madsen: He is engaging with physicians in this center in 17 states.

Jan Madsen: This was also a country to bring them to re completions in <unk>.

Jan Madsen: Most countries, we know must navigate regional access and tender management at local hospital levels six weeks for patients to begin treatment and we will start to see commercial patients come online in most countries during the second quarter, though.

Jan Madsen: We will begin to see increasing contribution to our net sales from its countries in 2025.

Jan Madsen: Slide 25 and last slide.

Jan Madsen: We continue to advance country by country with EMC re now available for polysilicon and Obs in 12 countries outside.

Jan Mazabro: In exploring this exciting opportunity, we considered multiple avenues to advance separate times in Japan. We made the decision to move forward with a direct presence. And with that, Rhythm will truly become a global rare neuroendocrine disease company able to leverage our footprint in Japan for future opportunities. Next slide.

Jan Madsen: The United States and Canada.

Jan Madsen: The trends we have paid early access available for Bbs as we negotiate with French authorities in pricing.

Jan Madsen: We're in the midst of some negotiation now and hope to finalize it by the end of this year.

Jan Madsen: So let me go visit influence we have pre NDA approval early access as well both of these early access programs are administered patient by patient does take time, but we are building a strong foundation in terms of our relationship with government authorities, we Didnt Express key centers of excellence in patient Association.

Jan Mazabro: Our work in Japan is off to a strong start. In our discussion with the Japanese PMDA, we had the benefit of one leading Japanese expert in hypothalamic obesity, who was able to emphasize the unmet medical need in Japan and the relevance of enrolling Japanese patients directly in our phase 3 trial. Just last week, we held our first rhythm-sponsored symposium in Nagoya City during the yearly congress of the Japanese Society for Hypothalamic and Pituitary Tumors, and it was a very successful one. Slide 23

Jan Madsen: Looking ahead, the next of the larger European markets to come online with reimbursement for Bbs of the UK and the Netherlands boost in the second half of the year.

Jan Madsen: Now I will turn the call over to Andrew.

Andrew: Thank you Jan.

Andrew: Let's start with a snapshot of the Q4 P&L on slide 27.

Andrew: We recorded $24 2 million in net product revenue in the fourth quarter versus $8 8 million. During the same quarter last year, an increase of $15 4 million or 175% for the full year net product revenue totaled $77 4 million versus $16 9 million in 2022.

Jan Mazabro: Meanwhile, our launch in Germany is progressing well, meeting our expectations, with approximately 250 patients living with BBS already identified, and importantly, a subset of approximately 800 patients diagnosed with BDS in Germany. Our team remains focused on engaging with physicians caring for patients and with the many centers where they are treated. We are expanding the number of treatment centers and large hospitals we are engaging with. Now that we are more than nine months into the launch, we have received prescriptions from 15 treatment centers, which are all within large and very well-structured and resourced university hospitals. In addition... Our Rhythm at Home services program, through which we provide patient support for each patient and their caregivers, has been quite successful. Our team sets treatment expectations with physicians and offers very tailored services to patients, with, for example, in-home visits when needed. And since December, pre-filled syringes have been available for both BBS and POM-CV PAR patients. Next slide

Andrew: Quarter over quarter, we saw an increase of $1 7 million or 8% of net product revenue driven primarily by continued growth in the number of patients on <unk> therapy.

Andrew: <unk> therapy in our international region in the U S revenues were relatively flat quarter over quarter due to the shift of 30 basis through our bridge program earlier in the quarter as David and Jennifer mentioned.

Andrew: Given the 30 patients loss reimbursement early in the quarter that change represented approximately a little more than 2 million forgone potential revenue in the fourth quarter.

Andrew: Excluding that discrete event at the beginning of the quarter drivers of revenue E prescriptions and reimbursement, whereas expected. This pattern is consistent with our belief that revenue growth in rare diseases. It is difficult to trend quarter over quarter, but in the long term and globally.

Andrew: Slow and steady growth continues.

Andrew: In the fourth quarter volumes of vials dispensed to patients where essentially the same as vials shipped to our specialty pharmacy.

Andrew: Resulting in no significant impact on revenue from inventory growth.

Andrew: The specialty pharmacy.

Andrew: Gross to net for U S sales quarter over quarter increased to 85% from 83% in the third quarter, primarily due to a Medicaid rebate adjustment in the quarter, which was based on actual rebates paid as compared to rebate levels of crude.

Andrew: Our practice is to recruit for Medicaid rebates based upon expected payer mix or an actual Medicaid invoices are received this may result in differences versus crude amounts.

Jan Mazabro: We also recently announced that we achieved reimbursement for MCV in Spain and Italy. In Italy, we received a positive reimbursement decision for BBS two weeks ago, and we have started to launch MCV. We believe that there are approximately 200 patients diagnosed and identified under the care of a known physician. And our team in Italy is focused on engaging with physicians in hospitals and medical centers in 21 states throughout the country.

Andrew: Cost of sales during the fourth quarter was $3 2 million or approximately 13, 3% of net product revenue, representing a two 6% increase quarter over quarter.

Andrew: Cost of sales consists primarily of product costs, and our 5% royalty to epson under our original licensing agreement for <unk>.

Andrew: R&D expenses were $29 9 million for the fourth quarter of 2003 compared to $23 5 million during Q4, 'twenty, two and an 11% decrease compared to Q3 'twenty three.

Jan Mazabro: In Spain, the recently announced positive reimbursement decision covers both BBS and POM-CD-PAR bilateral patients. There are approximately 100 patients with BBS identified, and our team there is engaging with physicians and health care centers in 17 states throughout the country to bring in theory to patients and families. In both countries, we now must navigate regional access and tender management at local hospital levels.

Andrew: SG&A was $32 4 million for the fourth quarter this year versus $26 3 million in the fourth quarter of 2002.

Andrew: And an increase of six 2% from the sequential quarter basis.

Andrew: For the fourth quarter weighted average common shares outstanding were $59 2 million, an increase of approximately $1 3 million shares over last quarter.

Andrew: <unk>, primarily from the full waiting this quarter of our equity issuance under the ATM program in Q3.

Andrew: Quarterly net loss per share was <unk> 70.

Andrew: A few highlights on slide 28.

Andrew: The reported 2270 $6 million of cash and cash equivalents at December 31, 2023. This cash on hand is sufficient to fund all planned activities into the second half of 2025.

Jan Mazabro: It takes weeks for patients to begin treatment, and we will start to see commercial patients come online in both countries during the second quarter. We will begin to see increasing contribution to our net sales from each of these countries in 2025. Slide 25, the last slide.

Andrew: On the net revenue for the quarter of $24 2 million, 76% of these revenues were generated in the United States. This proportion of revenue the proportion of revenue generated by our international region increased from 20% to 24% quarter over quarter, reflecting strong growth in Bbs patients on therapy in Germany.

Jan Mazabro: We continue to advance country by country with MCRENAO available for POM, CILIPA, and our BBS in 12 countries outside the United States and Canada. In France, we have paid early access available for BBS as we negotiate with French authorities on pricing. We're in the midst of the negotiation now and hope to finalize it by the end of this year. For hypothalamic obesity in France, we have pre-EMA approval and paid early access as well. Both of these early access programs are administered patient by patient; it takes time, but we are building a strong foundation in terms of our relationship with the government authorities, payers, leading experts, key centers of excellence, and patient associations. Looking ahead, the next of the larger European markets to come online with reimbursement for VBS are the UK and the Netherlands, both in the second half of the year. Now, I will turn the call over to Hunter.

Andrew: Fourth quarter operating expenses, including stock based compensation of $8 7 million for the quarter and $23 6 million for 2023.

Andrew: For 'twenty three we guided.

Andrew: To an opex range of a non-GAAP opex opex range and our spend came within that range non-GAAP operating expenses for the year ending December 31, 23 were 29, $219 9 million inclusive inclusive of GAAP operating expenses.

Andrew: $261 8 million minus $9 3 million in cost of sales and minus $32 6 million of stock based compensation.

Andrew: Turning to slide 29.

Andrew: I ask that you all pay attention to the left hand side of the.

Andrew: The guidance the Textbox here and make sure this is modeled appropriately.

Andrew: We committed to pay a $100 million in fixed cost to LG Chem for global rights there'll be 546 that was $40 million cash in January and we issued to them more than 430000 rhythm shares of common stock valued at $20 million at the same time.

Hunter C. Smith: Thank you, Jan. Let's start with a snapshot of the Q4 P&L on slide 27. We recorded $24.2 million in net product revenue in the fourth quarter versus $8.8 million during the same quarter last year, an increase of $15.4 million, or 175%. For the full year, net product revenue totaled $77.4 million versus $16.9 million in 2022.

Andrew: We are also committed to pay $40 million in cash 18 months from the close which was in January.

Andrew: This $100 million will be accounted for in R&D expenses during Q1 2024.

Andrew: And when the achievement of development and commercial milestones becomes probable we will recognize these costs as R&D expense as well.

Andrew: Also for 'twenty four as we did for 2023 and we offer guidance on non-GAAP operating expenses.

Hunter C. Smith: Quarter over quarter, we saw an increase of 1.7 million, or 8%, in net product revenue, driven primarily by continued growth in the number of patients on MCIV re-therapy in our international region. In the U.S., revenues were relatively flat quarter over quarter due to the shift of 30 patients to our bridge program early in the quarter, as David and Jennifer mentioned. Given the 30 patients lost reimbursement early in the quarter, that change represented approximately a little more than $2 million foregone potential revenue in the fourth quarter, including that discreet event at the beginning of the quarter. Drivers of Revenue, i.e., prescriptions and reimbursement, were as expected. This pattern is consistent with our belief that revenue growth in rare diseases is difficult to trend quarter over quarter, but in the long term and globally, so slow and steady growth can happen.

Andrew: We anticipate approximately $250 million to $270 million and non-GAAP opex comprised of SG&A non-GAAP operating expenses of $105 million to $110 million R&D non-GAAP operating expenses of $145 million to $160 million. This RMB amount includes $10 million to $15 million of development costs related to <unk>.

Andrew: This amount excludes both stock based compensation and consideration paid to LG Chem and considered in connection with the licensing of <unk>.

Andrew: The growth rate at the midpoint of this range is 18% year over year, excluding the impact of it will be $5 640, the growth rate would have been just under 15%.

Andrew: Finally, we are not offering revenue guidance, we have not offered revenue guidance in the past are not doing so again this year and series sales in the U S. We will continue to be the main driver of revenue growth for rhythm for revenues from our International region, Germany will continue to be the main driver, while Spain, and Italy are coming online for bvs. It will take time to get up and running.

Hunter C. Smith: In the fourth quarter, volumes of vials dispensed to patients were essentially the same as vials shipped to our specialty pharmacies, resulting in no significant impact on revenue from inventory growth at these specialty pharmacies. Gross to net for U.S. sales quarter over quarter increased to 85% from 83% in the third quarter, primarily due to a Medicaid rebate adjustment in the quarter, which was based on actual rebates paid as compared to rebate levels accrued. Our practice is to accrue for Medicaid rebates based upon expected payer mix, and when actual Medicaid invoices are received, this may result in differences versus accrued amounts. Cost of sales during the fourth quarter was $3.2 million, or approximately 13.3% of net product revenue, representing a 2.6% increase quarter over quarter.

Andrew: As we navigate the local hospital systems in their budgets, the Netherlands, and the UK come on later in the year and we do not expect sales in those regions to be a significant contributor for 2024.

Andrew: That I will turn the call back over to David.

David: Thanks Hunter.

David: So thanks I'll, let concludes the formal presentation I hope what you are taking away from this is that rhythm is maturing we are firming up the components, which are driving the underlying value of rhythm or executing on our global strategy. We are executing on our developmental strategy, where we're exploring all of the incremental potential opportunities relate.

David: To the emcee for pathway and we're setting up as I said, a year or 2024, it's hard to believe we're already two months into the year given the amount that's already happened, but two.

David: 2024 will be about execution and as I said 2025, we will have a series of really impactful.

Hunter C. Smith: The cost of sales consists primarily of product costs and our 5% royalty to Ipsen under our original licensing agreement for set melanotype. R&D expenses were $29.9 million for the fourth quarter of 2023, compared to $23.5 million during Q4-22 and an 11% decrease compared to Q3-23. SG&A was $32.4 million for the fourth quarter of this year, versus $26.3 million in the fourth quarter of 2022, and an increase of 6.2% on a sequential quarter basis. For the fourth quarter, weighted average common shares outstanding were 59.2 million, an increase of approximately 1.3 million shares over the previous quarter, resulting primarily from the full weighting of this quarter of our equity issuance under the ATM program in Q3. The quarterly net loss per share was $0.70.

David: Milestone readouts for rhythm so with that.

David: <unk>.

Speaker Change: Can it up for questions operator.

Speaker Change: Thank you as a reminder to ask a question. Please press star one on your telephone and wait for your name to be announced to withdraw. Your question. Please press star one again, please standby, while we compile the Q&A roster.

Speaker Change: Okay.

Speaker Change: The first question comes from <unk> Ahmed with Bank of America. Your line is open.

Ahmed: Hi, guys. Good morning, Thanks for taking my questions. David I was hoping to get a little bit of color on the comments that you made in your perhaps remarks about the cluster with Bbs patients within a particular date.

Ahmed: Just given all the work you've done on the ultra.

Ahmed: Altra rare.

David: Was that something that you would have anticipated happening and can you also give us color on what would cause.

David: Particularly large number of patients to be clustered in a close.

David: Close proximity and how are you getting confidence you wont be seeing similar events in other states as you said on the call.

Hunter C. Smith: A few highlights are on slide 28. Rhythm reported $276 million in cash and cash equivalents at December 31, 2023. This cash on hand is sufficient to fund all planned activities into the second half of 2025. On the net revenue for the quarter of $24.2 million; 76% of these revenues were generated in the United States. This proportion of revenue, the proportion of revenue generated by our international region increased from 20% to 24% quarter over quarter, reflecting strong growth in BBS patients on therapy in Germany. Fourth quarter operating expenses, including stock-based compensation of $8.7 million for the quarter and $23.6 million for 2023. For 23, we guided to a non-GAAP OPEX range, and our spend came within that range. Non-GAAP operating expenses for the year ending December 31st, 23, were $219.9 million, inclusive of GAAP operating expenses of $261.8 million, minus $9.3 million in cost of sales, and minus $32.6 million in stock-based compensation.

Speaker Change: Yes, thanks, Susan So it's a good question. So your first part of that was did we have.

Speaker Change: Line of sight to this answer was no.

Speaker Change: What do we think is going on there are pockets in every rare disease or many rare diseases, where you have a concentration of patients related to a founder effect. The most publicly and clear example of this and the Bbs world as in Newfoundland.

Speaker Change: Canada, where if you look at an expected prevalence for Bbs of 1% to 75001 and 100000.

Speaker Change: Prevalent in that Canadian provinces about 1% and 18000.

Speaker Change: So.

Speaker Change: So that <unk>.

Speaker Change: Ellen we know exists we werent expecting to see it in this state, but if you looked at the demographics of the state there.

Speaker Change: Demographics are consistent with the fact that you could have a founder effect and we think that that's what's going on in the second piece of this was that we also had positions in that state who were.

Speaker Change: Very interested very motivated early on and we are.

Speaker Change: Writing scripts as I said early and so for this specific state Medicaid plan.

Speaker Change: <unk>.

Speaker Change: They were an early adopter in the sense that they had a policy in place early and we're trying to quote unquote do the right thing, but they saw a much higher level of scripts than what they had they had modeled and their plan and their expected prevalence and Jennifer and I had a call with their their leadership, which was incredibly constructive.

Hunter C. Smith: Turn to slide 29. I ask that you all pay attention to the left-hand side of the text box here and make sure this is modeled appropriately. We committed to pay $100 million in fixed costs to LG Chem for global rights to LV54640. That was $40 million in cash in January, and we issued to them more than 430,000 Rhythm shares of common stock, valued at $20 million at the same time. We have also committed to pay $40 million in cash 18 months from the close, which was in January. This $100 million will be accounted for in R&D expenses during Q1 2024. And when the achievement of development and commercial milestones becomes probable, we will recognize these costs as an expense as well. Also, for 24, as we did for 2023, we offer guidance on non-GAAP operating expenses. We anticipate approximately $250 to $270 million in non-GAAP OPEX, comprised of SG&A non-GAAP operating expenses of $105 to $110 million.

Speaker Change: They said there was no antagonism or <unk>.

Speaker Change: Concerns about wanting to treat Bbs in that sense, we basically just.

Speaker Change: Overwhelm them to a certain extent with relative to what they had expected to see so.

Speaker Change: So long story short.

Speaker Change: What we think drove the disproportionate the second part of your question I mean, I'll, let Jennifer speak to in terms of the other states here and why we see this as a very unique situation related to this one state Medicaid plan.

Speaker Change: So.

Speaker Change: Just in terms of the unit.

Speaker Change: No.

Jennifer Li: Killer stages, David Iterate is when you look at what the estimated prevalence could be based off of the announced or it is more.

Speaker Change: Broad based.

Speaker Change: Pipelines estimates.

Speaker Change: Mountain Express really surpassed.

Speaker Change: Expectation in terms of this particular Medicaid I will reiterate we still have a positive policy in place and we're just working through the system.

Speaker Change: In contrast.

Speaker Change: Not unusual we're just a little over a year from clients in terms of Bbs.

Hunter C. Smith: R&D non-GAAP operating expenses of $145 to $160 million. This R&D amount includes $10 to $15 million of development costs related to LB54640. This amount excludes both stock-based compensation and consideration paid to LG Chem in connection with the licensing bill. The growth rate at the midpoint of this range is 18% year over year; excluding the impact of LB54640, the growth rate would have been just under 50%. Finally, we are not offering revenue guidance. We have not offered revenue guidance in the past and are not doing so again this year.

Speaker Change: Look at every other state Medicaid in terms of estimated profit lines versus the.

Speaker Change: Number of scripts that we have received and other states. We are vastly under just in terms of.

Speaker Change: Number of active patients versus what they may have projected in terms of potential for this product. So we really do feel confident that this is a unique situation where the numbers were up a.

Speaker Change: A bit surprising, but once again, we're just working collaboratively together with the physicians and the Medicaid in terms of working this through.

Speaker Change: Okay. Thanks for all that color and maybe just one last quick question, what's your current mix of Medicaid patients.

Hunter C. Smith: MCIVRI's sales in the U.S. will continue to be the main driver of revenue growth for Rhythm. For revenues from our international region, Germany will continue to be the main driver. While Spain and Italy are coming online for BVS, it will take time to get up and running as we navigate the local hospital systems and their budgets. The Netherlands and the U.K. come online later in the year, and we do not expect sales in those regions to be a significant contributor for 2024. And with that, I'll turn the call back over to David. Thanks, Hunter.

Speaker Change: On reimbursement.

Speaker Change: And then a question what is the current mix of Medicaid So a breakout Medicaid versus your current mix what is the proportion of Medicaid patients.

Speaker Change: Alright, So we said that 90% of patients constantly.

Speaker Change: Our commercial versus Medicaid with Medicaid accounting for slightly more than commercial patients.

Speaker Change: Okay. Thank you.

Speaker Change: Okay.

Speaker Change: Yes.

Speaker Change: Please standby for the next question.

Speaker Change: The next question comes from Jeffrey Hung with Morgan Stanley. Your line is open.

David P. Meeker: So, thanks, all. That concludes the formal presentation. I hope what you're taking away from this is that Rhythm is maturing.

Speaker Change: Hi, Good morning. This is Katherine on for Jeff. Thank you so much for taking our question.

Katherine: We just had one with your <unk> agonist profile now consisting of vanilla tied or in 2017 and now L. P. 546, 40 can you provide more color on how you are thinking about positioning and potential points of differentiation here for example to patients place more value on the ease of route of administration or.

David P. Meeker: We're firming up the components, which are driving the underlying value of Rhythm. We're executing on our global strategy. We're executing on our developmental strategy, where we're exploring all the incremental potential opportunities related to the MC4 pathway. And we're setting up, as I said, a year 2024. It's hard to believe we're already two months into the year, given the amount that's already happened.

Katherine: Are they emphasizing other aspects related to safety like hyper pigmentation.

Operator: But 2024 will be about execution, and as I said, 2025, we'll have a series of really impactful, milestone readouts for Rhythm. So with that, I'll open it up for questions, Operator. Thank you. As a reminder, to ask a question, please press star 1-1 on your telephone and wait for your name to be announced. To withdraw your question, please press star 1-1 again.

Speaker Change: Yes, thanks, Kevin.

Speaker Change: So perfect I think both of our next generation.

Speaker Change: Therapies potential therapies offer their own unique value proposition. So the weekly both of them are hyper pigmentation sparing. So that's a huge issue for some patients not all it's not a huge percentage of patients, but what we're seeing is there is a very consistent.

Operator: Please stand by while we compile the Q&A roster. The first question comes from Tazeen Ahmad with Bank of America. Your line is open.

Speaker Change: Number of percentage of patients that.

Speaker Change: Who are bothered by the Hyperpigmentation, 100% of the patients will have some change in their skin pigmentation, but much smaller percentage of bothered by it but particularly non Caucasian populations. It's an issue. So so both of the next generation products will offer that as a benefit and then you have the convenience issue, which is one is a weekly injectable to others a daily.

Tazeen Ahmad: Hi guys, good morning. Thanks for taking my questions. David, I was hoping to get a little bit of color on the comments that you made in your prepared remarks about the cluster of BDS patients. Was this something that you would have anticipated happening? And can you also give us color on what would cause a particularly large number of patients to be clustered in close proximity? And how are you getting confidence that you won't be seeing similar events in other states?

Speaker Change: Oral and Thats really going to come down to patient preference. So your question about what's our strategy as we think about developing a portfolio of options for these patients as we'll be indifferent again, assuming that both of these molecules progress through development will be indifferent. If the goal is to offer patients physician the ability to choose a treatment which gives their patients.

David P. Meeker: Thanks. Yeah, thanks, Tazeen. So, it's a good question. So, your first part of that was, did we have a line of sight to this? The answer was no. What do we think is going on?

Speaker Change: Best chance of getting the result that they want in a compliant tolerable.

David P. Meeker: There are pockets in every rare disease or many rare diseases where you have a concentration of patients related to a founder effect. The most public and clear example of this in the BBS world is in Newfoundland, Canada, where if you look at an expected prevalence for BBS of one to 75,000, one in 100,000, the prevalence in that Canadian province is about one in 18,000. So, um, so that element we know exists.

Speaker Change: Well well accepted way so that's it.

Speaker Change: No more than that it will be dictated by the data, we'll see how they turn out.

Speaker Change: Again, both products do well they should clearly be better drugs and set in Atlanta tied in then we'll reevaluate the role of <unk> in that World of course once.

Speaker Change: As always you don't keep an inferior molecule out there if you've got clearly better alternatives.

Speaker Change: Okay. Thank you.

Speaker Change: Thank you.

Speaker Change: One moment for our next question.

Speaker Change: The next question comes from Corrine Johnson with Goldman Sachs. Your line is now open.

David P. Meeker: We weren't expecting to see it in this state, but if you looked at the demographics of this state, the demographics are consistent with the fact that you could have a founder effect, and we think that's what's going on. The second piece of this was that we also had physicians in that state who were very interested, very motivated early on, and were writing scripts, as I said earlier. And so for this specific state Medicaid plan, they were an early adopter in the sense that they had a policy in place early and were trying to, quote unquote, do the right thing, but they saw a much higher level of scripts than what they had modeled in their plan and their expected prevalence. Jennifer and I had a call with their leadership, which was incredibly constructive. I mean, they said there was no antagonism or concerns about wanting to treat BBS in that sense. We basically just, you know, overwhelmed them to a certain extent relative to what they had expected to see.

Corrine Johnson: Good morning, maybe as a follow on to that question I guess, how are you thinking about what a successful efficacy outcome looks like from the signal trial.

Particularly how does the oral form factor influence your view of what sufficient efficacy could be.

Corrine Johnson: How do you think it will differ.

Corrine Johnson: They like the efficacy front versus the Injectables.

Speaker Change: Yes, Thanks, Ken.

So to be honest with you I don't expect it to be better than <unk>, and we did incredibly well was set in Atlanta tied and I think we're probably getting in terms of emcee for agonism or probably getting the desired effect maybe at the maximum level you can achieve.

Speaker Change: What might allow either the weekly or daily oral to do better than that May show up more in the real world is in terms of compliance.

Speaker Change: In our <unk> phase III trial compliance was extremely high in that trial overall, so assuming a similar level of compliance I'm not sure we'll differentiate on efficacy, but so long answer to your question is we will be looking for something that would be similar.

David P. Meeker: So long story short, that's what we think drove the disproportionate. The second part of your question, may I let Jennifer speak to in terms of the other states here and why we see this as a very unique situation related to this one-state Medicaid plan? Yeah.

Speaker Change: But not exactly the same probably.

Speaker Change: Okay. Thank you.

Speaker Change: One moment for our next question.

Arlinda Anna Lee: So just in terms of the uniqueness of this particular state, as David iterated, when you look at what the estimated prevalence could be based off of, you know, sort of more broad-based prevalence estimates, the manuscripts really surpassed, you know, the expectation in terms of this particular Medicaid. I will reiterate, we still have a positive policy in place, and we're just working through the system. In contrast, you know, not unusual; we're just a little over a year from launch in terms of BBS.

Speaker Change: The next question comes from Derek <unk> with Wells Fargo. Your line is open.

Derek: Hey, good morning, and congrats on the progress here.

Derek: Couple of questions. So just first on the reauthorization denials I guess, what's the typical reason why that occurs and how long does it take you to eventually get those approved that's question. One and then question. Two is any color that you can share on what youre seeing from a discontinuation rate in DVS, thus far in the launch thanks.

Arlinda Anna Lee: If you look at every other state Medicaid in terms of estimated prevalence versus the number of scripts that we have received in other states, we are, you know, vastly under just in terms of the number of active patients versus what they might have projected in terms of potential for this product. So we really do feel confident that this is a unique situation where the numbers were a bit surprising, but once again, we're just working collaboratively together with the physicians and Medicaid in terms of working this through. Okay, thanks for all of that color. And maybe just one last quick question. What's your current mix?

Derek: <unk>.

Speaker Change: Thanks for the question.

Speaker Change: Starting with the first one in terms of the Reoffer denials.

Arlinda Anna Lee: The question was the current mix of Medicaid, so the breakup of Medicaid versus... In your current mix, what is it? Right, so we said that 90% of patients are approximately commercial versus Medicaid, with Medicaid accounting for slightly more than commercial patients in that mix. Please stand by. Standby for the next question. The next question comes from Jeffrey Hung with Morgan Stanley. Your line is open. Hi, good morning. This is Catherine on for Jeff.

Jeff Hung: Thank you so much for taking our question. We just have one. With your MC4 agonist profile now consisting of thamelotide, RM17, and now LB54640, can you provide more color in how you're thinking about positioning and potential points of differentiation here? For example, do patients place more value on the ease of route of administration, or are they emphasizing other aspects related to safety like hyperpigmentation? Yeah, thanks, guys. Perfect. I think both of our next-generation therapies, potential therapies offer their own unique value proposition. So the weekly and the monthly are both hyperpigmentation sparing. So that's a huge issue for some patients, not all. It's not a huge percentage of patients, but what we're seeing is there's a very consistent number of patients that who are bothered by the hyperpigmentation. 100% of the patients will have some change in their skin pigmentation, but a much smaller percentage are bothered by it. But, you know, particularly in non-Caucasian populations, it's an issue.

Speaker Change: Certainly plans, where we've been able to get an approval, but they didn't necessarily have a specific in temporary policy in place. Some of those also don't have a particular reauthorization policy in place that we're having to re go through the process and the teams just work continuously.

Speaker Change: In terms of making sure that we were able to get those Ah Ah for both moving forward and have been successful.

Speaker Change: On the question of discontinuation you know in in overall the discontinuation rate has increased from what we last reported currently being approximately 20 per cent if neck. Our access we do expect this to have increased.

Speaker Change: Especially with a chronic lifelong therapy.

Speaker Change: And the reasons have remained consistent in terms of what we thought line before some personal reasons I'm due to a E, including nausea, and hyper pigmentation, but I think that they the main piece here for US is also there's opportunity for follow up we noticed.

David P. Meeker: So both of the next-generation products will offer that as a benefit. And then you have the convenience issue, which is one is a weekly injectable, and the other is a daily oral, and that's really gonna come down to patient preference. So your question about what our strategy as we think about developing a portfolio of options for these patients is that we'll be indifferent. Again, assuming that both of these molecules progress through development, we'll be indifferent.

Speaker Change: That in terms of the disc on you know the highest prevalence of the Discontinuations really are within the first Ah two Ah dispenses notes an opportunity for our teams to focus just in terms of making sure patients are a tad trading appropriately and also.

David P. Meeker: The goal is to offer patients, physicians, the ability to choose a treatment that gives their patients the best chance of getting the result that they want in a compliant, tolerable, you know, well-accepted way. So that's it. No more than that.

David P. Meeker: It'll be dictated by the data. We'll see how they turn out. Again, if both products do well, they should clearly be better drugs than setmelanotide. And then, you know, we'll reevaluate the role of setmelanotide in that world. Of course, as with always, you don't keep an inferior molecule out there if you've got clearly better alternatives.

Speaker Change: Pulling up in terms of maintaining them. During this this period of time. So that's that's an opportunity for us. The other piece is as patients discard we have seen patients who have restarted just because of the sort of resurgence in terms of the hyperphagia.

Corrine Johnson: Thank you. Thank you. One moment for our next question. The next question comes from Corrine Johnson with Goldman Sachs. Your line is now open. Good morning.

Speaker Change: And there's a different examples of people coming back and and maintaining on therapy. Even after they have originally discontinued so opportunities here just in terms of the teams to work through.

David P. Meeker: Maybe as a follow-on to that question, I wonder how you think a successful efficacy outcome from the SIGNL trial would look like? Particularly, how does the oral form factor influence your view of what sufficient efficacy could be? And how do you think it will differ, anything in particular, in the efficacy front versus... Yeah, thanks, Grant. So to be honest with you, I don't expect it to be better than setmelanotide, and we did incredibly well with setmelanotide. And I think we're probably getting, in terms of MC4 agonism, we're probably getting the desired effect, maybe at the maximal level you can achieve. What might allow either the weekly or the daily oral to do better, and that may show up more in the real world, is in terms of compliance.

Speaker Change: And then one more question policy beautiful.

Speaker Change: Is that something we should expect.

Speaker Change: Yeah No Robert.

Speaker Change: For van vacated the program was moving more focused on it.

Speaker Change: Regarding your move food Bruce Bruce Peter Voldemort comments here I'm really focused on getting that prescription dose March if everything goes well, we should be comfortably ruined neutral patients from the back half of this year, but we won't have you read out until 2025.

Speaker Change: [laughter].

Speaker Change: <unk> one moment for the next question.

Derek Archila: We know in our HO Phase 2 trial, compliance was extremely high in that trial overall. So assuming a similar level of compliance, I'm not sure we'll differentiate on efficacy, but the long answer to your question is, we'll be looking for something that would be similar, but not exactly the same. One moment for our next question. The next question comes from Derek Archila with Wells Fargo. Your line is open.

Speaker Change: The next question comes from film I do with T V. Cowan. Your line is now open.

Speaker Change: Gordon Congrats on progress and thanks for taking our questions couple of Orange parents and one on commercial in terms of Japan.

TV Cowan: The primary important necessary for dropping the following it is it.

TV Cowan: An analysis of all.

David P. Meeker: Hey, good morning, and congrats on the progress. So just first on the reauthorization denial, I guess what's the typical reason why that occurs, and how long does it take you to eventually get it?

TV Cowan: All the patients in the trial on the maternal primary endpoint to 120 that'll be used to follow me around shnewer determine or overruled, possibly 12 in Japan.

Arlinda Anna Lee: Question one, and then question two: is there any color that you can share on what you're seeing in terms of the discontinuation rate in BBS thus far in the law? Thanks for the question. Starting with the first one, in terms of the re-auth denials, they sort of fall into a couple of different categories.

Speaker Change: Or is there a special analysis, but this struck me as regulars recording to do on the Japanese population specific.

Speaker Change: Yeah, it'd be pregnant so it'll be both it'll be based on the analysis of all patients treated that'll be the primary we will analyze the Japanese patient independently of course and would there'll be looking for since we're not powered.

Arlinda Anna Lee: The first category may be that the patient has received benefits, clinical benefits, that have been appreciated by the physician as well as the patient since their desire to continue on therapy, but they may be just shy in terms of reaching the 5% weight loss. Interesting enough, several of these patients, as we went through the appeals process, actually did hit the 5%, so that's one category, just in terms of overall clinical benefit versus that particular measurement. The other piece is that sometimes the physician just needs to provide some additional information to be able to move the process forward. Just working with the physician in terms of making sure the package is full, we've been able to get some of those appeals through as well. The final category, I would say, is certain plans where we've been able to get approval, but they didn't necessarily have a specific policy in place. Some of those also don't have a particular reauthorization policy in place, so we're having to go through the process again.

Speaker Change: The stand alone Japan cohort of 12 patients of course, there'll be looking for consistency with the other results.

Speaker Change: Okay.

Speaker Change: And then in terms of the Japanese market would you anticipate pricing similar to what you've been able to to achieve in the U S.

Speaker Change: Yeah.

Speaker Change: Yes, well. Thank you so pricing in Japan is usually consistent twitch.

Speaker Change: The mortgage is the use of.

Speaker Change: <unk> because most pricing system.

Speaker Change: Compare it also.

Speaker Change: More in line with European prices and <unk> <unk>.

Speaker Change: Mm you too the Germans or French fries, and the price of course.

Speaker Change: That's fine.

Speaker Change: Okay, and then last question in terms of the 30 patient to.

Speaker Change: Discontinued commercial therapy and went on the bridge therapy because of the Medicaid issue or all three of those patients back on commercial therapy, now or any visibility on when they'll be able to return to a commercial therapy.

Arlinda Anna Lee: The teams just work continuously just in terms of making sure that we are able to get those approvals moving forward and have been successful. On the question of discontinuation, you know, overall, the discontinuation rate has increased from what we last reported, currently being approximately 20% of NEC-RXs. We do expect this to have increased, especially with chronic lifelong therapy, and the reasons have remained consistent in terms of what we've outlined before. Some personal reasons, some due to AEs, including nausea and hyperpigmentation, but I think that the main piece here for us is also that there is opportunity for follow-up.

Speaker Change: Yeah.

Speaker Change: The patients are still on our bridge program as.

Speaker Change: As we outlined at it as a bit of a process in terms of needing to get specific input from specialist on different clinical manifestations to support the diagnosis.

Speaker Change: Can't imagine it takes quite a bit of time sometimes to.

Speaker Change: Get those appointments overall, so we're still in process and they are selling our branch program at this point in time.

Arlinda Anna Lee: We noticed that in terms of the discons, you know, the highest prevalence of discontinuations really is within the first two dispenses, so it's an opportunity for our teams to focus just in terms of making sure our patients are titrating appropriately and also following up in terms of maintaining them during this period of time, so that's an opportunity for us. The other piece is as patients discon, we have seen patients who have restarted just because of the sort of resurgence in terms of the hyperphagia, and there are different examples of people coming back and maintaining on therapy even after they have originally discontinued, so opportunities here just in terms of the teams to work through. And then one more question, just in terms of Part C data for 718, is that something we should expect? Yeah, thanks. No, I'd love it to be this year.

Speaker Change: Maybe just a little bit, though I mean, alright, Jennifer said, it's gonna take time, so <unk> going to drop back in next quarter and secondly, there's elements of the B b S diagnosis or a bit subjective so.

Speaker Change: Requirement bring peace documentation, there's no guarantee that we get all 30 patients back on treatment, but we will for sure get some of them back on but it's been the most important thing about this whole process aside from the constructive interactions you've had with all the different parties and stakeholders is the rest of the U S is more than compensated is running and so the state is now you know, it's it's it'll be up.

Speaker Change: Besides work current equation.

Speaker Change: However, it comes back and whatever time of your comes back in.

Speaker Change: That's very helpful. Thanks for taking our questions.

Speaker Change: Thanks for that one.

Speaker Change: One moment for the next question.

Speaker Change: The next question comes from Whitney at Jim with Canaccord. Your line is open.

Philip M. Nadeau: I think, as I indicated, that program is moving forward. We're incredibly focused on it. We're guiding this to the first dose in the first half here. I told you in my comments here that I'm really focused on getting that first patient dose in March. If everything goes well, you know, we should be comfortably enrolling HO patients in the back half of this year, but we won't have the readout until 2025. Thank you. One moment for the next question. The next question comes from Phil Nadeau with TD Cowan. Your line is now open. Good morning, congrats on the progress, and thanks for taking our questions. A couple on Japan and then one on commercial.

Whitney: Hey, guys. Thanks for taking the questions I have a few but one quick follow up on the [noise] give me last time and on the work to get this uhm 30 patients back on is there is the genetic diagnosis not enough here are using the patients didn't have genetic then there was more of a clinical diagnosis made.

Speaker Change: So there's two components for this particular pair in terms of Ah Ah securing access which is the genetics component as well as the clinical diagnosis component. So both of those are you know in process.

Speaker Change: Going.

Speaker Change: Got it got it Okay. That's helpful and then in Japan.

David P. Meeker: In terms of Japan, just so we're clear on the primary endpoint necessary for Japanese filing, is it... an analysis of all the patients in the trial on the trial's primary endpoint. So the 120 that'll be used to find the US and Europe plus the 10 that are overenrolled plus the 12 in Japan. Or is there a special analysis that the Japanese regulators are requiring to do on the Japanese population? Yeah, good question.

Speaker Change: Have you is there any reason to suspect against differential P. K safety and efficacy in the Japanese group. There do you have data in any of your other trials are in Japanese patients to speak to that.

Speaker Change: No I mean, we we have a very very small number of Asian patients Sandwich doesn't tell you exactly Japan of course, there's no nothing that stands out in a small number of patients that we have one what is different is you know it's just it's a smaller physically smaller population and so we designed this trial for.

David P. Meeker: So it'll be both. It'll be based on the full analysis of all patients treated. That'll be the primary. We will analyze the Japanese patients independently, of course, and what they'll be looking for, since we're not powered to have the standalone Japanese cohort at 12 patients, of course, they'll be looking for consistency with the other results. Got it.

Speaker Change: Western Society, and the cut off for obesity of greater than 30, uhm as well above you know what would be a cut off you know Britain twenty-five in Japan is determining an individual who's overweight. So uhm, so <unk> patients to get into the trial they need to meet our inclusion criteria that we set for the Western Society. So let's see.

David P. Meeker: Okay. And then, in terms of the Japanese market, would you anticipate pricing? Similar to what you've been able to achieve in the U.S. Yeah, you on? Yes, thank you. So pricing in Japan is usually consistent with European prices. The MOH either use a comparator model or a cost-price pricing system; it's no comparator, so it's more in line with European prices, and they also look as references, such as the UK, the German, the French price, and the US price, of course, so in that in that, Got it.

Speaker Change: <unk> narrows a bit the population will be targeting for the trial.

Speaker Change: In terms of your question about P. K and differences I mean, we have a ton of PK data pediatric via P. K data down you know and you have a very very young kids and there's a consistency in the way of this drug perform so there's no reason to believe that we're gonna have a significant difference in hell. This drug is handled by by the Japanese population.

Speaker Change: Got it Okay and then last question should we be expecting an update and H one from the C. Two L. T E. This year with additional copy on that October empty from last year.

Philip M. Nadeau: Okay. And then last question, in terms of the 30 patients who discontinued commercial therapy and went on bridge therapy because of the Medicaid issue, are all 30 of those patients back on commercial therapy now, or any visibility on when they'll be able to return to commercial therapy? Yeah, so the patients are still on our bridge program. As we outlined, it is a bit of a process in terms of needing to get specific input from specialists on different clinical manifestations to support the diagnosis. And as you can imagine, it takes quite a bit of time sometimes.

Speaker Change: I don't think so I mean, we're in the process of putting out publications. We haven't you know plan necessarily another follow up a medium what we'll reevaluate that if we if we did anything it'll be in the fall but.

Speaker Change: Yeah, it's not through the current plan I think we've given a good series of updates there for the moment.

Speaker Change: Okay, great. Thank you very much.

Speaker Change: Thank you one moment for the next question.

Speaker Change: The next question comes from days gone home with Stiefel. Your line is open.

Speaker Change: Hey, good morning, guys. Thanks for taking my questions and congrats on the progress maybe a few I'll just kind of starting with the E. U side of the B B S equation I was wondering if you could comment on sort of the German Lodge progress I think you mentioned 15 academic centers or large treatment centers.

Arlinda Anna Lee: Get those appointments overall. So we're still in the process, and they are still in our bridge program at this point in time. May I just add a little bit, Phil? I mean, as Jennifer said, it's going to take time. So, one, yeah, don't expect them to drop back in next quarter.

Speaker Change: Maybe I missed it but did you mentioned how many patients are currently on therapy, and as we think about Spain, and Italy Lodge, how could the dynamics there differ versus the German lodge and then switching over to the clinical side. If we think about the H O I would kind of expect that the <unk>.

David P. Meeker: And secondly, some elements of the BBS diagnosis are a bit subjective. So, you know, with the requirement for in-case documentation, there's no guarantee that we get all 30 patients back on treatment, but we will for sure get some of them back on. What's been the most important thing about this whole process, aside from the constructive interactions we've had with all the different parties and stakeholders, is that the rest of the US is more than compensated and is running. And so this state is now, you know, it'll be an upside to our current equation, however it comes back and whatever timing it comes back. That's very helpful.

Speaker Change: Free H O enrollment progress to kind of facilitate if not a tailwind to your other signal if not seven when a trial. So can we expect won't have 25 data from all three of those studies and if so how should we think about the cadence between the three thanks so much.

Speaker Change: Yep.

Speaker Change: I'll go first <unk>, yes, it was stuffed with Germany. So no I have no I have not given <unk> number.

Speaker Change: Which I I <unk> for sure. So they said is progressing well, we'll get to your expectations.

Philip M. Nadeau: Thanks for taking our question. One moment for the next question. The next question comes from Whitney Adjim with Canaccord. Your line is open.

Speaker Change: <unk> those interact as well as a key gentleman center so.

Whitney Adjim: Hey, guys, thanks for taking the questions. I have a few, but one quick follow up on the last comment on the work to get those 30 patients back on. Is genetic diagnosis not enough here?

Speaker Change: Terms of selectivity interactions I think we're doing a very good job.

Speaker Change: What is important is that the feedback from Z H G B's and <unk> and <unk>, we're supposed to keep those two large patient identification hold on one four G. I Bill population, one supposed to feed us with populations will.

Arlinda Anna Lee: Or are you saying those patients didn't have genetics and there was more of a clinical diagnosis? So there are two components for this particular payer in terms of securing access, which is both the genetic component, as well as the clinical diagnosis component. So both of those are, you know, in process and ongoing.

Speaker Change: Which will help us to identify your <unk> 425, and beyond so I don't have a specific number of so called Yemeni, but <unk> is is going with.

Speaker Change: Spain, and Italy, I can maybe speak about the two countries to give them because.

Whitney Adjim: Okay. That's helpful. And then in Japan.

Speaker Change: Many come and dine any so it will be slow and steady as usual <unk>.

David P. Meeker: Have you, is there any reason to expect, I guess, differential PK or safety and efficacy in the Japanese group there? Do you have data from any of your other trials in Japanese patients to speak to that? No, I mean, we have a very, very small number of Asian patients, which doesn't tell you exactly where Japan is, of course. There's nothing that stands out in the small number of patients that we have. What is different is, you know, it's a smaller, physically smaller population, and so we designed this trial for, you know, Western society, and the cutoff for obesity of greater than 30 is well above what would be a cutoff of greater than 25 in Japan as determining an individual who's overweight.

Speaker Change: Both countries.

Speaker Change: And you'll be assistance and <unk> negotiate the price, which is really good there.

Speaker Change: There are also very decent per line. So we have to engage with bush original deals and local hospitals and individual states.

Speaker Change: And that's why we need slow in the city of course, we focus initially on the <unk> <unk> <unk> <unk> <unk> on the market access point of view as I said earlier, you know 21 states.

Speaker Change: And 16 in Spain. So we are focusing on the one with the most patients in this.

Speaker Change: <unk> is based in terms of access.

Speaker Change: And in general what I would say about Europe and and.

Speaker Change: <unk> <unk>.

Speaker Change: <unk> 420, 24, gentlemen, who will be the main driver.

Speaker Change:

Whitney Adjim: So for Japan's patients to get into the trial, they need to meet our inclusion criteria that we set for Western society, so that significantly narrows the population we'll be targeting for the trial, but in terms of your question about PK and differences, I mean, we have a ton of PK data, you know, in pediatrics. We have PK data down, you know, in very, very young kids, and there's a consistency in Should we be expecting an update on HO from Phase 2 LTE this year with additional follow-up beyond the October update from last year? I don't think so.

Speaker Change: <unk>, let me tell you will become more meaningful in 2025, when we will <unk>.

Speaker Change: Alright.

Speaker Change: And they're gonna need your clinical question, which is yeah, we we enrolled incredibly well uhm a phase three trial and that does speak to uhm demand interest him and his trial and that for sure will spill over into potential enrollment for both of our weekly program and the the small molecule daily oral program I don't until we get.

Speaker Change: Neither one of those programs have we dosed in H O patient as I said <unk> you know for the weekly we've Gotta go through the healthy volunteer study for the the small molecule, where I'm just getting those sites up and it's gotten.

Speaker Change: Gotten to the point, where would dosing so until we get that part of the <unk>. The trials established we don't I don't have a <unk> line of sight to when exactly we would guide to read out to you. So I'm going to defer that what what we will commit to it will for sure be 2025 as you can imagine were highly motivated to get it as soon as possible but.

David P. Meeker: I mean, we're in the process of putting out publications. We haven't necessarily planned another follow-up to the meeting. We'll reevaluate that. If we do anything, it'll be in the fall.

Whitney Adjim: Yeah, it's not the current plan to give a good series of updates there for the moment. Okay, great. Thank you very much. Thank you. One moment for the next question. The next question comes from Day Ganha with Stiefel. Your line is open.

Speaker Change: I have to leave it there.

Speaker Change: Cool thanks, so much.

Speaker Change: Thanks.

Speaker Change: Please stand by for the next question.

Speaker Change: The next question comes from Joseph Stringer with need your line is open.

Day Ganha: Hey, good morning, guys. Thanks for taking my questions and congrats on the progress. Maybe a few, just kind of starting with the EU side of the BBS equation, I was wondering if Jan could comment on sort of the German launch progress. I think you mentioned 15 academic centers or large treatment centers. Maybe I missed it, but did you mention how many patients are currently on therapy? And as we think about the Spain and Italy launches, how could the dynamics there differ versus the German launch?

Joseph Stringer: Hi, good morning, Thanks for taking our questions first one on just looking at the interact suit you can be down slightly the last two quarters. Just wondering if you could comment on this train do you feel like you'd reach a point in the U S where there'd be a relatively steady state quarterly new prescription add and <unk>.

Joseph Stringer: What would that look like and then secondly on H O in Japan can you.

Jan Mazabro: And then switching over to the clinical side, if we think about the HO, I would kind of expect that the phase 3 HO enrollment progress to kind of facilitate, if not add tailwind to your other signal, if not 718 trials. So can we expect 1 out of 25 data from all three of those studies? And if so, how should we think about the cadence between the three?

Joseph Stringer: Maybe talk about the H O patient community community an organization relative to what it is in the U S are there any significant differences in diagnosis or registries and also are there any differences in the outlook or attitude of how the physicians and Japan view using <unk>.

Joseph Stringer: Weight loss drug to try and treat H O compared to what physicians in the U S view of that thank you.

David P. Meeker: Thanks so much. Yeah. Yann, you want to go first? The German launch? Yes, I will start with Germany.

Speaker Change: Okay. So Joey I'll start and then hand, it over to Jennifer I think we've tried to be pretty consistent messaging around scripts that we view that is the hardest thing to predict so.

Jan Mazabro: So no, I have not given patient numbers, but I can comment on the launch for sure. So, as I said, it's progressing well. We are meeting our expectations. The country is led by a very experienced GM, and our field team interacts with all the key German centers.

Joseph Stringer: So we expect variability we feel very good about the level that we're at both from our <unk> and Ah reimbursed patients on therapy perspective, but we do think it's gonna be consistently difficult to model. If you will and so and Jennifer can obviously go into the details of this.

Jan Mazabro: So again, in terms of field activity interactions, I think we are doing a very good job. What is important is that the feedback from the HCPs and the feedback from patients through the HCPs is very good, and the discontinuation rate that we observe is low.

Jennifer Li: To the y but.

Jennifer Li: Yeah, you know like what's interesting is okay. So when you look at <unk>.

Jennifer Li: You know a cat like it could be up to a year and the first thing I <unk> for a physician to be educated.

Jan Mazabro: We also have kicked off two large patient identification programs, one for the adult population and one for the pediatric population, which will help us to identify new patients for 25 and beyond. So I don't have specific numbers for Germany, but I can tell you that it's going well. Spain and Italy; I can maybe speak about the two countries together because there are many common dynamics, so it will be slow and steady as usual or as often with rare diseases.

Jennifer Li: To be you know really evaluating their patients to even come to a D. V. S. A diagnosis and then eventually got to a scratch, which is what makes it difficult.

Jennifer Li: To predict corner on the corner and what I will say, it's likely ticket take a look at different matrix, including as we outlined so there's like a new number of prescribers too at at the bank.

Jennifer Li: And educated in terms of awareness M. P. B S N.

Jan Mazabro: Both countries are single-payer systems and have a national negotiated price, which is very good. They are also very decentralized, so we have to engage with both regional payers and local hospitals in individual states. And that's why it will be slow and steady. Of course, we focus initially on where the identified patients are and in the fastest regions from a market access point of view. As I said earlier, there are 21 states in Italy and 16 in Spain.

Jennifer Li: Cause that Florida as well as the ones that are already prescribed and add a good experience with their patient.

Jennifer Li: Are also interested in <unk> any additional patients that come across and that's that's what we want and character and really experiencing the benefits.

Jennifer Li: For the Baby S. S population will remain positive in terms of the opportunity for <unk> you know, there's still a ways to go in terms of really achieving at a breathless estimate that we have out there and we're just going to continue to go quite out of a corner.

Jan Mazabro: So we are focusing on the one with the most patients and the fastest pace in terms of access. And in general, what I would say about Europe, and Hunter mentioned this also in his slides, for 2024, Germany will be the main driver, and both Spain and Italy will become more meaningful in 2025 when we will also have the UK and the Netherlands kicking in. And on your clinical question, which is, yeah, we enrolled incredibly well in the phase 3 trial, and that does speak to demand for this trial. And that, for sure, will spill over into potential enrollments for both our weekly program and the small molecule daily oral program. I don't think that until we get neither one of those programs, have we dosed an HO patient?

Speaker Change: And you wanted to provide a little more color on the patient situation, Japan, Yeah. So I can speak a little too Mmm H U in Japan and.

Jennifer Li: <unk>.

Jennifer Li: <unk>.

Speaker Change: <unk> the U S. So one thing that <unk> is that.

Jennifer Li: When.

Jennifer Li: <unk> in the U S and Europe, most of the time and those of chaos endocrinologist after the surgery.

Jennifer Li: In Japan, there already food <unk> medical specialties, which I think is good because some of those patient identification <unk> medical specialties that we can speak to <unk> and we will make sure that we have <unk>. One of your question was about <unk>.

David P. Meeker: As I said, first, you know, for the weekly, we've got to go through the healthy volunteer study for the small molecule. We're just getting those sites up, and we've gotten to the point where we're dosing. So, until we get that part of the trials established, I don't have a line of sight to when exactly we would guide to readouts here. So, I'm going to defer that, but we will commit to it. We'll for sure be in 2025.

Jennifer Li: Two registries existing.

Jennifer Li: <unk> scientific societies, and we have worked with those societies and <unk> to set up <unk> <unk>.

Jennifer Li: Filled in with Olivia walking <unk> <unk> <unk> point of view in Japan as you know that they're all very good. That's all those people that are so we have used claims.

Day Ganha: As you can imagine, we're highly motivated to get it as soon as possible, but I have to leave it there. Okay. Thanks so much. Please stand by for the next question. The next question comes from Joseph Stringer with Needham.

Jennifer Li: <unk>, but who will continue to use that we're supposed to I don't decide <unk> essentials, where physicians and of course, a lot of food that sounds that will help us from an economic point of view.

Joseph Stringer: Your line is open. Hi, good morning. Thanks for taking our questions. First one on just looking at the NRX, which seemed to be down slightly the last two quarters. Just wondering if you could comment on this trend. Do you feel like you'd reach a point in the US where there'd be a relatively steady state quarterly new prescription ad? And what would that look like?

Jennifer Li: What's your question was about the use of <unk>.

Jennifer Li: Until the communication.

Jennifer Li: <unk> for us to to to say, but what we have observed.

Jennifer Li: Two weeks ago during the symposium there were a lot of questions.

Jennifer Li: <unk> details in too.

Jennifer Li: <unk> and.

Jennifer Li: So I can only report, which we have heard of is Susan <unk> of the <unk>.

David P. Meeker: And then secondly, on HO in Japan, can you maybe talk about the HO patient community and organization relative to what it is in the US? Are there any significant differences in diagnosis or registries? And also, are there any differences in the outlook or attitude of how physicians in Japan view using, say, the GLIP weight loss drug to try and treat HO compared to what physicians in the US view it as? Thank you. Okay, so Joey, I'll start and then hand it over to Jennifer.

Jennifer Li: Of any society.

Jennifer Li: And mentioned that Jeevan <unk> species, the specifics of a true and the mechanism infection of Cyprinoid items in British in medicine specs.

Jennifer Li: You should consider hypnotized.

Jennifer Li: <unk>, so <unk> to say, but I think.

Jennifer Li: <unk> interacting with the market that sounds very promising full force.

Speaker Change: Thank you.

Speaker Change: Okay, great well. Thank you so much for the yeah. Thanks, so much for the color.

Speaker Change: Next question.

Speaker Change: One moment for our last question.

Arlinda Anna Lee: I think we've tried to be pretty consistent in our messaging around scripts, that we view that as the hardest thing to predict. So we expect variability. We feel very good about the level that we're at, both from the RX growth and the reimbursed patients on therapy perspective, but we do think it's going to be consistently difficult to model, if you will. And so, and Jennifer can obviously go into the details as to the why, but Yeah,

Speaker Change: The last question comes from Michael Higgins with Latin burnt down in your line is now open.

Michael John Higgins: Thank you all for Ya and how congrats as well guys in a corner give me a.

Michael John Higgins: A quick one here, David if you could confirm forest.

Michael John Higgins: And marketing in Japan, and you've reached a message population. Thanks.

Michael John Higgins: My <unk> my <unk> I missed it.

David: So I can confirm it looks like we're gonna.

Speaker Change: Yeah, hopefully the call will go through here just trying to clarify your marketing plan in Japan are you Gonna go alone again of Hardwork, others, Yeah. Okay. Good. Thanks.

Arlinda Anna Lee: You know, what's interesting is sometimes when you look at some of the scripts that came in, it was, you know, it took, like, up to a year from the first interaction for the physician to be educated and then to be, you know, really evaluating their patients to even come up with a BBS patient diagnosis and then eventually go to a script, which is what makes it difficult just in terms of really being able to predict quarter over What I will say is, like, we took a look at different metrics, including, as we outlined, sort of, like, the new number of prescribers who have been increased and educated in terms of awareness of BBS, and that has remained consistent quarter over quarter, as well as the ones that have already prescribed and had a good experience with their patients, hence they are also interested in terms of putting any additional patients that come across. And that's what we want in terms of them really experiencing the benefits of this specific therapy for the BBS patient population. So we remain positive in terms of opportunities for growth.

Speaker Change: Perfect Yep. Thanks.

Speaker Change: Yeah. So as I said earlier, so we will go alone we will.

Speaker Change: It's doubly sure it must be.

Speaker Change: In Japan, we have a little Lady.

Speaker Change: Two people working for us <unk>, one person in my teens.

Michael John Higgins: To the market and we will build a structure.

Michael John Higgins: In the next month as needed as you know in Japan, there are some positions that.

Michael John Higgins: The three before failing so we are currency, you're looking for fossils and as I also said well Oh Lucky with these two two consultants to establish relationship <unk>, keeping your details and medical societies, Yes stand alone.

Michael John Higgins: And and moving for Awhile I'd really like that.

Speaker Change: Yeah, and just remind if I think our overall strategy and John strategy here is being successful in rare diseases, particularly outside the U S. It's all about the people you have on the ground and we've done well with people like Yahoo of a deep experience and for Japan, We're gonna get back into.

Arlinda Anna Lee: You know, there's still a ways to go in terms of really achieving the prevalence estimates that we have out there, and we're just going to continue to grow quarter over quarter. And Yohan, do you want to provide a little more color on the patient situation in Japan? Yes, so I can speak about the H.O. in Japan.

Michael John Higgins: Genzyme, Sanofi genzyme roster as well I'm looking for some people we've worked within the past two again.

Jan Mazabro: And one of your questions was also about the difference or comparison with the U.S. So one thing that we have observed first is that when these patients in the U.S. and in Europe are most of the time under the care of endocrinologists after the surgery. In Japan, they are really followed closely by those two medical specialties, which I think is good because, from a patient identification point of view, we have two medical specialties that we can speak to, but we have observed that very early, and we will make sure that we are covering those two specialties very well. One of your questions was about registries. Yes, there are two registries existing led or under the umbrella of scientific societies, and we have worked with those societies and with these registries to set up the prevalence numbers that I've given earlier. So yes, they exist.

Michael John Higgins: <unk> familiarity with the Japanese market and like so when when you answer we we feel we can do this alone we would talk to partners and it will never say never on partnering but but I think this is approachable and given the size and value of this overall rhythm picture on the bar to do anything else, but go directly would be extremely hot.

Michael John Higgins: With that I think I'm going to allow these guys question yeah thankfully.

Speaker Change: So thanks to Oregon.

Speaker Change: Sorry.

Michael John Higgins: Yeah.

Speaker Change: So I think thanks again, everybody for tuning in and we very much look forward to reporting out again and another busy are coming up for for rhythm section.

Speaker Change: This concludes today's conference call. Thank you for participating you may now disconnect.

Jan Mazabro: They are well filled, and we are already working on using them. Another good aspect from a patient point of view in Japan, as you know, is that there are very good data or hospital data, so we have used claims database analysis for the prevalence, but we will continue to use that also to identify where the largest centers are, where the patients are, and, of course, a lot of data that will help us from an economic point of view. One of your questions was about the use of other anti-obesity medications. I mean, it's a bit early for us to say, but what we have observed. Two weeks ago, during the symposium, there were a lot of questions from the audience to the speakers about that. What should they do?

Speaker Change: [music].

Jan Mazabro: So I can only report what we have heard. So the president of the Japanese society stood up and mentioned that given the specifics of HO and the mechanism of action of set melanotide and the precision medicine aspect, they should consider using set melanotide to treat these patients. So very early to say, but I think we are observing, and we are interacting with a market that sounds very promising for us. Great, thank you.

Joseph Stringer: Great, thank you so much for the call. Next question. One moment for our last question. The last question comes from Michael Higgins with Lattenberg Thalmann. Your line is now open. Thank you, operator, and our congratulations as well, guys, in the quarter. Give us a quick one here.

Michael John Higgins: David, if you could confirm for us the marketing plan in Japan and reaching that patient population. Mike, Mike, I missed the call. Sorry, I'm just trying to clarify your marketing plan in Japan. Are you going to go alone?

Jan Mazabro: Are you going to partner with others? Yeah, okay. Perfect. Yep. Thanks, Jan. Yes, as I said earlier, we will go alone. We will establish an affiliate in Japan. We already have two people working for us on the ground. One person in my team is also dedicated to the market, and we will build the structure for the next month as needed. As you know, in Japan, there are some positions that are mandatory before registration.

Jan Mazabro: So we are currently looking for those. And as I also said, we are working with these two consultants to establish a relationship with the key opinion leaders and medical society. So yes, stand alone and move forward like that. Yeah, and just to remind people, I think our overall strategy and Jan's strategy here is being successful in rare diseases, particularly outside the U.S. It's all about the people you have on the ground.

Speaker Change: [music].

David P. Meeker: And, you know, we've done well with people like Jan who have deep experience. And for Japan, we're going to dip back into that Genzyme, Sanofi Genzyme roster as well. I'm looking for some people we've worked with in the past again, who have high familiarity with the Japanese market. So when Jan said we felt we could do this alone, we've talked to partners, and we'll never say never to partnering, but I think this is achievable. And given the size and value of this, the overall rhythm picture, the bar to do anything else but go direct would be extremely high.

Operator: So with that, I think that was the last question. Yeah, thanks. So thanks all again, sorry.

Operator: So I think, thanks again, everybody for tuning in. And we very much look forward to reporting out again in another busy year coming up for Rhythm. This concludes today's conference call. Thank you for participating. You may now disconnect. © The Ultimate Parody Site! Thank you for watching! ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? © The Ultimate Parody Site!

Operator: www.RhythmPharmaceuticalsInc.com Ladies and gentlemen, thank you for standing by. Welcome to Rhythm Pharmaceuticals' fourth quarter and full year 2023 earnings conference call. At this time, all participants are in the listen-only mode.

Operator: After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you will need to press star 11 on your telephone. You will then hear an automated message advising that your hand is raised.

Operator: To withdraw your question, please press star 11 again. Please be advised that today's conference is being recorded. I would like now to turn the conference over to David Connolly, Investor Relations and Corporate Communications. Please go ahead.

David Connolly: Thank you, Michelle. I'm Dave Connolly here at Rhythm Pharmaceuticals. For those of you participating in the call, our slides can be accessed and controlled by going to the Investors section on the Investors page of our website, ir.rhythmtx.com. This morning, we issued a press release that provides our fourth-quarter and year-end 2023 financial results and a business update, which is available on our website. As listed on slide two is our agenda. Here with me today in Boston are David Meeker, Chair, Chief Executive Officer, and President of Rhythm Pharmaceuticals; Jennifer Lee, Executive Vice President, Head of North America; Hunter Smith, our Chief Financial Officer; and Jan Mazabro, 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.

David Connolly: Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in our most recent annual or quarterly reports on file with the SEC. In addition, any forward-looking statements represent our views as of only today and should not be relied upon as representing our views as of any subsequent dates. We specifically disclaim any obligation to update such statements.

David Connolly: With that, I'll turn the call over to David Meeker, who will begin on slide five. Thank you, Dave. Good morning, everyone.

David P. Meeker: And thank you for joining the call. So 2023 was truly a transformational year for Rhythm, commercially, developmentally, financially, and strategically, as we have expanded potential indications to the next generation product. 2024 will be a year focused on execution, setting up an exciting year of milestone achievements in 2025. So on slide five, we've got the three boxes, which highlight the important aspects of rhythm. And on the first box, HO remains the cornerstone of rhythm value.

David P. Meeker: We finished the year having over-enrolled our phase three trial, now with all 120 patients in the primary analysis cohort dosed, and these 120 will form the basis of the US and EMA filings, keeping us firmly on track for the first half 2025 top line readout. Execution in that trial remains strong with a high level of site and patient engagement. We're excited also to announce that today we have concluded extremely constructive interactions with the Japan Regulatory Authority, the PMDA, which will allow us to include 12 Japanese patients in the phase three trial without requiring an independent study in Japanese patients. Japan is continuing to evolve its regulatory process to further facilitate the development of innovative medications for the Japanese population.

Speaker Change: [music].

David P. Meeker: And they were highly motivated to ensure that Japanese patients would be able to participate in the call in the phase three trial. We were joined in our interactions by one of the leading experts in Japan, who helped them understand the severe unmet medical need and the potential benefits of cephalanotide. What's particularly interesting about Japan Opportunity is that the prevalence of HO is two times higher than in the U.S., with our initial epidemiology work suggesting there are 5,000 to 8,000 patients, which is about the same number as in the U.S., albeit with a population a little more than half the size of the U.S. So, if this opportunity plays out as we think it will, the Japan opportunity could become the second most valuable part of the overall Rhythm portfolio behind the USHO opportunity.

Speaker Change: Welcome to rhythm Pharmaceuticals, fourth quarter and full year 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 this session you will need to press star one on your tele.

Speaker Change: Town you what's in here in an amazing message of bites in your hand, just raised to withdraw your question. Please press star. One again, please be advised that today's conference is being recorded I would like now to turn the conference over to David Connolly Investor Relations and corporate communications.

David Connolly: Please go ahead.

David P. Meeker: So Jan will expand more on that epidemiology and our plans going forward. Second, we made great progress advancing several programs. Both our newly acquired daily small molecule from LG Chem and our weekly formulation 718 are progressing well. I'll comment further on those in a couple of slides.

David Connolly: Thank you Michele I'm, Dave constantly here at rhythm Pharmaceuticals for those of you participating on the conference.

David Connolly: Our slides can be accessed in control by going to the investors section on the investors page of our website.

David Connolly: <unk> Dot rhythm TX Dot com. This morning, we issued a press release that provides our fourth quarter and year end 2023 financial results at a business update which is available on our website.

David P. Meeker: With regard to the pediatric program, I will show you two slides you've seen before, reminding you of the strength of that data and why we think it is so important. We have filed, as previously reported, to expand the use of insurgery to patients between the ages of two and five in the US, sorry, in the EU, and we'll file in the US in the first half. Third, we had another solid quarter commercially with $24.2 million in revenue, over 100 new prescriptions, and more than 70 approvals for reimbursement. We are excited about our recent reimbursement approvals for BBS in Spain and Italy. And with those two approvals, Incivery is now available commercially in 14 countries, including the U.S. and Canada.

David Connolly: As listed on Slide two is our agenda here with me today in Boston are David Meeker Chair, Chief Executive Officer, and President of Rhythm Pharmaceuticals, Jennifer Li Executive Vice President head of North America Hunter Smith, our Chief Financial Officer, and John <unk> Executive Vice President and head of International is on the line joining us from Europe.

David Connolly: 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 in our most recent annual or quarterly.

David P. Meeker: Revenues in the quarter were impacted by a change in policy made by a single Medicaid program in one state in response to a disproportionately high volume of prescriptions. The state has a favorable policy in place and continues to cover patients, but it is now requiring a higher level of documentation than previously required. For example, if a patient has eye findings consistent with the diagnosis of BBS, they will now require an ophthalmology consult to confirm the diagnosis, whereas previously it was simply the attestation of the prescribing physician. With this change in policy, 30 patients came off coverage early in the quarter and were transitioned to our bridge program, which is a free drug program provided while we work through coverage. There is no read-through to any other Medicaid program, as this situation is unique to a specific demographic in this state with a higher prevalence of BBS patients who came on to treatment early.

David Connolly: Our reports on file with the SEC. In addition, any forward looking statements represent our views as of today and should not be relied upon as representing our views as of any subsequent dates we specifically disclaim any obligation to update such statements with that I'll turn the call over to David Meeker, who will begin on slide five.

David P. Meeker: Thank you Dave Good morning, everyone and thank you for joining the call.

David P. Meeker: So 2023 was truly a transformational year for rhythm commercially developmentally financially and strategically as we have expanded potential indications.

David P. Meeker: Between call next generation products.

David P. Meeker: 2024 will be a year focused on execution setting up an exciting year of milestone achievements in 2025.

David P. Meeker: So on slide five we've got three buckets boxes, which highlight the important aspects of rhythm at that first box.

David P. Meeker: The impact of 30 patients coming off reimbursed treatment early in the quarter and going on to the BRIDGE program was about $2 million. Importantly, despite this dip in U.S. patient numbers at the start of the quarter, the remainder of the U.S. story continues to grow as expected. And we finished the quarter in a very good place. And Jennifer will, of course, provide more color in her section. So moving to slide six. So a little more on Japan.

David P. Meeker: <unk> remains the cornerstone of rhythm value, we finished the year, having over enrolled our phase III trial now with all 120 patients and the primary analysis cohort dosed.

David P. Meeker: This $1 20 will form the basis of the U S and EMA filings keeping us firmly on track for first half of 2025 top line readout.

David P. Meeker: Typically, Japanese regulatory authorities require PK studies to be conducted in Japanese subjects in advance of testing and investigational therapy in patients. However, following extremely constructive discussions with Japan's Pharmaceutical Medical Device Agency, or the PMDA, we have agreed on a plan to enroll 12 Japanese patients into our current phase 3 trial. We will collect PK data in those 12 patients, and there will be no requirement to perform an independent study in Japanese subjects. Importantly, as I said, the additional cohort of Japanese patients and the timing for them to be added to and complete the study will have no impact on our timelines to complete the pivotal cohort, get to top line data, and submit our filings. Specifically, we will file for approval in the U.S. and EU on the results from the first 120 patients who finish the trial.

David P. Meeker: Execution in that trial remains strong with a high level of site and patient engagement.

David P. Meeker: We're excited also to announce today, we have concluded extremely constructive interactions with the Japan regulatory authority, the <unk>, which will allow us to include 12 Japanese patients in the phase III trial without requiring an independent study in Japanese patients, Japan is continuing to evolve the regulatory process to further facilitate the <unk>.

David P. Meeker: <unk> innovative bit innovative medications for the Japanese population.

David P. Meeker: They were highly motivated to ensure that the Japan patients would be able to participate in the call.

David P. Meeker: In the phase III trial, we were joined in our interactions by one of the leading experts in Japan will help them understand the severe unmet medical need and the potential benefit outset Atlanta type work.

David P. Meeker: What's particularly interesting about Japan opportunity is that the prevalence of <unk> is two times higher than in the U S. With our initial epidemiology work, suggesting there are five to 8000 patients which is about the same number as in the U S, albeit with a population of little more than half the size of the U S. So if this opportunity plays forward.

David P. Meeker: The remaining patients, the approximately 10 plus patients who are part of the over-enrolled patients outside of Japan, and the 12 Japanese patients will be part of a second study which will be used to support Japanese approval. And we will, of course, seek orphan drug designation in Japan and Paraguay. So on slide seven, this is just to remind you of our phase three trial design for HO, which you all know well. The phase three trials enrolled patients aged four years and older with hypothalamic obesity, randomized two-to-one to cephalanotide therapy or placebo for a total of 60 weeks, which includes up to eight weeks for dose titration. The primary endpoint for this trial is the mean percent change in BMI from baseline after approximately 52 weeks on a therapeutic regimen of cephalanotide compared with placebo.

David P. Meeker: As we think it will the Japan opportunity could become the second most valuable part of the overall rhythm portfolio behind the U S. H O opportunity, so Jan will expand more on that epidemiology and our plans going forward.

Speaker Change: Second we made great progress advancing several programs both our newly acquired daily small molecule from LG Chem and our weekly formulation seven eight are progressing well I'll comment further on those in a couple of slides with regard to the pediatric program I will show again, two slides you've seen before reminding you of the strength of that data and <unk>.

David P. Meeker: We are 99, as I told you before, 99.5% power to achieve a 10-point differential between the therapeutic arm and placebo. And given our 12-month data showing consistent response across all patients who adhere to the prescribed therapy and the consistent safety profile of cephalanotide and other indications, we are quite confident in the outcome. On slide 8, I'll speak for a moment about LG Chem's molecule.

Speaker Change: Why we think it is so important.

Speaker Change: <unk> filed as previously reported to expand the use of <unk> to patients between the ages of two and five in the U S. Sorry in the EU and we will file in the U S. In the first half of this year.

Speaker Change: Third we had another solid quarter commercially with $24 2 million in revenue over 100, new prescriptions and more than 70 approvals reimbursement. We are excited about our recent reimbursement approvals for Bbs in Spain, and Italy, and with those two approvals and Sebree is now available commercially in 14 countries, including the U S and Canada.

David P. Meeker: We're particularly excited about the acquisition of the global rights for LB54640 and yes, which we announced early in January. We believe this drug candidate could provide patients with an important new treatment option and could be an important long-term value driver for our country. LG Chem, a highly regarded company with deep chemistry and early translational experience and expertise, has developed an oral drug candidate that, based on the early clinical data generated to date, suggests they have identified a specific therapy for MC4R diseases that will not result in hyperpigmentation or have associated cardiovascular side effects.

Speaker Change: Revenues in the quarter were impacted by a change in policy made by a single Medicaid program in one state in response to a disproportionately high volume of prescriptions. The state has a favorable policy in place and continues to cover patients, but is now requiring a higher level of documentation than previously required.

Speaker Change: For example, if a patient has I findings consistent with the diagnosis of Bbs. They will now require an ophthalmology console to confirm the diagnosis, whereas previously it was simply the attestation of the prescribing physician with this change in policy 30 patients came off coverage early in the quarter and were transitioned to our bridge program.

David P. Meeker: We have had a highly collaborative working interaction with the LG team as we move to transfer full responsibility for the program to Rhythm. We anticipate the transfer to be largely complete within three months of signing and remain on track. In the meantime, we are jointly progressing the two trials, with the primary focus being on site initiation of the signal trial for hypothalamic obesity. A parallel focus will be on developing a pediatric formulation, which will allow us to move to treating younger patients who, as we know, for both HO and the genetic causes of MC4 pathogenesis are in need of treatment. On slide nine, a little more about the molecule LB54640.

Speaker Change: Which is a free drug program provided while we work through coverage issues. There is no read through to any other Medicaid program. As this situation is unique to a specific demographic in this state with a higher prevalence of Bbs patients who came on to treatment early the impact of 30 patients coming off reimburse.

Speaker Change: <unk> treatment early in the quarter and going onto the bridge program was about $2 million.

Speaker Change: Importantly, despite this dip in U S patient numbers at the start of the quarter. The remainder of the U S story continues to grow as expected and we finished the quarter in a very good place and Jennifer will of course provide more color in her section.

David P. Meeker: As previously described, we were impressed by their robust preclinical package and by the data in their phase one study in healthy volunteers with obesity, which showed the expected dose-dependent decrease in BMI at four weeks. Importantly, they did not see hyperpigmentation or any cardiovascular signal, which is consistent with their preclinical work. Slide 10 shows the design of the signal trial, a phase two, 28 patient open-label trial, sorry, placebo-controlled trial to evaluate the molecule in patients with hypothalamic obesity. The trial is designed to evaluate safety, tolerability, pharmacokinetics, and weight loss efficacy, with an efficacy endpoint of mean percent change in BMI from baseline at 14 weeks. The trial is four arms, three different dose groups in placebo, and would be followed by an open-label extension period of up to 52 weeks. This is very similar to the exception of the placebo control to the trial we ran originally with sepmal antibody in HL. We are fortunate to have a model such as HL that appears to be quite sensitive to the effects of an MC4R agonist.

Speaker Change: So moving to slide six.

Speaker Change: So we're more in Japan.

Speaker Change: Japanese regulatory authorities require PK studies to be conducted in Japanese subjects in advance of testing an investigational therapy in patients. However, following extremely constructive discussions with Japan's pharmaceutical and medical device agency or the <unk>. We have agreed on a plan to enroll 12 Japanese patients into our current phase III trial, we will.

Speaker Change: Collect PK data in those 12 patients and there'll be no requirement to perform an independent study in Japanese subjects importantly, as I said, the additional cohort of Japanese patients and the timing for them to be added to and complete. The study we will have no impact on our timelines to complete the pivotal cohort get to top line data and submit our filings.

Speaker Change: The United States and Europe, specifically, we will file in the U S and EU on the results from the first 120 patients who finished the trial the remaining patients. The approximately 10 plus patients who are part of the over enrolled patient group outside of Japan, and the 12 Japanese patients will be part of a second close which will be used to support Japanese approval.

David P. Meeker: So our expectation is that this relatively small trial will give us good insight into the efficacy, safety, and importantly, the dose range, which we will look to develop as the program advances. On slide 11, the 718 weekly program, as I highlighted in my intro, is advancing well. The IND is filed.

Speaker Change: And we will of course seek orphan drug designation in Japan in parallel.

Speaker Change: So on slide seven this is just to remind you of our phase III trial design for HR, which you all know well.

Speaker Change: The phase II trials enrolled patients aged four years and older with hyperkalemia obesity randomized two to one to set monotype therapy or placebo for a total of 60 weeks, which includes up to eight weeks for dose titration. The primary endpoint for this trial. The mean percent change of BMI from baseline after approximately 52 weeks on a therapeutic regimen of step Atlanta compared with placebo.

David P. Meeker: We have selected our CRO and are looking to dose our first patients in the first half of this year. And I can tell you that we are aiming to have those first patients dosed in March here. We're committing to the first half of this year.

David P. Meeker: As a reminder, we will begin conventionally with single and then multiple ascending dose cohorts in normal volunteer patients with obesity, followed by Part C, which will enroll HO patients and follow them for 28 days. Those patients will be eligible to enter into a long-term extension study once we complete our chronic toxicity studies, which are required to support longer dosing, and those chronic toxicity studies are ongoing and running in parallel. Now, on slide 12, and on my last two slides, I want to revisit the data in pediatric patients we showed at our R&D day in December. I find these results quite remarkable for a couple of reasons.

Speaker Change: So we are 99 as we told you before at 99, 5% powered to achieve a 10 point differential between the therapeutic arm and placebo and given our 12 month data showing consistent response across all patient to adhere to their prescribed therapy in the consistent safety profile separately and other indications we are quite confident in the outcome.

Speaker Change: On slide eight speak a moment about LG <unk> molecule, we're particularly excited about the acquisition of the global rights for <unk> 641, Yes, we will be working on a name for that which we announced early in January we believe this drug candidate could provide patients with an important new treatment option and could be an important long term value.

Speaker Change: Driver for our company LG Chem, a highly regarded company with deep chemistry, and early translational experience and expertise has developed an oral drug candidate that based on the early clinical data generated to date suggests they have identified a specific therapy for <unk> four are diseases that will not result in hyper pigmentation or <unk>.

David P. Meeker: One is that despite their extremely young age, patients between the ages of 2 and 5, with either POMC, lepidodeficiency, or BBS, were severely affected. That should not be a surprise given the genetic cause of the disease, which means in most cases it has been present since birth. Despite the severity, we know from multiple anecdotes, these patients are not being recognized as having an underlying disease, and in the worst cases, the parents are blamed for their inability to control their child's food intake.

Speaker Change: Associated cardiovascular side effects, we have had a highly collaborative working interaction with the LG team as we move to transfer full responsibility for the program to rhythm we anticipate the transfer it to be largely complete within three months of signing and remain on track for that in the meantime, we are jointly progressing the two trials with the primary focus being on site.

David P. Meeker: As you can see on this slide, patients responded extremely well to treatment with a mean decrease in weight of more than 18% at one year. With Flight 13, I think this is where the real story lies in the individual results, which show a waterfall plot of the individual results for the 12 patients. Two takeaways. The y-axis shows the BMI Z-score, which is basically the number of standard deviations the child is away from normal.

Speaker Change: Initiation of this signal trial for Hypothermic obesity, a parallel focus will be on developing a pediatric formulation, which will allow us to move to treating the younger patients who as we know for both HR and the genetic causes of emcee for pathway seasons are in need of treatment.

David P. Meeker: The graph shows the change in BMI Z-score with treatment. For the first two groups, starting from left to right, on the left-hand side of the graph, these children are experiencing a 5 to 7 point decrease in their BMI Z-scores from a starting point as high as 12. It is important to remember a BMI Z-score, changes greater than 0.2, is considered clinically meaningful. BBS patients who are not quite as severely affected still show a one to two points. The only two patients who did not have a meaningful, highly meaningful change in their BMI Z-score were one patient who was lost to follow-up early in the trial, and a second patient who was non-compliant with the medication. Expanding the label to children two and above will not open up a significant additional market opportunity.

Speaker Change: On slide nine a little more about the molecule EB 540 641. As previously described we were impressed by their robust preclinical package and by the data in their phase one study in healthy volunteers with obesity, which showed the expected dose dependent decrease in BMI at four weeks importantly, they did not see hyperpigmentation, nor any cardiovascular signal, which is consistent with.

Speaker Change: The preclinical work.

Speaker Change: Slide 10 shows the design of the signal trial, a phase 228 patient open label trial placebo.

Speaker Change: Zeebo controlled trial to evaluate the molecule in patients with hyperkalemia obesity. The trial is designed to evaluate safety tolerability pharmacokinetics weight loss efficacy with an efficacy endpoint of mean percent change in BMI from baseline of 14 weeks. The trial has four arms three different dose groups and placebo and would be followed by <unk>.

David P. Meeker: It will add incrementally, of course, but it will reinforce the importance of thinking about genetic causes when confronted with early-onset obesity. It will remind people that cumulative morbidity begins early, and the earlier you intervene with a specific therapy, the better your chance to modify the long-term outcomes. And third, it reinforces the safety of the medication and that it can be given and should be given to children as young as two, if clinically indicated. So, as I said, we filed for our European label expansion, and we look forward to filing in the U.S. 4. With that, I'll turn the call over to you.

Speaker Change: Open label extension period of up to 52 weeks. This is very similar to the exceptional placebo control to the trial. We ran originally and with several Antitype NHL. We are fortunate to have a model such as HR, which appears to be quite sensitive to the effects of an empty for our agonist. So our expectation is that this relatively small.

Speaker Change: Bill will give us good insight into the efficacy safety and importantly, the dose range, which we will look to develop as the program advances.

Speaker Change: On slide 11.

Speaker Change: $700 eight weekly program as I highlighted in my intro is advancing well. The IND is filed we reflected our CFO and are looking to dose our first patients in the first half of this year and I can tell you that we are aiming to have those first patients dosed in March here, we're committing to the first half of this year. As a reminder, we will begin conventionally with single and multiple ascending dose.

Arlinda Anna Lee: Thank you, David. We continue to see solid commercial execution this quarter with new prescriptions, prescribers, and reimbursements. Beginning on slide 15, we remain pleased with the growth and consistent demand for Sivri since launching in June of 2022, marking six full quarters and our first full calendar year. In addition, we continue to see gains in the depth and breadth of prescribers and positive reauthorization decisions. During the fourth quarter of 2023, we received more than 100 new prescriptions and more than 70 approvals for reimbursement from payers. However, as David mentioned earlier, these positive trends were offset by a challenge associated with one pair.

Speaker Change: Cohorts in normal volunteer patients with obesity, followed by a part C, which one will HL patients followed for 28 days those patients will be eligible to enter into a long term extension study once we complete our chronic toxicity studies, which are required to support longer dosing and dose chronic toxicity studies are ongoing and running in parallel now.

Speaker Change: On Slide 12, my last two slides I wanted to revisit the data in pediatric patients. We showed at R&D day in December and find these results quite remarkable for a couple of reasons. One is that despite the extremely young age patients between the ages of two and five with either policy led by deficiency or <unk> as they were severely effect that's enough.

Arlinda Anna Lee: One state Medicaid, because of a higher than expected volume of prescriptions for BBS patients, which was above their estimated prevalence of BBS, had requested additional documentation to support the diagnosis for previously approved and reimbursed patients. In the meantime, coverage for these patients was rescinded. To ensure these patients do not have any gaps in treatment for emphysema, we transitioned 30 patients to free drugs through our bridge program. Therefore, during Q4, the total number of reimbursed patients dropped below where we exited Q3. This event was limited to one state, where there appears to be a high prevalence of BBS patients, making this a unique situation. We are working with this Medicaid program and prescribers to ensure patients diagnosed with BBS continue to receive access to MCBRI therapy.

Speaker Change: It should not be a surprise given the genetic cause of the disease, which means in most cases. It has been present since birth. Despite this severity we know from multiple anecdotes. These patients are not being recognized as having an underlying disease and in the worst cases. The parents are blamed for their inability to control their child's food intake as you can see on this.

Speaker Change: Patients responded extremely well to treatment with a mean decrease in weight of more than 18% at one year.

Speaker Change: Slide 13, I think this is where the real story lies in the individual results, which show a waterfall plot of the individual results for the 12 patients two takeaways the Y axis shows the BMI Z score, which is basically the number of standard deviation. The child is away from normal the graph shows the change in.

Speaker Change: <unk> score with treatment for the first two groups starting from left to right pumps and left bar on the left hand side of the graph. These children are experiencing a five to seven point decrease in their BMI Z scores from our starting point as high as 12.

Arlinda Anna Lee: It is important to note that this state Medicaid still has a policy in place to cover MCIV rates. Going back to the 70 approvals in the quarter, we are seeing these come through faster and with fewer appeals than in prior quarters. Over 70% of approvals for reimbursement during the quarter came at the time of prior authorization or sooner, a trend that has shown incremental improvement each quarter since launch. Next slide.

Speaker Change: Important to remember a BMI Z score changes greater than 0.2 is considered clinically meaningful the Bbs patients who are not quite as severely affected still showed a 1% to two point decrease the only two patients who did not have a meaningful highly meaningful change in their BMI Z score was one patient who has lost to follow.

Speaker Change: Early in the trial and a second patient who is noncompliant with the medications.

Arlinda Anna Lee: More than half of MCIVERY prescriptions for BBS continue to come from adult patients, accounting for 59% of BBS prescriptions launched to date. This is a positive trend as we believe many adult BBS patients who may have aged out of participating in the annual surveys of the CRIBS registry or were lost to receiving specific care for BBS are re-engaging with their healthcare providers. As we've discussed, this is typical of rare diseases where the first approved therapy for a disease raises awareness and paves the way for the re-engagement of the broader diagnosed patient population. Next slide.

Speaker Change: Expanding the label to children to and above will not open up a significant additional market opportunity. It will add incrementally of course, but it will reinforce the importance of thinking about genetic causes when confronted with early onset obesity that will remind people. The cumulative morbidity begins early in the earlier you intervene with the specific there'll be the better your chance to.

Speaker Change: Modify the long term outcomes and third it reinforces the safety of the medication and then it can be given and should be given to children as young as two if clinically indicated.

Speaker Change: So as I said, we filed for our European label expansion and we look forward to filing in the U S. In Q3 of 2000 and for that I'll turn the call over to Jennifer.

Jennifer Li: Thank you David.

Jennifer Li: We continue to see solid commercial execution this quarter with new prescriptions prescribers and reimbursement beginning.

Arlinda Anna Lee: We see continued progress with additional first-time prescribers, as well as repeat prescribers, while the breakdown by specialty remains consistent. Adult and pediatric endocrinologists account for 45 percent of prescribers launched to date, consistent with launch-to-date metrics reported during the last few quarters. New prescribers to Rhythm or physicians or territory managers had not previously called on prior to the prescription being received remains consistent at 28% of all prescribers. We are pleased to see this source of growth continue as we find new prescribers through our non-personal promotion efforts. In addition, first-time prescribers, or those who wrote their first MCIVory script, have stayed very consistent, averaging 48 new prescribers per quarter in 2023. And in Q4, we were consistent with this at 46 first-time writers.

Jennifer Li: Beginning on slide 15, we remain pleased with the growth and consistent good longtime February since launching in June of 2022.

Jennifer Li: I can't fix for Cologuard, and our first full calendar yet.

Jennifer Li: In addition, we continue to see.

Jennifer Li: The depth and breadth of prescribers and positive reauthorization discussions.

Jennifer Li: During the fourth quarter of 2023, we received more than 100, new prescriptions.

Jennifer Li: More than 70 approval for reimbursement from payers.

Jennifer Li: As David mentioned earlier these positive trends were offset by a challenge associated with one path.

Jennifer Li: One state Medicaid because of a higher than expected volume of prescriptions for Bbs patients.

Jennifer Li: Above the estimated prevalence of Evs had requested additional documentation to support the diagnosis.

Jennifer Li: Yes, Lee of crest and reimbursed patients.

Jennifer Li: And then meantime in February cap rates for these patients.

Arlinda Anna Lee: And we are seeing incremental increases in the depth of prescribers. 30% of prescribers launched to date have written two or more prescriptions, which marks an increase from prior quarters. Prescribers are seeing their patients benefit from Insivory, and they remain interested in prescribing for additional BBS patients identified. Next slide.

Jennifer Li: So are these patients do not have any gasoline treatment within three weeks.

Jennifer Li: We transitioned 30 patients to free drug through our branch program.

Jennifer Li: Program.

Jennifer Li: Therefore during Q4, the total number of reimbursed patients.

Jennifer Li: And when we exited Q3.

Jennifer Li: This event with limited to one state where there appears to be a high prevalence of Bbs patients, making this a unique situation.

Arlinda Anna Lee: Overall, the pair mix for BBS remains consistent, with almost 90% of prescriptions since launch falling under a commercial or Medicaid plan. We continue to see incremental improvement in securing access and reimbursement with regard to overall coverage by state Medicaid programs. As we've done in recent quarters, we look at Medicaid coverage measured through covered lives. We introduced this concept at the end of the first quarter when we reported that approximately 75% of Medicaid-covered lives were in states with either a positive ancillary policy or in a state where we had been able to gain positive coverage in at least one instance in the absence of an ancillary policy. The remaining 25% of Medicaid lives were in states where we either had not yet had a prescription for MSIFRI, or we were still working to secure access to a prescription, or, finally, where we had not been successful in gaining access through the appeals process. In Q2 and Q3, this breakdown shifted to 80-20. And at the end of this quarter, it was 85-15.

Jennifer Li: We are working with its Medicaid program and prescribers cancer patients diagnosed with Bbs continued to receive access to separate therapy.

Jennifer Li: It is important to note that the state Medicaid still has a policy in place to cover and CFA.

Jennifer Li: Going back to that 70, a profile during the quarter. We are seeing these come through faster and with fewer appeal than in prior quarters.

Jennifer Li: Over 70% approval for reimbursement during the quarter came at the time of prior authorization or sooner.

Jennifer Li: Trend that has shown incremental improvement each quarter since launch next slide.

Jennifer Li: More than half of every prescriptions for Bbs continues to come from adult patient accounting for 59% of Bbs prescription blocks today.

Jennifer Li: This is a positive trend as we believe many adult Bbs patients who may have H AD of participating in the annual survey of the Cribbs registry or were lost to receiving specific cap. Our Bbs are re engaging with their health care providers.

Arlinda Anna Lee: Within this 85%, we have stronger coverage for MCIVRI as we have increased the number of states with a specific MCIVRI policy in place. Next slide. Lastly, we are seeing strong success in reauthorization, as a vast majority of RE-AUTs have been approved. This is indicative of patients benefiting from MCIV re-therapy as well as payers recognizing these benefits. Launched to date, we've had 110 approvals for reauthorizations for continued emphysema therapy. Most of these come at the one-year-on-therapy time point, but there are a few pairs whose policies call for reauthorization decisions at three or six months. As of the end of the fourth quarter, we've only had 10 denials since launch, and six of these denials have been approved through appeal, and we are working to get the remaining four approved as well.

Jennifer Li: As we've discussed this is typical of legacy where the first approved therapy for disease raises awareness and paves the way for a re engagement of the broader diagnosed patient population.

Jennifer Li: Next slide.

Jennifer Li: We see continued progress with additional first time prescribers as well as repeat prescribers, while their breakdown by specialty remains consistent.

Jennifer Li: Adult and pediatric endocrinologists account for 45% of prescribers blacks today.

Jennifer Li: With lots to date metrics reported during the last few quarters.

Jennifer Li: Near to rhythm prescribers or physicians, our territory managers had not previously called on prior to the prescription being received.

Arlinda Anna Lee: Overall, the fourth quarter and the first full year of BBS commercialization have been strong. We will continue focusing our efforts on expediting diagnosis of BBS patients and supporting access to MCIFRI. With that, I will hand it over to Jan.

Consistent at 28% of our prescribers.

We're pleased to see the source of growth to continue as we find new prescribers through our non personal promotion effects.

Jennifer Li: In addition, first time prescribers or those who wrote their first in February scrap has stayed very consistent averaging 48, new prescribers per quarter in 2023 and in Q4, we were consistent with the 46 first time riders.

Jan Mazabro: Thank you, Jennifer. 2023 was a very successful year for the international organization. With the BBS launch in Germany, the pre-EME approval, early access program in France for hypothalamic obesity, many commercial patients in new countries, and all the work that led up to our recent announcements about reimbursement for BBS in Spain and Italy. We're looking forward to a strong year in 2024 as well, as we begin the year by announcing our development strategy in Japan, slide 21. Japan will become a very important market for us. The per capita prevalence for hypothalamic obesity in Japan is two to three times higher than the prevalence rate in the United States and Europe. Through our discussion with local key experts, with the Japanese Pediatric Neurosurgery Society, data from the Japanese Brain Tumor Registry, and also a high-level hospital claims database analysis, it has been confirmed that there is a much higher prevalence of craniopharyngioma in Japan, with the same frequency of obesity development as in the U.S. and in Europe.

And we are seeing incremental increases and the depth of prescribers.

Jennifer Li: 30% of prescribers to date have written two or more prescriptions, which marks an increase from prior quarters.

Jennifer Li: Krish fibers are seeing their patients benefit from mix that fray and they remain interested prescribed for additional Bbs patients identify next.

Next slide.

Overall, the payer mix for Bbs remains consistent with almost 90% of prescriptions since launch following under a commercial or Medicaid plan, we continue to see incremental improvement carrying access and reimbursement with regards to overall coverage by state Medicaid programs.

As we've done in recent quarters, we look at Medicaid coverage measure their covered lives.

We introduced this concept at the end of the first quarter. When we reported that approximately 75% of Medicaid covered lives or in states with either a positive in every policy or in a state where we had been able to gain positive coverage and at least one instance in the absence of separate policy.

Jan Mazabro: And we believe that there are between 5,000 and 8,000 patients with hypothalamic obesity living in Japan. There are more than 100 key hospitals or treatment centers in Japan that care for patients with craniopharyngiomas and other brain tumors that may cause hypothalamic abilities. Building relationships with this center will be key to our strategy, and we have already started to do so. In addition, Japan, like many European countries, is a single-payer system with an established history of recognizing rare diseases and dedicating the resources to care for them. Japan is the third largest economy measured by GDP, and as David already said, in the long term, we believe that it will become the second most important market for Rhythm behind the United States.

The remaining 25% of Medicaid lives were in states, where we either had not yet had a prescription firms Geoffrey or we were still working to secure access for a prescription are finally, where we had not been successful in gaining access through the appeals process.

In Q2 and Q3 this breakdown shifted 80 20.

At the end of this quarter. It was 80 515.

Within that 85%, we have stronger coverage from CFA as we have increased the number of states with a specific and separate policy in place.

Jan Mazabro: In exploring this exciting opportunity, we considered multiple avenues to advance separated time in Japan. We made the decision to move forward with a direct presence. And with that, Rhythm will truly become a global rare neuroendocrine disease company able to leverage our footprint in Japan for future opportunities. Next slide. Our work in Japan is off to a strong start.

Next slide.

Lastly, we are seeing strong success and reauthorization at the vast majority of Ria have been approved this is indicative of patients benefiting from its every therapy as well as payors recognizing these benefits.

Jan Mazabro: In our discussion with the Japanese PMDA, we had the benefit of one leading Japanese expert in hypothalamic obesity, who was able to emphasize the unmet medical need in Japan and the relevance of enrolling Japanese patients directly in our Phase III trials. Just last week, we held our first rhythm-sponsored symposium in Nagoya City during the yearly congress of the Japanese Society for Hypothalamic and Pituitary Tumors, and it was a very Slate 23.

To date, we've had 110 a profile for reauthorization for continued in February therapy most.

Most of these come at the one year on therapy time point, but there are few pairs, whose policies call for reauthorization decisions at three or six months.

As of the end of the fourth quarter, we only had 10 denials since launch and six of these denials have been approved or appeal and we are working to get the remaining portion of that as well.

Jan Mazabro: Meanwhile, our launch in Germany is progressing well, meeting our expectations, with approximately 250 patients living with BBS already identified, and importantly, a subset of approximately 800 patients diagnosed with BDS in Germany. Our team remains focused on engaging with physicians caring for patients and with the many centers where they are treated. We are expanding the number of treatment centers and large hospitals we are engaging with. Now that we have more than nine months into the launch, we have received prescriptions from 15 treatment centers, which are all within large and very well-structured and resourced university hospitals. In addition... Our Rhythm at Home services program, through which we provide patient support for each patient and their caregivers, has been quite successful. Our team sets treatment expectations with physicians and offers very tailored services to patients, with, for example, in-home visits when needed. And since December, pre-filled syringes have been available for both BBS and POM-CV PAR patients.

Overall, the fourth quarter and the first full year of Bbs commercialization has been strong we will continue focusing our efforts on expediting diagnosis of Bbs patients and supporting access James Jeffrey with that let me hand, it over to Jan.

Thank you Jennifer.

2023 was a very successful year for the international organization.

With the Bbs launch in Germany.

EMEA approval early access programming trends for hyperkalemia.

Many commercial patients in new countries and all the work that led to our recent announcements about three investments for Bbs and sustainable.

We're looking forward to a strong year in 2024 as well as we begin the year.

And then signal developments once again, Jeff.

Slide 21.

Japan will become a very important market for us.

Presenting for hypothetical visiting Japan is two to three times higher under prevalence rates.

In the United States and Europe.

Through our discussion with local key sales is a Japanese pediatric neurosurgery so safety.

That does from the Japanese brain tumor registry and also a high level. What's the total claims that are these analyses. It has been confirmed that there is a much higher prevalence of <unk> hundred one in Japan with the same frequency of visit to be resilient in the U S and Europe.

And we believe that there are between 5000 8000 patients with hyperkalemia Kobe city living in Japan.

Jan Mazabro: Next slide. We also recently announced that we achieved reimbursement for MCV in Spain and Italy. In Italy, we received a positive reimbursement decision for BBS two weeks ago, and we have started to launch MCV. We believe that there are approximately 200 patients diagnosed and identified under the care of a known physician. And our team in Italy is focused on engaging with physicians in hospitals and medical centers in 21 states throughout the country.

There are more than 100 with key hospital of treatments and sales in Japan that care for patients with <unk> and also Brent tumor that may cause I put amicably.

Building the relationship with the center will be key to our strategy and we have already started to do it.

In addition, Japan like many European countries as a single payer system with an established history of recognizing rare disease and dedicating the resources carefully.

Japan is still not just couldnt be measured by GDP and as David already say that in the long term, we believe that it will become a single most important markets for rhythm.

At this stage.

In exploring this exciting opportunity we consider multiple avenues to advance submitted I think in Japan, we made the decision to move forward with a direct presence and was that resembled truly become a global rare neuroendocrine diseases company able to leverage our footprint in Japan for future opportunities.

Jan Mazabro: In Spain, the recently announced positive reimbursement decision covers both BBS and POMCD-PAR bilated patients. There are approximately 100 patients with BBS identified, and our team there is engaging with physicians and health care centers in 17 states throughout the country to bring surgery to patients and families. In both countries, we now must navigate regional access and tender management at local hospital levels. It takes weeks for patients to begin treatment, and we will start to see commercial patients come online in both countries during the second quarter. We will begin to see increasing contribution to our net sales from each of these countries in 2025. Slide 25, the last slide,

Next slide.

Our work in Japan is off to a strong start.

A discussion with the Japanese <unk>, we had the benefit of when leading Japanese expense I forgot an eco busy team was able to emphasize even meaningful.

Clinical need in Japan, and the relevance of enrolling Japanese patients directly.

Phase III trial.

Just last week, we held our first reasons consoled symposium in <unk> city during the yearly Congress of the Japanese Society for hypothalamic pituitary tumor cells and this was a very successful one.

Slide 23.

Meanwhile, our launch in Germany is progressing well meeting our expectations with approximately 250 patients living with UBS already identified.

And importantly, a subset of approximately 800 patients diagnosed with <unk> in Germany.

Jan Mazabro: We continue to advance country by country, with MCV now available for POM, CILIPA, and or BBS in 12 countries outside the United States and Canada. In France, we have paid early access available for BBS as we negotiate with French authorities on pricing. We're in the midst of the negotiation now and hope to finalize it by the end of this year. For hypothalamic obesity in France, we have pre-EMA approval and paid early access as well. Both of these early access programs are administered patient by patient.

<unk> remains focused on engaging with physicians caring for patients and with the many centers, where they are pretty big.

We are expanding the number of treatment centers and not just the tools we are engaging with.

Note that we have more of a nine months into the launch we have received prescriptions from 15 treatments until which are all within a large and very well structured and Resourced University hospitals.

In addition, our.

Our original services program through which we provide efficient support for each patient and <unk> has been quite successful.

Our team sits treatment expectations physicians and wholesale retail or services to patients with for example in home visits when needed and since December Prefilled syringes have been available for both CBS and Fox television stations.

Next slide.

We also recently announced that we achieved reimbursement for <unk> in Spain and Italy.

In Italy, we received a positive reimbursement decision for Bbs two weeks ago, and we're starting to launch in theory. We believe that there are approximately 200 patients diagnosed and identified under those are.

Jan Mazabro: It takes time, but we are building a strong foundation in terms of our relationship with government authorities, payers, leading experts, key centers of excellence, and patient associations. Looking ahead, the next of the larger European markets to come online with reimbursement for VBS are the UK and the Netherlands, both in the second half of the year. Now, I will turn the call over to Hunter.

Non physician and our team in Italy has focused on engaging with physicians and hospitals and medical centers in 21 states.

As a country.

In Spain, the recently announced positive reimbursement decision covers both DBS and pumps to be pumped biologic patients.

Approximately 100 patients with Bbs identified and now they're always engaging with physicians and <unk> Center in 17 States.

So as a country to bring <unk> to patients in 17.

Hunter C. Smith: Thank you, Jan. Let's start with a snapshot of the Q4 P&L on slide 27. We recorded $24.2 million in net product revenue in the fourth quarter, versus $8.8 million during the same quarter last year, an increase of $15.4 million, or 175%. For the full year, net product revenue totaled $77.4 million, versus $16.9 million in 2022.

In most countries, we now must navigate regional access and Tinder management at local hospital levels six weeks for patients to begin treatment and we will start to see commercial patients come online in both countries during the second quarter, though.

We will begin to see increasing contribution to our net sales from each of these countries in 2025.

Slide 25 and last slide.

We continue to advance country by country with EMC re now available for polysilicon and Obs in 12 countries outside.

The United States and Canada.

The trends we are paid early access available for Bbs as we negotiate with French authorities in pricing.

We're in the midst of some negotiation now and hope to finalize it by the end of this year.

So let me go visiting friends, we have paid.

Hunter C. Smith: Quarter over quarter, we saw an increase of 1.7 million, or 8%, in net product revenue, driven primarily by continued growth in the number of patients on emphysema therapy in our international region. In the U.S., revenues were relatively flat quarter over quarter due to the shift of 30 patients to our bridge program early in the quarter, as David and Jennifer mentioned. Given that 30 patients lost reimbursement early in the quarter, that change represented approximately a little more than $2 million foregone potential revenue in the fourth quarter, including that discreet event at the beginning of the quarter. Drivers of Revenue, i.e., prescriptions and reimbursement, were as expected.

<unk> access as well.

Most of these early access programs, our new cell patient by patient and takes time, but we are building a strong foundation in terms of our relationship with the government authorities, we Didnt Express key centers of excellence in patient Association.

Looking ahead to next of the larger European markets to come online with reimbursement for Bbs and <unk>.

In the Netherlands.

In the second half of the year.

I will turn the corner over 200.

Thank you Jan.

Let's start with a snapshot of the Q4 P&L on slide 27, we.

We recorded $24 2 million in net product revenue in the fourth quarter versus $8 8 million. During the same quarter last year, an increase of $15 4 million or 175% for the full year net product revenue totaled $77 4 million versus $16 9 million in 2022.

Quarter over quarter, we saw an increase of $1 7 million or 8% of net product revenue driven primarily by continued growth in the number of patients on <unk> therapy.

Hunter C. Smith: This pattern is consistent with our belief that revenue growth in rare diseases is difficult to trend quarter over quarter, but in the long term and globally, so slow and steady growth can happen. In the fourth quarter, volumes of vials dispensed to patients were essentially the same as vials shipped to our specialty pharmacies, resulting in no significant impact on revenue from inventory growth at these specialty pharmacies. Gross to net for U.S. sales quarter over quarter increased to 85% from 83% in the third quarter, primarily due to a Medicaid rebate adjustment in the quarter, which was based on actual rebates paid as compared to rebate levels accrued. Our practice is to accrue for Medicaid rebates based upon expected payer mix, and when actual Medicaid invoices are received, this may result in differences versus accrued amounts. Cost of sales during the fourth quarter was $3.2 million, or approximately 13.3% of net product revenue, representing a 2.6% increase quarter over quarter.

<unk> therapy in our international region in the U S revenues were relatively flat quarter over quarter due to the shift of 30 patients through our bridge program early in the quarter as David and Jennifer mentioned.

Given the 30 patients loss reimbursement early in the quarter that change represented approximately a little more than 2 million forgone potential revenue in the fourth quarter.

Excluding that discrete event at the beginning of the quarter drivers of revenue I E prescriptions and reimbursement were as expected. This pattern is consistent with our belief that revenue growth in rare diseases. It is difficult to trend quarter over quarter, but in the long term and globally.

Slow and steady growth continues.

In the fourth quarter volumes of vials dispensed to patients where essentially the same as vials shipped to our specialty pharmacy.

Resulting in no significant impact on revenue from inventory growth.

The specialty pharmacy.

Gross to net for U S sales quarter over quarter increased to 85% from 83% in the third quarter, primarily due to a Medicaid rebate adjustment in the quarter, which was based on actual rebates paid as compared to rebate levels of crude.

Our practice is to accrue for Medicaid rebates based upon expected payer mix or an actual Medicaid invoices are received this may result in differences versus crude amounts.

Cost of sales during the fourth quarter was $3 2 million or approximately 13, 3% of net product revenue, representing a two 6% increase quarter over quarter.

Hunter C. Smith: The cost of sales consists primarily of product costs and our 5% royalty to Ipsen under our original licensing agreement for Satmalanitide. R&D expenses were $29.9 million for the fourth quarter of 2023, compared to $23.5 million during Q4-22 and an 11% decrease compared to Q3-23. SG&A was $32.4 million for the fourth quarter of this year versus $26.3 million in the fourth quarter of 2022, and an increase of 6.2% on a sequential quarter basis. For the fourth quarter, weighted average common shares outstanding were 59.2 million, an increase of approximately 1.3 million shares over the previous quarter, resulting primarily from the full weighting of this quarter of our equity issuance under the ATM program in Q3. The quarterly net loss per share was $0.70.

Cost of sales consists primarily of product costs, and our 5% royalty to epson under our original licensing agreement for <unk>.

R&D expenses were $29 9 million for the fourth quarter of 2003 compared to $23 5 million during Q4, 'twenty, two and an 11% decrease compared to Q3 'twenty three.

SG&A was $32 4 million for the fourth quarter. This year versus 20 643 million in the fourth quarter of 2002.

And an increase of six 2% from the sequential quarter basis.

For the fourth quarter weighted average common shares outstanding were $59 2 million, an increase of approximately $1 3 million shares over last quarter.

<unk>, primarily from the full waiting this quarter of our equity issuance under the ATM program in Q3.

Quarterly net loss per share was <unk> 70.

Hunter C. Smith: A few highlights on slide 28. Rhythm reported $276 million in cash and cash equivalents at December 31, 2023. This cash on hand is sufficient to fund all planned activities into the second half of 2025. On the net revenue for the quarter of $24.2 million, 76% of these revenues were generated in the United States. This proportion of revenue, the proportion of revenue generated by our international region, increased from 20% to 24% quarter over quarter, reflecting strong growth in BBS patients on therapy in Germany. Fourth quarter operating expenses, including stock-based compensation of $8.7 million for the quarter and $23.6 million for 2023. For 23, we guided to a non-GAAP OPEX range, and our spend came within that range. Non-GAAP operating expenses for the year ending December 31st, 23, were $219.9 million, inclusive of GAAP operating expenses of $261.8 million, minus $9.3 million in cost of sales, and minus $3 Turn to slide 29.

A few highlights on slide 28.

For the reported 2270 $6 million of cash and cash equivalents at December 31, 2023. This cash on hand is sufficient to fund all planned activities into the second half of 2025.

While the net revenue for the quarter of $24 2 million, 76% of these revenues were generated in the United States. This proportion of revenue the proportion of revenue generated by our international region increased from 20% to 24% quarter over quarter, reflecting strong growth in Bbs patients on therapy in Germany.

Fourth quarter operating expenses, including stock based compensation of $8 7 million for the quarter and $23 6 million for 2023.

For 'twenty three we guided.

To an opex range of a non-GAAP opex opex range and our spend came within that range non-GAAP operating expenses for the year ending December 31, 23 were 29, $219 9 million inclusive inclusive of GAAP operating expenses.

$261 8 million minus $9 3 million in cost of sales and minus $32 6 million of stock based compensation.

Turning to slide 29.

Hunter C. Smith: I ask that you all pay attention to the left-hand side of the text box here and make sure this is modeled appropriately. We committed to pay $100 million in fixed costs to LG Chem for global rights to LB54640. That was $40 million in cash in January, and we issued to them more than 430,000 Rhythm shares of common stock, valued at $20 million at the same time. We have also committed to pay $40 million in cash 18 months from the close, which was in January. This $100 million will be accounted for in R&D expenses during Q1 2024. And when the achievement of development and commercial milestones becomes probable, we will recognize these costs as expenses as well. Also for 24, as we did for 2023, we offer guidance on non-GAAP operating expenses. We anticipate approximately $250 million to $270 million in non-GAAP OPEX, comprised of SG&A non-GAAP operating expenses of $105 million to $110 million.

I ask that you all pay attention to the left hand side of.

The guidance the Textbox here and make sure this is modeled appropriately.

We committed to pay a $100 million in fixed cost to LG Chem for global rights there'll be 540, <unk> that was $40 million cash in January and we issued to them more than 430000 rhythm shares of common stock valued at $20 million at the same time.

We are also committed to pay $40 million in cash 18 months from the close which was in January.

This $100 million will be accounted for in R&D expenses during Q1 2024.

And when the achievement of development and commercial milestones becomes probable we will recognize these costs as R&D expense as well.

Also for 'twenty four as we did for 2023, we offer guidance on non-GAAP operating expenses.

We anticipate approximately $250 million to $270 million and non-GAAP opex comprised of SG&A non-GAAP operating expenses of $105 million to $110 million R&D non-GAAP operating expenses of $145 to $160 million. This R&D amount includes $10 million to $15 million of development costs related to <unk>.

Hunter C. Smith: R&D non-GAAP operating expenses of $145 to $160 million. This R&D amount includes $10 to $15 million of development costs related to LB54640. This amount excludes both stock-based compensation and consideration paid to LG Chem in connection with the licensing bill B54640. The growth rate at the midpoint of this range is 18% year over year; excluding the impact of LB54640, the growth rate would have been just under 50%. Finally, we are not offering revenue guidance. We have not offered revenue guidance in the past and are not doing so again this year.

This amount excludes both stock based compensation and consideration paid to LG Chem and in connection with the licensing of <unk>.

The growth rate at the midpoint of this range is 18% year over year, excluding the impact of that will be $5 640, the growth rate would have been just under 15%.

Finally, we are not offering revenue guidance, we have not offered revenue guidance in the past are not doing so again this year and series sales in the U S. We will continue to be the main driver of revenue growth for rhythm for revenues from our International region, Germany will continue to be the main driver, while Spain, and Italy are coming online for bvs. It will take time to get up and running.

Hunter C. Smith: MCBRI's sales in the U.S. will continue to be the main driver of revenue growth for Rhythm. For revenues from our international region, Germany will continue to be the main driver. While Spain and Italy are coming online for BBS, it will take time to get up and running as we navigate the local hospital systems and their budgets. The Netherlands and the U.K. come online later in the year, and we do not expect sales in those regions to be a significant contributor for 2024. And with that, I'll turn the call back over to David. Thanks, Hunter. So thanks, all. That concludes the formal presentation. I hope what you're taking away from this is that Rhythm is maturing.

As we navigate the local hospital systems in their budgets, the Netherlands, and the UK come on later in the year and we do not expect sales in those regions to be a significant contributor for 2024.

That I will turn the call back over to David.

Thanks Hunter.

So thanks I'll, let concludes the formal presentation I hope what you are taking away from this is that rhythm is maturing we are firming up the components, which are driving the underlying value of rhythm or executing on our global strategy. We are executing on our developmental strategy, where we're exploring all the incremental potential opportunities relate.

David P. Meeker: We're firming up the components, which are driving the underlying value of Rhythm. We're executing on our global strategy. We're executing on our developmental strategy, where we're exploring all the incremental potential opportunities related to the MC4 pathway. And we're setting up, as I said, a year 2024. It's hard to believe we're already two months into the year, given the amount that's already happened.

Added to the <unk> pathway, and we're setting up as I said, a year or 2024, it's hard to believe we're already two months into the year given the amount that's already happened but.

Operator: But 2024 will be about execution, and, as I said, 2025 will have a series of really impactful, milestone readouts for Rhythm. So with that, I'll open it up for questions, Operator. Thank you. As a reminder, to ask a question, please press star 1-1 on your telephone and wait for your name to be announced. To withdraw your question, please press star 1-1 again. Please stand by while we compile the Q&A roster. The first question comes from Tazeen Ahmad with Bank of America. Your line is open.

2024 will be about execution and as I said 2025, we will have a series of really impactful.

Milestone readouts for rhythm.

So with that.

Oh.

Often it up for questions operator.

Thank you.

Minder to ask a question. Please press star one on your telephone and wait for your name to be announced to withdraw. Your question. Please press star one again, please stand by while we compile the Q&A roster.

Okay.

The first question comes from Devine, Amit with Bank of America. Your line is open.

Tazeen Ahmad: Hi guys, good morning. Thanks for taking my questions. David, I was hoping to get a little bit of color on the comments that you made in your prepared remarks about the cluster of DDS patients. ASIC.

Hi, guys. Good morning, Thanks for taking my questions. David I was hoping to get a little bit of color on the comments that you made in your perhaps remarks about the cluster of Bbs patients within a particular date.

David P. Meeker: Lauren, thank you so much for joining us. Was this something that you would have anticipated happening? And can you also give us some color on what would cause a particularly large number of patients to be clustered in a close proximity? And how are you getting confidence that you won't be seeing similar events?

Just given all the work you've done on this ultra rare disease.

Is that something that you would have anticipated happening and can you also give us color on what would cause.

A particularly large number of patients to be clustered in a in a close.

Close proximity and how are you getting confidence you wont be seeing similar events in other states as you said on the call.

David P. Meeker: Thanks. Yeah, thanks, Tazeen. So, good question. So your first part of that was, did we have a line of sight to this? The answer was no. What do we think is going on?

Yes, thanks, Susan So it's a good question. So your first part of that was did we have.

Line of sight to this answer was no.

What do we think is going on there are pockets in every rare disease or many rare diseases, where you have a concentration of patients related to a founder effect. The most publicly and clear example of this is the Bbs world as in Newfoundland.

David P. Meeker: There are pockets in every rare disease or many rare diseases where you have a concentration of patients related to a founder effect. The most public and clear example of this in the BBS world is in Newfoundland, Canada, where if you look at an expected prevalence for BBS of 1 to 75,000, 1 in 100,000, the prevalence in that Canadian province is about 1 in 18,000. So, um, so that element we know exists.

Canada, where if you look at an expected prevalence for Bbs of 1% to 75001 and 100000.

Prevalent in that Canadian provinces about 1% and 18000.

So that.

Ellen we know exists we werent expecting to see it in this state, but if you looked at the demographics of the state there.

David P. Meeker: We weren't expecting to see it in this state, but if you look at the demographics of this state, the demographics are consistent with the fact that you could have a founder effect, and we think that's what's going on. The second piece of this was that we also had physicians in that state who were very interested, very motivated early on, and were writing scripts, as I said earlier. And so for this specific state Medicaid plan, they were an early adopter in the sense that they had a policy in place early and were trying to, quote unquote, do the right thing, but they saw a much higher level of scripts than what they had modeled in their plan and their expected prevalence. Jennifer and I had a call with their leadership, which was incredibly constructive. I mean, they said there was no antagonism or concerns about wanting to treat BBS in that sense. We basically just, you know, overwhelmed them to a certain extent relative to what they had expected to see.

The demographics are.

Consistent with the fact that you could have a founder effect and we think that that's what's going on the second piece of this was that we also had positions in that state who we are.

Very interested very motivated early on and we are.

Writing scripts as I said early and so for this specific state Medicaid plan.

<unk>.

They were an early adopter in the sense that they had a policy in place early and we're trying to quote unquote do the right thing, but they saw a much higher level of scripts than what they had a bad model and their plan and their expected prevalence and Jennifer and I had a call with their their leadership, which was incredibly constructive.

As I said, there is no antagonism or <unk>.

Concerns about wanting to treat Bbs in that sense, we basically just.

Overwhelm them to a certain extent with relative to what they had expected to see so.

David P. Meeker: So long story short, that's what we think drove the disproportionate. The second part of your question, I'm going to let Jennifer speak to in terms of the other states here and why we see this as a very unique situation related to this one-state Medicaid plan. Yeah.

So long story short.

What we think drove the disproportionate the second part of your question I mean, I'll, let Jennifer speak to in terms of the other states here and why we see this as a very unique situation related to this one state Medicaid plan, yes.

Arlinda Anna Lee: So just in terms of the uniqueness of this particular state, as David iterated, when you look at what the estimated prevalence could be based off of, you know, sort of more broad-based preference estimates, the amount of scripts really surpassed, you know, the expectation in terms of this particular Medicaid. I will reiterate, we still have a positive policy in place, and we're just working through the system. In contrast, you know, not unusual; we're just a little over a year from launch in terms of BBS.

Just in terms of the uniqueness at this particular stage is David iterate. It when you look at what the estimated prevalence could be based off of the announced or there's more.

Broad based.

Yes pipeline estimates.

That's really surpassed.

The expectation in terms of this particular Medicaid I will reiterate we still have a positive policy in place and we're just working through the system.

Contrast.

Not unusual we're just a little over a year from clients in terms of Bbs.

Arlinda Anna Lee: If you look at every other state Medicaid in terms of estimated prevalence versus the number of scripts that we have received in other states, we are, you know, vastly under just in terms of the number of active patients versus what they might have projected in terms of potential for this product. So we really do feel confident that this is a unique situation where the numbers were a bit surprising, but once again, we're just working collaboratively together with the physicians and Medicaid in terms of working this through. Okay, thanks for all of that color. And maybe just one last quick question. What's your current mix?

If you look at every other state Medicaid in terms of estimated profit lines versus.

Number of scripts that we have received and other states. We are vastly under just in terms of.

Our number of active patients versus what they may have projected in terms of potential for this product. So we really do feel confident that this is a unique situation where the numbers were.

A bit surprising, but once again, we're just working collaboratively together with the physicians and the Medicaid in terms of working this through.

Okay. Thanks for all of that color and maybe just one last quick question, what's your current mix of Medicaid patients.

Arlinda Anna Lee: The question was the current mix of Medicaid, so the breakup of Medicaid versus... In your current mix, what is it? Right, so we said that 90% of patients are approximately commercial versus Medicaid, with Medicaid accounting for slightly more than commercial patients in that mix. Please stand by. Standby for the next question. The next question comes from Jeffrey Hung with Morgan Stanley. Your line is open. Hi, good morning. This is Catherine on for Jeff.

On reimbursement.

And then a question what is the current mix of Medicaid So a breakout Medicaid and your current mix what is the proportion of Medicaid patients.

Alright, So we said that 90% of patients approximately.

Our commercial versus Medicaid with Medicaid accounting for slightly more than commercial patients.

Yeah.

Okay. Thank you.

Ladies.

Yes.

Please standby for the next question.

The next question comes from Jeffrey Hung with Morgan Stanley. Your line is open.

Hi, Good morning. This is Katherine on for Jeff. Thank you. So much for taking our question. We just had one with your <unk> agonist profile now consisting of 10, olive tied or in 2017 and now LP 546, 40 can you provide more color on how you are thinking about positioning and potential points of differentiation here for example.

Jeff Hung: Thank you so much for taking our question. We just have one. With your MC4 agonist profile now consisting of thamelatide, RM17, and now LB54640, can you provide more color in how you're thinking about positioning and potential points of differentiation here? For example, do patients place more value on the ease of route of administration, or are they emphasizing other aspects related to safety like hyperpigmentation? Yeah, thanks, guys. So, perfect.

Multi patients place more value on the ease of route of administration or are they emphasizing other aspects related to safety like hyper pigmentation.

Yes, thanks, Kevin.

So perfect I think both of our next generation.

David P. Meeker: I think, you know, both of our next generation therapies, potential therapies, offer their own unique value propositions. So the weekly and both of them are hyperpigmentation sparing. So that's a huge issue for some patients, not all. It's not a huge percentage of patients, but what we're seeing is there's a very consistent number and percentage of patients that are bothered by the hyperpigmentation. 100% of the patients will have some change in their skin pigmentation, but a much smaller percentage are bothered by it. But, you know, particularly in non-Caucasian populations, it's an issue.

Therapies potential therapies offer their own unique value proposition. So the weekly both of them are hyper pigmentation sparing. So that's a huge issue for some patients not all it's not a huge percentage of patients, but what we're seeing is there is a very consistent.

A number of percentage of patients that.

Who are bothered by the hyper pigmentation of 100% of the patients will have some change in their skin pigmentation, but.

Much smaller percentage of bothered by it but particularly in non Caucasian populations. It's an issue. So so both of the next generation products will offer that as a benefit and then you have the convenience issue, which is one is a weekly injectable to others, a daily oral and Thats really going to come down to patient preference. So your question about what's our strategy as we think about developing a portfolio of.

David P. Meeker: So, both of the next-generation products will offer that as a benefit. And then you have the convenience issue, which is one is a weekly injectable, and the other is a daily oral, and that's really going to come down to patient preference. So your question about what our strategy as we think about developing a portfolio of options for these patients is that we'll be indifferent. Again, assuming that both of these molecules progress through development, we'll be indifferent. The goal is to offer patients, physicians, the ability to choose a treatment that gives their patients the best chance of getting the result that they want in a compliant, tolerable, well, and well accepted way. So that's it. No more than that. It'll be dictated by the data. We'll see how they turn out.

Options for these patients as we'll be indifferent again, assuming that both of these molecules progress through development will be indifferent. If the goal is to offer patients physician the ability to choose a treatment, which gives their patients the best chance of getting the result that they want in a compliant tolerable.

Well well accepted way so that's it.

No more than that it will be dictated by the data, we'll see how they turn out.

David P. Meeker: If, if, again, if both products do well, they should clearly be better drugs than set melanotide, and then, you know, we'll reevaluate the role of set melanotide in that world. Of course, once again, as with always, you don't keep an inferior molecule out there if you've got clearly better alternatives.

Both products do well they should clearly be better drugs and set in Atlanta tied in then we'll reevaluate the role of <unk> in that World of course once.

As always you don't keep an inferior molecule out there if you've got clearly better alternatives.

Corrine Johnson: Thank you. Thank you. One moment for our next question. The next question comes from Corrine Johnson with Goldman Sachs. Your line is now open.

Yeah.

Alright, thank you.

Thank you.

One moment for our next question.

The next question comes from Corrine Johnson with Goldman Sachs. Your line is now open.

David P. Meeker: Good morning. Maybe as a follow-on to that question, I wonder how you think about what a successful efficacy outcome looks like from the SIGNL trial? Particularly, how does the oral form factor influence your view of what sufficient efficacy could be? And how do you think it will differ, anything in particular, on the efficacy front versus... Yeah, thanks, Grant. So to be honest with you, I don't expect it to be better than setmelanotide, and we did incredibly well with setmelanotide. And I think we're probably getting, in terms of MC4 agonism, we're probably getting the desired effect, maybe at the maximal level you can achieve. What might allow either the weekly or the daily oral to do better, and that may show up more in the real world, is in terms of compliance. We know in our HO Phase 2 trial, compliance was extremely high in that trial overall. So assuming a similar level of compliance, I'm not sure we'll differentiate on efficacy, but the long answer to your question is that we'll be looking for something that would be similar, but not exactly the same. One moment for our next question.

Good morning, maybe as a follow on to that question I guess, how are you thinking about what a successful efficacy outcome looks like from the signal trial.

Particularly how does the oral form factor influences your view of what sufficient efficacy could be.

How do you think it will differ anything particular, I know like the efficacy front versus the injectables.

Yes, Thanks Brent.

So to be honest with you I don't expect it to be better than <unk>, and we did incredibly well was set in Atlanta tied and I think we're probably getting in terms of emcee for agonism will probably getting the desired effect maybe at the maximum level you can achieve.

What might allow either the weekly or daily oral to do better than that May show up more in the real world is in terms of compliance and we know in our <unk> phase II trial compliance was extremely high in that trial overall, so assuming a similar level of compliance I am not sure will differentiate on efficacy, but so.

Long answer to your question is we will be looking for something that would be similar.

But not exactly the same probably.

Alright, thank you.

One moment for our next question.