Q3 2023 Rhythm Pharmaceuticals Inc Earnings Call

Speaker 1: Good day and thank you for standing by. Welcome to the Redmond Pharmaceuticals Third Quarter 2023 Earnings Conference Call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you will need to press star 1-1 on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star 1-1 again.

Good day, and thank you for spending.

By walking to the retina Pharmaceuticals third quarter 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 answer session.

Ask a question during the session you will need to press star one on your telephone you wouldn't hear.

And automated message lighting. Your hand is raised to withdraw your question. Please press star one again, please be advised today's conference is being recorded.

Speaker 1: Please be advised today's conference is being recorded. I would now like to hand the conference over to our speaker today, David Connolly, investor relations and corporate communications. Please go ahead.

Again, the conference over to Speaker today, David Connolly Investor Relations and corporate Communications. Please go ahead.

Speaker 2: Thank you, Victor. I'm Dave Connolly here at Rhythm Pharmaceuticals. For those of you participating on the conference call, our slides can be accessed and controlled by going to the investors section on the investors page of our website at ir.rhythmtx.com.

Thank you Victor.

The economy here at rhythm Pharmaceuticals for those of you participating on the conference call. Our slides can be accessed in control by going to the investors section on the investors page of our website at IR Dot rhythm TX Dot com.

This morning, we issued a press release that provides our third quarter 2023 financial results and a business update which is available on our website.

Speaker 2: This morning we issued our press release that provides our third quarter, 2023 financial results and a business update, which is available on our website. As listed on slide two, here with me today in Boston, our David Meager, Chair, Chief Executive Officer and President of Earth and Pharmaceuticals, Jennifer Chen, Executive Vice President, head of North America, Hunter Smith, our Chief Financial Officer, and Jan Mazavro, Executive Vice President, head of international, is joining us on the line from Europe .

Listed on slide two.

Here with me today in Boston are David Meeker Chair, Chief Executive Officer, President of Rhythm Pharmaceuticals, Jennifer Chen Executive Vice President head of North America Hunter Smith, our Chief Financial Officer, and John <unk> Executive Vice President and head of International is joining us on the line from Europe.

Speaker 2: 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 reports on file with the S&P.

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 reports on file with the SEC.

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

Speaker 2: In addition, any forward looking statements represents our views only as of today, it 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.

Speaker 3: Thank you, Dave, and good morning, everyone. Thank you for joining the call. So we're pleased to report out another very strong quarter with continued execution across all parts of our business.

Thank you, Dave and good morning, everyone. Thank you for joining the call.

So we're pleased to report out another very strong quarter with continued execution across all parts of our business.

Speaker 3: Two near-term drivers of rhythm value, building the BBS commercial opportunity globally, and enrollment into our phase 3 HO trial remain on track.

Two near term drivers that rhythm value building, the Bbs commercial opportunity globally and enrollment into our phase III <unk> trial remain on track.

Speaker 3: I'm incredibly impressed by the performance of our North American and international organizations, DBS and the monogenic forms of MC4R pathway diseases. We are approved to treat ARM, as we have discussed multiple times, highly meaningful rare disease opportunities. But they do fall in the ultra rare category with all of the challenges these patients face getting to a diagnosis and then accessing the appropriate therapy.

I'm incredibly impressed by the performance of our North American and international organizations Bvs in the monogenic forms of MFC for our pathway diseases. We are approved to treat arm as we have discussed multiple times highly meaningful rare disease opportunities, but they do fall in the ultra rare category with all of the challenges these patients face getting to a die.

Gnosis, and then accessing the appropriate therapy.

The sheer volume of noise around the management of obesity as a disease and the use of <unk>, specifically as both aided the cause health care providers are looking more closely at patients who presented with obesity and doing the appropriate work ups and hindered the cost where the availability of powerful therapies such as DLP. One medications has led many to believe that all of these NGL.

Speaker 3: The sheer volume of noise around the management of obesity as a disease and use of GLP1 specifically has both aided the cause. Healthcare providers are looking more closely at patients who present with obesity and doing the appropriate workups. And hindered the cause, whether it is a vulnerability or powerful therapy such as GLP1 medication has led many to believe that all obesity is the same and GLP1 represents.

NGL coupons represents a universal solution.

Speaker 3: As we know, that is not correct. Obesity is not one disease, but many diseases, and as with most forms of medical therapy, the more targeted and specific the solution, the better.

As we know that is not correct obesity is not one disease, but many diseases and as with most forms of medical therapy, the more targeted and specific the solution the better the.

Speaker 3: The medical community continues to learn more about the factors which control hunger, the role of the different pathways and the effect of different drugs play in modulating those pathways. Our story remains relatively simple. We're replacing a supple signal, which is efficient. So if you're managing a patient, why wouldn't you start there?

The medical community continues to learn more about the factors, which control hunger the role of the different pathways and the effect of different drugs play and modulating those pathways. Our story remains relatively simple, we're replacing us up we're replacing sorry, or supplementing a hormonal signal, which is deficient. So if you're managing a patient by once you start there.

Speaker 3: Revenues in the quarter came in at 22.5 million, showing exactly the steady growth we had hoped to see. We're pleased with the script volume in the US, where the team is doing a great job educating on the MC4 pathway and the value of precision therapy. And we're incredibly excited to cross the 100 patient threshold in Europe , where in addition to the usual challenges facing rare disease communities, market access across the different healthcare systems can be particularly challenging. We have experienced teams in all geographies who are remarkably skilled at navigating these challenges.

Revenues in the quarter came in at $22 5 million showing exactly to the steady growth. We had hoped to see we're pleased with the script volume in the U S where the team is doing a great job educating on the <unk> pathway and the value of precision therapy, and we are incredibly excited to cross the 100 patient threshold in Europe, where in addition to the usual challenges facing rare disease.

It is market access across the different health care systems can be particularly challenging we have experienced teams in all geographies were remarkably skilled at navigating these challenges so although it will never be easy patient by patient we find solutions as you know, we do not provide financial guidance, but for those of you building models my experience working in rare.

Speaker 3: So although it will never be easy, patient by patient, we find solutions.

Speaker 3: As you know, we do not provide financial guidance, but for those of you building models, my experience working in rare diseases with many similarities to our current world has taught me, it never gets easier. The revenue trajectory does not inflect, but these opportunities continue to grow over time.

Diseases with many similarities to our current World has taught me and never gets easier the revenue trajectory does not inflect, but these opportunities continue to grow overtime.

H O phase III enrollment continues on track with two thirds of the patient screen. That's our proxy for enrollment is almost none of these patients screen fail. The majority of patients needed to complete enrollment have their screening visits already scheduled and we still have sites. We're just opening more scheduled to open and who are eager to get their patients enroll we did get early access approval for.

Speaker 3: H.O. Phase 3 enrollment continues on track with two thirds of the patient's screen. That's our proxy for enrollment is almost none of these patients screened fail. The majority of patients needed to complete enrollment have their screening visits already scheduled. And we still have sites where are just opening or scheduled to open and who are eager to get their patients.

Speaker 3: We did get early access approval for H.O. in the third quarter in France, based on the 18 patient phase two data alone. This is an incredible recognition about the unmet medical need in this population and the potential significant impact treatment may have. The first patient's young will outline should be treated before year F.

<unk> in the third quarter in France based on the 18th patient Phase II data alone. This is an incredible recognition about the unmet medical need in this population and the potential significant impact treatment may have the first patients as John will outline should be treated before year end.

Finally, we look forward to providing additional updates at our R&D day, particularly with regard to a next generation formulation of <unk>.

Speaker 3: Finally, we look forward to providing additional updates to our R&D day, particularly with regard to our next generation weekly formulation, the daybreak trial, and our pediatric recall.

DAYBREAK trial, and our pediatric results.

Speaker 3: So, moving to slide six, we recently had a separate analyst call following a very successful toss meeting in Dallas with multiple presentations which are outlined here. What's particularly gratifying about these meetings, it's the opportunity to meet with a community in person and feel literally the growing interest and learning more about the different forms of obesity, including MC4R pathway disease.

So moving to slide six we recently had a separate analyst call. Following a very successful <unk> meeting in Dallas with multiple presentations, which are outlined here, what's particularly.

Gratifying about these meetings, it's the opportunity to meet with the community in person and field literally the growing interest in learning more about the different forms of obesity, including EMC for our pathway diseases.

On slide seven I want to take you through all of the 12 month HR data that we reviewed on the last call.

Speaker 3: On slide seven, I want to take you through all of the 12 month HO data that we reviewed on the last call.

Speaker 3: 14 patients entered the long-term extension and results for all 14 are shown in this slide. We saw a robust mean 25% BMI decrease across the 12 patients who had 12 months of data. And I remind you that this is a blend, this trial is a blend of ages with 11 and 12 of the patients, pediatric patients. And the pediatric patients are growing where you would expect the BMI to actually increase with that growth.

14 patients entered the long term extension and the results for all of 2014 are shown in this slide we saw a robust meaning 25% BMI decreased across the 12 patients who had 12 months of data and I remind you that this is a blend as trials a blend of ages with 11 of 12 patients pediatric patients in the pediatric patient.

We're growing where you would expect the BMI to actually increase with that growth.

Speaker 3: The two panels on the right are the two patients who are off treatment for some period of time. A short message here is if you take the therapy, most patients respond. And when you stop treatment, i.e., you stop this hormonal replacement therapy, your BMI weight improves.

The two panels on the right are the two patients who are off treatment for some period of time a short message here is if you take the therapy most patients respond and when you stop treatment I E. You stop this hormonal replacement therapy your BMI weight.

Increases.

Finally, there's growing interest in the quality of the weight loss, meaning losing fat mass as good but losing large amounts of lean mass is not good. Our early results suggest we do pretty well in that category as shown in the Texas scan results, which we presented on the poster and one other graphic on the poster shows the shift in obesity class experienced by patients with three of the pediatric <unk>.

Speaker 3: Finally, this growing interest in the quality of the weight loss, meaning losing fat mass is good, but losing large amounts of knee mass is not good. Our early results, who just we do pretty well in that category, is shown on the dexascam results and which we presented on the poster. And one other graphic on the poster shows the shift in obesity class experience by the patients with three of the pediatric patients actually getting back into the normal BMI range for their age.

It's actually getting back into the normal BMI range for their age.

Slide eight this is just to remind you of the trial design, where we are targeting 120 patients and is noted two thirds of the patients have been screen and the majority of the balance of patients needed to complete the trial have already scheduled their screening visits and.

Speaker 3: Slide 8, this just reminds you of the trial design where we are targeting 120 patients and has noted two thirds of the patients have been screened. And the majority of the balance of patients needed to complete the trial have already scheduled their screening visit.

And importantly, and I think this is again its still early here, but.

Speaker 3: And importantly, and I think this is, you know, it's kind of still early here, but I'm grateful worthy.

Worthy.

Speaker 3: Of the patients treated, we've had almost no trial discontinuation.

Of the patients treated we've had almost no trial discontinuation.

Speaker 3: So finally, on slide nine, this slide is to remind you that we are working on meaningful opportunities.

So finally on slide nine slide is to remind you that we are working on meaningful opportunities you could build a very profitable company around Bbs and the policy and left bar monogenic opportunities were approved for today. However, we are investing significantly in R&D because those opportunities that we're pursuing are even greater.

Speaker 3: You could build a very profitable company around VBS and the Ponzi and Leopard monogenic opportunities we are approved for today. However, we are investing significantly in R&D because those opportunities that we are pursuing are even greater. And as you know, for example, the HO opportunity itself represents a large, well-identified patient population with no approved therapy.

And as you know for example, the HR opportunity itself represents a large well identified patient population with no approved therapy.

And with that I'll turn the call over to Jennifer.

Speaker 4: Thank you, David. We are pleased with the continued progress we are seeing with our BBS commercial launch. Hundreds of patients with BBS in the US are now realizing the benefits of the seborrheic therapy. We continue to hear the positive, life-changing impact we are making to the lives of patients and families.

Thank you David.

We are pleased with the continued progress we are seeing with our Bbs commercial lines hundreds of patients with Bbs and the U S are now realizing the benefits of being separate therapy with.

We continue to hear the positive life changing impact we are making to the lives of patients and families.

Speaker 4: Recently, we heard from one mother who son is on a syphur therapy, and and Syvery has had a profound effect on his weight and his hyperphasia. He is full for the first time, leads the dinner table before everyone else in the family. And for the very first time, he told his mother he does not like certain foods like lima beans, tomatoes, and pickles.

Recently, we heard from one mother Nissan is on a separate therapy.

I'm sorry.

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For the first time.

We've got a clear path before everyone else in the family.

The very first time he told his mother, he does not like certain like limousine tornadoes and put color.

Speaker 4: In the mother's words, we are experiencing him as a kid, not a hungry kid.

And the mother's where we are.

Great. Thank you.

Not hundreds.

And so everything only therapy approved specifically to treat obesity JCB UBS and we are thrilled to hear these stories from patients and families who now have access to therapy.

Speaker 4: And severity is the only therapy approved specifically to treat obesity due to BBS. And we are thrilled to hear these stories from patients and families who now have access to therapy.

Beginning on slide 11.

Speaker 4: We are pleased with the growth and consistent strong demand for emciphery over the first five quarters.

We are pleased with the growth reflects strong demand for <unk> over the first five quarters.

Throughout the launch from Janssen could fall 2022, or the end of the third quarter of 2020, we now have received more than 545, NATO Bbs prescriptions coming from more than three great prescribers.

Speaker 4: Throughout the launch from June 16, 2022 through the end of the third quarter of 2023, we now have received more than 545 new BBS prescriptions, coming from more than 300 prescribers.

Speaker 4: Of these prescriptions, we have greater than 330 approval for reimbursement and payers.

This first question, we have greater than 330 approval for reimbursement from payers.

Speaker 4: On the next slide, I will cover results within the third quarter.

On the next slide I will cover results within the third quarter.

We received greater than 120 questions with 80 approval within the third quarter.

Speaker 4: We received greater than 120 perspiration with 80 approval within the third quarter.

Several of these approvals were from prescriptions received within the quarter, while others were written in prior quarters.

Speaker 4: Several of these approvals were from prescription's received within the quarter, while others were written in prior quarter.

We continue to identify more Bbs patients and what the feedback is that.

Speaker 4: We continue to identify more BBS patients and work to speed diagnosis. Our active engagement with physicians remain focused on disease awareness, diagnosis, and the benefits of in-sieve rates.

Our active engagement with physicians remain focus on disease awareness diagnosis and the benefits have been separate.

And a rhythm of Gen team.

Speaker 4: And our Rhythm and Tune team continues to deliver support to provide both to patients and families and health care providers every step of the way. Next slide.

You deliver.

Both the patients and families and health care providers every step of the way next slide.

Here's a snapshot of the patients with Bbs behind it.

Speaker 4: Here is a snapshot of the patients with VBS behind these prescription.

Yes.

Speaker 4: We continue to see an upward trend in terms of prescriptions received from adult patients.

We continue to see an upward trend in terms of prescriptions received from adult patient.

Speaker 4: As we touched on before, this trend diverges from the AIDS distribution in the crib's registry. A global registry has a data on the VF patient where approximately 80% of registry participants are 18 or younger.

As we touched on before this trend diverges from the age distribution and the Cribbs registry.

Mobile registry, having data on DVS basin, where approximately 80% of registered participants are 18 or younger.

Speaker 4: We believe this trend is representative of adult patients who simply age out of participating in this annual survey or who are lost at follow-up.

We believe this trend is representative of adult patients with simply they are participating in this annual survey or who are lost to follow up.

One subsidiary was approved steroid education efforts. Many of these patients will reengage with their physicians. This is not uncommon in rare disease, where the first approved therapy for a disease causes not only increase the awareness of the disease, but also allows for increased bringing engagement of the broader diagnosed.

Speaker 4: Once MCIVRI was approved, through our education efforts, many of these patients were reengaged with their physicians. This is not uncommon in rare disease, where the first approved therapy for a disease causes not only increased awareness of the disease, but also allows for increased reengagement of the broader diagnosed patient population. Next slide.

Patient population.

Next slide.

Entrepreneurs fiber.

Endocrinology, both adult and pediatric remains consistent over the last few quarters as our top specialty accounting for 45% of prescribers.

Speaker 4: Endocrinology, both adult and pediatric, remains consistent over the last few quarters at their top specialty, accounting for 45% of prescribers.

We are seeing an increase in the portion of new two rhythm prescribers or physicians our territory managers had not previously called on directly prior to perception, which now accounts for 28% of our prescriber base.

Speaker 4: We are seeing an increase in the portion of new tourism prescribers or physicians our territory managers had not previously called on directly prior to prescription, which now accounts for twenty eight percent of our prescriber base.

This reinforces the conviction we have in our non personal promotion efforts.

Speaker 4: This reinforces the conviction we have in our non-personal promotion efforts.

Speaker 4: Lastly, we are seeing an increase in the depth of prescribers as 28% of them have written more than one prescription launch to date, which is up from 25% as reported on the last quarterly call.

Lastly, we are seeing an increase and the depth of prescribers at 28% of them have written more than one prescription launch to date, which is up from 25% as reported on the last quarterly call.

We remain focused on a greater breadth of prescribers every time as well as more and more physicians to identify additional patients and prescribers Jeffrey for these second or more patients based on their own positive experience.

Speaker 4: We remain focused on a greater breadth of prescribers over time, as well as more and more physicians who identify additional patients and prescribe in SIFRE for these second or more patients based off their own positive experience.

Next slide.

Access and reimbursement remained consistent with regard to overall coverage by state Medicaid and the overall payer mix.

Speaker 4: Access and reimbursement remain consistent with regard to overall coverage by state Medicaid and the overall payer MIPS.

Speaker 4: If we look at Medicaid coverage through Covered Lives, launched to date, approximately 80% of Medicaid Covered Lives are in states with either a positive MCIVory policy in place or in a state where we have been able to gain positive coverage in at least one instance in the absence of an MCIVory policy.

If we look at Medicaid coverage covered lives launched to date approximately 80% of Medicaid covered lives are in states with either a positive in every policy in place.

Or in a state where we have been able to gain positive coverage and at least one is done and the absence of an EMS Jeffrey policy.

The remaining 20% of Medicaid lives represent states, where we either have not yet had a prescription forms Jeffrey that would trigger a coverage decision or we are still working to secure access for prescription or finally, where we have not been successful in gaining access through the appeals process.

Speaker 4: The remaining 20% of Medicaid lives represent states where we either have not yet had a prescription for MCIPRI that would trigger a coverage decision, or we are still working to secure access for a prescription, or finally, where we have not been successful in gaining access through the appeals process.

The payer mix for bvs remains consistent.

Speaker 4: The Paramix, or BBS, remains consistent as almost 90% of prescriptions since launch fall under commercial or Medicaid plans.

Almost 90% of prescriptions since launch fall under commercial and Medicaid Glenn.

The average timeframe for approval is approximately one to three months with some tail extending out several months.

With our previous report.

Overall, we are pleased with achievements to date and securing approval.

Next slide.

Now more than one year into launch we are seeing a very strong rate of reauthorization for continued in separate coverage with approximately 75 positive reauthorization decision.

Speaker 4: Now, more than one year into launch, we are seeing a very strong rate of reauthorization for continued and SIFRE coverage, with approximately 75 positive reauthorization decisions.

Speaker 4: The vast majority of these reauthorizations are approved initially and we have seen roughly a half dozen positive reauthorizations come upon appeal.

The vast majority updates reauthorization or approved initially and we have seen roughly a half dozen positive decisions come upon appeal.

Most of the Big positive appeal had required additional clinical documentation to allow for a reauthorization of profile.

Speaker 4: Most of these causes of appeals had required additional clinical documentation to allow for reauthorization approval.

We have had a few denials to date and we are in the process of appealing to provide some color on the <unk>.

Speaker 4: We have had a few denials to date and we are in the process of appealing. To provide some color on these,

Speaker 4: we have patients who have experienced overall clinical benefit but have not achieved 5% body weight loss. For example, one had a reauthorization within four months of its SIFRI initiation, while our label outlines a 12-month efficacy touchpoint.

Patients who have experienced overall clinical benefit but have not achieved 5% body weight loss.

For example, one had a reauthorization within four months of Jeffrey initiation, while our label outlines a 12 month efficacy touch points.

Another patient saw other clinical benefits and was just shy of 5% weight loss requirement.

Speaker 4: Another patient saw other clinical benefits and was just shy of the 5% waste loss requirement.

Speaker 4: In both cases, we are working with the advocating physician and patient through the appeals process. Next slide.

In both cases, we are working with the advocating physician and patient through the appeals process.

Next slide and final slide for me.

We were very pleased to announce that a new ICD 10 diagnostic code was established for Bbs.

Speaker 4: we were very pleased to announce that a new ICD-10 diagnosis code was established for BBS. This is a long-term positive for the BBS community and for Rhythm as this improves understanding of the diagnostic and treatment journeys of patients and may enhance access to physicians with BBS patients.

This is a long term positive for the Bbs community algorithms at this improved understanding of the diagnostic and treatment journey of patients and may impact access to physicians with Bbs.

Speaker 4: We remain focused on engaging with the community to find already diagnosed patients while expediting the identification of individuals with DDS who do not yet have a diagnosis.

We remain focused on engaging with the community to find already diagnosed patients while expediting the identification of individuals with Bbs, who do not yet have a diagnosis.

Speaker 4: We are excited about our progress and the opportunities in front of us. With that, I'll hand it over to Jan.

Excited about our progress and the opportunities in front of us with that I'll hand, it over to Jan.

Thank you Jennifer and good morning.

Speaker 5: Thank you, Jennifer, and good morning, slide 19.

19.

Today, we are very pleased to announce that we have achieved a significant international in my store with more than 100 patients 11 countries outside of North America on reimbursed therapy.

Speaker 5: Today, we are very pleased to announce that we have achieved a significant international milestone with more than 100 patients from 11 countries outside of North America on the reimbursed therapy as of the end of October .

At the end of October.

Since patients on reimbursed drug started with <unk>, having friends for your part efficiencies in March of 2022.

Speaker 5: Our first patients on reimbursed drugs started with the AP2 program in France for POMSI and LIPAR deficiencies in March of 2022. And it has been a gradual and steady build since then, as new countries came online for POMSI and LIPAR, and that continues as new countries come online for BBS, beginning with reimbursed early access in France, and now fully launched in Germany.

It doesn't mean that the gradual and steady Butte, Susan as you can treat as Kim on 90 475 and that continues as you can please come online for Bbs beginning with reimbursed early access in France, and now fully launched in Germany.

Regarding the fringe in Q1.

Speaker 5: Regarding the French AP1 pre-EME approval reimbursed early access program for hypothalamic obesity, we are now working through the process to get it started. This program often starts slow because of the administrative requirements. We have not treated any patients yet under this program, but we may be in position to treat a few patients during the fourth quarter.

EMEA approval reimbursed early access program for hypothalamic obesity, we are now working through the process to getting started is often not slow because of the administrative requirements, we have not treated any patients yet.

We may be in position to treat a few patients during the fourth quarter.

Speaker 5: Overall, Europe is a key market for rare diseases for a reason. European countries typically are better organized and more centralized in their approach to rare diseases compared to the United States.

Overall Europe is a key market for rare diseases for reason European countries, typically are better organized and more centralized approach to <unk> compared to the United States.

Speaker 5: Even though these diseases are quite rare, the opportunity is meaningful. As a reminder, in the EU focus UK, we estimate the prevalence for Barley-Middle syndrome to be 4,000 to 5,000 patients, which is a prevalence similar to the U.S. And we have already more than 1,500 patients identified in this country.

Even though these diseases are quite rare youll coffee it is meaningful as a reminder.

You focus UK, we estimate the preventive for bodybuilders in rooms to be 4000 to 5000 patients, which is a prudent and similar to the U S. And we are already more than 1500 patients identified in these countries.

Speaker 5: We are pleased with progress to date in achieving market access for in-sibery in a large number of international markets.

We are pleased with progress to date in achieving market access for <unk> and allows them to international markets.

Next slide.

Speaker 5: Our launch in Germany is off to a solid start following the unanimous decision of the German Federal Joint Committee or GBA to exclude MCV from Germany's lifestyle exemption list and thereby make it eligible for full reimbursement for BDS.

Our launch in Germany is off to a solid start flowing into the unanimous decision of the gentleman sitting joint committee or GBA, two excluding CRE from Germany's lifestyle exemption list and thereby eligible for reimbursement for Bds.

Our team is focused on engaging with physicians caring for patients with Bbs and with the medicine until we've now treated.

Speaker 5: Our team is focused on engaging with physicians caring for patients with BBS and with the many centers where they are treated.

Speaker 5: Building off our initial launch in POMSI and NIPA, we had a very well-established relationship in place as a handful of key experts already had positive experience within theory. In addition, we benefited from a full commitment from key treatment centers, and in parallel, our German team continued engaging with additional large academic centers in Germany's decentralized healthcare system.

This is <unk>.

Initial launch and function.

Well established relationship in place at the hip.

<unk> already had a positive experience with <unk>. In addition, we benefited from a full commitment from key treatment centers and in parallel in our German team continued engaging with additional large academic centers.

Decentralized, hence gift system.

We are seeing a strict adherence to therapy things to a rhythm of whom patient support program similar to the U S rhythm ensuring Puma, we provide support tailored specifically for each patients in the <unk> for some sort of book may come by our political risk.

Speaker 5: We are seeing strong adherence to therapy thanks to our rhythm at home patient support program. Similar to the US rhythm insurance program, we provide support tailored specifically for each patient and their caregivers. For some, our support may come via phone call, others may receive at home visits and injections to the board.

We see that home visits and <unk> Stifel.

Based on what we know, but typical rare disease drug launches in Germany with steady and methodical.

Speaker 5: Based on what we know about typical rare diseases, drug launches in Germany, we expected a steady and methodical start. With a strong foundation in place based on our POM CILIPA experience, continuously increasing numbers of diabetes treatment centers and the positive impact of RISM at home, we are very well positioned to achieve continued success in Germany.

With a strong foundation in place based on the <unk> experience continuously increasing numbers of Bbs treatments until and the positive impact of reason with whom we are very well positioned to achieve continued success in Germany.

Next slide.

Speaker 5: More broadly, we are making tremendous progress in engaging physicians throughout Europe . We had a very strong presence at the European Society for Pediatric Endocrinology in September with four oral presentations. Two presentations showcased data that demonstrate set melanocytes potential to reduce risk of metabolic syndrome, cardiovascular disease, and type 2 diabetes in pediatric patients with POMC or lipar deficiency or Bardemidal syndrome.

More broadly, we're making tremendous progress in engaging physicians throughout Europe, we had a very strong presence at the European Society for Paediatric Endocrinology at September with four oral presentations.

Presentations showcase that does demonstrate <unk> potential to reduce our risk of metabolic syndrome cardiovascular disease and type two diabetes patient response, he only part of the efficiency of <unk> syndrome.

Also presented data from a real genetic testing program through which we have collected more than 2000 sequencing samples from individuals with CDO obesity and hyperphagia.

Speaker 5: We also presented data from a raw genetic testing program through which we have collected more than 2,000 sequencing samples from individuals with severe obesity and hyperfetion.

In addition, we hosted a symposium titled.

Speaker 5: In addition, we hosted a symposium titled Hyperphagia and Early Onset Severe Obesity, the Role of Precision Medicine in the Treatment of FC4R Pathway Disease. As you can see on this slide, it was very well attended. We had, in fact, 400 physicians in the room.

<unk> is a world of precision medicine.

And the treatment of <unk> plus <unk>.

As you can see on this slide it was very well attended with impactful and with physicians.

We look forward to continuing this momentum so going international meeting on possibly at <unk> improved conference in December in Paris, We are looking for work to a series of presentations discussions and engagement focusing on rare and see for Opex with the disease Monogenic, one syndromic like Bbs and hypothalamic obesity.

Speaker 5: We look forward to continuing this momentum at our second international meeting on pathway-related obesity, the IMPROVE conference in December in Paris. We are looking forward to a series of presentations, discussions, and engagement focusing on rare and C4R pathway diseases, monogenic ones, syndromic like BBS, and hypothalamic obesity, with more than 150 leading physicians and scientists coming from more than 10 countries. With that, I will turn the call over to Hunter.

With more than 150, leading physicians and scientists coming from more than 10 countries.

With that I will turn the call over to until in Boston.

Thank you John.

Where there remains tightly focused on global execution of commercial strategy across both our North America and international regions and continued development of the potential of at Sebree, and our pipeline all while staying committed to financial discipline and delivering shareholder value.

Speaker 6: Rhythm remains tightly focused on global execution of commercial strategy across both our North America and international regions and continued development of the potential of every and our pipeline, all while staying committed to financial discipline and delivering shareholder value.

Speaker 6: Let's start with a snapshot of the Q3 P&L on slide 23.

Start with a snapshot of the Q3 P&L on slide 23.

We recorded $22 5 million in net product revenue in the third quarter versus $4 3 million during the same quarter last year, an increase of $18 2 million.

Speaker 6: We recorded 22.5 million in net product revenue in the third quarter, versus 4.3 million during the same quarter last year, an increase of 18.2 million. Q3 last year was our first full quarter of BBS commercial sales in the United States.

Q3 last year was our first full quarter of Bbs commercial sales in the United States.

Which followed FDA approval on June 16th 2022.

Speaker 6: which followed FDA approval on June 16, 2022.

Quarter over quarter, we saw an increase of $3 3 million or 17% of net product revenue driven by continued growth in the number of patients on <unk> therapy in both the U S and international regions in.

Speaker 6: Quarter over quarter, we saw an increase of 3.3 million or 17% in that product revenue driven by continued growth in the number of patients on every therapy in both the US and international region.

Speaker 6: In last quarter's results, we highlighted that 1.6 million of our revenue resulted from shipments to our specialty pharmacy in excess of amounts that it dispensed to patients, resulting in an increase in inventory days on hand at quarter end. This quarter, shipments to the SP and dispenses to patients were very closely matched, resulting in a de minimis difference in value. Because of the larger number of patients on incivory therapy at the end of the third quarter, inventory days on hand at the SP decreased, but remained within a normal range.

In last quarter's results, we highlighted that $1 $6 million of our revenue resulted from shipments to our specialty pharmacy in excess of amounts that are dispensed to patients, resulting in an increase in inventory days on hand at quarter end.

This quarter shipments to the ESP and dispenses the patients were very closely matched resulting a de minimis difference in value.

Because of the larger number of patients on <unk> therapy at the end of the third quarter inventory days on hand at the SPE decreased but remained within a normal range.

Speaker 6: Gross to net for U.S. sales quarter over quarter decreased to 83 percent from 85 percent in the second quarter, primarily due to a Medicaid rebate adjustment in that quarter.

Gross to net for U S sales quarter over quarter decrease to 83% from 85% in the second quarter, primarily due to a Medicaid rebate adjustment in that quarter.

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

Speaker 6: 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 amount.

Cost of sales during the third quarter was $2 4 million or approximately 10, 7% of net product revenues, representing a slight percentage decrease quarter over quarter cost of sales consisted primarily of product costs are 5% royalties under our original licensing agreement for <unk> in Atlanta.

Speaker 6: Cost of sales during the third quarter was 2.4 million, or approximately 10.7% of net product revenue, representing a slight percentage decrease quarter over quarter. Cost of sales consisted primarily of product costs are 5% royalty to Ipsum under our original licensing agreement for sepmalanitide, as well as amortization of previously capitalized sales-based milestone payments.

As well as amortization of previously capitalized sales based milestone payments.

R&D expenses were $33 6 million for the third quarter of 2003 compared to $21 1 million. During Q3 dollars 22, and essentially flat compared to Q2 2023 R&D expenses of $33.

Speaker 6: R&D expenses were 33.6 million for the third quarter of 23 compared to 21.1 million during Q3 22 and essentially flat compared to Q2 2023 R&D expenses of 33 and a half.

SG&A expenses were $30 5 million for the third quarter this year versus $21 9 million for the third quarter of 2002, and also essentially flat quarter over quarter versus $30 million in the second quarter of 2023.

Speaker 6: SG&A expenses were $30.5 million for the third quarter this year versus $21.9 million for the third quarter of 2022, and also essentially flat quarter-over-quarter versus $30 million in the second quarter of 2023.

Yes.

Speaker 6: In the third quarter, weighted average common shares outstanding were 57.9 million, an increase of approximately 1 million shares over last quarter, resulting primarily from our equity issuance under the ATM program during the quarter. Quarterly net loss per share was 76 cents.

In the third quarter weighted average common shares outstanding were $57 9 million an increase of approximately 1 million shares over the last quarter, resulting primarily from our equity issuance under the ATM program during the quarter quarterly quarterly net loss per share was <unk> 76.

Now on slide 24.

With the third and final investment tranche of $25 million from our capped royalty financing agreement with healthcare royalty partners and gross proceeds of approximately $50 million from our ATM program. During the quarter, we are very well financed with $299 $3 million in cash on hand. This cash on hand is sufficient to fund all planned activities into 2026.

Speaker 6: With the third and final investment tranche of 25 million from our cap royalty financing agreement with health care royalty partners and gross proceeds of approximately 50 million from our ATM program during the quarter, we are very well financed with 299.3 million in cash on hand this cash on hand is sufficient to fund all planned activities into 2026.

On the net revenue for this quarter of $22 5 million, 80% of these revenues were generated in the United States. The proportion of revenue generated by our international region increased from 14% to 20% quarter over quarter.

Speaker 6: On the net revenue for this quarter of $22.5 million, 80% of these revenues were generated in the United States. The proportion of revenue generated by our international region increased from 14% to 20% quarter over quarter.

Year to date net revenue was $53 2 million in North America sales accounted for 83% of that total.

Speaker 6: Year-to-date net revenue was $53.2 million, and North America sales account for 83% of that total. International sales growth continues with much of the quarter-over-quarter increase due to sales in Germany following the PBS launch, with this third quarter being the first full quarter of PBS sales in Germany.

International sales growth continues with much of the quarter over quarter increase due to sales in Germany. Following the Bbs launch with this third quarter being the first full quarter of PBS sales in Germany.

As well as an increase in patients with Bbs in France, receiving commercial drug as part of the French AP two program for reimbursed early access.

Speaker 6: as well as an increase in patients with BBS in France receiving commercial drug as part of the French AP2 program for reimbursed early access.

Third quarter operating expenses include a total stock based compensation of $8 5 million for the quarter.

Speaker 6: Third quarter operating expenses included total stock based compensation of $8.5 million for the quarter, which represents $23.9 million in OPEX year to date.

This represents $23 9 million.

Opex year to date.

Lastly, we have narrowed the range of our non-GAAP operating expense guidance for 2023 to between 210 $220 million. Please note that this amount excludes stock based compensation with that I'll turn the call back over to David.

Speaker 6: Lastly, we have narrowed the range of our non gap operating expense guidance for 2023 to between 210 and 220 million. Please note that this amount excludes stock based compensation with that. I'll turn the call back over to David.

Thanks Hunter, So I think hopefully you've heard.

Speaker 3: Thanks, Hunter. So I think hopefully you've heard we're really happy with how the commercial opportunity is beginning to develop here, obviously, in the US. And now you've heard international is becoming an increasingly important part of this overall picture, as it will continue to do going forward.

We're really happy with how the commercial opportunity is beginning to develop here obviously in the U S and now you've heard US international is becoming an increasingly important part of this overall picture is that we will continue to do going forward and on the HR side just to highlight a moment of thanks here I might think thanks to our investigators and the patient.

Speaker 3: And on the HO side, just to highlight a moment of thanks here, I think thanks to our investigators and the patient community who have been incredibly engaged here and supportive of getting this trial going. Not an easy trial, it's a double-blind placebo-controlled 2-to-1, but you know, you sign up, there's a chance you'll end up for a year on a placebo therapy.

<unk> have been incredibly engaged here in supportive of getting this trial going not an easy trial double blind placebo controlled two one but.

Sign up for the chance, you'll end up per year on a placebo therapy. So again <unk> been really pleased with the reaction from the community and their engagement here and a final note. Thanks to the rhythm team.

Speaker 3: pleased with the reaction from the community and their engagement here. And a final note, thanks to the RHYTHM team. And not an easy trial, it's a complicated trial, we're collecting a lot of data.

Not an easy trial is a complicated trial, reflecting volume information important information will be the one of the perhaps our last chance to get this kind of robust information in a controlled trial setting so they've done a great job again getting us to this position and putting us in place to be able to meet our ended the year.

Speaker 3: important information will be one of the perhaps our last chance to get this kind of robust information in a controlled trial setting. So they've done a great job again getting us to this position and putting us in place to be able to meet our end-of-the-year enrollment targets. So with that we'll open it up to questions.

Enrollment targets, so with that we'll open it up to questions.

Thank you and as a reminder to ask a question. Please press star one on your telephone and wait for your name to be now.

Speaker 1: Thank you, and as a reminder to ask a question, please press star 11 on your telephone and wait for your name to be announced. To withdraw your question, please press star 11 again. One moment for our first question.

To be announced.

Your question. Please press Star one again, one moment for our first question.

Yes.

Our first question comes from the line of Karen Jenkins from Goldman Sachs. Your line is open.

Speaker 1: Our first question comes from line up Corinne Jenkins from Goldman Sachs. Your line is.

Good morning.

Speaker 7: Good morning. Thanks for taking our question. I guess a couple from us, maybe first, how should we think about the development for RM718 as compared to the way you developed in SIVRI? Will it largely mirror or are there some kind of faster paths that you can take on that asset?

Thanks for taking our question I asked a couple from US maybe first how should we think about the development for RMS Stefan one eight as compared to the way you developed in February will largely mirror or are there or are there some kind of faster paths that you can take on that asset.

Speaker 7: And then as a follow-up, kind of separate question, where are the bulk of these 100 international patients, both with respect to region, as well as BBS versus the PPL indication? And how does that kind of compare to where you were at the end of September ?

And then as a follow up kind of separate question.

Where are the bulk of these 100 international patients both with respect to region as well as Bbs versus the PPL indication.

And how does that kind of compare to where you were at the end of September.

Yeah. Thanks, Brian So I'll take the first one and then I'll turn it over to you. So on 701 eight.

Speaker 3: Thanks, Corinne. So I'll take the first one and then Jan, I'll turn it over to you. So on 718, there is a pass or pass. I mean, you remember the very first trials that were done were in Sievery, were done in Palm Sea, leptin receptor biallelic patients. Again, we were learning about dosing. There was a lot of just we had to learn about the mechanism. So we benefited from all of that prior learning. HO, we had no clue of at that point. And HO, as we have seen, looks like a very sensitive model here.

There is a fast surpassed your.

You remember the very first trials that were done were in sebree were done at Palm C. Leptin receptor biallelic patients again, we were learning about dosing. There was a lot of just we had to learn about the mechanism. So we benefit from all of that prior learning HR. We had no clue of at that point in <unk> as we have seen them looks like a very sensitive model.

Ear so organic.

Speaker 3: Great place to start. So the strategy for 718 will be after we've done our normal volunteer SAD-MAD, the single ascending dose and multiple ascending dose portions of that volunteer study, we'll have a cohort of HO patients which hopefully will give us the insight that we need for dosing to then go to the additional indication.

Great place to start so the strategy for 701 eight will be after we've done our normal volunteer sad Mad the single ascending dose and multiple ascending dose portions of that volunteer study, we will have a cohort of <unk> patients, which hopefully will give us the insight that we need for dosing to them go.

The additional indications.

So it should go Patrick will go faster there is no question will go faster.

Speaker 3: So it should go faster, will go faster. There's no question it'll go faster. Yeah, I hope on the 100 patients.

Yes.

Yes.

On the 100 patients.

Speaker 5: Yes. So, first of all, in terms of geographic repartition, two-thirds of the patients are in France and in Germany, and the rest spread across four or five countries, Turkey, Italy, Netherlands, UK. The split between POMC, LIPAR, and BBS, right now, it's about 50-50, which is a reason because we did launch POMC and LIPAR first.

Yes, so first of all.

In terms of geography crude competition.

Some of the patients insurance in Germany.

The risks.

Read across.

Five countries to key.

<unk> UK.

Is it split between the CD and DBS right now it's about 50 50.

<unk>.

The reason is because we did launch from <unk>.

Speaker 7: But given the more important prevalence BDS, we will catch up quickly and BDS will outpace from CNVPAR soon. Very good. That's helpful. Thank you.

But given the more important preventing CBS we got.

Got you quickly and.

Yes.

From C&I.

Sure.

Very good Thats helpful. Thank you.

Yes.

Your next question.

One moment for our next question.

And our next question comes from the line of Phil Naidoo from TD Cowen Your line is open.

Speaker 1: And our next question comes from Phil Naidoo from TD Calvin. Your line is open.

Good morning, Congrats on the progress and thanks for taking my questions three from raws to pipeline and one commercial.

Speaker 8: Good morning, congrats on the progress and thanks for taking our questions. Three from us, two pipeline in one commercial. On the pipeline in terms of the HO Pivotal study, should we look at the 25.5% mean BMI reduction that was shown in the 12-month extension as a reasonable proxy for what could be seen

On the pipeline.

In terms of the <unk> pivotal study should we look at the 25, 5% mean BMI reduction that was shown in the 12 month extension as a reasonable proxy for what could be seen on the primary endpoint.

On the H O pivotal.

That's first question and second any update on the M&A enrollment and then third in terms of commercial curious to hear your most recent estimates of how penetrated you are.

Speaker 8: That's first question. Second, any update on the M&A enrollment? And then third, in terms of commercial, current is to hear your most recent estimates of how penetrated the US diagnosed BBS market is, any sense of the number of diagnosed patients that are out there today.

US diagnose TB market is any sense of the number of diagnosed patients that are out there today. Thanks.

Thanks.

Sure.

Speaker 3: Sure. So let me take the first two. So is the 25% a good proxy? I mean, obviously, that's an incredibly robust result. We're very happy. I've said many times it's

Let me, let me take the first two.

So is the 25% a good proxy I mean, obviously, that's an incredibly robust results, we're very happy I've said.

Many times it's.

Speaker 3: it's a little bit less about the magnitude of the change because we have a heterogeneous group of patients. We have very young kids, we have older adults, we're mixing them all together. That confounds a little bit that number going to read through, but what is remarkable is the consistency of the response. I mean, literally every patient in that trial, if they took the medication, is having a

It's a little bit less about the magnitude of the change because we have a heterogeneous group of patients who have very young kids, we have older adults for mixing them altogether.

Oh that confounds a little bit.

Is that number going to read through but what is remarkable.

The consistency of the response I mean literally every patient in that trial. If they took the medication is having a front. So we're powered for 10% difference I think theres little risk knock on wood.

Speaker 3: So, you know, we're powered for 10% difference. I think there's little risk, knock on wood, that, you know, we wouldn't do better than that. And the 25% speaks to, you know, that level of it. We're highly powered, 99% better powered to show the 10.

That.

We wouldn't do better than that in the 25% speaks to that level a bit.

Highly powered 99% better powered to show that.

Speaker 3: So a long way of saying, I don't think you can take the 25% necessarily as a read-through, but it's highly consensual if you want to get some of that.

So the long way of saying I don't think you can take the 25% necessarily as a read through but it's highly.

Yes.

And this patient group.

Speaker 3: and then emanate. So we're making progress there again.

And then M&A, so we're making progress there again, we haven't highlighted it so much because we're still it's still a work in progress, but I think it would be sorted out.

Speaker 3: We haven't highlighted it so much because we're still working progress, but I think it boarded out the issues which put us well behind here on that trial and that trial is now in running. Enrolling strongly. A couple of the cohorts are enrolling ahead of two of the other cohorts, which is not unexpected. We didn't expect all four. So I think what we'll do is we'll be reading out in 24.

Issues, which put us well behind here on that trial and that trial is now running enrolling strongly.

A couple of the cohorts are enrolling ahead of two of the other cohorts, which is not unexpected we didn't expect all four so I think what we'll do is we'll we'll be reading out in 2004.

Speaker 3: We're sorry, we'll announce in 24 that we fully enrolled as a year study once we're fully enrolled for when at least 2 of those cohorts have enrolled.

Sorry, we will announce in 2000 and for that we fully enrolled as of year study once we're fully enrolled.

Four when at least two of those cohorts have enrolled.

<unk>.

Speaker 9: And then on the commercial side, in terms of penetration, Jennifer, I mean, again, we make these epidemiologic estimates of 4,000 to 5,000, and there's uncertainty in those numbers, but how do you think penetrating against that?

And then on the commercial side in terms of penetration Jennifer I mean again, we make these epidemiologic estimates of four to 5000. This uncertainty in those numbers, but how do you think penetrating against that.

So we have not updated the number of patients that have been diagnosed I would just say that a.

Speaker 4: So we have not updated the number of patients that have been diagnosed. So we'll just say that, and we've been focusing more in terms of those who have had a prescription. But with that said, the teams are doing an amazing job just in terms of the education efforts. And we continue to get more and more patients or find HCPs that have BBS patients or educating to have them also diagnose additional patients.

Okay. Thank you alright in terms of that too.

But with that said the teams are doing an amazing job just in terms of education effort and we continue to.

To get more and more patients for five agencies that have cvs patients or educating too.

Have them also diagnosed additional patients.

Speaker 10: I would say that in terms of, you know, opportunity that remains, there still remains a large opportunity in terms of not only defined, but also the pull-through in terms of, you know, dignospations to in-ims of represcription to lots of opportunities that still remain ahead. That's very helpful. Thanks for taking our questions.

I would say that in terms of.

Opportunity that remains there still remains a large opportunity in terms of not only the fines, but also the pull through in terms of.

Diagnose patients too.

And surgery prescription lots.

Lots of opportunities that still remain.

That's very helpful. Thanks, again for taking our questions.

Thank you.

And one moment for our next question.

Our next question comes from the line of Derrick Our Chiller from Wells Fargo. Your line is open.

Speaker 1: Our next question of conflain of Derek Archila from Wells Fargo. He landed on the...

Hey, good morning, Thanks for taking the questions and congrats on the progress here. So just two from us.

Speaker 11: Hey, good morning. Thanks for taking the questions and congrats on the progress here. So just two from us. It's like it's of the physicians that have written more than one script for BBS. I guess how long between the first script do they write the second? And I guess do you find the driver being then going out and finding more patients or just getting more experience with the drug and they already have patients that they're treating? And then they start treating those.

So I guess of the physicians that have written more than one script for Bbs I guess, how long between the first script right. The second and I guess do you find the driver being.

Going out and finding more patients and we're just getting more experienced with the drug and they already have patients that they're treating and then they start treating those so that's question one and then the second.

Speaker 11: So that's question one. And then the second, I guess what is left to be done to get each of patients on in-sigree under the AP-1 system in France? Like, how do we think about the magnitude of the impact next year on new patients on therapy from that? Thanks.

What is left to be done to get patients on in February under the AP, one systemic France I guess, how do we think about the magnitude of the impact next year on new patients on therapy from that thanks.

Yes, Jennifer.

Speaker 4: Jennifer? So I would say that the timing is variable because the situation is also variable position by position.

So I would say that the timing is variable because the situation is also variable physician by physician.

Speaker 4: Some were physicians that had more than one patient, even prior to our launch.

Some were physicians that had more than one patient even prior to our launch.

Speaker 4: And that could take time just in terms of that patient coming back in to have a dialogue with the physician, just in terms of interest to get on to therapy.

And that's it.

It could take time, just in terms of that patient coming back.

To have a dialogue with a physician just in terms of interest to get onto therapy.

And then there are also others that.

Speaker 4: And then there's also others that, through our education efforts, they diagnose the first patient and similar to rare disease. Once you find that first patient, it's no longer this unicorn that's not in your practice, but something that you need to pay attention to, just in terms of differential diagnosis of additional patients that have come to them in the past or will be coming to them in the future to remember that understanding the different symptoms to get to a clinical diagnosis is important to bear in mind.

All of our education efforts they diagnose the first patient.

Similar to rare disease. Once you find that first patient that no longer the corner that's not in your practice, but something that you need to pay attention to just in terms of.

Differential diagnosis additional patients.

Tom to them in the past or will be coming to them in the future.

You'll remember that.

Understanding the different symptoms to get to a clinical diagnosis is important to bear in mind.

Speaker 4: So it's a bit of a mix of both of them and both of those also impact the timing in terms of the first to the next prescription.

So it's a bit of a mix of both of them and both of those also impact the timing in terms of the first to the next prescription.

Okay.

Yes.

Speaker 3: And Yann, maybe just a little bit more color on the process for the AP1HO, and then how should we think about 2024?

Maybe just a little bit more color on the process for the <unk> and then how should we think about 2024.

Yes, sure. So first of all of course, we are very pleased with this achievement.

Speaker 5: Yes, sure. So first of all, of course, we are very pleased with this achievement. It's very rare and to get such a pre-any-a approval in front based on three-two data. And to be more precise, there are just two rare these therapies with such tattoos in front.

It's very rare.

To get such a pre NDA approval in France based on the phase two data and to be more precise down just two rare disease therapies with such status influence.

Speaker 5: So I've mentioned we are now working through the process and to answer to your questions. This program's...

I've mentioned, we are now working through the process and to answer your questions.

Just programs.

Speaker 5: I've had administrative requirements, so we get it granted and now we have to go through a few steps.

Frankly requirements. So we get it granted no we have to go through a few <unk> one is.

Speaker 5: One is an agreement in terms of data collections with the sensors of reference and the French EVA.

Agreement in terms of debtor collections resistance of reference and differentiate.

And the second is also central the FERC <unk> setting up mid teens.

Speaker 5: And the signal is also the center of the reference are setting up.

Speaker 5: multidisciplinary decision-making meetings.

Decision, making meetings to reviews of patient cases, so and Thats usual rules and we have been through that we've considered.

Speaker 5: to review the patient cases. So, and that's the usuals, and we have been through that with PonCi-Liparth and also with BBS, so we know how it works, and it is the same for all the rare diseases drugs. So those tests are currently, we are working on them.

Also with DBS. So we know it works and it is as simple as you've had to use drugs. So those tests.

Sure.

Currently we are working we are working on is in full.

For your second question in terms of nimble efficiency to be difficult to see today, what we know because we have been.

Speaker 5: for your second question in terms of number of patients, it's a bit difficult to say today what we know because we have been...

Speaker 9: It has been known and we have been reached out by a lot of experts, and we are working also with experts. There are a lot of patients who are in need, and we have a lot of physicians interested to treat these patients. So as soon as we will have these administrative requirements ready, we will have the first prescriptions, and the first patients will be treated. Still difficult to say how much in 2024. More to come on that, Derek. We're learning here.

It has been known and we have reached out by a lot of experience and we are working on so we.

Now a lot of patients in need.

And we have a lot of physicians to treat these patients who have soon as we would have.

These first two requirements ready.

We will have some sales prescriptions and the contributions would be treated still difficult to see how much in 2024.

Good morning to come on that Derik, we're learning here.

Alright, thank you.

In Q1 moment, our next question.

And our next question comes from the line of Dae Gon Ha from Stifel. Your line is open.

Speaker 1: And our next question of offline of day gone hot from Seafull. The line is open.

Speaker 8: Hey, good morning guys. Thanks for taking the question and congrats on the progress. Two from us, one on the commercial and one on H.O. So on the commercial front, I thought it was interesting. You pointed out the divergence between your experience versus crib.

Hey, good morning, guys. Thanks for taking my question and congrats on the progress to from US one on the commercial and one on <unk>. So on the commercial front I thought it was interesting you pointed out the divergence between your experience versus cribs.

Speaker 8: Since you do have a significant proportion of prescribers being Pied Endos, what kind of strategy are you thinking in terms of penetrating that segment to the market? I guess a little bit more aggressively and have more representation in your prescriber base. And just to clarify on the nomenclature, is it?

Since you do have a significant proportion of prescribers being Pete and does was wondering what kind of strategies are you thinking in terms of penetrating that segment of the market I guess, a little bit more aggressively and have more representation in Europe prescriber base and just to clarify on the nomenclature is it you're going guidance is going to be on prescriptions.

Speaker 8: Your going guidance is going to be on prescriptions because you've previously talked about star forms. I just want to make sure that's what we should be looking at next.

Because you've previously talked about start forms I just wanted to make sure that that's what we should be looking at next and then on <unk>. If you can maybe go into the screen failure commentary a little bit more David I guess, what are the dynamics youre seeing with regards to enrollment and how are you balancing rapid enrollment to reach that <unk> completion.

Speaker 8: And then on H.O., if you can maybe go into the screen failure, commentary a little bit more, David. I guess what are the dynamics you're seeing with regards to enrollment and how are you balancing rapid enrollment to reach that 4Q completion date and ensuring you avoid any compromises along the way? Thanks so much.

Date, and ensuring you avoid any compromises along the way thanks, so much.

Hi, Jennifer.

So sorry for clarification.

Speaker 4: So, sorry for clarification. The...

Yes.

The metric is the start forms that we are focused on and are.

Are there new start forms are not repeat scripts for the same patient.

Speaker 4: And regarding your question, regarding the crib's piece, you know, for sure the pediatric and their chronologist that is a treater and prescriber for in-civary remain a key specialty focus of our themes. And that's one that our, you know, territory managers are calling on.

And regarding your question regarding the cribbs.

For sure.

Pediatric endocrinologists.

Schrader and prescriber for <unk> remain a key specialty focus of our teams.

And Thats why our <unk>.

Tori managers.

Our calling on.

Speaker 4: But we also supplement their efforts just with a lot of non-personal promotion efforts. We knew up front that when we took a look at that crypt distribution of 80% less than 18 years of age, that these patients do not die at 18 years of age. And so we knew that there were a lot more patients, either that were diagnosed and lost in the system. And oftentimes they may stop going to specific positions. So there was quite a breadth in terms of different specialties that we wanted to educate to get to those adults, which I think has been helpful in addition to the on-ground field team efforts in terms of getting to the...

But we also supplement their efforts just with a lot of non personal promotion efforts, we knew upfront that when we took a look at that credit distribution of 80% less than 18 years of age.

These patients do not die at 18 years of age and so we knew that there were a lot more patients either that were diagnosed the loss in this of stem and oftentimes. They they may stop going to specific positions. So there was quite a bit.

Breath in terms of different specialties that we wanted to educate.

Two.

Get to those adults, which I think has been helpful. In addition to the on ground sales team efforts in terms of getting to the.

Tim a distribution of patients that Gil.

Speaker 4: human distribution of patients that feel a bit more right just based off of the, you know, the age distribution of BBS patients in general.

More right just based off that.

Sure.

Its distribution of Bbs patients in general.

Speaker 3: Thanks, and dig on on the HL on the screen failure rate. So just to put that number a little more specific.

Great. Thanks, and then dig in on the HR the screen failure rate so.

To put that number a little more specifically I think we've had for screen failures with over two thirds of the patients screened or actively in screening.

Speaker 9: I think we've had four screen failures with over two thirds of the patient screen or actively in screening.

Speaker 9: And even in that small number of screen failures, we've had at least one patient who's been brought back in to re-screen. There was a minor issue and so they may ultimately turned out to be not a screen failure.

And even in that small number of screen failures. We've had at least one patient who has been brought back in to re screen.

There was a minor issue and so they may ultimately turned out to be not a screen failure and the reason. It's so low is when we started this effort and we're looking picking the sites, we've probably had.

Speaker 9: And the reason it's so low is when we started this effort and we're looking at picking the sights we probably had

Speaker 9: A total, the sites themselves had their list of patients, which were easily more than two times the number of patients we needed to enroll in this trial. So they were all starting with a list of...

A total.

The sites themselves have their list of patients, which were easily more than two times. The number of patients we needed to enroll in this trial. So they were all starting with a list of patients. They werent looking and then.

Speaker 9: They weren't looking and then they, as I said, they knew the entry criteria. They don't want to disappoint patients. So they're bringing in patients who they feel, based on their knowing the patients.

They knew the entry criteria, they don't want to disappoint patients so they're bringing in patients who they feel based on knowing the patient that they meet entry criteria and therefore, the risks with screen failure is low so pushing to enroll this trial I have no fear if you will that we're going to have a low quality patient enrollment.

Speaker 9: that they meet entry criteria and therefore the risk of screen failure is low so in pushing to enroll this trial I have no fear, if you will, that we're going to have a low quality patient enrollment, meaning people are working on the edges I think we're going to have patients who very much meet entry criteria because there's a, like I said, a good selection of patients who are.

People are working on the edges I think we're going to have patients who very much meet entry criteria because there's.

Like I said, a good selection of patients who are eager to get out.

Awesome. Thanks, very much yeah that helps thank you so much.

Speaker 8: Awesome. Thanks very much. Oh, yeah, that helps. Thank you so much.

That's great.

One moment our next question.

Okay.

And our next question comes from the line of Jeff Hung from Morgan Stanley. Your line is open.

Speaker 1: And our next question will come from line of Jeff Hong from Morgan Stanley , you're lying to the...

Thanks for taking my questions you talked about a couple of patients that didn't meet the 5% weight loss, we're going through that would be helpful. Peels process do you have a sense for the proportion of Bbs patients that discontinued based on the one year recommendation and then how does that compare to what you've seen for the other approved mutations and then I have a follow up.

Speaker 12: Thanks for taking my questions. You talked about a couple patients that didn't meet the 5% weight loss who are going through the BDOP Pills process. Do you have a sense for the proportion of BDS patients that just continue based on the one-year recommendation and then how does that compare to what you've seen for the other approved mutations?

Yes.

Speaker 4: So, the, the patients that are referred to just in terms of not meeting the requirements for the 5% weight loss is really at this point just a handful of patients. So, not many that fall into that category, but even so, you know, because of the, the belief from the physician as well as the desire for the patient to remain on therapy. We are helping them through the appeals process, just in terms of trying to maintain them in terms of authorization there.

So.

The patients that I referred to just in terms of not meeting the Riyadh requirements for the 5% weight loss is really at this point just a handful of patients.

Not many that fall into that category, but even so.

Because of the belief from the physician as well as the desire for patients to remain on therapy, we are helping them through the appeals process just in terms of trying to.

And then in terms of authorization there.

Speaker 4: You were asking a separate question, I believe, on the discontinuations on therapy overall.

Youre asking a separate question I believe on the discontinuation on therapy overall.

So.

Speaker 4: So we now do have a larger number of patients who have been on therapy for a longer period of time since our launch.

We now do you have a larger number of patients who have been on therapy for a longer period of time since our launch.

Speaker 4: And the discount rate to date has crept up a bit from the 10% that we had outlined to 13% of our access.

The discount rate to date has crept up a bit from the 10% that we had outlined to 13% of our axis.

The reason why have not really changed just in terms of why they are discounting it.

Characterize it as.

Almost half of them for more personal reasons.

And about half of them for adverse event rate.

It is still an opportunity, though for James just in terms of follow up because the hyper phase.

Speaker 4: You know, that it is still an opportunity, though, for change, just in terms of follow up, because the hyper fascia for those who are responding does come back quickly and they may, you know, consider coming back on therapy in the future.

For those who are responding does come back quickly and they may.

Consider coming back on therapy in the future.

Great. Thanks, and then you mentioned that.

Speaker 12: Great, thanks. And you mentioned that about half or upwards of half of discontinuations are for personal reasons. Do you have any data indicating the proportion of those who discontinued who are coming back to be treated again? And then my follow-up question was that for the prescribers who have not written more than one prescription, are the main reasons because they're relatively new to prescribing set melanotide or they don't have additional BBS patients or maybe something else? Thanks.

Half are upwards of half a discontinuation for personal reasons do you have any data, indicating the proportion of those who discontinued were coming back to be treated again and then my follow up question was that for the prescribers, who have not written more than one prescription are the main reasons because they are relatively new to prescribing <unk> Atlanta tied or they don't have additional bbs patients or maybe something else. Thanks. So much.

Yeah. So I'll answer the last question first.

Speaker 4: Yeah, so I'll answer the last question first. So the reasons are variable. They may only have one patient, you know, just in terms of a lot of our scripts also is.

So the reasons are variable they they may only have one patient.

You know just in terms of a lot of our specs also is.

Speaker 4: You know, patients who are been on therapy for a shorter period of time. So that may be the case just in terms of the, the reason for the 1 script and it may also be the case just in terms of position having 2 patients for that patient either has not come in or it's not ready to initiate therapy.

No.

Patients who are been on therapy for a shorter period of time, so that may be the case just in terms of the the reason for the one script and May also be the case just in terms of position, having two patients for that patient.

And then or is not ready to initiate therapy.

Speaker 9: In terms of the other questions, personal patients in the personal reason group and have any of those come back or

In terms of the other questions personal patients in the personal reason group and have any of those come back or likely to come.

Speaker 4: likely to come back. I see. We don't have enough data right now in terms of that point just to outline or I don't have it on me right now. I do know that there have been a couple of patients who discontinued and wanted to re-

Sure.

We don't have enough data right now in terms of to that point just to outline or I don't have it on me right now I do know that there have been.

A couple of patients who discontinued and wanted to re start therapy because of the hyperphagia, but it's only a handful at this point of time.

Speaker 4: start therapy because of the hyperfascia, but it's only a handful at this point in time.

Speaker 9: The other thing, Jeff, just on the 5% in general in terms of how people experience some benefit, this is a group because of their underlying mechanism.

The other thing Jeff just on the 5% in general in terms of how people experience some benefit.

Because.

Are there underlying mechanism.

Their inability to respond to some of the other therapy, certainly diet and exercise in some of the other medications isn't there and so simply stopping the weight gain is a major advantage and then as Jennifer said the overwhelming story, we've heard as we recounted on all of these calls is just the quieting of their hyperphagia.

Speaker 9: their inability to respond to some of the other therapy, certainly diet and exercise, and some of the other medications isn't there. And so simply stopping the weight gain is a major advantage. And then as Jennifer said, the overwhelming story we've heard as we recounted on all these calls is just the quieting of their hyperphagia. Ability to leave the table, leave food on the table is a pretty significant change for them.

To leave the table the food on the table.

Pretty significant change for them.

Great. Thank you.

Okay.

Our next question.

And our next question comes from the line of Whitney <unk> from Canaccord Genuity. Your line is open.

Speaker 1: And our next question comes from Whitney Asian from Kennecore Genuity, United.

Speaker 13: Hey, morning, guys. Going back to France and thinking particularly about BBS, can you remind us, I guess, where you are in the conversations for sort of regular way reimbursement? I know the logistics of the early access are slower than presumably it would be once you can flip over to regular reimbursement. I'm just curious where you are, the timing around that.

Hey, good morning, guys going.

Going back to France, and thinking, particularly about Bbs I can you remind us I guess, where you are in the conversations for sort of regular way reimbursement I know the the logistics of the early access are.

Slower than presumably it would be.

Once you can flip over to regular reimbursement just curious where you are at the timing around that.

Sure John Yes, sure. So we have started in pricing negotiations with.

Speaker 5: Sure, yes, sure. So we have started the pricing negotiations with the pricing committee. It usually takes between nine months to two, three years.

<unk> Committee.

It usually takes between nine months two to three years.

We are seeing is that we will have and then.

Speaker 5: we think that we will have an end mid next year, something like that. So we are in the third round technically and so far it has been good from both an understanding of the unmet medical need and the benefit from MCV and also the relationship and the openness and the transparency in the discussion. So we are at the beginning for something that should end mid next year.

Next year something like that so we are in this syndrome technically and so far it has been good.

And then the funding of unmet medical need.

<unk>.

Sebree and also.

Sure Steve.

Openness and transparency in the discussion. So we are at the beginning of something Thats through the end of mid next year.

Perfect. Thanks, and then on 718, I guess can you remind us I know you've talked about it being more potent.

Speaker 13: Perfect, thanks. And then on 718, I guess, can you remind us, I know you've talked about it being more potent in terms of its activity at the receptor. Is the idea behind the TPP there, better weight loss kind of efficacy picture or lower dosing safety profile or just how you're thinking about that?

In terms of its activity at the receptor is the does the idea behind the TPP there.

Better weight loss kind of efficacy picture or lower dosing safety profile or just how youre thinking about that thanks.

Yes, it's actually not it's not a more potent technically in terms of activity at the receptor, but it's more specific so that's the major feature here, which is our current set of Atlanta tied as you know we ship both the emcee for an EMC won with Chi which is contributes to the hyperpigmentation and so.

Speaker 9: Yeah, it's actually not technically, it's not more potent technically in terms of activity at the receptor, but it's more specific.

Speaker 9: So that's the major feature here, which is our current set melanocytes. As you know, we hit both the MC4 and the MC1, which contributes to the hyperpigmentation. And so we removed that.

We removed that.

Speaker 9: It's very specific. So the probability we will have hyperpigmentation is low. And we have animal data to support that. So that's the major advantage here. And then, of course, it's weekly, so we have convenience. And, of course, we have an IP protection that goes out to 2041. And so those are the major elements that make this a really critical program for us.

It's very specific so the probability we will have hyperpigmentation is low.

We have animal data to support that so that's the major advantage here.

And then of course, it's weekly it's we have a convenience and of course, we have an IP protection.

Protection that goes out to 2041 and so those are the major elements that make this a really critical program for us.

Great. Thanks very much.

One moment our next question.

And our next question comes from the line of Joseph Stringer from Needham Your line is open.

Speaker 1: And our next question comes in the line of Joseph Stringer from Needham. Your line is open.

Speaker 14: Hi, good morning. Thanks for taking our question with regards to the upcoming phase 3 readout and the 2 to 6 year old DBS patients. Just curious. You're all the patient identification work that you've done for DBS today in the US. How many. You estimate are in that 2 to 6 year old range and. Uh, what do you expect to see sort of a bullet or how do you think that would impact? The launch, uh, it can win the labels expended to include those patients.

Hi, Good morning, Thanks for taking my question with regards to the upcoming phase III readout in two to six year old DBS patients. Just curious you all of the patient identification work that you've done for Bbs today in the U S. How many.

You estimate are in that 2% to six year old range.

Would you expect to see sort of a bolus or how do you think that would impact the launch if and when the label is expanded to include those patients.

Yeah, So maybe I'll lead and Jennifer can add anything here I think.

Speaker 9: Yeah, so maybe I'll lead and Jennifer can add anything here. I think, A, it's not a large number of patients. What we see is a higher hit rate when a two to six-year-old group is screened. That very early onset, you know, obviously the history is very good there. They have true early onset obesity. And so, the screening hit rate is a little bit higher in that group. And so, that's an important part of this, number one. But it's not a large number of patients. So, there won't be a big impact to the overall patient population. But I think what's really important about, you know, this, A, it's a genetic disease. You want to treat all patients. Getting in early is hugely important. So, medically, I think this is very important. And it also builds, I think, an increasing recognition about what differentiates these diseases and the need to manage and think about them differently. So, it will help us in different ways, but the absolute number will not be large.

It's not a large number of patients what we see is a higher hit rate when a 2% to six year old group is screen that very early onset of Hispanic.

Obviously the history is very good there they are true early onset obesity and so the screening hit rate is a little bit higher in that group and so that's an important part of this number one but it's not a large number of patients. So there won't be a big impact to the overall patient population, but I think what's really important about.

<unk>, it's a genetic disease you want to treat all patients getting an early hugely important so a medically I think this is very important and it also build some I think an increasing recognition about what differentiates these diseases and the need to manage and think about them differently. So it will help us in different ways, but the absolute number will not be large.

Great. Thank you for taking our question.

Speaker 15: Great. Thank you for taking our question.

Good morning.

Thank you I'm not showing any further questions in the queue I'd like to turn the conference back to David Meeker, Chairman CEO and President for closing remarks.

Speaker 1: Thank you. I'm not showing any further questions in the queue. I'd like to turn the conference back to David Meeker, Chairman, CEO , and President for closing remarks.

Speaker 9: Thanks, Victor. So, um, thanks again, everybody for tuning in and excited about the progress we're making, as you've heard, and we very much look forward to seeing everybody or hopefully people will be able to either show up in person or call into our R&D day on December 6.

Thanks, Victor so thanks again, everybody for tuning in and excited about the progress, we're making as you've heard and we very much look forward to seeing everybody or hopefully people will be able to show up in person or call into our R&D day on December six where we have updates we will have a hyperplastic.

Speaker 9: Updates, we'll have a hypothalamic KOL from our hypothalamic obesity world so that will be interesting in addition to the data updates on our 718 program, the daybreak trial and we will provide the data on the pediatric trial at that time.

Kols from our hypothalamic obesity world. So that will be interesting. In addition to the the data updates on our <unk> program. The DAYBREAK trial, we will provide the data on the pediatric trial at that time.

So with that we'll sign up a good day.

This concludes today's conference call. Thank you for participating you may now disconnect everyone have a great day.

Speaker 1: This concludes today's conference call. Thank you for participating. You may now disconnect. Everyone have a great day.

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Speaker 1: Good day and thank you for standing by. Welcome to the Redmond Pharmaceuticals third quarter 2023 earnings conference call. At this time, all participants are in listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you will need to press star one, one on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star one, one again.

Good day and thank you.

And by and welcome to the rhythm Pharmaceuticals third quarter 2023 earnings Conference call. At this time all participants are in a listen only mode. After the speaker's presentation. There will be a question and answer session to ask a question. During the session you will need to press star one on your telephone.

Automated message advising your hand is raised to withdraw your question. Please press star one again, please be advised today's conference is being recorded.

I'd like to hand, the conference over to your Speaker today, David Connolly Investor Relations and corporate Communications. Please go ahead.

Thank you Victor.

Speaker 2: Thank you, Victor. I'm Dave Connolly here at Rhythm Pharmaceuticals. For those of you participating on the conference call, our slides can be accessed and controlled by going to the investors section on the investors page of our website at ir.rhythmtx.com.

The economy here at rhythm Pharmaceuticals for those of you participating on the conference call. Our slides can be accessed in control by going to the investors section on the investors page of our website at IR Dot rhythm TX Dot com.

Speaker 2: This morning, we issued our press release that provides our third quarter 2023 financial results and a business update, which is available on our website.

This morning, we issued a press release that provides our third quarter 2023 financial results and a business update which is available on our website at.

Speaker 2: As listed on slide two, here with me today in Boston are David Meagher, Chair, Chief Executive Officer and President of Earth and Pharmaceuticals, Jennifer Chen, Executive Vice President, Head of North America, Hunter Smith, our Chief Financial Officer, and Jan Mazabro, Executive Vice President, Head of International, is joining us on the line from Europe .

As listed on slide two.

Here with me today in Boston are David Meeker Chair, Chief Executive Officer, President of Rhythm Pharmaceuticals, Jennifer Chen Executive Vice President head of North America Hunter Smith, our Chief Financial Officer, and John <unk> Executive Vice President and head of International is joining us on the line from Europe.

Speaker 2: America, Hunter Smith, our Chief Financial Officer, and Jan Mazebro, Executive Vice President and Head of International, is joining us on the line from Europe . 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 reports on file with the SEC. In addition, any forward-looking statements represent our views only as of today and should not be relied upon as representing our views as of any subsequent dates. We specifically

Speaker 2: 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 reports on file with the S&P.

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 reports on file with the.

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

Speaker 2: In addition, any forward-looking statements represent our views only as of today and should not be relied upon as representing our views as of any subsequent dates. We specifically disclaim any obligation to update such statements. With that, I'll turn the call over to David Meeker, who will begin on slide five.

Speaker 9: Thank you, Dave, and good morning, everyone. Thank you for joining the call. So we're pleased to report out another very strong quarter with continued execution across all parts of our business.

Thank you, Dave and good morning, everyone. Thank you for joining the call. So we're pleased to report out another very strong quarter with continued execution across all parts of our business. The two near term drivers of rhythm value building, the Bbs commercial opportunity globally and enrollment into our phase III trial, we remain on track.

Speaker 9: Two near-term drivers of rhythm value, building the BBS commercial opportunity globally and enrollment into our Phase 3 HO trial remain on track.

Speaker 9: I'm incredibly impressed by the performance of our North American and international organizations. DBS and the monogenic forms of MC4R pathway diseases, we are approved to treat, are, as we have discussed multiple times, highly meaningful rare disease opportunities. But they do fall in the ultra-rare category, with all of the challenges these patients face getting to a diagnosis and then accessing the appropriate therapy.

I'm incredibly impressed by the performance of our North American and international organizations DBS in the monogenic forms of emcee for our pathway diseases. We are approved to treat arm as we have discussed multiple times highly meaningful rare disease opportunities, but they do fall in the ultra rare category with all of the challenges these patients face getting towards.

Diagnosis, and then accessing the appropriate therapy.

Speaker 9: The sheer volume of noise around the management of obesity as a disease and the use of GLP-1 specifically has both aided the cause, healthcare providers are looking more closely at patients who present with obesity and doing the appropriate workup, and hindered the cause, where the availability of powerful therapies such as GLP-1 medications has led many to believe that all obesity is the same and GLP-1 is representative.

The sheer volume of noise around the management of obesity as a disease and the use of <unk> specifically has both aided the cause health care providers are looking more closely at patients who presented with obesity and doing the appropriate work ups and hindered the cost where the availability of powerful therapies such as DLP. One medications has led many to believe that all obesity.

<unk> represents a universal solution as we know that is not correct obesity is not one disease, but many diseases and as with most forms of medical therapy, the more targeted and specific the solution the better.

Speaker 9: As we know, that is not correct. Obesity is not one disease, but many diseases, and as with most forms of medical therapy, the more targeted and specific the solution, the better.

Speaker 9: The medical community continues to learn more about the factors which control hunger, the role of the different pathways, and the effect of different drugs play in modulating those pathways. Our story remains relatively simple. We're replacing or supplementing a hormonal signal, which is deficient. So if you're managing a patient, why wouldn't you start there?

The medical community continues to learn more about the factors, which control hunger the role of the different pathways and the effect of different drugs play and modulating those pathways. Our story remains relatively simple, we're replacing we're replacing sorry or supplementing a hormonal signal, which is deficient. So if you're managing a patient by once you start there.

Revenues in the quarter came in at $22 5 million showing exactly the steady growth. We had hoped to see we're pleased with the script volume in the U S where the team is doing a great job educating on the <unk> pathway and the value of precision therapy, and we are incredibly excited to cross the 100 patient threshold in Europe, where in addition to the usual challenges facing rare disease.

Speaker 9: Revenues in the quarter came in at 22.5 million showing exactly the steady growth we had hoped to see. We're pleased with the script volume in the U.S. where the team is doing a great job educating on the MC4 pathway and the value of precision therapy. And we're incredibly excited to cross the 100 patient threshold in Europe where in addition to the usual challenges facing rare disease communities, market access across the different healthcare systems can be particularly challenging. We have experienced teams in all geographies who are remarkably skilled at navigating these challenges.

It is market access across the different health care systems can be particularly challenging we have experienced teams in all geographies were remarkably skilled at navigating these challenges so although it will never be easy patient by patient we find solutions as you know, we do not provide financial guidance, but for those of you building models my experience working on rare.

Speaker 9: So although it will never be easy, patient by patient, we find solutions.

Speaker 9: As you know, we do not provide financial guidance, but for those of you building models, my experience working in rare diseases with many similarities to our current world has taught me, it never gets easier. The revenue trajectory does not inflect, but these opportunities continue to grow over time.

Diseases with many similarities to our current World has taught me and never gets easier the revenue trajectory does not inflict but these opportunities continue to grow over time.

Speaker 9: HO Phase 3 enrollment continues on track with two-thirds of the patients screen. That's our proxy for enrollment as almost none of these patients screen fail. The majority of patients needed to complete enrollment have their screening visits already scheduled, and we still have sites who are just opening or scheduled to open and who are eager to get their patients.

H O phase III enrollment continues on track with two thirds of the patient screen. That's our proxy for enrollment is almost none of these patients screen fail. The majority of patients needed to complete enrollment have their screening visits already scheduled and we still have sites. We're just opening are scheduled to open and who are eager to get their patients enroll.

Speaker 9: We did get early access approval for HO in the third quarter in France based on the 18 patient phase two data alone. This is an incredible recognition about the unmet medical need in this population and the potential significant impact treatment may have. The first patients, as Jan will outline, should be treated before year end.

Did get early access approval for <unk> in the third quarter in France based on 18 patient phase II data alone. This is an incredible recognition of both the unmet medical need in this population and the potential significant impact treatment may have the first patients as John will outline should be treated before year Adam.

Speaker 9: Finally, we look forward to providing additional updates at our R&D day, particularly with regard to our next generation weekly formulation, the day break trial, and our pediatric results.

Finally, we look forward to providing additional updates at our R&D day, particularly with regard to our next generation weekly formulation, the David DAYBREAK trial, and our pediatric results.

Speaker 9: So, moving to slide six, we recently had a separate analyst call following a very successful TOSS meeting in Dallas with multiple presentations, which are outlined here. What's particularly gratifying about these meetings, it's the opportunity to meet with a community in person and feel, literally, the growing interest in learning more about the different forms of obesity, including MC4R pathway disease.

So moving to slide six we recently had a separate analyst call. Following a very successful <unk> meeting in Dallas with multiple presentations, which are outlined here was particularly gratifying about these meetings, it's the opportunity to meet with the community in person and field literally the growing interest in learning more about the different forms of obesity, including emcee for our pathway diseases.

Sure.

Speaker 9: On slide seven, I want to take you through all of the 12-month HO data that were reviewed on the last call.

On slide seven I want to take you through all of the 12 month HR data that we reviewed on our last call <unk>.

Speaker 9: Fourteen patients entered the long-term extension, and results for all 14 are shown in this slide. We saw a robust mean 25% BMI decrease across the 12 patients who had 12 months of data. And I remind you that this is a blend, this trial, is a blend of ages with 11 of 12 of the patients, pediatric patients, and the pediatric patients are growing where you would expect the BMI to actually increase with that growth.

14 patients entered the long term extension and the results for all 14 are shown in this slide.

Our robust, meaning 25% BMI decrease across the 12 patients who had 12 months of data and I remind you that this is a blend. This trial is a blend of ages with 11 of 12 patients pediatric patients in the pediatric patients are growing where you would expect the BMI to actually increase with that growth.

Speaker 9: The two panels on the right are the two patients who are off treatment for some period of time. The short message here is, if you take the therapy, most patients respond, and when you stop treatment, IE, you stop this hormonal replacement therapy, your BMI, wait, and...

The two panels on the right are the two patients who are off treatment for some period of time a short message here is if you take the therapy most patients respond and when you stop treatment I E. You stop this hormonal replacement therapy your BMI weight increases.

Speaker 9: Finally, there's growing interest in the quality of the weight loss, meaning losing fat mass is good, but losing large amounts of lean mass is not good. Our early results suggest we do pretty well in that category as shown on the DEXA scan results, which we presented on the poster. And one other graphic on the poster shows the shift in obesity class experience by the patients with three of the pediatric patients actually getting back into the normal BMI range for their age.

Finally, there is growing interest in the quality of the weight loss, meaning losing fat mass as good but losing large amounts of lean mass is not good. Our early results suggest we do pretty well in that category as shown on the Texas scan results, which we presented on the poster and one other graphic on the poster shows the shift in obesity class experienced by patients with three of the pediatric patients.

Actually getting back into the normal BMI range for their age.

Speaker 9: Slide eight, this is just to remind you of the trial design where we are targeting 120 patients. And as noted, two thirds of the patients have been screened. And the majority of the balance of patients needed to complete the trial have already scheduled their screening visits.

Slide eight this is just to remind you of the trial design, where we are targeting 120 patients and is noted two thirds of the patients have been screened in the majority of the balance of patients needed to complete the trial have already scheduled theyre screening visits and.

Speaker 9: And importantly, and I think this is, you know, it's kind of still early here, but quite worthy.

And importantly, I think this is.

It's still early here, but quite noteworthy.

Of the patients treated we've had almost no trial discontinuation.

Speaker 9: Of the patients treated, we've had almost no trial discontinuation.

Yeah.

Speaker 9: So finally, on slide nine, this slide is to remind you that we are working on meaningful.

So finally on slide nine slide is to remind you that we are working on meaningful opportunities.

Speaker 9: you could build a very profitable company around BBS and the POMC and LEPR monogenic opportunities we are approved for today. However, we are investing significantly in R&D because those opportunities that we are pursuing are even greater. And as you know, for example, the HO opportunity itself represents a large, well-identified patient population with no approved therapy.

Build a very profitable company around Bbs and the policy and left bar monogenic opportunities were approved for today.

However, we are investing significantly in R&D, because those opportunities that we're pursuing are even greater and as you know for example, the HR opportunity itself represents a large well identified patient population with no approved therapies.

And with that I'll turn the call over to Jennifer.

Speaker 4: Thank you, David. We're pleased with the continued progress. We're seeing with our BBS commercial launch. Hundreds of patients with BBS in the US are now realizing the benefits of every therapy. We continue to hear the positive life changing impact we are making to the lives of patients and families.

Thank you David.

We are pleased with the continued progress we are seeing with our Bbs commercial lines hundreds of patients with Bbs and the U S are now realizing the benefits of being separate therapy.

We continue to hear the positive life changing impact we are making to the lives of patients and family.

Speaker 4: Recently we heard from one mother whose son is on MCIVRI therapy and MCIVRI has had a profound effect on his weight and his hyperphagia. He is full for the first time, leaves the dinner table before everyone else in the family and for the very first time he told his mother he does not like certain foods like lima beans, tomatoes, and pickles.

Recently, we heard from one mother with Amazon of Sebree therapy.

I'm sorry.

Found effects on weight and have hyperphagia.

He is full for the first time.

With that our table before everyone else in the family and for the very first time. He told his mother, if he does not like certain like Lima, beans tornadoes and takeout.

Speaker 4: In the mother's words, we are experiencing him as a kid, not a hungry kid.

And the mother's whereas we are not.

Not hundreds.

Speaker 4: And CIVRI is the only therapy approved specifically to treat obesity due to BBS. And we are thrilled to hear these stories from patients and families who now have access to therapy.

And so there is the only therapy approved specifically to treat obesity JCB UBS and we are thrilled to hear these stories from patients and families who now have access to therapy.

Beginning on slide 11.

Speaker 4: We are pleased with the growth and consistent strong demand for emciphery over the first five quarters.

We are pleased with the growth.

Strong demand for separate over the first five quarters.

Speaker 4: Throughout the launch from June 16, 2022 through the end of the third quarter of 2023, we now have received more than 545 new BBS prescriptions coming from more than 300 prescribers.

Throughout the launch from Gentex, Paul 2022, or the end of the third quarter of 2023, we now have received more than 545, new Bbs prescriptions coming from more than 300 prescribers.

Speaker 4: Of these prescriptions, we have greater than 330 approvals for reimbursement from payers.

This first question, we have greater than 330 approval for reimbursement from payers.

Speaker 4: On the next slide, I will cover results within the third quarter.

On the next slide I will cover results within the third quarter.

Speaker 4: We received greater than 120 prescriptions with 80 approval within the third quarter.

We receive greater than 121st question with 80 approval within the third quarter.

Speaker 4: Several of these approvals were from prescriptions received within the quarter, while others were written in prior quarters.

Several of these approvals were from prescriptions received within the quarter, while others were written in prior quarters.

Speaker 4: We continue to identify more BVS patients and work to speed diagnosis. Our active engagement with physicians remains focused on disease awareness, diagnosis, and the benefits of insuffering.

We continue to identify more Bbs patients and what BJ said.

Our active engagement with physicians remain focus on disease awareness diagnosis and the benefits have been separate.

Speaker 4: And our Rhythm and Tune team continues to deliver support to provide both to patients and families and healthcare providers every step of the way. Next slide.

And a rhythm of Gen team continues to deliver.

Hi, Bill.

The patients families and health care providers every step of the way next slide.

Speaker 4: Here's a snapshot of the patients with BBS behind these prescriptions.

Here's a snapshot of the patients with Bbs behind this perception.

Speaker 4: We continue to see an upward trend in terms of prescriptions received from adult patients.

We continue to see an upward trend in terms of prescriptions received from adult patients.

Speaker 4: As we've touched on before, this trend diverges from the age distribution in the CRIBS registry, a global registry housing data on BVS patients, where approximately 80% of registry participants are 18 or younger.

As we touched on before this trend diverges from the age distribution and the Cribbs registry, a global registry, having data on DBS basin, where approximately 80% of registered participants are 18 or younger.

Speaker 4: We believe this trend is representative of adult patients who simply age out of participating in this annual survey or who are lost at follow-up.

We believe this trend is representative of adult patients with simply Asia, they're participating in this annual survey or who are lost to follow up.

Speaker 4: Once MCIVRI was approved, through our education effort, many of these patients were reengaged with their physicians. This is not uncommon in rare disease, where the first approved therapy for a disease causes not only increased awareness of the disease, but also allows for increased reengagement of the broader diagnosed patient population. Next slide.

One subsidiary was approved steroid education effort. Many of these patients will reengage with their physicians. This is not uncommon in rare disease, where the first approved therapy for a disease causes not only increase the awareness of the disease, but also allows for increased re engagement of the broader diagnosed.

Patient population.

Next slide.

Entrepreneurs fiber.

Speaker 4: Endocrinology, both adult and pediatric, remains consistent over the last few quarters at their top specialty, accounting for 45% of prescribers.

Endocrinology, both adult and pediatric remains consistent over the last few quarters as our top specialty accounting for 45% of crisp Robert.

Speaker 4: We are seeing an increase in the portion of new tourism prescribers or physicians. Our territory managers had not previously called on directly prior to prescription, which now accounts for twenty eight percent of our prescriber base.

We are seeing an increase in the portion of new two rhythm prescribers or physicians our territory managers had not previously called on directly prior to perception, which now accounts for 28% of our prescriber base.

Speaker 4: This reinforces the conviction we have in our non-personal promotion effort.

This reinforces the conviction we have in our non personal promotion efforts.

Speaker 4: Lastly, we are seeing an increase in the depth of prescribers as 28% of them have written more than one prescription launched today, which is up from 25% as reported on the last quarterly call.

Lastly, we are seeing an increase and the depth of prescribers at 28% of them have written more than one prescription likes to date, which is up from 25% as reported on the last quarterly call.

Speaker 4: We remain focused on a greater breadth of prescribers over time, as well as more and more physicians who identify additional patients and prescribe in SIFRI for these second or more patients based off their own positive experience.

We remain focused on a greater breadth of prescribers over time as well as more and more physicians to identify additional patients and prescribers Jeffrey for these second or more patients based on their own positive experience.

Next slide.

Speaker 4: Access and reimbursement remain consistent with regard to overall coverage by state Medicaid and the overall payer MIPS.

Access and reimbursement remained consistent with regard to overall coverage by state Medicaid and the overall payer mix.

Speaker 4: If we look at Medicaid coverage through Covered Lives, launched to date, approximately 80% of Medicaid Covered Lives are in states with either a positive MCIVory policy in place or in a state where we have been able to gain positive coverage in at least one instance in the absence of an MCIVory policy.

If we look at Medicaid coverage covered lives launched to date approximately 80% of Medicaid covered lives are in states with either a positive in every policy in place.

Or in a state where we have been able to gain positive coverage and at least one is done and the absence of the Nims Jeffrey policy.

Speaker 4: The remaining 20% of Medicaid lives represent states where we either have not yet had a prescription for MSIFRI that would trigger a coverage decision, or we are still working to secure access for a prescription, or finally, where we have not been successful in gaining access through the appeals process.

The remaining 20% of Medicaid lives represent states, where we either have not yet had a prescription forms Jeffrey that would trigger a coverage decision or we are still working to secure access for prescription or finally, where we have not been successful in gaining access through the appeals process.

Speaker 4: The pair mix, or BBS, remains consistent as almost 90% of prescriptions since launch fall under commercial or Medicaid plans.

The payer mix or bvs remains consistent.

About 90% of prescriptions since last fall under commercial and Medicaid Glenn.

Speaker 4: The average time frame for approval is approximately one to three months, with some tails extending out several months, consistent with our previous report. Overall, we are pleased with achievements to date in securing approval. Next slide.

The average timeframe for approval is approximately one to three months with some tail extending out several months consistent with our previous report.

We are pleased with our achievements to date and securing approval.

Next slide.

Speaker 4: Now, more than one year into launch, we are seeing a very strong rate of reauthorization for continued NCIFRI coverage, with approximately 75 positive reauthorization decisions.

Now more than one year and two blocks, we are seeing a very strong rate of reauthorization for continued in separate coverage with approximately 75 positive reauthorization decision.

Speaker 4: The vast majority of these reauthorizations are approved initially and we have seen roughly a half dozen positive reauthorizations come upon appeal.

The vast majority updates reauthorization or approved initially and we have seen roughly a half dozen positive decisions come upon appeal.

Speaker 4: Most of these positive appeals had required additional clinical documentation to allow for a reauthorization of Progol.

That's a big positive appeal had required additional clinical documentation to allow for a reauthorization of profile.

Speaker 4: We have had a few denials to date, and we are in the process of appealing. To provide some color on these,

We have had a few denials debate and we are in the process of appealing to provide some color on beef.

Speaker 4: We have patients who have experienced overall clinical benefit, but have not achieved 5% body weight loss. For example, one had a reauthorization within 4 months of its CHIP re-initiation, while our label outlined a 12-month efficacy touchpoint.

We have patients who have experienced overall clinical benefit but have not achieved 5% body weight loss.

For example, one had a reauthorization within four months of Jeffrey initiation, while our label outlines a 12 month efficacy touch points.

Speaker 4: Another patient saw other clinical benefits and was just shy of the 5% waste loss requirement.

Another patient other clinical benefits and with just shy of 5% weight loss requirement.

Speaker 4: In both cases, we are working with the advocating physician and patient through the appeals process.

In both cases, we are working with the advocating physician and patient through the appeals process.

Next slide and final thoughts or me.

Speaker 4: We were very pleased to announce that a new ICD-10 diagnosis code was established for BBS. This is a long-term positive for the BBS community and for rhythm, as this improves understanding of the diagnostic and treatment journeys of patients and may enhance access to physicians with BBS patients.

We were very pleased to announce that a new ICD 10 diagnostic code was established for Bbs.

This is a long term positive for the Bbs community algorithm at this improved understanding of the diagnostic and treatment journey of persons EMEA impact access to physicians with DBS.

Speaker 4: We remain focused on engaging with the community to find already diagnosed patients while expediting the identification of individuals with DDS who do not yet have a diagnosis. We are excited about our progress and the opportunities in front of us. With that, I'll hand it over to Jan.

We remain focused on engaging with the community to find already diagnosed person while expedited <unk>.

But Europe with Bbs, who do not yet have a diagnosis.

Excited about our progress and the opportunities in front of us with that I'll hand, it over to Jan.

Thank you Jennifer and good morning.

Speaker 5: Thank you, Jennifer, and good morning, slide 19.

19.

Speaker 5: Today, we are very pleased to announce that we have achieved a significant international milestone with more than 100 patients from 11 countries outside of North America on the reimbursed therapy as of the end of October .

Today, we are very pleased to announce that we have achieved a significant international milestone with more than 100 patients 11 countries outside of North America on reimbursed therapy as of the end of October.

Speaker 5: Our first patients on reimbursed drugs started with the AP2 program in France for POMC and LIPAR deficiencies in March of 2022, and it has been a gradual and steady build since then, as new countries came online for POMC and LIPAR, and that continues as new countries come online for BBS, beginning with reimbursed early access in France, and now fully launched in Germany.

Our first patients on reimbursed drug started with <unk>, having friends for CME part efficiencies in March of 2022.

It has been gradual and steady built Susan as you can treat it came on line for <unk> and that continues as new countries come online for Bbs, beginning with reimbursed early access in France, and now fully launched in Germany.

Speaker 5: Regarding the French AP1 pre-EME approval reimbursed early access program for hypothalamic obesity, we are now working through the process to get it started. This program often starts slow because of the administrative requirements. We have not treated any patients yet under this program, but we may be in a position to treat a few patients during the fourth quarter.

Regarding the fringe in Q1.

EMEA approval reimbursed early access program for hypothalamic obesity, we are now working through the process to get it started.

Im often start slow because of the administrative requirements, we have not treated any patients yet.

We may be in position to treat a few patients during the fourth quarter.

Speaker 5: Overall, Europe is a key market for rare diseases for a reason. European countries typically are better organized and more centralized in their approach to rare diseases compared to the United States.

Overall Europe is a key market for rare diseases for reason European countries, typically are better organized and more centralized approach to <unk> compared to the United States.

Speaker 5: Even though these diseases are quite rare, the opportunity is meaningful. As a reminder, in the EU focus UK, we estimate the prevalence for Barley-Middle syndrome to be 4,000 to 5,000 patients, which is a prevalence similar to the U.S. And we have already more than 1,500 patients identified in this country.

Even though this is a quite rare the opportunity is meaningful as a reminder, you focus UK, we estimate the prepayments for bodybuilders in rooms to be 4000 to 5000 patients.

Which is a prudent and similar to the U S and we are already more than 1500 patients identified in these countries.

Speaker 5: We are pleased with progress to date in achieving market access for ancillary in a large number of international markets.

We are pleased with progress to date in achieving market access for <unk> and allows them to international markets.

Next slide.

Our launch in Germany is off to a solid start flowing to the unanimous decision of the gentleman said it will join committee or GBA, two excluding CRE from Germany's lifestyle exemption list and thereby make it eligible for reimbursement for Bbs.

Speaker 5: Our team is focused on engaging with physicians caring for patients with BBS and with the many centers where they are treated.

Our team is focused on engaging with physicians caring for patients with Bbs and with the medicine sales we have now treated.

Speaker 5: Building off our initial launch in POMSI and NIPAA, we had a very well-established relationship in place as a handful of key experts already had positive experience within series. In addition, we benefited from a full commitment from key treatment centers. And in parallel, our German team continued engaging with additional large academic centers in Germany's decentralized healthcare system.

This is <unk>.

Initial launch in function the bond, we have well established relationships in place as a handful of key expense already had positive experience with <unk>. In addition, we benefited from a full commitment from key treatment centers and in parallel in our German team continued engaging with additional large academic centers in Germany, and decentralized healthcare system.

We are seeing strong adherence to therapy things to a rhythm of whom patient support program similar to the U S rhythm, ensuring we provide support tailored specifically for each patients and their caregivers.

Speaker 5: We are seeing strong adherence to therapy thanks to our Rhythm at Home patient support program. Similar to the US Rhythm in Tune program, we provide support tailored specifically for each patient and their caregivers. For some, our support may come via phone call. Others may receive at-home visits and injections support.

Awesome support may come by our political risk.

We see that home visits and injections Stifel.

Speaker 5: Based on what we know about typical rare diseases, drug launches in Germany, we expected a steady and methodical start. With a strong foundation in place based on our POM CILIPA experience, continuously increasing numbers of diabetes treatment centers and the positive impact of RISM at home, we are very well positioned to achieve continued success in Germany.

Based on what we know, but typical rare disease drug launches in Germany, we expected steady and methodical.

With a strong foundation in place based on the <unk> experience continuously increasing number of these treatments until and the positive impact of rhythmic, whom we are very well positioned to achieve continued success in Germany.

Next slide.

Speaker 5: More broadly, we are making tremendous progress in engaging physicians throughout Europe . We had a very strong presence at the European Society for Pediatric Endocrinology in September with four oral presentations. Two presentations showcased data that demonstrates set melanotypes potential to reduce risk of metabolic syndrome, cardiovascular disease, and type 2 diabetes in pediatric patients with POMC, or lipar deficiency, or Bardet-Middle syndrome.

More broadly we are making tremendous progress in engaging physicians throughout Europe, we had a very strong presence at the European Society for Paediatric Endocrinology in September with four oral presentations.

Presentations showcased that does demonstrate <unk> potential to reduce our risk of metabolic syndrome, cardiovascular disease and type two diabetes big exhibitions, we spun see only part efficiency of <unk> syndrome.

Speaker 5: We also presented data from a raw genetic testing program through which we have collected more than 2,000 sequencing samples from individuals with severe obesity and hyperfetion.

Also presented data from a real genetic testing program through which we have collected more than 2000 sequencing samples from individuals with severe obesity and hyperphagia.

In addition, we hosted a symposium titled <unk>.

Speaker 5: In addition, we hosted a symposium titled Hyperphagia and Early Onset Severe Obesity, the Role of Precision Medicine in the Treatment of FC4R Pathway Disease. As you can see on this slide, it was very well attended, with in fact 400 physicians in the room.

<unk> is a world of precision medicine.

The treatment of SP plus.

You can see on this slide it was very well attended with impactful and with physicians.

Speaker 5: We look forward to continuing this momentum at our second international meeting on pathway-related obesity, the IMPROVE conference in December in Paris. We are looking forward to a series of presentations, discussions, and engagement focusing on rare MC4R pathway diseases, monogenic one, syndromic like BBS, and hypothalamic obesity, with more than 150 leading physicians and scientists coming from more than 10 countries. With that, I will turn the call over to Hunter.

We look forward to continuing this momentum.

The international meeting on possibly a <unk> improve conference in December in Paris, We are looking for work to a series of presentations discussions and engagement focusing on rare encephalopathy diseases monogenic, one syndromic like DBS and hypothalamic obesity with more than 150, leading physicians and scientists.

Coming from more than 10 countries.

With that I will turn the call over to until in Boston.

Thank you John.

Speaker 6: Rhythm remains tightly focused on global execution of commercial strategy across both our North America and international regions and continue development of the potential of every and our pipeline, all while staying committed to financial discipline and delivering shareholder value.

Where there remains tightly focused on global execution of commercial strategy across both our North America and international regions and continued development of the potential of a surgery and our pipeline all while staying committed to financial discipline and delivering shareholder value.

Speaker 6: Let's start with a snapshot of the Q3 P&L on slide 23.

Let's start with a snapshot of the Q3 P&L on slide 23.

Speaker 6: We recorded $22.5 million in net product revenue in the third quarter versus $4.3 million during the same quarter last year, an increase of $18.2 million. Q3 last year was our first full quarter of BBS commercial sales in the United States.

We recorded $22 5 million in net product revenue in the third quarter versus $4 3 million during the same quarter last year, an increase of $18 2 million Q.

Q3 last year was our first full quarter of Bbs commercial sales in the United States.

Speaker 6: which followed FDA approval on June 16, 2022.

Which followed FDA approval on June 16th 2022.

Speaker 6: Quarter over quarter, we saw an increase of 3.3 million or 17% in that product revenue driven by continued growth in the number of patients on every therapy in both the US and international region.

Quarter over quarter, we saw an increase of $3 3 million or 17% of net product revenue driven by continued growth in the number of patients on <unk> therapy in both the U S and international regions in.

Speaker 6: In last quarter's results, we highlighted that 1.6 million of our revenue resulted from shipments to our specialty pharmacy in excess of amounts that it dispensed to patients, resulting in an increase in inventory days on hand at quarter end. This quarter, shipments to the SP and dispenses to patients were very closely matched, resulting in a de minimis difference in value. Because of the larger number of patients on incivory therapy at the end of the third quarter, inventory days on hand at the SP decreased, but remained within a normal range.

In last quarter's results, we highlighted that $1 $6 million of our revenue resulted from shipments to our specialty pharmacy in excess of amounts that are dispensed to patients, resulting in an increase in inventory days on hand at quarter end.

This quarter shipments to the ESP and dispenses the patients were very closely matched resulting a de minimis difference in value.

Because of the larger number of patients on <unk> therapy at the end of the third quarter inventory days on hand at the SPP decreased but remained within a normal range.

Speaker 6: Gross to net for U.S. sales quarter over quarter decreased to 83 percent from 85 percent in the second quarter, primarily due to a Medicaid rebate adjustment in that quarter.

Gross to net for U S sales quarter over quarter decreased to 83% from 85% in the second quarter, primarily due to a Medicaid rebate adjustment in that quarter.

Speaker 6: 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 amount.

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

Speaker 6: Cost of sales during the third quarter was $2.4 million, or approximately 10.7% of net product revenue, representing a slight percentage decrease quarter over quarter. Cost of sales consisted primarily of product costs, our 5% royalty to Ipsum under our original licensing agreement for set and allanatide, as well as amortization of previously capitalized sales-based milestone payments.

Cost of sales during the third quarter was $2 4 million or approximately 10, 7% of net product revenues, representing a slight percentage decrease quarter over quarter cost of sales consisted primarily of product costs are 5% royalty to ipsen under our original licensing agreement for <unk> in Atlanta.

As well as amortization of previously capitalized sales based milestone payments.

Speaker 6: R&D expenses were 33.6 million for the third quarter of 23 compared to 21.1 million during Q3 22 and essentially flat compared to Q2 2023 R&D expenses of 33 and a half.

R&D expenses were $33 6 million for the third quarter of 2003 compared to $21 1 million during Q3 dollars 22 and <unk>.

Essentially flat compared to Q2, 2023 R&D expense of $33.

Speaker 6: as G&A expenses were 30.5 million for the third quarter this year versus 21.9 million for the third quarter of 22, and also essentially flat quarter over quarter versus 30 million in the second quarter of 2023.

SG&A expenses were $30 5 million for the third quarter of this year versus $21 9 million for the third quarter of 2002, and also essentially flat quarter over quarter versus $30 million in the second quarter of 2023.

Yes.

Speaker 6: In the third quarter, weighted average common shares outstanding were 57.9 million, an increase of approximately 1 million shares over last quarter, resulting primarily from our equity issuance under the ATM program during the quarter. Quarterly net loss per share was 76 cents.

In the third quarter weighted average common shares outstanding were $57 9 million an increase of approximately 1 million shares over the last quarter, resulting primarily from our equity issuance under the ATM program during the quarter quarterly quarterly net loss per share was <unk> 76.

Now on slide 24.

Speaker 6: With the third and final investment branch of 25 million from our cap royalty financing agreement with health care royalty partners and gross proceeds of approximately 50 million from our ATM program during the quarter, we are very well financed with 299.3 million in cash on hand this cash on hand is sufficient to fund all planned activities into 2026.

With the third and final investment tranche of $25 million from our capped royalty financing agreement with healthcare royalty partners and gross proceeds of approximately $50 million from our ATM program. During the quarter, we are very well financed with $299 3 million in cash on hand.

Cash on hand is sufficient to fund all planned activities into 2026.

Speaker 6: On the net revenue for this quarter of $22.5 million, 80% of these revenues were generated in the United States. The proportion of revenue generated by our international region increased from 14% to 20% quarter over quarter.

On the net revenue for this quarter of $22 5 million, 80% of these revenues were generated in the United States. The proportion of revenue generated by our international region increased from 14% to 20% quarter over quarter.

Speaker 6: Year-to-date net revenue was $53.2 million, and North America sales account for 83% of that total. International sales growth continues with much of the quarter-over-quarter increase due to sales in Germany following the PBS launch, with this third quarter being the first full quarter of PBS sales in Germany.

Year to date net revenue was $53 $2 million in North America sales account for 83% of that total.

International sales growth continues with much of the quarter over quarter increase due to sales in Germany. Following the Bbs launch with this third quarter being the first full quarter of PBS sales in Germany.

Speaker 6: as well as an increase in patients with BBS in France receiving commercial drug as part of the French AP2 program for reimbursed early access.

As well as an increase in patients with Bbs in France, receiving commercial drug as part of the French AP two program for reimbursed early access.

Speaker 6: Third quarter operating expenses included total stock based compensation of $8.5 million for the quarter, which represents $23.9 million in OPEX here today.

Third quarter operating expenses include a total stock based compensation of $8 5 million for the quarter, which represents $23 9 million.

Opex year to date.

Speaker 6: Lastly, we have narrowed the range of our non gap operating expense guidance for 2023 to between 210 and 220 million. Please note that this amount excludes stock based compensation with that. I'll turn the call back over to David.

Lastly, we have narrowed the range of our non-GAAP operating expense guidance for 2023 to between $210 million to $220 million. Please note that this amount excludes stock based compensation with that I will turn the call back over to David.

Speaker 9: Thanks, Hunter. So I think hopefully you've heard we're really happy with how the commercial opportunity is beginning to develop here, obviously, in the US. And now you've heard international is becoming an increasingly important part of this overall picture, as it will continue to do going forward.

Thanks, Andrew So I think hopefully you've heard.

I'm really happy with how the commercial opportunity is beginning to develop here obviously in the U S and now you've heard internationally.

Becoming an increasingly important part of this overall picture as it will continue to do going forward and on the HR side just to highlight a moment of thanks here I am I think thanks to our investigators and the patient community who have been incredibly engaged here in supportive of getting this trial going not an easy trial double blind placebo controlled two one but.

Speaker 9: And on the HO side, just to highlight a moment of thanks here, I think thanks to our investigators and the patient community who have been incredibly engaged here and supportive of getting this trial going. Not an easy trial, it's a double blind placebo controlled 2 to 1, but you know, you sign up, there's a chance you'll end up for a year on a placebo therapy. So again, I've been.

When you sign up for the chance you'll end up per year on a placebo therapy. So again <unk> been really pleased with the reaction from our community and their engagement here and a final note. Thanks to the rhythm team.

Speaker 9: pleased with the reaction from the community and their engagement here. And a final note, thanks to the RHYTHM team. And not an easy trial, it's a complicated trial, but we're collecting a lot of.

An easy trial is a complicated trial, reflecting client information important information will be the one of the perhaps our last chance to get this kind of robust information in a controlled trial setting so they've done a great job again getting us to this position and putting us in place to be able to meet our end of the year.

Speaker 9: important information will be the one of the perhaps our last chance to get this kind of robust information in a controlled trial setting so they've done a great job again getting us to this position and putting us in place to be able to meet our end-of-the-year enrollment targets. So with that we'll open it up to questions.

Enrollment targets, so with that we'll open it up to questions.

Thank you and as a reminder to ask a question. Please press star one on your telephone and wait.

Speaker 1: Thank you, and as a reminder to ask a question, please press star 11 on your telephone and wait for your name to be announced. To withdraw your question, please press star 11 again. One moment for our first question.

For your name to be announced can withdraw your question. Please press star one again, one moment for our first question.

Yes.

Our first question comes from the line of Karen Jenkins from Goldman Sachs. Your line is open.

Speaker 1: Our first question. Com line of kan Jenkins from gloman Sachs Landa.

Good morning.

Speaker 7: Good morning. Thanks for taking our question. I guess a couple from us, maybe first, how should we think about the development for RM718 as compared to the way you developed in SIVRI? Will it largely mirror or are there some kind of faster paths that you can take on that asset?

Thanks for taking our question I asked a couple from US maybe first how should we think about the development for RMB 718, as compared to the way you developed in Safari will largely mirror or are there or are there some kind of faster paths that you can take on that asset.

Speaker 7: And then as a follow-up, kind of separate question, where are the bulk of these 100 international patients, both with respect to region as well as BBS versus the PPL indication? And how does that kind of compare to where you were at the end of September ?

And then as a follow up kind of separate question.

Where are the bulk of these 100 international patients both with respect to region as well as bvs versus the PPL indication.

And how does that kind of compare to where you were at the end of September.

Yeah.

Yeah. Thanks, Brian So I'll take the first one and then I'll turn it over to you. So on 701 eight.

Speaker 9: Thanks, Corinne. So I'll take the first one and then, Jan, I'll turn it over to you. So on 718, there is a faster path. I mean, you remember the very first trials that were done were in Sievery, were done in Palm Sea, leptin receptor biallelic patients. Again, we were learning about dosing. There was a lot of just we had to learn about the mechanism. So we benefited from all of that prior learning. HO, we had no clue of at that point. And HO, as we have seen, looks like a very sensitive model here.

There is a faster path.

You remember the very first trials that were downward sebree were done at Palm C. Leptin receptor biallelic patients again, we were learning about dosing. There was a lot of just we had to learn about the mechanism. So we benefit from all of that prior learning HR. We had no clue of at that point in <unk> as we have seen them looks like a very sensitive model.

So again, a great place to start so the strategy for 701 eight will be after we've done our normal volunteer sad Mad the single ascending dose and multiple ascending dose portions of that volunteer study will have a cohort of <unk> patients, which hopefully will give us the insight that we need for dosing to them go to the additional <unk>.

Speaker 9: Great place to start. So the strategy for 718 will be after we've done our normal volunteer SAD-MAD, the single ascending dose and multiple ascending dose portions of that volunteer study, we'll have a cohort of HO patients which hopefully will give us the insight that we need for dosing to then go to the additional indication.

<unk>.

Speaker 9: So it should go faster, will go faster, there's no question it'll go faster. Yeah, I hope on the 100 patients.

So it should go Patrick will go faster there is no question, we'll go faster.

On the.

On the 100 patients.

Speaker 5: Yes. So, first of all, in terms of geographic repartition, two-thirds of the patients are in France and in Germany, and the rest spread across four or five countries, Turkey, Italy, Netherlands, UK. The split between POMC, LIPAR, and DBS, right now, it's about 50-50, which is the reason because we did launch POMC and LIPAR first.

Yes, so in terms of geographic repartition.

Two thirds of patients.

Trends in Germany.

And the rest spread across.

Five countries to key.

<unk> UK.

Is it split between the CD pound UBS right now it's about 50 50.

Sure.

The reason is because we did launch from <unk>.

Speaker 7: But given the more important prevalence BDS, we will catch up quickly, and BDS will outpace from CNVPAR soon. Very good. That's helpful. Thank you.

But given the more importantly, prevent and CBS, we will catch them quickly and yes, we are.

CMS is now.

Soon.

Very good Thats helpful. Thank you.

Yes.

Your next question.

One moment for our next question.

And our next question comes from line of Phil Naidoo from TD Cowen Your line is open.

Speaker 1: And our next question, cuffline, of Phil Nadoe from TD Calvin, United.

Speaker 10: Good morning, congrats on the progress and thanks for taking our questions. Three from us, two pipeline and one commercial. On the pipeline, in terms of the HO Pivotal study, should we look at the 25.5% mean BMI reduction that was shown in the 12-month extension as a reasonable proxy for what could be seen on the primary endpoint in the HO Pivotal?

Good morning, Congrats on the progress and thanks for taking my questions three from raws to pipeline and one commercial on the pipeline.

In terms of the <unk> pivotal study should we look at the 25, 5% mean BMI reduction that was shown in the 12 month extension as a reasonable proxy for what could be seen on the primary endpoint.

H O pivotal.

Speaker 10: That's the first question. Second, any update on the M&A enrollment? And then third, in terms of commercial, curious to hear your most recent estimates of how penetrated the U.S. diagnosed BBS market is. Any sense of the number of diagnosed patients that are out there today?

This first question second any update on the M&A enrollment and then third in terms of commercial curious to hear your most recent estimates of how penetrated the U S. Diagnosed PV market is any sense of the number of diagnosed patients that are out there today.

Thanks.

Speaker 9: Sure. So let me take the first two. So is the 25% a good proxy? I mean, obviously, that's an incredibly robust result. We're very happy. I've said many times it's

Sure. So let me let me take the first.

Too so.

So is the 25% a good proxy I mean, obviously that's.

An incredibly robust results, we're very happy I have said many times it's.

Speaker 9: it's a little bit less about the magnitude of the change, because we have a heterogeneous group of patients, we have very young kids, we have older adults, we're mixing them all together, so that confounds a little bit that number we're going to read through, but what is remarkable is the consistency of the response. I mean, literally every patient in that trial, if they took the medication, is having a

A little bit less about the magnitude of the change because we have a heterogeneous group of patients who have very young kids that have older adults were mixing them altogether.

Oh that confounds a little bit.

Is that number going to read through but what is remarkable.

The consistency of the response I mean literally every patient in that trial. If they took the medication is having a front so.

Speaker 9: We're powered for 10% difference. I think there's little risk, not going to what. That we wouldn't do better than that. And the 25% speaks to that level a bit. We're highly powered, 99% better power to show the talent.

We're powered for 10% difference.

I think theres little risk knock on wood.

That.

We want to do better than that in the 25% speaks to that level a bit.

We're highly powered 99% better powered to show that.

Speaker 9: So a long way of saying, I don't think you can take the 25% necessarily as a read-through, but it's highly consensual if you want that.

So.

A long way of saying I don't think you can take the 25% necessarily as a read through but it is highly.

Yes.

Okay.

In this patient group.

Speaker 3: and then emanate. So we're making progress there again.

And then M&A, so we're making progress there again, we haven't highlighted it so much because we're still it's still a work in progress, but I think sorted out.

Speaker 3: we haven't highlighted it so much because we're still it's still a work in progress, but I think we've sorted out the issues which, you know, put us well behind here on that trial and that trial is now in running, enrolling strongly. A couple of the cohorts are enrolling ahead of, you know, two of the other cohorts, which is not unexpected. We didn't expect all four. So I think what we'll do is we'll we'll be reading out N24.

Issues, which put us well behind here on that trial and that trial is now in running enrolling strongly.

A couple of the cohorts are enrolling ahead of two of the other cohorts, which is not unexpected we didn't expect all four so I think what we'll do is we'll be reading out in 'twenty four.

Speaker 9: Sorry, we'll announce in 24 that we fully enrolled. It's a year study once we're fully enrolled for when at least two of those cohorts have enrolled.

Sorry, well announced in 2000 and for that we fully enrolled as of year study once we're fully enrolled.

For at least two of those cohorts have enrolled.

<unk>.

Speaker 9: And then on the commercial side, in terms of penetration, Jennifer, I mean, again, we make these epidemiologic estimates of 4,000 to 5,000, and there's uncertainty in those numbers, but how do you think penetrating against that?

And then on the commercial side in terms of penetration Jennifer I mean again, we make these epidemiologic estimates of $4 to 5000. This uncertainty in those numbers, but how do you think penetrating against that.

So we have not updated the number of patients that have been diagnosed I would just say that and we think a good thing.

Speaker 4: So, we have not updated the number of patients that have been diagnosed. So, we'll just say that and we've been focusing more in terms of those who have had a prescription, but with that said, the teams are doing an amazing job just in terms of the education efforts. And we continue to get more and more patients or find that have CBS patients or educating to have them also diagnose additional patients.

Alright in terms of that too.

But with that said the teams are doing an amazing job.

The education efforts and we continue to.

Get more more patients for find agencies that have bbs patients or educating too.

Have them also diagnosed additional patients.

Speaker 8: I would say that in terms of, you know, opportunity that remains, there still remains a large opportunity in terms of not only the fines, but also the pull-through in terms of, you know, diagnoses patients to in-ims of represcription. So, lots of opportunities that still remain ahead. That's right, a whole thank you. We have for taking our questions.

I would say that in terms of.

Opportunity that remains there still remains a large opportunity in terms of not only the fines, but also the pull through in terms of.

Patient two.

And I'm sorry for a prescription.

Lots of opportunities that still remain high.

That's very helpful. Thanks, again for taking our questions.

Thank you.

Yeah.

And one moment for our next question.

Yeah.

Speaker 1: Our next question will come from Derek Archila from Wells Fargo.

Our next question comes from the line of Derrick Our Chiller from Wells Fargo. Your line is open.

Hey, good morning, Thanks for taking the questions and congrats on the progress here. So just two from us.

Speaker 11: Hey, good morning. Thanks for taking the questions and congrats on the progress here. So just two from us. So I guess of the physicians that have written more than one script for BBS, I guess how long between the first script do they write the second and I guess do you find the driver being them going out and finding more patients or just getting more experience with the drug and they already have patients that they're treating and then they start treating those.

So I guess of the physicians that have written more than one script for Bbs I guess, how long between the first script right. The second and I guess do you find the driver being.

Going out and finding more patients and we're just getting more experienced with the drug and they already have patients that they're treating and then they start treating those so that's question one and then the second.

Speaker 11: So that's question one. And then the second, I guess, what is left to be done to get HO patients on incivory under the AP1 system in France? And I guess, how do we think about the magnitude of the impact next year on new patients on therapy from that? Thanks.

What is left to be done to get patients on in February under the AP, one systemic France I guess, how do we think about the magnitude of the impact next year on new patients on therapy from that thanks.

Yes, Jennifer.

Speaker 4: Jennifer, first? Yeah. So I would say that the timing is variable because the situation is also variable physician by physician.

So I would say that the timing is variable because the situation is also variable physician by physician.

Speaker 4: Some were physicians that had more than one patient, even prior to our launch.

Some were physicians that had more than one patient even prior to our launch.

Speaker 4: and that could take time just in terms of that patient coming back in to have a dialogue with the physician just in terms of interest to get onto therapy.

That could that could take time, just in terms of that patient to me back in.

To have a dialogue with the physician just in terms of interest to get onto therapy.

Speaker 4: And then there's also others that, you know, through our education efforts, they diagnose the first patient and, you know, similar to rare disease. Once you find that first patient, it's no longer this unicorn that's not in your practice, but something that you need to pay attention to just in terms of differential diagnosis of additional patients that have come to them in the past. We'll be coming to them in the future to remember that, you know, understanding the different symptoms to get to a clinical diagnosis is important to bear in mind.

And then there are also others that.

Through our education efforts day diagnosed the first patient.

Similar to rare disease. Once you find that first patient that no longer the corner that's not in your practice.

Something that you need to pay a question just in terms of.

<unk> diagnosis.

Self pay churn.

<unk> has come to them in the past or will be coming to them in the future.

Remember that.

I understand.

Sometimes they get to a clinical diagnosis is important to bear in mind.

Speaker 4: So it's a bit of a mix of both of them, and both of those also impact the timing in terms of the first to the next prescription.

So it's a bit of a mix of both of them and both of those also impact the timing in terms of the first to the next prescription.

Speaker 3: And Jan, maybe just a little bit more color on the process for the AP1 HO, and then how should we think about 2024?

Okay.

Maybe just a little bit more color on the process for the <unk> and then how should we think about 2024.

Speaker 5: Yes, sure. So first of all, of course, we are very pleased with this achievement. It's very rare and to get such a pre-MEA approval in France based on phase 2 data. And to be more precise, there are just two rare disease therapies with such status in France.

Yes, sure. So first of all of course, we are very pleased with this achievement.

It's very rare.

To get such a pre NDA approval in <unk> based on the phase two data and to be more precise down just two rare disease therapies with such status influence. So I've mentioned, we are now working through the process and.

Speaker 5: So as mentioned, we are now working through the process and to answer to your question.

<unk> for your questions.

Just programs.

Speaker 5: of administrative requirements, so we get it granted and now we have to go through a few steps.

Administrative requirements. So we get it granted no we have to go through a few <unk> one is.

Speaker 5: One is a agreement in terms of data collections with the centers of reference and the French FDA.

Agreement in terms of the debtor collections uses in terms of reference and differentiation.

Speaker 5: And the second is also the Center of Reference are setting up.

And the second is also central the preference of setting up mid teens.

Speaker 5: multidisciplinary decision-making meetings.

Decision, making meetings to reuse of patient cases, so and Thats usual rules and we have been through that with <unk> and also with DBS. So we know it works and it is the same for ultra rare disease drug so those tests.

Speaker 5: to review the patient cases. So in that view, you know, then we have been through that with PonciliPARF and also with BBS. So we know how it works. And it is the same for all the rare diseases drugs. So those tests are currently, we are working on them.

Currently we are walking walking on zoom for.

Speaker 5: For your second question in terms of number of patients, it's a bit difficult to say today what we know because we have been.

For your second question in terms of nimble efficiency to be difficult to see today, what we know because we have been.

Speaker 3: It has been known and we have been reached out by a lot of experts, and we are working also with experts. There are a lot of patients who are in need, and we have a lot of physicians interested to treat these patients. So as soon as we will have these administrative requirements ready, we will have the first prescriptions, and the first patients will be treated. Still difficult to say how much in 2024. More to come on that, Derek. We're learning here.

It has been known and we have been reached out by a lot of experience and we are working on so we know a lot of patients in need.

And we have a lot of physicians to treat these patients who have soon as we will have this at least for two requirements ready.

We will have some sales prescriptions and because patients will be treated still difficult to see how much in 2024.

The more to come on that Derik, we're learning here.

Alright, thank you.

Thank you one moment our next question.

Yeah.

Speaker 1: And our next question comes from Dagon Ha from Sifu. Your line is open.

And our next question comes from the line of Dae Gon Ha from Stifel. Your line is open.

Speaker 8: Hey, good morning, guys. Thanks for taking the question and congrats on the progress, two from us, one on the commercial and one on a show. So on the commercial front, I thought it was interesting. You pointed out the divergence between your experience versus cribs.

Hey, good morning, guys. Thanks for taking my question and congrats on the progress to from US one on the commercial and one on <unk>. So on the commercial front I thought it was interesting you pointed out the divergence between your experience versus cribs. Since you do have a significant proportion of prescribers being Pete and I was wondering.

Speaker 8: Since you do have a significant proportion of prescribers being peed and dose, I was wondering what kind of strategy are you thinking in terms of penetrating that segment to the market I guess a little bit more aggressively and have more representation in your prescriber base. And just to clarify on the nomenclature is it...

What kind of strategies are you thinking in terms of penetrating that segment of the market I guess, a little bit more aggressively and have more representation in Europe prescriber base and just to clarify on the nomenclature is it you're going guidance is going to be on prescriptions, because you've previously talked about start forms I just wanted to make sure that that's what we should be looking at next.

Speaker 8: Your going guidance is going to be on prescriptions because you've previously talked about start forms. I just want to make sure that's what we should be looking at next.

And then on eight show if you can maybe go into the screen failure commentary a little bit more David I guess, what are the dynamics youre seeing with regards to enrollment and how are you balancing rapid enrollment to reach that <unk> completion date, and ensuring you avoid any compromises along the way. Thanks so much.

Speaker 8: And then on H-O, if you can maybe go into the screen failure commentary a little bit more, David. I guess what are the dynamics you're seeing with regards to enrollment and how are you balancing rapid enrollment to reach that 4Q completion date and ensuring you avoid any compromises along the way? Thanks so much.

Hi, Jennifer.

So sorry for clarification.

Speaker 4: So, I'm sorry for clarification, the.

Speaker 4: The metric is the stop forms that we are focused on and they're new stop forms so not repeat scripts for the same patient.

The metric is.

What forms that we are focused on and are.

Their new start.

Not repeat scripts for the same patient.

Speaker 4: And regarding your question regarding the CRIBS piece, you know, for sure, the pediatric endocrinologist that is a treater and prescriber for MCIVRI remain a key specialty focus of our teams, and that's one that our, you know, territory managers are calling on.

Regarding your question regarding the cribbs.

For sure the pediatric endocrinologists that treater and prescriber.

And as Jeffrey remain a key specialty focus of our teams and.

And Thats why our territory managers.

Our calling on.

Speaker 4: But we also supplement their efforts just with a lot of non-personal promotion efforts. We knew up front that when we took a look at that CRIBS distribution of 80 percent less than 18 years of age, that these patients do not die at 18 years of age, and so we knew that there were a lot more patients either that were diagnosed and lost in the system, and oftentimes they may stop going to specific physicians. So there was quite a breadth in terms of different specialties that we wanted to educate to, you know, get to those adults, which I think has been helpful in addition to the on-ground field team efforts in terms of getting to the...

But we also supplement their efforts just with a lot of non personal promotion efforts, we knew upfront that when we took a look at that credit distribution of 80% less than 18 years of age.

Patients do not die at 18 years of age and so we knew that there were a lot more patients either that were diagnosed the loss in this sort of stem and oftentimes they may stop going too specific at this time.

There was quite a.

Abreast in terms of different specialties that we wanted to educate.

Two.

Get to those adults, which I think has been helpful. In addition to the on ground sales team efforts in terms of getting to the.

Speaker 4: to a distribution of patients that feel a bit better.

Tim a distribution of patients that Gil.

Speaker 4: more right just based off of the, you know, the age distribution of BBS patients in general.

More right just based off that.

Its distribution of Bbs patients in general.

Great. Thanks, and then dig in on the HR the screen failure rate so.

Speaker 3: Great, thanks. And Dagon, on the HO, the screen failure rate, so just to put that number a little more specific.

To put that number a little more specifically I think we've had for screen failures with over two thirds of the patients screened or actively in screening and even in that small number of screen failures. We've had at least one patient who has been brought back to re screen.

Speaker 9: I think we've had four screen failures with over two thirds of the patients screened are actively in screening.

Speaker 9: And even in that small number of screen failures, we've had at least one patient who's been brought back in to re-screen. There was a minor issue, and so they may ultimately turned out to be not a screen failure.

There was a minor issue and so they may ultimately turned out to be not a screen failure and the reason. It's so low is when we started this effort and we're looking picking the sites, we've probably had.

Speaker 9: And the reason it's so low is when we started this effort and we're looking and picking the sites, we probably had

Speaker 9: a total, the sites themselves had their list of patients which were easily more than two times the number of patients we needed to enroll in this trial. So they were all starting with a list of patients. They weren't looking. And then they, as I said, they knew the entry criteria. They don't want to disappoint patients. So they're bringing in patients who they feel, based on their knowing the patient.

A total of the sites themselves.

Cells had their list of patients which were easily more than two times the number of patients we needed to enroll in this trial. So they were all starting with a list of patients. They werent looking and then.

They knew the entry criteria, they don't want to disappoint patients so they're bringing in patients who they feel based on knowing the patient that they meet entry criteria and therefore, the risk of screen failure is low so im pushing to enroll this trial have no fear. If you will that we're going to have a low quality patient enrollment.

Speaker 9: that they meet entry criteria, and therefore the risk of screen failure is low. So in pushing to enroll this trial, I have no fear, if you will, that we're going to have a low-quality patient enrollment, meaning people are working on the edges. I think we're going to have patients who very much meet entry criteria because there's, like I said, a good selection of patients who are.

People are working on the edges I think we're going to have patients who very much meet entry criteria because there's.

Like I said, a good selection of patients who are eager to get out.

Awesome. Thanks, very much yeah that helps thank you so much.

Speaker 8: Awesome, thanks very much. Oh, yeah, that helps. Thank you so much. Great.

That's great.

One moment our next question.

Okay.

Speaker 1: And our next question will come from the line of Jeff Hung from Morgan Stanley .

And our next question comes from the line of Jeff Hung from Morgan Stanley. Your line is open.

Speaker 12: Thanks for taking my questions. You talked about a couple of patients that didn't meet the 5% weight loss who are going through the appeals process. Do you have a sense for the proportion of BDS patients that discontinue based on the one-year recommendation? And then how does that compare to what you've seen for the other approved mutations?

Thanks for taking my questions you talked about a couple of patients that didn't meet the 5% weight loss, we're going through that would be helpful. Peels process do you have a sense for the proportion of Bbs patients that discontinued based on the one year recommendation and then how does that compare to what you've seen for the other approved mutations and then I have a follow up.

Okay.

Speaker 4: So, the, the patients that are referred to just in terms of not meeting the requirements for the 5% weight loss is really at this point just a handful of patients. So, not many that fall into that category, but even so, you know, because of the, the belief from the physician as well as the desire for the patient to remain on therapy. We are helping them through the appeals process, just in terms of trying to maintain them in terms of authorization there.

So the.

Patients that I referred to just in terms of not meeting the requirements for the 5% weight loss is really at this point just a handful of patients.

Not many that fall into that category, but even so.

Because of the delays from the physician as well as the desire for patients to remain on therapy, we are helping them through the appeals process just in terms of trying to.

And then in terms of authorization there.

Speaker 4: You were asking a separate question, I believe, on the discontinuations on therapy overall.

Youre asking a separate question I believe on the discontinuation on therapy overall.

Speaker 4: So we now do have a larger number of patients who have been on therapy for a longer period of time since our launch.

So we.

We now do you have a larger number of patients who have been on therapy for a longer period of time since our launch and the discount rate to date has crept up a bit from the 10% that we had outlined to 13% of our axis.

Speaker 4: And the discount rate to date has crept up a bit from the 10% that we had outlined to 13% of Rx's.

Speaker 4: The reasons why have not really changed just in terms of, you know, why they are discounting it. I would characterize it as almost half of them for more personal reasons and about half of them for adverse event reasons.

The reason why have not really changed just in terms of why they are discounting it.

Characterize it as.

Almost half of them for more personal reasons.

About half of them for adverse event rate.

Speaker 4: You know, that it is still an opportunity, though, for our teams, just in terms of follow up, because the hyper fascia for those who are responding does come back quickly and they may consider coming back on therapy in the future.

It is still an opportunity, though for James just in terms of follow up because the hyper phase.

For those who are responding does come back quickly and they may.

Consider coming back on therapy in the future.

Speaker 12: Great. Thanks. And you mentioned that about half or upwards of half of discontinuations are proportional reasons. Do you have any data indicating the proportion of those who discontinue who are coming back to be treated again? And then my follow-up question was that for the prescribers who have not written more than one prescription, are the main reasons because they're relatively new to prescribing set melanotide or they don't have additional BBS patients or maybe something else? Thanks.

Great. Thanks, and then you mentioned that about half are upwards of half a discontinuation for personal reasons do you have any data, indicating the proportion of those who discontinued were coming back to be treated again and then my follow up question was that for the prescribers, who have not written more than one prescription are the main reasons because they are relatively new to prescribing <unk> Atlanta tied or they don't have additional bbs patients.

Or maybe something else. Thanks, so much.

Speaker 4: Yeah, so I'll answer the last question first. So the reasons are variable, they may only have one patient, you know, just in terms of a lot of our scripts also is...

Yeah. So I'll answer the last question first.

So the reasons are variable they they may only have one patient.

You know just in terms of a lot of our spreads also is.

Speaker 4: You know, patients who are been on therapy for a shorter period of time. So that may be the case just in terms of the reasons for the 1 script and it may also be the case just in terms of position having 2 patients for that patient either has not come in or it's not ready to initiate therapy.

No.

Patients who are been on therapy for a shorter period of time, so that may be the case.

In terms of the recent further one script.

May also be the case just in terms of position, adding two patients for that patient.

And then or is not ready to initiate therapy.

Speaker 9: In terms of the other questions, personal patients in the personal reason group and have any of those come back or

In terms of the other questions personal basins in the personal reason group and have any of those come back or likely to come back.

Speaker 4: I see, we don't have enough data right now in terms of that point just to outline or I don't have it on me right now. I do know that there have been a couple of patients who discontinued and wanted to read.

And we don't have enough data right now in terms of to that point just to outline all I don't have it on me right now I do know that there have been.

A couple of patients who discontinued and wanted to re start therapy because of the hyperphagia, but it's only a handful at this point of time.

Speaker 4: start therapy because of the hyperfascia, but it's only a handful at this point in time.

Speaker 9: The other thing I'm Jeff just on the 5% in general in terms of how people experience some benefit. This is a group, because of their underlying mechanism.

The other thing Jeff just on the 5% in general in terms of how people experience. Some benefit this is the.

Group.

Because of their underlying mechanism.

Speaker 9: their inability to respond to some of the other therapy, certainly diet and exercise and some of the other medications isn't there. And so simply stopping the weight gain is a major advantage. And then as Jennifer said, the overwhelming story we've heard as we recounted on all these calls is just the quieting of their hyperphagia ability that leave the table, leave food on the table is a pretty significant change for them.

Their inability to respond to some of the other therapy, certainly diet and exercise in some of the other medications isn't there and so simply stopping the weight gain is a major advantage and then as Jennifer said the overwhelming story, we've heard as we recounted on all these calls is just the quieting of their hyperphagia ability to leave the table.

Food on the table.

A pretty significant change for them.

Great. Thank you.

Great. Thank you one moment for our next question.

Speaker 1: And the next question from Flannin, a Whitney Asian from Kenned Court Genuity United.

And our next question comes from the line of Whitney <unk> from Canaccord Genuity. Your line is open.

Speaker 13: Hey, morning guys. Going back to France and thinking particularly about BBS, I can you remind us, I guess, where you are in the conversations for a sort of regular way reimbursement. I know the logistics of the early access are slower than presumably it would be once you can flip over to regular reimbursement. I'm just curious where you are at the timing around.

Hey, good morning, guys going.

Going back to France, and thinking, particularly about Bbs I can you remind us I guess, where you are in the conversations first sort of regular way reimbursement I know the the logistics of the early access are.

Slower then presumably it would be.

Once you can flip over to regular reimbursement just curious where you are or the timing around that.

Speaker 5: Sure, yes, sure. So we have started the pricing negotiations with the pricing committee. It usually takes between nine months to two, three years.

Sure, Yes, sure. So we have started the pricing negotiations with.

<unk>.

It usually takes between nine moves to <unk>.

Speaker 5: we think that we will have an end mid-next year, something like that. So we are in the third round, technically. And so far, it has been good from both an understanding of the unmet medical need and the benefit from MCV and also the relationship and the openness and the transparency in the discussion. So we are at the beginning for something that should end mid-next year.

We have seen is that we will have and then.

Next year something like that so we are in the cell drone technically and so far it has been good.

And then just ending of unmet medical need.

Terrific.

Sebree and also.

Sure Steve.

Openness and transparency in the discussion. So we are at the beginning of something Thats through the end of mid next year.

Speaker 13: Perfect, thanks. And then on 718, I guess, can you remind us, I know you've talked about it being more potent in terms of its activity at the receptor, is the idea behind the TPP there better weight loss, kind of efficacy picture or lower dosing, safety profile, or just how you're thinking about that?

Perfect. Thanks, and then on 718, I guess can you remind us I know you've talked about it being more potent.

In terms of its activity at the receptor is the does the idea behind the TPP there.

Better weight loss kind of efficacy picture or lower dosing safety profile or just how youre thinking about that thanks.

Speaker 9: Yeah, it's actually not, it's not more potent technically in terms of activity at the receptor, but it's more specific.

Yes, it's actually not it's not a more potent technically in terms of activity at the receptor, but it's more specific so that's the major feature here, which is our current set of Atlanta tied as you know we hit both the emcee for an AMC, one with Chi which is contributes to the hyperpigmentation and so we removed.

Speaker 9: So that's the major feature here, which is our current set melanocytes. As you know, we hit both the MC4 and the MC1, which contributes to the hyperpigmentation. And so we removed that.

That two of them.

Speaker 9: It's very specific. So the probability we will have hyperpigmentation is low. And we have animal data to support that. So that's the major advantage here. And then, of course, it's weekly. So we have convenience. And, of course, we have an IP protection that goes out to 2041. And so those are the major elements that make this a really critical program for us.

It's very specific so the probability we will have hyperpigmentation is low.

Animal data to support that so that's the major advantage here.

And then of course, it's weekly's, we have convenience and of course, we have an IP protection.

Protection that goes out to 2041 and so those are the major elements that make this a really critical program for us.

Great. Thanks very much.

One moment our next question.

And our next question comes from the line of Joseph Stringer from Needham Your line is open.

Speaker 1: And our next question will come from the line of Joseph Stringer from Needham. Your line is open.

Speaker 14: Hi, good morning. Thanks for taking our question with regards to the upcoming phase 3 readout and the 2 to 6 year old DBS patients. Just curious. You're all the patient identification work that you've done for DBS today in the US. How many. Do you estimate are in that 2 to 6 year old range and what do you expect to see sort of a bullet or how do you think that would impact. The launch and when the label is expanded to include those patients.

Hi, Good morning, Thanks for taking my question with regards to the upcoming phase III readout in two to six year old Bbs patients. Just curious you all the patient identification work that you've done for Bbs to date in the U S. How many do.

You estimate are in that 2% to six year old range.

Would you expect to see sort of a bolus or how do you think that would impact the launch if and when the label is expanded to include those patients.

Speaker 9: Yeah, so maybe I'll lead and Jennifer can add anything here. I think, A, it's not a large number of patients. What we see is a higher hit rate when a two to six-year-old group is screened. That very early onset, you know, obviously the history is very good there. They have true early onset obesity. And so the screening hit rate is a little bit higher in that group. And so that's an important part of this, number one. But it's not a large number of patients. So there won't be a big impact to the overall patient population. But I think what's really important about, you know, this, A, it's a genetic disease. You want to treat all patients. Getting in early is hugely important. So medically, I think this is very important. And it also builds, I think, an increasing recognition about what differentiates these diseases and the need to manage and think about them differently. So it will help us in different ways, but the absolute number will not be low.

Yes, so maybe I'll lead and Jennifer can add anything here I think.

It is not a large number of patients what we see is a higher hit rate when a 2% to six year old group is screened that very early onset of Hispanic.

Obviously the history is very good there they have true early onset obesity and so the screening hit rate is a little bit higher in that group and so that's an important part of this number one but it's not a large number of patients. So there won't be a big impact to the overall patient population, but I think what's really important about.

<unk>, it's a genetic disease you want to treat all patients getting an early hugely important so a medically I think this is very important and it also builds I think an increasing recognition about what differentiates these diseases and the need to manage and think about them differently. So it will help us in different ways, but the absolute number will not be large.

Great. Thank you for taking my question.

Speaker 15: Great. Thank you for taking our question.

Sorry.

Speaker 1: Thank you. I'm not showing any further questions in the queue. I'd like to turn the conference back to David Meeker, Chairman, CEO , and President for closing remarks.

Thank you I'm not showing any further questions in the queue I'd like to turn the conference back to David Meeker, Chairman CEO and President for closing remarks.

Speaker 9: Thanks, Victor. So, thanks again, everybody for tuning in and excited about the progress we're making, as you've heard, and we very much look forward to seeing everybody or hopefully people will be able to either show up in person or call into our R&D day on December 6th, where

Thanks, Victor so thanks again, everybody for tuning in and excited about the progress, we're making as you've heard and we very much look forward to seeing everybody or hopefully people will be able to show up in person call into our R&D day on December six where we have update.

Speaker 9: Updates, we'll have a hypothalamic KOL from our hypothalamic obesity world so that will be interesting in addition to the data updates on our 718 program, the daybreak trial and we will provide the data on the pediatric trial at that time.

<unk> will have a hyperplastic.

Kols from our Hypovolemic obesity world. So that will be interesting. In addition to the the data updates on our <unk> program. The DAYBREAK trial, we will provide the data on the pediatric trial at that time.

So with that we'll sign up a good day.

Speaker 1: This concludes today's conference call. Thank you for participating. You may now disconnect. Everyone have a great day.

This concludes today's conference call. Thank you for participating you may now disconnect everyone have a great day.