Q2 2022 Rhythm Pharmaceuticals Inc Earnings Call

Welcome to the Rhythm Pharmaceuticals' second quarter 2022 earnings conference call.

You know, that's our starting point going in.

Two from us on the BBS launch.

At this time, all participants are in a listen-only mode.

We'll see where that goes.

Just to clarify, you previously mentioned you have 350 identified and diagnosed BBS patients in the U.S.

Do the 50 prescriptions, the 50 TRX, is that a part of the 350?

And then secondly, I know it's early on in the launch, but have you encountered any prior authorization or requirements, or genetic testing confirmation requirements from those 50 prescriptions written to date?

Thank you.

The conference will begin shortly to raise your hand during Q&A you can dial star one one.

[music].

After the speaker's presentation, there will be a question-and-answer session.

And as we said, I don't think it needs to be a large trial.

Thanks for the question.

Okay.

Thank you.

To ask a question during this session, you will need to press star 1-1 on your telephone keypad.

We know just mathematically it doesn't need to be a large trial given the effect size that we've seen.

So regarding the patients that we've received scripts from, I would say that it comes from a mix of different groupings.

Gentlemen, and thank you for standing by welcome to the rhythm Pharmaceuticals second quarter 2022 earnings Conference call. At this time all participants are in a listen only mode. After the speaker's presentation. There will be a question and answer session to ask a question. During this session you will need to press star one one on your telephone keypad at this time I would like.

So, it doesn't require so many patients to prove statistically efficacy, safety, you know, the size of the trial to support the safety of the drug and its new indication.

Certainly there are physicians with patients that our territory managers have been engaging with up front that have written scripts. So some of them come from those physicians.

But we were also excited because within the syndication, we also heard and now saw that there were patients who also heard, about the approvals, and that can happen in various different ways.

But, you know, we had ongoing non-personal promotions, both ACPs as well as patients, to educate them on disease, and also share their news. We had engagements with the patient associations where they were also very happy to share the news of approvals. So, you know, word gets out in these small communities as new therapies are finally available for these patients.

To turn the conference over to Mr. Dave Connelly, Sir please begin.

Thank you.

<unk> head of IR and corporate communications gear at rhythm Pharmaceuticals for those of you participating via conference call. The accompanying slides can be accessed in control by going to the events section of our investors page on our website at IR dot rhythms, TX dot com.

At this time, I would like to turn the conference over to Mr. Dave Connolly.

That'll be a point of discussion.

And that was also another source just in terms of either patients are actively going to their physicians seeking treatment, or other physicians who heard about it and had patients that are now part of the RISM home in terms of our CRM and outreach efforts.

Sir, please begin.

So, I mean, those are the elements.

Regarding the prior authorization, very aligned with the current clinical practice for BBS.

I mean, we've been through these trials before with MC4 agonists, semilanotides.

Thank you.

I'm Dave Connolly, head of IR and corporate communications here at Rhythm Pharmaceuticals.

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 report on file with the SEC.

For those of you participating via the conference call, the accompanying slides can be accessed and controlled by going to the events section of our investors page on our website at ir.rhythmtx.com.

BBS is a clinical diagnosis that was also what was outlined in our PI.

I'll remind you that this call contains remarks concerning future expectations, plans, and prospects, which constitute forward-looking statements.

So, to date, we really have not seen there being a genetic requirement in terms of genetic confirmation as part of the PA.

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 report on file with the SEC.

In addition, any forward looking statements represent our views as of today, only and should not be relied upon as representing our views as of any subsequent dates.

It's fair to say that they very much stick to the label.

In addition, any forward-looking statements represent our views as of today only and should not be relied upon as representing our views as of any subsequent dates.

Yes.

We specifically disclaim any obligation to update such statements.

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

Typically disclaim any obligation to update such statements.

On our call today and here with me in Boston are David Meeker, chair, president, and chief executive officer of Rhythm, Jennifer Chen, executive vice president, head of North America, and our chief financial officer, Hunter Smith.

One other clarification, Joey, just the 350, just to remind you, that was 350 plus back in February.

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

Obviously, we've continued to identify more patients since then.

The short answer is not so controversial, but there's two or three really important pieces we'll need to iron out.

And to reinforce what Jennifer said, no, it's a quarter-ish, you know, that 22% of these current early scripts that are coming in are not part of that group.

On our call today and here with me in Boston are David Meeker Chair, President and Chief Executive Officer.

Perfect.

So, you know, that does speak to the fact that, you know, once you have a therapy, people do reengage with the healthcare system who may have been sitting on the sidelines and not in your line of sight.

Jennifer Chen Executive Vice President head of North America, and our Chief Financial Officer, Hunter Smith, and calling in from France, as John <unk> Executive Vice President and head of International.

Thanks for taking our questions and congrats again on the progress.

Great.

And calling in from France is Jan Mezebro, executive vice president, head of International, today.

Thank you.

Thank you for taking our questions.

And our next question or comment comes from the line of Derek Archila from Wells Fargo.

Thank you.

With that I'll turn the call over to David who will begin on slide five.

Mr. Archila, your line is open.

Our next question or comment comes from the line of Michael Higgins from Lakenburg-Fowlman.

Thank you, Dave and thanks to all of you for tuning in this morning.

Hey, good morning.

Stand by.

Another strong quarters between the regulatory approvals siting these data readouts and extending our cash runway with a royalty financing deal all of that speaks to a very successful.

Congrats on the quarter.

Thanks, guys.

Hopefully you can hear me here.

In the past few months, so we're very eager to share our update on the first six weeks of the ancillary Bbs launch here in the U S and the ongoing progress we continue to make in our international markets. So let's start on slide five.

A lot of things to be excited about here.

So, just a few questions from us.

With that, I'll turn the call over to David, who will begin on slide five.

Maybe to start, can you just help us understand where you are in your thinking of having tens of patients on therapy in the first couple of years for the POMPSI, PCSK1, and the LEPR patients?

Congrats on the terrific performance so far this year that we're seeing.

Thank you, Dave, and thanks to all of you for tuning in this morning.

It's been another strong quarter between the regulatory approvals, exciting new data readouts, and extending our cash runway with a royalty financing deal. All of that speaks to a very successful recent past few months.

We are executing on our global strategy, we are developing a precision medicine and surgery for tier one met medical needs. Yes. There are a growing number of options for the management of obesity, but there's also a growing understanding that not all of the city has the same obesity is a disease, but it's not one disease. It has many diseases and optimal medical management starts with under.

So we're very eager to share our update on the first six weeks of the Incivory BBS launch here in the U.S. and the ongoing progress we continue to make in our international markets.

You put out some new numbers, you know, I guess in Europe, of patients you've identified, and then also in light of the news in France, it's seemingly that those are all positive.

I want to ask some questions on BVS, but first I think the next driver being MC4, maybe we can spend some time on that.

Let's start on slide five.

When should we look for data?

How many patients are we looking for?

Standing, which disease, you have and then matching it with the appropriate there.

We're off to a really good start with Bds and Jennifer will provide much more color I have been clear leading up to this moment that launches in general are difficult to forecast rare disease launches, even more difficult. So don't judge us on the first six months.

That said, we do think Thats, a very good start increasing the strength of our conviction and the total opportunity.

The major question and any rare disease opportunity as well and you find the patients while they seek therapy will doctors prescribed for the system reimbursed. It is early you can't run the numbers, but the short answer to all of those questions is yes.

Patients are there they want the therapy doctors are prescribing and our early experience with the reimbursement processes positive. This start is reflective of all the good work done leading up to launch.

And Europe Yamal update you on our steady I'll call it remarkable progress in Europe .

Getting approvals at better than average timelines for each of these health care systems. The international markets in Europe , specifically are incredibly important opportunities for us as we have said many times and you will hear from them from Jan today Europe is better organized more patients identified in those health care systems are embracing subsidiary.

Finally, we have much still to do on the development side of the equation. We're obviously excited about the recently released hypothalamic obesity data, which I will discuss briefly on subsequent slides and all of our other development programs are progressing well.

Can you provide any feedback for us from this open-label trial and remind us again how many ID'd in the community?

I am moving to slide six I'm going to use the next three slides remind you why we're excited about hypersound with obesity. This slide is a brief primer that Dr. Bruce <unk> used on a prior call to explain the anatomy tumors are rising and the junction between the pituitary in the hypothalamus potentially can injure both two and three in the hydropower.

Thanks.

Yeah.

Thanks.

The MC4, so our goal is to put that out again in association with a medical event in the fall here.

Since this is an area referred to as <unk> ouch.

We haven't specified the exact timing of that, so we're still working that out.

<unk> with tumors in that area are likely to require replacement hormones related to pituitary injury and about 50% will go on to develop hyperkalemia obesity as a consequence of injury to the hypothalamus itself, either due to the tumor and or to the surgery and radiotherapy used to treat the tumor or in rare situations Klamath.

This is one of the more common, the most common genetic driver, monogenetic driver of obesity.

But the big question we've always had with that is, you know, if you have a variant, genetic variant in the receptor affecting the receptor itself, do you render the receptor nonresponsive?

And so what you'll hear is our attempt to divide those groups between those who are non-rescuable, where the receptor, where their variant renders that receptor nonresponsive, from those who might have a response to a certain melanotype.

So, again, more to come on that, but look for some update here later in the fall.

Tori condition or trauma.

Patients with hyperkalemia obesity have a classic presentation that clearly differentiates them from patients with a tumor that does not involve the hypothalamus to the same degree if you do not develop hyperplastic obesity patients experience rapid weight gain children literally exploding off their growth chart and I remind you that example that Dr. Bruce showed on the last.

I think that was your only question so far.

Just to follow up on that, the number of ID'd patients.

Thanks.

Call and about 50% of these patients will develop the classic hyper phase will be associated with MSC for pathway diseases, but not all patients and strikingly the majority of these patients with HBO become less active in complaining theyre energy expenditure, both resting energy expenditure and activity levels are low.

Well, the number is very large.

Interestingly the clinical presentation. The apparent response to certain Atlanta tied on top of supporting preclinical data.

Two a potential unifying hypothesis that impairment to the <unk> pathway with both an increase in Hungary, and a decrease in energy expenditure is a critical element in the development of Hypothermic obesity.

On slide seven is the interim results, we shared last call. The first 11 patients in their strike not so much for the extent of the weight loss in a short period of time, which is quite good but for their consistency.

All 11 patients, including the two patients who discontinued last week, the clinical presentation, which includes rapid weight gain as temporary associated with injury to the hypothalamus new development of hyperphagia.

And probably more importantly here the change in energy expenditure all point to impairment of the <unk> pathway.

I mean, but, again, I'm not, you know, about 6% of patients on your screen might have a variant for MC4-R.

Now we have evidence that a precision medicine targeting the <unk> receptor results and consistent clinical improvement that consistency, which suggests that morning on Hittite. In addition to working through residual <unk> receptors in the hypothalamus is likely working to receptors outside the hypothalamus, which interact with the autonomic nervous system and play a critical role in energy expense.

Sure.

Slide eight.

The real issue is how many of those might be responsive versus nonresponsive.

So this is a rare disease, but unlike many rare diseases has a number of advantages with regard to our ability to identify and reach patients. The patients are diagnosed they know where they are this is a very well understood complication of these tumors and their management.

So, based on our preclinical assay, or our assay, you know, we've done an estimate based on our sequencing data that about 15,000 patients in the U.S. have rescuable variants in the MC4-R.

But that is not an identified patient number, that's a genetic epi number.

And the vestibule part of that is defined by a preclinical assay, so our challenge and, goal is to look and try to understand whether that predicts vestibulity, so more to come on that.

That's terrific.

Our best understanding of the overall prevalence is about five to 10000 with the range, reflecting uncertainty about the population who was out more than 10 years.

I did have a question on BBS, but just to follow up from that, another question we had, coming into the call was the number of screenings that you've been able to perform this year and how that's been trending versus prior years.

Median survival is on the order of 20% to 25 years. There is no reason to believe that 30 year old patient whether tumor resected at age five we're not solely seeking help for their HLA.

Yeah, I mean, we're on track.

We'll screen between 10,000 and 15,000 patients overall this year.

The yearly incidence assuming about 50% of patients with these benign intracranial tumors will develop H O is about 500 per year in the U S.

As always we have shared use epidemiology data, but it is not fundamentally different in Europe and may not be so different in Asia. Although we are early in our assessment.

So our next steps the goal is to present, the full 18 patient cohort data at a fall meeting we've requested our end of phase two meeting with the FDA and we look forward to initiating the phase III trial as early as possible in 2023.

The frequencies that we've talked about for each one of our genes has been remarkably, consistent, so again, that's been quite reassuring.

Slide nine.

In summary, why is <unk> so important.

What it tells us is that we're not screening every patient with obesity, which is actually, not what we'd want to do, that we really are, the healthcare providers really are targeting those patients who have a history of early-onset obesity, you know, plus minus a stronger history of hyperphagia.

As we expand our scope from genetically impaired defects in the AMC four pathways to genetic and acquired forms. So one is it reinforces the importance of the <unk> pathway is a key driver in some forms of obesity reminding you again obesity is not one disease, but many diseases.

So we are executing on our global strategy.

So I think we're getting consistent screening with pretty consistent results.

We're developing a precision medicine in Incivory for two unmet medical needs.

Thanks.

And yes, there are a growing number of options for the management of obesity, but there's also a growing understanding that not all obesity is the same.

And then my second question is, just on the BBS launch, can you talk about the conversion you're seeing for the scripts written for patients that are actually receiving treatment?

And then one last one, if I could, here for Jennifer, of these new docs, 22% or so, I, think is what I heard, that were not prior targeted.

<unk> seven <unk> as a targeted medicine to the <unk> receptor and provides key insights into the underlying pathophysiology of H O.

So that's telling you not just about receptivity, but what can that do for you in terms of your, strategy in trying to reach out to more of these?

Three it provides potential evidenced further supporting the importance of the energy expenditure side of the equation further validating the role of an <unk> agonist and the management of keep what pathway diseases.

Obesity is a disease, but it's not one disease. It is many diseases. And optimal medical management starts with understanding which disease you have and then matching it with the appropriate therapy.

I know it might be early, but any thoughts there would be helpful.

Have you had discussions with these docs to find out how they found out about an incivory, in BBS?

Before.

How does that adjust your marketing going forward?

Potentially incredibly meaningful opportunity for rhythm patients are identified in our genetic testing as required patients are engaged with the system requiring specialist care in most cases endocrinologist to manage the other complications of Purion hyperkalemia injury.

We're off to a really good start with BBS, and Jennifer will provide much more color.

Yeah, maybe I'll take a comment on the first question and Jennifer on the second BBS conversion.

Thanks.

I have been clear leading up to this moment that launches in general are difficult to forecast.

So, we're sticking, I mean, the tens of patients I think is highly descriptive.

All right.

The unmet medical need is high there is no approved therapies, which exist although many of them trade.

Rare disease launches even more difficult, so don't judge us on the first six months.

It's consistent with where we are today.

So on slide 10, here's our pipeline our pipeline is progressing with multiple potential meaningful contributors to the portfolio of addressable <unk> pathway diseases and a specific note we announced today completion of enrollment in our <unk> study with an expected readout in mid 2023. This trial has enrolled and mix of patients with pumps, the left bar and Bebe.

That said, we do think this represents a very good start, increasing the strength of our conviction and the total opportunity.

The major question in any rare disease opportunity is will it work?

Can you find the patients?

Will they seek therapy?

So as we receive scripts, we also are able to understand the prescriber and certainly, that is added in terms of targets for our TMs to go out and educate and also make sure that there's ongoing engagement with them throughout the process of patients are also being initiated on therapy.

Yes between the ages of two and six and this is important as we know from our genetic screening genetic diseases by definition often start manifesting at an early age. Many of these patients are being screened and our early data suggests a somewhat higher probability of a positive genetic test in this age group patients know their child has a problem in Mexico.

Will doctors prescribe?

So they will always be added just in terms of our sphere.

Will the system reimburse?

I think the thrust of your question was, how does the approval in Europe impact that?

We do expect that, you know, on top of the efforts of the TMs on ground, we are going, to come across additional physicians who have patients and are, you know, maybe interested in terms of prescribing this therapy for their patients just because of our broad based non-personal promotion efforts, which expands our reach beyond, you know, the ability of our TMs on ground.

Jan has highlighted the fact that we have about 100 patients identified so far across the major markets, and those major markets are coming on. So, obviously those patients will contribute.

It is early, you, can't turn the numbers, but the short answer to all those questions is yes. Patients are there, they want the therapy, doctors are prescribing, and our early experience with the reimbursement process is positive. This start is reflective of all the good work done leading up to launch.

It's still going to leave us in the tens, hopefully getting up into the high tens in that scenario.

So we expect that the prescriber base is going to continue to evolve as we move forward and, as additional physicians and patients learn about the benefits of incivory for this patient population.

But I wouldn't, you know, change our overall positioning around this initial bilayer with POMSI-LEPR group.

With that I will turn it over to Jennifer to talk about our encouraging start in the U S et cetera.

Incredibly fortunate in hindsight that we started with that, largely because it's taught us so much about this market and it's allowed us to engage with the healthcare systems in a very constructive, non-threatening way, if you will.

And maybe just one comment on the role of the patient themselves and the social network.

Thank you David.

Yeah.

I'll be starting on slide 12 today.

So we are really proud to lead the development and brand in the region.

Sure.

February is the only FDA approved therapy that targets the root cause of hyperphagia and early onset therapy today in patients with Bbs.

And I think it's laid the foundation for what we're now seeing as some very early strong success with the BBS launch.

And I think that like within rare disease, you know, there are different states just, in terms of organization.

And we are pleased to report that the commercial launch.

I would say that within the BBS patient population, you know, the BBS Foundation itself is quite, strongly organized.

Alright.

They did quite a nice job just in terms of organizing these past events to have that, opportunity for the patients to engage with each other, learn from each other.

Physicians are writing prescription the initial permic receptor Tim Jeffrey.

But also we had the opportunity to present information just in terms of incivory itself.

Patients with Bbs are initiating therapy.

Next slide.

Thanks to the extensive patient identification and physician engagement efforts for Bbs as well as all the learnings from our commercialization and prostate Pts Ky and look back over the past 15 months, we are starting bvs flat from a position of strength.

So, you know, it's nice to have that type of strong community and advocacy for this, patient population.

And that's the point that these patients themselves may be drivers in those.

They learn about it and they go to their physician who may not have heard about it, but they're, motivated and they help that physician engage and then reconnect.

Thanks, David, Jennifer.

Whereas at these launches are challenging and difficult to project.

It's very helpful.

With the experienced team we have assembled together with them.

Thank you.

<unk> Bbs community.

And then, of course, Europe opening up also suggests that was the right entry point.

Our next question or comment comes, from the line of Corinne Jenkins from Goldman Sachs.

Their caregivers and healthcare providers and a drug that meet the high unmet need.

So, that's where I leave it.

It's a tens recommendation or guidance, if you will, Derek.

Ms. Jenkins, your line is open.

We're up and running.

As we executed on our commercial availability strategy for our initial indication.

Jennifer on BBS?

Good morning.

We're able to deliver in February beginning of March of 2021.

Beginning in September of that year, we deployed our territory managers to engage with physicians mandate educate them on Bbs AMC for a pathway and now in February .

And February was approved on June 16th about six weeks ago, making June and July quite exciting for us.

Our cross functional sales and marketing teams got together to prepare for the launch of in February during the week of June 5th here in Boston.

Quickly following we had a significant presence at endo in Atlanta, with seven data presentation, and a robust schedule of physician engagement activity, including one on one meeting and speaker programs.

So, in terms of the scripts and where we are in terms of process, you know, we have received the scripts.

So maybe, I think a lot of our questions have been asked already, but perhaps from the patient hub that you started, have you had any feedback recently where you're starting to identify any potential pain points or other feedback that is helpful as you think about these initial 50 patients coming onto therapy?

So the opportunity to be able to have this type of high-level and high-tech service in-house has, been really incredibly important in rare disease in general, but also for this particular patient population.

And our timing could not have been better with several local bvs Foundation events held in the recent weeks following approval.

There have been several that have already been approved and shipped.

I will say that from the perspective of reimbursement, there are many similarities just in terms of this early on post-launch, in terms of the process that it is taking.

Every drug in this type of situation has a PA requirement, so that's a given, and we are fortunate to, I have to outline that the PA requirements are very much aligned with our PI, so it was quite, expected from that perspective.

I will say that in this particular disease stage, there are the CMS statutes just in terms of restriction of reimbursement of obesity medication, so there, are particular segments, including the Medicare population, the one that only has Medicare as a source of reimbursement, that will remain a challenge for us.

There may be other payers who, from a first-pass perspective, without the background in education, may lean more towards that type of exclusion.

However, as we have heard through our initial dialogue, research and such, there are also opportunities to educate and gain exceptions for this particular patient population as payers can understand that quite the difference in terms of what is causing the early-onset obesity, the challenges around the hyperfascia, and the specific nature of the targeted approach that Anshupri outlined.

We are able to present background information on sebree at these events and hear the excitement in the community. After finally, having a therapy to treat the hyperphagia and severe obesity of Bbs.

And we are still in the process of moving forward with trying to gain access for the additional patients.

There was a total of over 50 bps family at these slides regional events and more than 170 attendee at the National Virtual conference.

Our activity led to the receipt of our first separate question two days after approval and our first shipment post CBS approval on June 29.

Next slide.

With FDA approval on June 16, we effectively had two weeks of what's remaining in the second quarter.

For the purpose of this call we want to share prescription and prescriber metrics that account for the initial six weeks of launch.

Since early days post-approval, we did expect it to be a process, just in terms of, you know, moving forward with the PA requirements and potential denials, just in terms of, you know, continuing to educate on both the patient population and drugs and ensuring that the patients that really need this therapy are able to access the therapy.

So, it's early days, and we're working through the process, and a lot of the work that's being done is what we expected as well.

We have talked in the past about the different sources of patient identification and health care provider engagement.

Great, and then maybe separately, can you just provide us an update on the timing for a potential readout of the weekly switch study, and then remind us what the registrational path is forward for that formulation, pending results from the phase three?

We have outlined the territory managers to prioritize engagement of providers identified by rhythms with already diagnosed Bbs patients.

Yeah.

So, two parts, as you know.

In addition, we have strong collaborative engagement with the team at Marshall as well as with patient advocacy organizations, including the Bvs Foundation of family Association and Foundation fighting blindness.

The switch study will read out in 2023.

We haven't further defined that exactly, and so it will be in 2023.

And then the second study, which is the de novo study, that will begin in the first half of 2023.

We also executed non personal promotion efforts targeting healthcare providers and patients to expand our education rates.

All of these efforts led to our current state where we are excited to report that as of July 29, we have received greater than 50 prescriptions forums debris for Bbs patients for over 35 unique prescribing physicians.

Next slide.

So who are these greater than 50 patients with Bbs.

We have clinical trial patients were converted to commercial drug.

And patients identified through our territory managers engaging with physicians.

The HVAC is evenly distributed so far with about a third aged 18 or older. A third between 12 and 17 years of age and a third between the ages of six and 11.

78% of them have come from physicians targeted by the territory managers and we are excited that 22% are new physicians to rhythm expanding our reach to additional physician with Bbs patients.

Next slide.

It's early days.

Is the snapshot of our initial and sebree prescribers for Bbs.

Almost half of our prescriptions for Bbs come from pediatric endocrinologists or endocrinologists.

So, ongoing dialogues and ongoing work with the team at this point of time.

Got it.

With the remainder coming from Pediatricians General practitioners family Medicine practitioners internal medicine or medical geneticists.

All right, I think we lost Derek, so maybe we go to the next question and if Derek comes, back we can put him back in the queue.

And maybe just one follow-up for Jennifer.

Is there any geographic consistency that you're seeing among those first 35 prescribers?

Next slide.

Thank you.

From a payer coverage standpoint, we see about 50% of commercial payers and 34% Medicaid.

No, Derek.

Although there are several prescriptions written for patients covered by Medicare and many of them have secondary coverage. So there are opportunities to seek reimbursement for these patients as well.

In Europe, Yann will update you on a study, I'll call it remarkable, of progress in Europe.

Our next question or comment comes from the line of Daegon Ha from Spiefel, stand by.

We are waiting for the auto-injector to begin that trial, and so that will complete the full Thank you.

This is in line with our expectations and our teams work together to secure coverage for Bbs patients, including our corporate accounts team with their active payer engagement, including all 50 state Medicaid with certain states prioritize based on analysis of grip and our own database.

We are getting approvals at better than average timelines for each of these healthcare systems.

Thanks for taking our questions.

Again, ladies and gentlemen, if you have a question or comment at this time, please press star then 1 on your telephone keypad.

The international markets in Europe specifically are incredibly important opportunities for us.

I hope I'm not having any technical difficulties.

Our next question or comment comes from the line of Jeff Hung from Morgan Stanley.

As we have said many times, and you will hear again from Yann today, Europe is better organized, more patients identified, and those healthcare, systems are embracing in several.

Congrats on the quarter.

Mr. Hung, your line is open.

And more importantly, we have motivated patient.

A couple of questions from us, too.

Congratulations on the progress and thanks for taking my questions.

<unk> people with a real need for a therapy.

And physicians willing to engage with us throughout the reimbursement process.

Next slide.

I've mentioned rhythm in June our patient support services on prior calls.

Finally, we have much still to do on the development side of the equation.

<unk> enables us to build and sustain educational and supportive of engagement with our patients and their caregivers.

When a patient who has been our teams helped achieve access with the ability to engage with their position and their insurance.

Is that treatment expectations, and also support patient adherence and continuous therapy.

Next slide.

Overall, we are excited by the first six weeks of the bvs plants.

Accomplishing everything we set out to do find diagnosed patients.

We're obviously excited about the recently released hypothalamic obesity data, which I will discuss briefly on subsequent slides, and all of our other development programs are progressing well.

<unk> position on the disease state to help additional patients get to an accurate DBS diagnose it.

Educate physicians on the empty for a pathway in a different way.

Facilitate reimbursement and insurance coverage and have a seamless initiation on EMS debris therapy with that let me hand, it over to my colleague John laws, but who will provide an update on the progress in the international region.

Thank you Jennifer and good morning, everyone Slide 21 please.

Moving to slide six, I'm going to use the next three slides to remind you why we are excited about hypothalamic obesity.

This slide is the brief primer that Dr. Abuzahab used on a prior call to explain the anatomy. Tumors arising in the junction, between the pituitary and the hypothalamus potentially can injure both the pituitary and the hypothalamus. This is an area referred to as Rafke's pouch.

I will start with a reminder, that Europe is an important market for <unk>.

Patients with tumors in that area are likely to require replacement hormones related to pituitary injury, and about 50% will go on to develop hypothalamic obesity as a consequence of injury to the hypothalamus itself, either due to the tumor and or to the surgery and radiotherapy used to treat the tumor or in rare situations, inflammatory condition, or trauma.

Patients with hypothalamic obesity have a classic presentation that clearly differentiates them from patients with a tumor that does not involve the hypothalamus to the same degree and who do not develop hypothalamic obesity.

Patients experience rapid weight gain, children literally exploding off their growth chart, and I remind you to the example that Dr. Abuzahab showed on the last call. And about 50% of these patients will develop the classic hyperphasia we associate with MC4 pathway diseases, but not all patients.

And strikingly, the majority of these patients with HO become less active and complain of fatigue. Their energy expenditure, both resting energy expenditure and activity levels, are low.

Already many patients identified across our initial indications.

Interestingly, the clinical presentation, the apparent response to thetmelanotide on top of supporting preclinical data, all point to a potential unifying hypothesis, that impairment to the MC4 pathway with both an increase in hunger and a decrease in energy expenditure is a critical element in the development of hypothalamic obesity.

In slide seven, these are the interim results we shared last call on the first 11 patients, and they're striking. Not so much for the extent of the weight loss in a short period of time, which is quite good, but for their consistency. All 11 patients, including the two patients who discontinued, lost weight.

The clinical, presentation, which includes rapid weight gain, is temporally associated with injury to the hypothalamus, the new development of hyperphasia, and probably more importantly here, the change in energy expenditure, all point to impairment of the MC4 pathway.

Actually for body business syndrome, as we've spoken in the past the European <unk> zone bid organized around <unk>.

Now we have evidence that a precision medicine targeting the MC4 receptor results in consistent, clinical improvement.

So in terms of the BBS launch, congrats on the first six weeks, looks great.

You indicated that 22% of the prescribing physicians were new.

That consistency would suggest that melanotide, in addition to working through residual MC4 receptors in the hypothalamus, is likely working through receptors outside the hypothalamus, which interact with the autonomic nervous system and play a critical role in energy expenditure.

Slide 8.

How many identified patients and written scripts does that correspond to?

And especially Ramsay for Sweden.

Established referral networks around centers of excellence and genetic testing is more advanced for this disease.

For the CPC is Q1, the lipoma indications estimated European prevalence is $6.

So this is a rare disease, but unlike many rare diseases, it has a number of advantages with regard to our ability to identify and reach patients. The patients are diagnosed. They know who they are.

Are these the metrics that you've settled on, prescribers as well as prescriptions, or should we expect different set of metrics going forward?

This is a very well understood complication of these tumors and their management.

And how are you, I guess, in the first couple of quarters thinking about the breakdown between, PPL and BBS-derived revenues?

2500 patients.

Our best understanding of the overall prevalence is about 5 to 10,000, with a range reflecting uncertainty about the population who is out more than 10 years.

And then I've got a follow-up on HO.

But importantly, we have already identified about 100 patients diagnosed and receiving care for their needs.

We know median survival is on the order of 20 to 25 years.

There is no reason to believe a, 30-year-old patient who had their tumor resected at age 5 would not still be seeking help for their HO.

The yearly incidence, assuming about 50% of patients with these benign intracranial tumors, will develop HOs about 500 per year in the U.S. As always, we have shared U.S. epidemiology data, but it is not fundamentally different in Europe and may not be so different in Asia, although we are early in our assessment.

Slide 9.

Yeah, I think with regard to metrics, obviously, you're interested, we're also following all, of these metrics closely.

So our next steps, the goal is to present the full 18 patient cohort data at a fall meeting.

We have requested our end of phase 2 meeting with the FDA, and we look forward to initiating the phase 3 trial as early as possible in 2023.

For patients with <unk> syndrome, while European prevalence is estimated to be approximately 2500, we know that there are more than 15 on with patients who are diagnosed and receiving care for their disease.

Slide 9.

Our goal is to share metrics that provide you as clear insight as we can give you reasonably.

In summary, why is HO so important as we expand our scope from genetically impaired defects in the MC4 pathway to genetic and acquired forms?

For this first call, it was clear that Scripps and this prescribing base, the 35-plus physicians, who are prescribing, did that.

So one is it reinforces the importance of the MC4 pathway as a key driver in some forms of obesity.

I think we'll evaluate each quarter what are the most meaningful metrics.

Reminding you again, obesity is not one disease, but many diseases.

So we're not going to commit to a consistent set of metrics at this time.

Two, septum lyanotide is a targeted medicine to the MC4 receptor and provides key insights into the underlying pathophysiology of HO.

Let's see how this overall market evolves, and ultimately, at some point in time, revenues, are going to become the primary metric, and you'll always have those.

Three, it provides potential evidence further supporting the importance of the energy expenditure, side of the equation, further validating the role of an MC4 agonist in the management of MC4 pathway diseases.

And then the question in terms of the PPL and BBS breakout, was that the question, in, terms of... Yeah, the revenue breakdown between the two.

And four, it's a potentially incredibly meaningful opportunity for rhythm.

And there are about 20 European academic medical centers with each more than 40 patients with Bbs mixed.

Patients are identified, no genetic testing is required, patients are engaged with the system requiring specialist care, in most cases endocrinologists, to manage the other complications of pituitary and hypothalamic injury.

Yeah, I think, I don't know we'll break it out specifically.

Next slide please.

For the CPC is Q1 and <unk> deficiency obesity is we have the strong support from the expense so to Europe , we've had very positive interactions with the various European his game authorities and we have already achieved market access in France and in Germany.

And three, the unmet medical need is high.

There's no approved therapies which exist, although many have been tried.

So on slide 10, here's our pipeline.

Our pipeline is progressing with multiple potential meaningful contributors to the portfolio of addressable MC4 pathway diseases. On a specific note, we announced today completion of enrollment in our PEAD study with an expected readout in mid-2023. This trial has enrolled a mix of patients with POMC, LEPR, and BDS between the ages of two and six.

And this is an important age group, as we know from our genetic screening.

Also two weeks ago, the UK nice recommended EMC re for treating obesity and controlling <unk>.

<unk> 95, and we will launch in October in the UK.

Genetic diseases, by definition, often start manifesting at an early age. Many of these patients are being screened, and our early data suggests a somewhat higher probability of a positive genetic test in this age group.

Patients know if their child has a problem and they seek help.

We also anticipate launching in Italy, and Netherlands by the end of this year.

In Spain, and Sweden, we have submitted your investments to see a few weeks ago, we expect to launch in early 2023.

And in Israel, and Argentina, we have identified patients and are currently seeking new investments on a named patient busy schedules.

Next slide please.

We are for many reasons, they're excited about not EBITDA syndrome in Europe .

They say that at the beginning we know that there are approximately 1500 patients diagnosed and receiving care at centers of excellence in Germany, and France, United Kingdom, Spain, Italy, but also in the Netherlands and Turkey.

With that, I will turn it over to Jennifer to talk about our encouraging start in the U.S.

As Doctor, Philippines, with one of the world's leading <unk> syndrome.

Thank you, David.

These patients living with <unk> syndrome are looking for a complex transformational treatments that can significantly reduce hunger and body weight.

I'm going to be starting on slide 12 today.

So, we are really proud to lead the development and bring mCivri to additional patients, mCivri is the only FDA-approved therapy that targets the root cause of hyperphagia and early onset severe obesity in patients with BBS, and we are pleased to report that the commercial launch is off to a strong start.

We know as a positive <unk> opinion and its recommendation to EMEA to extend the current marketing authorization for <unk> to include the treatment of obesity and controller for adults and pediatric patients six years of age and older.

With genetically confirmed <unk> syndrome.

Final authorization is expected to come from the European Commission in October .

So.

I can report that was submitted their application to the UK image hit ratio, but it is a syndrome of cruiser real items Porsche.

Which of those is to leverage our NDA submission.

I think the PPL, back to Garrett's earlier question, that's in the tens of patients that, will remain and become an increasingly smaller overall percentage of the total.

Yeah, we haven't broken out.

Finally, we will begin very soon engaging with the authorities in Germany, Italy, and Spain, and all of whom.

What we've given you the split is on the 35, you know, physicians, basically.

So we may or may not break that out, but I don't think it'll obscure the real progress, that we're making with BBS overall.

So we're not, you know, sort of breaking it down further than that.

And then, you know, as an extension of that, are we going to, you know, break out numbers, between the U.S. and Europe again?

I think it's actually quite a lot of information in the sense that, this early on, what we hope you're taking away is a breadth of prescribers, which is really the key, and strong engagement reflecting, you know, for a rare disease, as I've said many times, you don't write a script and go to your local CVS.

So it takes a little bit of a commitment and conviction to get even that first step of the script written.

I mean in theory.

I'll defer that.

So strong message there.

It has done in the United States, a walk with CPC is Q1, and the power of latest one condition, which will support but EBITDA syndromes related default.

Let's see how it all plays forward.

Okay.

For the moment, while it's early, you're getting one set of numbers with as much color as we, can give you about the different regions.

Mm-hmm.

Next slide please.

Sounds good.

Last but not least a few words about severely recent and I think unique achievement for instance, my own country and home to a few of us in the international team.

Im very proud of our team's many successes here.

<unk> LTE access granted to <unk> from the CPC is Q1, a new pop back in March this year.

Also just achieved a pre approval early access for <unk> syndrome called <unk>, one even before the <unk> recommendation and the EMEA approval.

We did so quite rapidly.

Certainly two days following FDA.

The approval, which I believe is a record time and trends and with no restrictions level.

AP, one lewisville early access to innovative therapies and trends when a positive benefit risk balance is recognized and when no. Other therapeutics in Tennessee is not available yet.

<unk> and CRE was guaranteed following a very comprehensive review of efficacy and safety data.

The program is fully covered by the French National Health system, and we will be reimbursed for any patients receiving treatment through this COVID-19 on.

With approximately 700 patients with <unk> syndrome diagnosed and are you anticipating trends there is a clear unmet need for therapies.

Yeah, Hey, Jeff <unk>.

In conclusion, we are making exciting and fast progress in Europe and with <unk>.

Turn over to him Joe.

Thank you very much.

Turning to slide 26.

As we announced in February was approved for Bvs in June we signed a cap revenue despite answering agreement with healthcare royalty partners, which resulted in a commitment to invest up to 100 million rhythms.

Healthcare royalty partners is one of the leading investors in royalty streams for pharmaceutical products and this investment demonstrates hcr's confidence and exit rate for patients with BARDA fetal syndrome, as well as rhythms potential to generate additional revenue from new indications.

Structure of this agreement, which we described in June and detailed here on slide six enables us to access significant financial resources to fund the continued growth of our business, while avoiding equity dilution and preserving shareholder value. This commitment also extends rhythms cash runway into the second half of 2024.

On slide 27, we have a financial snapshot of rhythms business in the second quarter of 2022 as compared to the comparable quarter of 2021.

We reported product revenues more in February totaling $2 3 million as compared to 300000 for the second quarter of 'twenty one.

Revenues for this quarter also include a modest contribution from commercial sales in both Germany and France.

Both Q2 and year to date results include recognition of $6 8 million in licensing revenue from rare stone associated with their exclusive license to commercialize subsidiary in China. This revenue relates to the $7 million upfront payment that rhythm received in Q4 2021 has no impact on cash flow in 2022.

And then a follow-up to what Phil was asking with regards to the end of Phase 2 meeting.

And then you said you've continued to identify patients beyond the 350 plus in BBS.

I guess, what are your early thoughts about the HO study as it pertains to perhaps a head-to-head, with either GLP-1s or even Trezepatai?

What's the updated number of identified patients and do you have a better sense for how many of them overlap with the CRIBS registry?

We've heard some of that interest from docs we've spoken to.

Cost of goods sold ran at approximately 16% of product revenue during the quarter the primary driver of Cogs.

So any thoughts there?

Thanks.

The amortization of previous commercial milestones.

As well as the royalty due to sit under our original licensing agreement.

So we haven't updated that further.

I mean, it was 350 plus in February and everything we do, literally in rhythm, supports another part of rhythm.

R&D expenses for <unk>, 'twenty, two with $31 5 million compared to $25 1 million in the second quarter of 2021.

So the, you know, the clinical trials we're running are phase two, phase three trials, daybreak and M&A.

This is primarily due to a $4 $6 million increase in clinical trial costs.

Thanks so much.

We're out engaged with the community.

Are those phase III emanate study our phase two DAYBREAK study as well as our two Registrational studies and a weekly formulation contributed the bulk of the increase in spending.

Sure.

Rhythm has more visibility.

So for sure, we will not be running a head-to-head. You only go head-to-head as a rule if there's an established approved therapy, a standard, of care, and in those cases, that may be a regulatory path that makes sense.

Semilanotide and SIVRI has more visibility.

SG&A expenses for Q2 were $22 3 million compared to $15 5 million in the previous quarter.

The primary driver of this increase was the Bbs commercial launch in the U S as well as increases in head count for our U S and international commercial organizations.

There is no approved therapy for hypothalamic obesity, number one.

All of that, again, supports ongoing education and awareness around things, including BBS.

The more general question of, you know, how do GLP-1s plus Trezepatai work in this group?

So that number is going up.

Our share count was $50 4 million basic and diluted shares in loss per common share was 89.

Physicians are writing prescriptions.

The initial pair mix is receptive to mCivri, and patients with BBS are initiating therapy.

Cash used by operating activities was $37 $2 million during the quarter. In addition, cash flow from investing activities included.

Next slide.

$4 million payment.

$4 million milestone payment.

We haven't updated it further, but we feel good about where we are.

For the first commercial sale.

Similarly in Europe .

We concluded the quarter in a strong financial position with cash cash equivalents and short term investments of $235 6 million, which including the additional $37 5 million dollar trends, we are entitled to receive upon EU approval for Bvs, We believe will be sufficient to fund rhythms operations into at least the second half of 2024.

And now I will turn the call back over to David for concluding remarks. Thank you.

Thank you Hunter, so I think hopefully as you've.

Understood. We believe this is a very good quarter Bds approval extended cash runway strong reception in Europe , and I really encourage you can start to our U S launch.

Pipeline of indications continues to advance and we are very much looking forward to updating you on our progress in hypothetical obesity.

And with that I will turn it back to the operator to begin Q&A.

Ladies and gentlemen, if you have a question or comment at this time. Please press Star then one one on your telephone keypad again, if you have a question or comment at this time. Please press star one one.

Please stand by while we compile the Q&A roster.

Our first question or comment comes from the line of Philip Nadeau from Cowen <unk> Company. Mr. Nadeau. Your line is open.

Good morning, Thanks for taking my questions a couple on the Bbs launch then one on <unk> on the PPS launch you mentioned 35 prescriptions.

Five physicians have written how many physicians are there in the target market and do you think that the.

Initial breakdown of the prescriber base is going to be consistent with ultimately who is who is writing for Bbs.

Okay.

Thank you.

Thanks for the question.

So.

As you outlined 35 current ATP greater 35 correct.

Again, early.

Thanks, Jeff.

It should have prescribed.

For Bbs.

Thank you.

We have outlined.

Past that we have approximately 150 <unk> position with approximately 350.

Bbs patients identified within there.

Their practice.

So we still have additional physicians who have not yet.

The drug and our territory managers are continuing to engage with them.

In addition, we are continuing to.

In terms of our disease education efforts to get additional patients to an accurate diagnosis as quickly as possible. So we expect that the physician population will also increase as we move forward with our activity in terms of prescribers.

We do target specific specialties in clothing.

Yes trick endocrinologist endocrinologist.

However, there are additional.

Waste that we go about insurance alright targeted education.

Efforts.

I do believe that the pediatric endocrinologists on the endocrinologist will remain a key physician specialty that will be.

Taking care of these patients, but additional physicians will also be.

Coming up in terms of participating in the care of Bbs patients have Rob.

And do you have a sense of how long it takes from when the prescription is written until reimbursement is secured I.

I appreciate that it's early in the launch.

Yeah. So I think early in the launch it's still early days right now.

We are encouraged in terms of how things are going as there've been scripts that have been received approved as well as ship.

This early in terms of post launch.

Scott.

It's going to be.

No time as payers are still in the evaluation process of evaluating this new indication for any different.

Oh, sorry.

So that can take anywhere from 30 to 90 days.

There are questions in the queue at this time.

And Charles F review with specific grab sense probably longer too.

I'd like to turn the conference back over to management for any closing remarks.

That event.

Okay, thanks.

Formulary itself.

Great and then last question on <unk>. It sounds like you have a pretty good idea of how you want to structure. The phase II trial, what key elements do you need to check with the FDA before you can initiate are there points of design.

I just I realize I answered a question there.

The question was overlap with the CRIBS registry.

Do you think could be controversial to the FDA or are you really need clarity from the agency before you implement the trial.

Thanks to extensive patient identification and physician engagement efforts for BBS, as well as all the learnings from our commercialization in Palsy, PCSK1, and Leper, over the past, 15 months, we are starting BBS launch from a position of strength.

Yes.

Good question. So the answer short answer is I don't know, what we said on the last call, which is where we still are.

Our specific guidance for the development of drugs in obesity.

Rare disease launches are challenging and difficult to protect, but with the experienced, team we have assembled here at Rhythm, a growing BBS community of patients, their caregivers, and healthcare providers, and a drug that meets a high unmet need, we are off and running.

I am sure.

It'll be a double blind randomized controlled trial I don't think that's probably going to debate that the guidance is it's a year long trial.

That's our starting point going and we'll see where that goes.

And as we said I don't think it needs to be a large trial. We know just mathematically it doesn't need to be a large trial given the effect size that we've seen so it doesn't require so many patients to prove statistically efficacy and safety.

Besides the trial to support the safety of the drug in this new indication that that'll be a point of discussion. So I mean those are the elements that we've been through these trials before.

<unk> four agonist several at a time so.

Short answer is not so controversial, but theres two or three really important pieces on the entire amount.

Perfect. Thanks for taking my questions and congrats again on the progress.

Thank you.

And our next question or comment comes from the line of Derek <unk> from Wells Fargo.

Sara Your line is open.

Hey, good morning, Congrats on the quarter a lot of things to be excited about here. So just a few questions from us.

Maybe to start can you just help us understand where you are in your thinking of having tens of patients on therapy in the first couple of years for the pop the Tcs K one in the left bar patients.

As we instituted on our commercial availability strategy for initial indication, we were able, to deliver mCivri beginning in March of 2021. Beginning in September of that year, we deployed our territory managers to engage with the, physician community, educate them on BBS, the mC4R pathway, and now mCivri, mCivri was approved on June 16th, about six weeks ago, making June and July quite exciting for us. Our cross-functional field and marketing teams got together to prepare for the launch of, mCivri during the week of June 5th here in Boston.

Quickly following, we had a significant presence at Endo in Atlanta with seven data presentations, and a robust schedule of physician engagement activities, including one-on-one meetings and speaker programs. And our timing could not have been better with several local BBS Foundation events held, in the recent weeks following approval. We were able to present background information on mCivri at these events and hear the excitement, of the community after finally having a therapy to treat the hyperphagia and severe obesity of BBS. There was a total of over 50 BBS families at these live regional events and more than, 170 attendees at the national virtual conference.

All our activities led to the receipt of our first mCivri prescription two days after approval, and our first shipment post-BBS approval on June 29th.

You put out some new numbers.

I guess in Europe Ah patients you've identified and then also in light of the news of France is seemingly those are all positive.

Next slide.

And then my second question is just on the Bbs launch can you talk about the conversion you're seeing for the scripts written for patients that are actually receiving treatment I know it might be early but any thoughts there would be helpful.

With FDA approval on June 16th, we effectively had two weeks of launch remaining in the second, quarter. But for the purpose of this call, we want to share prescription and prescriber metrics, that account for the initial six weeks of launch.

Yes, maybe ill comment.

Comment on the first question and Jennifer on the second Bvs conversion. So we're sticking I mean tens of patients I think is highly descriptive its consistent with where we are today I think so.

First of your question was how does the approval in Europe impact that.

We have talked in the past about the different sources of patient identification and health, care provider engagement.

John has highlighted the fact that we have about 100 patients identified.

We have outlined the territory manager's prioritized engagement of providers identified by rhythm, with already diagnosed BBS patients.

In addition, we have strong collaborative engagement with the team at Marshfield as, well as with patient advocacy organizations, including the BBS Foundation and Family Association and Foundation Fighting Blindness.

<unk> identified so far across the major markets in those major markets are coming on so obviously those patients will contribute is still going to leave us in the tens hopefully getting up into the high teens.

We also executed non-personal promotion efforts targeting health care providers and patients, to expand our education reach. All these efforts led to our current state where we are excited to report that as of, July 29, we have received greater than 50 prescriptions for MCIV or BDS patients from over 35 unique prescribing physicians.

Next slide.

So, who are these greater than 50 patients with BDS?

That scenario, but I wouldn't change our overall positioning around the this initial biola with pumps you up our group incredibly fortunate in hindsight that we started with that.

We have clinical trial patients who were converted to commercial drugs and patients identified, through our territory managers engaging with physicians.

So, again, we don't know exactly.

Largely because it's taught us so much about this market and it's allowed us to engage with the health care systems in a very constructive non threatening way if you will.

The age mix is evenly distributed so far with about a third age 18 or older, a third between, 12 and 17 years of age, and a third between the ages of 6 and 11.

We don't have a list of patients in CRIBS for sure.

I think it's.

Laid the foundation for what we're now seeing is some very early strong success.

Seventy-eight percent of them have come from physicians targeted by the territory managers, and we are excited that 22 percent are new physicians to Rhythm, expanding our reach to additional physicians with BDS patients.

Next slide.

There is overlap with CRIBS and we know we have some of the prescriptions, not surprisingly, being written out of the Marshfield Clinic and those patients are likely to be in CRIBS.

The Bbs launch and then of course Europe opening up also suggests that with the right entry point. So that's.

So there is for sure some overlap, but there's also for sure not 100 percent overlap.

Before I leave it it's still it's a <unk> recommendation or guidance, if you will allow derrick.

So, again, I'd encourage you to think about those things as complementary, not overlapping completely.

With that, thanks to all of you for tuning in this morning.

Yes.

Okay.

This script and where we are in terms of process.

We have received the scripts.

There have been several that have already been approved and shifts and we are still in that basket.

Forward.

Trying to gain access for the additional patients.

Early days post approval.

It's early days, but here's a snapshot of our initial MCIV prescribers for BDS. Almost half of our prescriptions for BDS come from pediatric endocrinologists or endocrinologists, with the remainder coming from pediatricians, general practitioners, family medicine practitioners, internal medicine, or medical geneticists.

Next slide.

From a payer coverage standpoint, we see about 50 percent are commercial payers and 34 percent, Medicaid.

Did expect it to be a process just in terms of.

Although there are several prescriptions written for patients covered by Medicare, many of, them have secondary coverage, so there are opportunities to seek reimbursement for these patients as well.

This is in line with our expectations and our teams work together to secure coverage, for BDS patients, including our corporate accounts team with their active payer engagement, including all 50 state Medicaid, with certain states prioritized based on analysis of pribs and our own database.

And more importantly, we have motivated patients, real people with a real need for a therapy, and physicians willing to engage with us throughout the reimbursement process.

Next slide.

Moving forward with.

With that, let me hand it over to my colleague, Yann Mazabraud, who will provide an update, on the progress in the international region.

I've mentioned Rhythm & Tune, our patient support services, on prior calls. Rhythm & Tune enables us to build and sustain educational and supportive engagements with, our patients and their caregivers. When a patient consents, our team helps achieve access with the ability to engage with their, physician and their insurance, accept treatment expectations, and also support patient appearance and continuity of therapy.

Thank you, Jennifer, and good morning, everyone.

Next slide.

Require marathon as potential denials just in terms of.

Slide 21, please.

Overall, we are excited by the first six weeks of the BDS launch.

We'll start with a reminder, that Europe is an important market for MCBRI, as there are already many patients identified across our initial indications, especially for Bardet-Billet syndrome. As we've spoken in the past, the European healthcare systems are better organized around rare disease, and especially rare MC4R pathway disease. There are established referral networks around centers of excellence, and genetic testing is more advanced for this disease.

We are accomplishing everything we set out to do, find diagnoses, and provide support, for our patients and their caregivers.

For POPSI, PCSK1, and LIPAR bialytic patients, the estimated European prevalence is 600 to 2,500 patients. But importantly, we have already identified about 100 patients who are diagnosed and receiving, care for their disease.

We are excited about the future of the BDS, and we look forward to working with you.

For patients with Bardet-Billet syndrome, while European prevalence is estimated to be approximately 2,500, we know that there are more than 1,500 patients who are diagnosed and receiving care for their disease.

Next slide.

And there are about 20 European academic medical centers with each more than 40 patients with DDS.

Continue to educate.

Education.

Next slide, please.

Educate physicians on the disease state to help additional patients get to an, accurate BBS diagnosis.

For POPSI, PCSK1, and LIPAR deficiency obesity, we have a strong support from the experts for South Europe.

Educate physicians on the MC4R pathway and MCBRI.

On the patient population that drug.

We've had very positive interaction with the various European healthcare authorities, and we have already achieved market access in France and in Germany.

Facilitate reimbursement and insurance coverage.

Also, a few weeks ago, the UK NICE recommended MC3 for treating obesity and controlling hunger caused by POPSI, PCSK1, and LIPAR, and will launch in October in the UK.

And have a seamless initiation on MCBRI therapy.

We also anticipate launching in, Italy and in the Netherlands by the end of this year.

In Spain and Sweden, we have submitted the reimbursement dossier a few weeks ago.

Terry.

We expect to launch in early 2023.

Daily maintenance therapy.

And in Israel and Argentina, we have identified patients and are currently seeking reimbursement on, a named patient basis for those.

Next slide, please.

We're able to access to therapy, so ongoing dialogue and ongoing work with the teams at this point of time.

We are, for many reasons, very excited about Bardet-Billet syndrome in Europe.

First, as I said at the beginning, we know that there are approximately 1,500 patients diagnosed and receiving care at centres of excellence in Germany, in France, United Kingdom, Spain, Italy, but also in the Netherlands and Turkey.

As Dr. Philbills, with one of the world's leading experts on Bardet-Billet syndrome said, these patients living with Bardet-Billet syndrome are looking for a transformational treatment that can significantly reduce hunger and body weight.

Second, we now have the positive CHMP opinion, and its recommendation to EMA to expand the current marketing organisation for MCV, to include the treatment of obesity and control of hunger in adults and pediatric patients six years of age and older with genetically confirmed Bardet-Billet syndrome. The final authorisation is expected to come from the European Commission in October.

Third, I can report that we have submitted our application to the UK MHRA for Bardemidal, Syndrome through the Reliance procedure, which allows us to leverage our EMEA submission.

Got it and maybe just one follow up for Jennifer is there any geographic consistency that you're seeing among those first 35% of their disorder.

And finally, we will begin very soon engaging with the authorities in Germany, Italy, and, Spain, and all of whom are very familiar with MCRA and Rhythm already.

As done in the United States, our work with POMC, PCSK1, and LIPA has laid a strong foundation, which will support our Bardemidal Syndrome-related effort.

Next slide, please.

Last but not least, a few words about a very recent and I think unique achievement.

Thank you very much, Jan.

France is my home country and home to a few of us in the international team.

Turning to slide 26, as we announced when MCIVRI was approved for BBS in June, we signed, a capped revenue interest financing agreement with healthcare royalty partners that resulted in a commitment to invest up to $100 million in LIPA.

That's why I'm very proud of our team's many successes here.

Healthcare royalty partners is one of the leading investors in royalty streams for pharmaceutical, products, and this investment demonstrates HCR's confidence in MCIVRI for patients with Bardemidal Syndrome, as well as Rhythm's potential to generate additional revenue from, new indications.

So I think, hopefully, as you've understood, we believe this is a very good quarter. BBS approval, extended cash runway, strong reception in Europe, and a really encouraging start to our U.S. launch.

Following the AP2 early access granted to MCRA for POMC, PCSK1, and LIPA back in March, this year, we also have just achieved a pre-approval early access for Bardemidal Syndrome called, AP1, even before the CHMP recommendation and the EMEA approval. We did so quite rapidly, only 32 days following the US FDA approval, which I believe is a, record time in France, and with no restriction to label.

The structure of this agreement, which we described in June in detail here on slide, 6, enables us to access significant financial resources to fund the continued growth of our business while avoiding equity dilution and preserving shareholder value. This commitment also extends Rhythm's cash runway into the second half of 2024.

Our pipeline of indications continues to advance, and we are very much looking forward to updating you on our progress in hypothalamic obesity.

AP1 allows for early access to innovative therapies in France when a positive benefit, risk balance is recognized and when no other therapeutic alternatives are available. The AP1 for MC3 was granted following a very comprehensive review of efficacy and safety, data.

On slide 27, we have a financial snapshot of Rhythm's business in the second quarter, of 2022 as compared to the comparable quarter of 2021.

And with that, we'll turn it back to the operator to begin Q&A.

The AP program is fully covered by the French National Health System and will be reimbursed, for any patients receiving treatment through this program.

We reported product revenues for MCIVRI totaling $2.3 million as compared to $300,000 for the, second quarter of 2021. Revenues for this quarter also include a modest contribution from commercial sales info Germany, Q2 and year-to-date results include recognition of $6.8 million in licensing revenue from, Rarestone associated with their exclusive license to commercialize subsidiary of China.

Ladies and gentlemen, if you have a question or comment at this time, please press star, then 1, 1 on your telephone keypad.

Okay.

With approximately 700 patients with Bardemidal Syndrome diagnosed and identified in France, there is a clear unmet need for therapies upstream. This is due to the hyperphagia and the severity of this disease.

This revenue relates to the $7 million upfront payment that Rhythm received in Q4 2021, has, no impact on cash flow in 2022.

Again, if you have a question or comment at this time, please press star, 1, 1.

Please stand by while we compile the Q&A roster.

In conclusion, we are making exciting and fast progress in Europe, and with that, I, will turn it over to Hunter.

Cost of goods sold ran at approximately 16% of product revenue during the quarter.

Okay.

The primary driver of costs is the amortization of previous commercial milestones paid to Ibsen, as well as the royalty due to Ibsen under our original licensing agreement.

R&D expenses for 2Q22 were $31.5 million compared to $25.1 million in the second quarter of 2021. This is primarily due to a $4.6 million increase in clinical trial costs. Rhythm's Phase III M&A study, our Phase II Daybreak study, as well as our two registrational studies in our weekly formulation contributed the bulk of the increase in spending.

Alright, Thanks, we lost.

SG&A expenses for 2Q22 were $22.3 million compared to $15.5 million in the previous quarter. The primary driver of this increase was the BBS commercial launch in the U.S., as well as increases in headcount for our U.S. and international commercial organizations.

The share count was $50.4 million basic and diluted shares, and loss per common share was $0.89. Cash used by operating activities was $37.2 million during the quarter. In addition, cash flow from investing activities included a $4 million milestone payment to Ibsen for the first commercial sale of IMSIVRI in Europe.

We concluded the quarter in a strong financial position with cash, cash equivalents, and short-term investments of $235.6 million, which, including the additional $37.5 million transfer, we are entitled to receive upon EU approval for BBS. We believe will be sufficient to fund Rhythm's operations into at least the second half of 2024.

Eric So maybe we go to the next question comes back to put them back in the queue.

Our first question or comment comes from the line of Philip Nadeau from Cowan & Company.

And now I'll turn the call back over to David for concluding remarks.

Thank you.

Thank you, Hunter.

Mr. Nadeau, your line is open.

Yeah.

Thank you.

Our next question or comment comes from the line of Dae Gon ha from Stifel standby.

Thanks for taking our questions I hope I'm, not having any technical difficulties congrats on the quarter or a couple of questions from us too.

So in terms of the Bbs launch congrats on the first six weeks looks great.

Are these are metrics that you've settled on prescribers as well as prescriptions or should we expect different set of metrics going forward.

Are you I guess in the first couple of quarters thinking about the breakdown between PPL Mbbs derive revenues and then I've got a follow up on HL.

Yes, I think with regard to metrics obviously.

You're interested we're also following all of these metrics closely our goal is to share metrics that provide you as clear insight as we can give you a reasonably for this first call it was clear that scripts.

This prescribing base for 35, plus physicians who are prescribing.

Yes.

I think we will evaluate each quarter what are the most meaningful metric. So we're not going to commit to a consistent set of metrics at this time, let's see how this overall market evolves and ultimately at some point in time revenues are going to become the primary metric and you always have goats.

What we do know is that earlier generations of GLP-1 agonists have been tried without, success.

There's case reports where individual patients respond.

And then the question in terms of.

I'd refer you back to the comment that Dr. Abouzahab made on her prior call.

The PPL and DBS breakout was that the question in terms of the revenue breakdown between the two.

She shared an anecdotal with that one patient where she had tried the patient on a GLP-1, with, you know, little response, and that patient subsequently had a very strong response to set melanotide.

Yes, I think.

We'll break it out specifically I think.

The PPL back to <unk> earlier question.

She's also shared that she has another patient anecdotally who's doing well on a GLP-1, but, I think she characterized overall that maybe 10 to 20% of the patients might have some response to GLP-1 agonists and put that, the magnitude of the response at 5 to 10% in conversations with other physicians.

In terms of patients some that will remain and become an increasingly smaller overall percentage of the total so we may or may not break that out, but I don't think it'll obscure.

Real progress that we're making with DBS overall, and then as an extension of that are we going to breakout the numbers between the U S. In Europe again, I'll defer that let's see how it all plays forward, but for the moment, while it's early youre getting one one set of numbers with as much color as we can give you about the different rhythms.

We ask, you know, I do and others ask them, Paul puts their opinion about this.

I think that's consistent, if anything, maybe a little bit high.

Again, this is a disease where you're destroying parts of the brain that these drugs work through, and the question is, is there a residual part of the brain that's going to allow them to meaningfully get the same results you might see in somebody whose brain is not impaired?

Uh-huh It sounds good and then a follow up to what Phil was asking with regards to the end of phase II meeting I guess.

What are your early thoughts about the <unk> study as it pertains to perhaps a head to head with either <unk> or even towards appetite. We've heard some of that interest from docs, we've spoken to so any thoughts there. Thanks so much.

So, again, much more to be learned, but, Degan, I don't, for sure we're not going head to, head, and I think our early understanding is GLP-1s may have a role or help some patients, but by no means the vast majority, just because it's very different biology.

Sure.

So for sure we will not be running a head to head you only go head to head as a rule. If there is an established approved therapy standard of care and in which those cases.

That may be a regulatory path makes sense. There is no approved therapy for hyperkalemia obesity number one.

Got it.

The more general question of.

How do <unk>, one slash two separate tide work in this group again early what we do know is that earlier.

Thanks for taking our questions and congrats.

Generations of DLP, one agonists have been tried without success Theres case reports for individual patients respond I'd refer you back to the comment that Dr. Boozer have made on our prior call shared an anecdotal one patient where she had tried the patient on a GOP one with little.

Thank you.

Thank you.

Lance unmet patient subsequent had a very strong response to <unk> and she is also sure that she has another patient anecdotally who is doing it now on a GOP one, but I think she'd characterize overall that maybe 10% to 20% of the patients might have some response to.

<unk>, one agonists and put that the magnitude of the response at 5% to 10%.

Conversations with other physicians so we ask.

You and others some pass them Paul puts their opinion about this.

I think thats consistent with anything maybe a little bit high.

We're going to go back to Mr. Derek Archila from Wells Fargo to ask his question.

Again, this is a disease, where you're destroying parts of the brain that these drugs work through and the question is is there a residual part of the brain will allow them to meaningfully get the same results you might see in somebody who's brand is not impaired so again much more to be learned but.

Mr. Archila, your line is open.

Again, we're excited about our start here.

Hey, sorry, guys.

There's a lot of really good signals to build on, both in the US and Europe, and we're excited about our pipeline.

So look forward to our next call when we can update you further on our progress.

It seems like I got cut off there.

Dan I don't for sure we're not going head to head and I think our early understanding of <unk> ones may have a role in helping us some patients but by no means.

Asked majority just because its very different biology.

Got it thanks for taking our questions and congrats.

Thanks Peter.

Thank you we're going to go back to Mr. Derrick <unk> from Wells Fargo.

Ask your question Mr. <unk> Your line is open.

Hey, sorry, guys. It seems like I got cut off there I was just following up on that question with Jennifer I just wanted to understand the kind of geographic consistency or not of the first 35 prescribers at Bds. She had any comments on that thanks.

Thanks, everybody.

Ladies and gentlemen, thank you for participating in today's conference.

Okay.

Good morning.

I was just following up on a question with Jennifer.

Yes.

Thanks for taking our questions.

Scriber basis, we were actually quite pleased to say that we had greater than 35 prescribers that were really.

I just wanted to understand the kind of geographic consistency or not of the first 35 prescribers at BDS.

A couple on the BBS launch, then one on the BBS launch.

Throughout the nation not.

Localized in any particular area.

So.

Sure.

This group is.

Distributed.

And not particularly focused in any particular area.

We expect that to remain the case.

So as we have seen the distribution in terms of a position that were within our spirit that we have identified with already identified.

Thanks, Bob.

And Derrick I'll, just add I think these questions your questions focused on the right thing.

You mentioned 35 prescriptions – sorry, 35 physicians have written.

If she had any comments on that.

How many physicians are there in the target market?

Thanks.

And do you think that the initial breakdown of the prescriber base is going to be consistent with ultimately who's writing for BBS?

From a prescriber base, we were actually quite pleased to see that we had greater than 35 prescribers that were really throughout the nation and not localized in any particular area throughout the U.S. So, this group is distributed and not particularly focused in any particular area.

Jennifer?

And we expect that to remain the case.

We're pleased with the 50 script plus start here, but this 35% plus physicians who are writing is a really important metric would be one thing if we were sitting here and Dr. Haws at.

Thanks for the question.

So, as you outlined, 35 current ACPs, greater than 35 current ACPs who have prescribed for VBS.

Also, as we have seen the distribution in terms of the positions that were within our sphere that we had identified with already identified BDS patients as well.

And Derek, I'll just add, I think, you know, these questions, your questions focused on the right thing.

You know, we're, you know, pleased with a 50 script plus start here, but this 35 plus physicians who are writing is a really important metric.

You know, it'd be one thing if we were sitting here and Dr. Haas at the Marshfield Clinic had written all the scripts, that would be a different story.

Marshfield clinic had written all the scripts that would be a different story, but the fact that we're getting broad based.

Engagement here and that's not inconsistent with the experienced Jennifer and I have had in other diseases, where.

We have outlined in the past that we have approximately 150 physicians with approximately 350 VBS patients identified within their practice. So, we still have additional physicians who have not yet prescribed the drug, and our territory managers are continuing to engage with them.

Physicians, who are following these patients.

As part of their primary care step up and become more expert and are willing to learn how to prescribe the drug and use. It. So this is very much following a template that we've seen multiple times in rare disease Theres very few couldnt quote experts and if you had to go through only the experts that would be challenging.

In addition, we are continuing to move forward in terms of our disease education efforts to get additional patients to an accurate diagnosis as quickly as possible.

Another step up.

Got it thanks, so much congrats on the quarter.

Next question. Thanks.

Thank you. Our next question or comment comes from the line of Joseph Stringer from Needham and company. Mr. Stringer. Your line is open hi, good morning.

Hi, good morning, Thanks for taking my questions and congrats on the progress.

So, we expect that the physician population will also increase as we move forward with our activities.

Two from us on the Bbs launch just to clarify you previously mentioned you have 350 identify and diagnose Bbs patients in the U S.

In terms of prescribers, we do target specific specialties, including pediatric endocrinologists and endocrinologists.

However, there are additional ways that we go about in terms of our targeted education efforts.

So, I do believe that the pediatric endocrinologists and the endocrinologists will remain a key physician specialty that will be taking care of these patients, but additional physicians will also be coming up in terms of participating in the care of VBS patients overall.

And do you have a sense of how long it takes from when the prescription is written until reimbursement is secured?

I'm appreciating that it's early in the launch.

Do the 50 prescriptions that 50 <unk>.

Is that a part of the 350 and then secondly.

I know it's early on in the launch but.

Encountered any.

Prior authorization requirements or genetic testing confirmation requirements from those.

<unk> prescriptions written to date. Thank you.

Yes, thanks for the question.

So regarding the patients that we receive scripts from I would say that it comes from a mix of different groupings. Certainly there are physicians with patients that our territory managers have been engaging with.

Yeah.

So, I think early in the launch, you know, it's still early days right now.

We are encouraged in terms of how things are going as there have been scripts that have been received, approved, as well as shipped.

Upfront that have written scripts, so some of them come from those.

Physicians.

But we were also excited because within this indication we also heard.

But the fact that we're getting broad based engagement here, and that's not inconsistent with the experience Jennifer and I've had in other diseases where physicians who are following these patients, you know, as part of their primary care, step up and become more expert and are willing to learn how to prescribe the drug and use it.

And now saw that there were patients who also.

Heard about the approval and that can happen in various different ways.

We had ongoing non personal promotion, both hcp's as well as patients to educate them on disease.

So, this is very much following a template that we've seen multiple times in rare disease.

There's very few, quote unquote, experts.

This concludes the program.

Also show the news we had engagement with.

Patient associations, where they were also very happy to share the news of our peripheral so.

And if you had to go to only the experts, that would be challenging.

You may now disconnect.

Where it gets out in the small community.

Everyone have a wonderful day.

You don't.

Speakers, stand by.

The conference will begin shortly.

New therapies are finally available for these patients.

To raise your hand during Q&A, you can dial star 11.

That was also another source, Jeff in terms of either patients proactively going to their physicians seeking treatments or other participants you heard about it and assure.

Others step up.

That are now part of it with them.

Joseph our CRM and outreach effort.

And regarding the prior authorization.

So.

Very aligned with the current clinical practice for Bbs Bbs is a clinical diagnosis.

Got it.

Thanks so much.

That was also what was outlined in our.

RPI so to date, we really have not.

Not saying theyre being genetic requirements in terms of genetic confirmation.

As part of the <unk>.

It's fair to say that payers are very much sticker labels camera one other clarification Joey just on the 350 to remind you that was 350 plus back in February obviously, we've continued to identify more patients since then and to reinforce what Jennifer said no.

A quarter ish, 22% of these current early scripts that are coming in are not part of that group.

That does speak to the fact that.

Once you have a therapy people do re engage with the health care system may have been sitting on the sidelines and not in Europe . Your line of sight.

Great. Thank you for taking my questions.

Thank you. Our next question or comment comes from the line of Michael Higgins from Ladenburg Thalmann standby.

February morning guidelines.

Thanks, guys hopefully you can hear me here.

Congrats on the terrific performance so far this year that we're seeing.

I asked some questions on bvs, but first I think the next driver being EMC four or maybe you could spend some time on that.

When should we look for data how many patients who were looking for.

Can you provide any feedback for us from this open label trial and.

Remind us again, how many I'd and the community.

Yes.

Thanks, <unk>. So our goal is to put that out again in association with <unk>.

Congrats on the quarter.

Medical event in the fall here, we haven't.

Next question.

Specify the exact timing of that so we're still working that out.

This is a one of the more common and the most common genetic driver of monogenetic driver of obesity, but the big question. We've always had with that is.

Thanks.

Thank you.

If you have a variant genetic variant in the receptor affecting the receptor itself do you render the receptor nonresponsive and so what you'll hear is our attempt to divide those groups between those who are non rescue ball, where the receptor variant vendors that receptor non responsive from those who might have a response to several of them to try it again.

Our next question or comment comes from the line of Joseph Stringer from Needham and Company.

Mr. Stringer, your line is open.

More to come on that but what for some update here later in the fall.

I think that was the only question so far.

Just a follow up on that the number of IBD patients. Thanks.

The number is very large I mean, but again.

Matt.

It's about 6% of patients who are screened might have influences. What are the real issue is how many of those might be responsive versus nonresponsive.

So based on R.

Our preclinical asset.

We've done an estimate based on our sequencing data that.

About 15000 patients in the U S.

Rescue bowls areas and the.

In the MMC for R. J.

But that is not an identified patient number that's genetic up the number.

And the valuable part of that is defined by a preclinical asset. So our challenge goal will be to look and try to understand whether that predicts west the ability to shop, so more to come on that.

Yeah.

That's terrific.

I didn't have a question on pvs, but just a follow up from that.

Another question, we had coming into the call was.

The number of screenings that you've been able to perform this year and how that's been trending versus prior years.

Yes.

We're on track.

Screen between 10, and 15000 patients overall this year the frequencies that we've talked about for each one of our jeans has been remarkably consistent so again thats been quite reassuring.

Tells us is were not screening every patient with obesity, which is absolutely not what we'd want to do that we really are.

Care providers really are targeting those patients.

A history of early onset obesity, plus minus a stronger history of hyperphagia. So I think were getting consistent screening were pretty consistent results.

Thanks, and then one last one if I could here for Jennifer.

These new docs, 22% or sort of thing is what I heard there were not prior targeted what's that telling you not just about receptivity. We're looking to do for you in terms of.

Your strategy in trying to reach out to more of these have you had discussions with these docs to find out how they found out about at Sebree and Bbs.

How does that adjust your marketing going forward. Thanks.

Alright.

So as we are.

Received scripts, we also are able to understand the prescriber and certainly that is added.

Added in cancer targets for RPM to go out and educate.

And also make sure that there is ongoing engagements with them throughout the process of patients are also being initiated on therapy.

There will always be added just in terms of our sphere.

We do expect that on top of the efforts of the Tms on ground, we are going to come across additional physicians, who have patients and our <unk>.

Hi.

May be interested in terms of Macquarie.

If I may just therapy for their patients.

Because of our broad based.

Promotion efforts, which expands our reach beyond that.

The.

The ability of our canton ground so.

We expect that the prescriber base is going to continue to evolve as we move forward additional physicians and patients.

What about the benefits of a separate for this patient population.

Maybe just one comment on the beat the role of the patient themselves into the social network.

Yeah, and I think that's right.

This early in terms of post-launch, we expect that there's going to be, you know, time as payers are still in the evaluation process of evaluating this new indication for MCIPRI.

Within rare disease.

The difference that state just in terms of organization.

Say that within the Bbs patient population.

The Bbs Foundation itself is quite strongly organized.

We get quite a nice job just in terms of.

Organizing these passive to have that opportunity for the patients to engage with each other and learn from each other but also we had the opportunity to present information just in terms of in February itself. So.

It's nice to have that type of strong community and advocacy for this patient population.

And that's the point that these patients themselves may be drivers.

They learn about it and they go to their physician, who may not have heard about it but they're motivated and they help that physician engagement and reconnect.

Thanks, David Jennifer it's very helpful.

Thanks, Mike.

Sure.

Our next question or comment comes from the line of Corinne Jenkins from Goldman Sachs.

Mr. <unk> your line is open.

Hey, good morning.

So maybe I think a lot of our questions have been asked already but perhaps from the patient hub that you started have you had any feedback recently, where youre starting to identify any potential pain points or other feedback that.

Helpful. As you think about these initial 50 patients coming onto therapy.

Jonathan.

So the opportunity to be able to.

This type of high level and high touch service in house.

Really incredibly important.

In rare disease in general, but also for this particular.

Patient population.

I will say that from the perspective of reimbursement there.

There are many similarities just in terms of this early on post launch in terms of the process is taking.

Every.

Drugs.

This type of situations Pat FTA.

Requirements.

That's a given.

And we're fortunate to have.

Happy to outline that EBITDA requirements are very much aligned with RPI.

It's quite expected from that perspective.

I will say that in this particular.

Disease state.

First there are the CMS statute just in terms of.

Our striction of reimbursement of obesity medication. So there are particular segments, including the Medicare.

Population the one that only has Medicare as.

A source of reimbursement that will remain a challenge for us.

And there may be other.

Payers to sort of.

Our first paas perspective without deep background in education.

Lean more towards that type of exclusion. However, as we have heard through our initial dialogues.

Search and such there.

Also opportunity to educate and gain exceptions for this particular patient population as per can understand it quite the difference in terms of what is causing the early onset obesity.

Challenges around the hyperphagia.

Vic nature of a targeted approach that is a free outline it.

It's early days and we're working through the process and a lot of the work that's being done.

While we expected it.

Great and then maybe separately can you just provide us an update on the timing for potential readout of the weekly switch study and then remind us what the Registrational path is forward for that formulation pending results from the phase III.

Yes.

Two parts.

No.

Switch study will readout in 2023, we haven't further defined that exactly.

And so there will be in 2023, and then the second study, which is the de Novo study that will begin in the first half of 2023, we are waiting for the auto injector to begin that trial and so.

That will complete the full.

Alright, just muting myself that will.

The full set of data and that would be a 2020 for filing.

Great. Thanks, that's all from us.

Thanks.

Thank you again, ladies and gentlemen, if you have a question or comment at this time. Please press Star then one on your telephone keypad.

Next question or comment comes from the line of Jeff Hung from Morgan Stanley . Mr. Hung Your line is open hey.

Congratulations on the progress and thanks for taking my questions you indicated a 22% of the prescribing physicians were new.

Many identified patients and written scripts does that correspond to.

Yeah.

Yes.

Broken out.

You have the split is on the <unk>.

<unk> 35.

Physicians basically.

So we're not sort of breaking it down further than that I think it's actually quite a lot of information in the sense that this early on.

Hope Youre, taking away is a breath.

Ascribed, which is really the key and strong engagement reflecting.

For a rare disease, it's as I've said many times you don't write a script and go to a local Cvs phones. So it takes a little bit of a commitment.

Conviction that too to get given that first step of the script written so strong message there.

And then you said you've continued to identify patients beyond the 350 plus bps, what's the updated number of identified patients and do you have a better sense for how many of them overlap with the cribbs registry. Thanks.

So we haven't updated that further I mean, it was 350 plus in February in everything we do.

So, that can take anywhere from 30 to 90 days just in terms of review of specific scripts and probably longer to, you know, get even on the formulary itself.

Good morning.

Great.

Hi.

And then, last question on HO.

It sounds like you have a pretty good idea of how you want to structure the Phase III trial.

Literally and rhythms supports another part of rhythms. So.

What key elements do you need to check with the FDA before you can initiate?

Are there points of design that you think could be controversial to the FDA or you really need clarity from the agency before you implement the trial?

Yeah.

That's a good question.

So, the short answer is I don't know.

The clinical trials, we're running a phase II phase III trials, DAYBREAK and M&A route engage with the community.

Like we said on the last call, which is where we still are, there's very specific guidance for the development of drugs in obesity.

I'm sure it'll be a double-blind randomized controlled trial.

I don't think that's…we're even probably going to debate that.

Rhythm has more visibility <unk> and sebree has more visibility all of that again supports ongoing education and awareness around things, including bps. So that number is going up we haven't updated it further but we feel good about it.

Where we are.

Thank you.

Thanks, Jeff.

Thank you Oh, sorry.

First in the queue at this time I would like to turn the conference back over to management for any closing remarks.

Okay. Thanks, So I just I realize I can answer just one question. There. The question was overlap with the.

The Cribbs registry. So again, we don't know exactly we don't have a list of patients increase for sure there is overlap.

Cribs, and we know we have some prescriptions not surprisingly being written out of the Marshfield clinic in most patients are likely to be cribs. So there is for sure. Some overlap but there is also for sure not 100% overlap. So again encourage you to think about those things was complementary.

For lapping completely.

With that thanks to all of you for tuning in this morning again.

We're excited about our start here.

A lot of really good signals to build on that both in the U S and Europe .

We're excited about our pipeline. So we look forward to our next call. We can update you further on our progress so thanks everybody.

Yes.

Ladies and gentlemen, thank you for participating in today's conference. This concludes the program you may now disconnect everyone have a wonderful day speakers standby.

The conference will begin shortly to raise your hand during Q&A you can dial one one.

[music].

Yes.

[music].