Q1 2022 Rhythm Pharmaceuticals Inc Earnings Call

May 3, 2022

Welcome to the Rhythm Pharmaceuticals first quarter 2022 earnings conference call.

Welcome to the rhythm Pharmaceuticals first quarter 2022 earnings Conference call. My name is Hilda and I will be your operator for today's call.

My name is Hilda and I will be your operator for today's call.

Thank you.

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

At this time all participants are in a listen only mode. Later, we will conduct a question and answer session.

Later, we will conduct a question and answer session.

During the question and answer session and at any time, if you have a question, please press 01 on your touchtone phone.

During the question and answer session and at anytime if you have a question. Please press <unk> one on your Touchtone phone.

I will now turn the call over to Mr. David Connolly, Investor Relations and Corporate Communications.

Welcome to the Rhythm Pharmaceuticals First Quarter 2022 Earnings Conference Call.

I will now turn the call over to Mr. David Connolly Investor Relations and corporate Communications you may begin.

You may begin.

Thank you and good morning, everybody.

My name is Hilda and I will be your operator for today's call.

Thank you and good morning, everybody I'm, Dave <unk> head of IR and corporate communications here at rhythm Pharmaceuticals for those of you participating via conference call. The accompanying slides can be accessed in control by going to be events section of the investors page on our website at IR Dot rhythm TX Dot com.

I'm Dave Connolly, Head of IR and Corporate Communications, here at Rhythm Pharmaceuticals.

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

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

Later we will conduct a question-and-answer session.

This morning, we issued a press release that provides our first quarter, and first quarter 2022 financial results and business update which is available on our website.

This morning, we issued a press release that provides our.

First quarter, and first quarter 2022 financial results and business update which is available on our website.

And as listed on slide two, today here with me in Boston, for the conference call are David Meeker, Chair, President, Chief Executive Officer of Rhythm.

During the question-and-answer session and at any time, if you have a question, please, press 01 on your touchtone phone.

And as listed on slide two today here with me in Boston for the conference call are David Meeker, Jr, President and Chief Executive Officer of rhythm.

I will now turn the call over to Mr. David Connolly, Investor Relations and Corporate, Communications.

You may begin.

Jennifer Chen, Executive Vice President, Head of North America.

<unk> Chen Executive Vice President head of North America, Linda Shapiro, our Chief Medical Officer Hunter Smith, our Chief Financial Officer, and John <unk> Executive Vice President head of International is on the phone joining us from France with.

Linda Shapiro, our Chief Medical Officer.

Hunter Smith, our Chief Financial Officer.

And Jan Mazabro, Executive Vice President, Head of Internationals, on the phone joining us from France.

Thank you and good morning, everybody.

I'm Dave Connolly, Head of IR and Corporate Communications here at Rhythm Pharmaceuticals.

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

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

With slide three I'll remind you this call contains.

This morning, we issued a press release that provides our first quarter 2022 Financial, Results and Business Update, which is available on our website.

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. In addition, any 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.

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

Represent our views only as of today and should not be relied upon as representing our views as of any subsequent date, we specifically disclaim any obligation to update such statements with that I'll turn the call over to David who will begin on slide five.

We specifically disclaim any obligation to update such statements.

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

As listed on slide two, today here with me in Boston for the conference call are David, Meeker, Chair, President, Chief Executive Officer of Rhythm, Jennifer Chen, Executive Vice President, Head of North America, Linda Shapiro, our Chief Medical Officer, Hunter, Smith, our Chief Financial Officer, and Yann Mazabreau, Executive Vice President, Head of International, is on the phone joining us from France.

Thank you, Dave.

Thank you, Dave and good morning, everyone. Thank you for tuning in this morning, and we look forward to updating you on the progress we've made in quarter one.

And good morning, everyone.

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

Thank you for tuning in this morning.

Financial 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.

And we look forward to updating you on the progress we've made in quarter one.

But before I do that, I'd like to start on slide five, with a bit of an unusual start here.

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

Before I do that I'd like to start on slide slide five with a bit of an unusual start here. This cartoon of our biology. Many of you know this slide well.

This is a cartoon of our biology.

Many of you know this slide well.

And as we all know, it's been a particularly difficult moment, in the markets generally, and it's been particularly difficult for small and mid-cap biotechnology companies.

And as we all know it's been a particularly difficult moment in the market generally and it's been particularly difficult for small and mid cap biotechnology companies.

And I think at moments like these, it's worth looking at fundamentals.

We specifically disclaim any obligation to update such statements.

Moments like these that so it's worth looking at fundamentals are always important but particularly so at these kind of moments. So I wanted to spend a couple of minutes just reviewing rhythms fundamentals.

They're always important, but particularly so at these kind of moments.

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

So I wanted to spend a couple of minutes just reviewing rhythms, fundamentals.

Thank you, Dave.

So number one, there's a clear unmet medical need that we're pursuing here. Patients who have a genetic variant that impairs the MC4 pathway, suffer from hyperphagia, decreased energy expenditure, and consequent early onset obesity, and all the comorbidities associated with that.

And good morning, everyone.

So number one there is a clear unmet medical need.

Pursuing here patients who have a genetic variance that compares the <unk> pathways suffered from hyperphagia.

Decreased energy expenditure and consequent early onset obesity and all of the comorbidities associated with that.

Two, the biology is incredibly strong, as highlighted on this slide.

The biology's incredibly strong as highlighted on this slide it's been well studied.

It's been well studied.

The pathway that we're pursuing, the MC4 pathway, the endogenous ligand, the alpha MSH, which interacts with the MC4 receptor. When it engages, it decreases the appetite, increases energy expenditure, and you get a reduction in weight.

The pathway that we're pursuing the emcee for our pathway the endogenous ligand.

The alpha MSH, which interacts with EMC for receptor when it engages with decreases the appetite increases energy expenditure and you get a reduction in weight.

And we've shown in, again, multiple trials that that's associated with other benefits, as well.

And we've shown and again multiple trials that that's associated with other benefits as well.

Third, we have a precision medicine, a solution to this problem.

Third.

We have a precision medicine solution to this problem.

The 7-lanotide is an analog for alpha MSH, and when it engages the receptor, you get, all those benefits, and we are essentially a replacement therapy.

Atlanta tied as an analog for alpha MSH and when it engages the receptor you got all of those benefits and we are essentially a replacement therapy.

It's very simple conceptually and biologically, and we're working in a world where other approaches, to try to manage this problem have not been reliably successful.

Simple conceptually and biologically and were working in a world where other approaches to try to manage this problem have not been reliably successful bariatric surgery, you can get weight loss, but you get it reliably and sustainably and that's the same for other approaches to weight loss management.

Bariatric surgery, you can get weight loss, but do you get it reliably and sustainably?

And that's the same for other approaches to weight loss management.

Or we're de-risked.

Or were de risked.

Most things fail in this industry, and we've been fortunate enough to get 7-lanotide through, the regulatory process in both FDA and EMEA.

Most things fail in this industry.

Unfortunately, not to get <unk> through the regulatory process in both FDA and EMEA you have an approved drug.

We have an approved drug with another one or two indications imminent coming up.

Another one or two indications imminent coming up and so from a.

And so from a risk standpoint, this is a company that's passed one of the very major hurdles, that we all aspire to.

Sure No risk standpoint, this is a company that.

Yes.

One of the very major hurdles that we all aspire to.

And finally, and it's not an endless list here, we know what we need to do commercially.

Five is not a.

And enlist this year.

We know we need to do commercially.

We know what we need to do clinically, and we know what we need to do financially. And we have the team to do it.

We need to do clinically and we know what we need to do financially and we have the team to do it so what youre going to year as we continue to update you.

So what you're going to hear as we continue to update you, we're executing, and as I said, I feel really good about the fundamentals that we're standing on.

Thank you for tuning in this morning.

We're executing in.

As I said I feel really good about the fundamentals that we're standing up.

So with that, let's go to the quarter.

And we look forward to updating you on the progress we've made in quarter one.

With that let's go to the quarter so slide six.

So slide six, we're on track.

But before I do that, I'd like to start on slide five with a bit of an unusual start here.

We're on track.

Let's talk about the U.S. first.

About the U S first.

We're very much looking forward to our PDUFA date on June 16th. We've used the time well, as you can imagine.

Very much looking forward to our <unk> date on June 16th.

Use the time.

As you can imagine with continued active patient identification and disease education efforts and Jennifer will highlight.

We've continued active patient identification and disease education efforts.

And Jennifer will highlight and provide a little more color around that effort.

I'll add a little more color around that effort.

The current commercial opportunity is playing out exactly as we had hoped.

The current commercial opportunity.

Is playing out exactly as we had hoped we have tens of patients on therapy. We continue to learn more about the market access situation, we are able to educate payers and that those interactions are laying a strong foundation for our Bbs launch and really importantly, as we've highlighted in the past we continue to get to interact with pace.

We have tens of patients on therapy.

We continue to learn more about the market access situation.

We are able to educate payers.

And those interactions are laying a strong foundation for our BBS launch.

And really importantly, as we've highlighted in the past, we continue to get to interact, with patients who have consented in to our patient services group, now called Intune. And that's hugely valuable insights as we think, about how we can provide the best service for that patient, how we can help them manage through the early part of getting a therapy like this, the daily administration, the early side effects and the like that all can be significantly benefited by that strong interaction.

<unk>, who have consented into our patient services group, but now called in June .

<unk>.

Usually valuable insights as we think about how we can provide the best service for that patient how we can help them manage through the early part of beginning a therapy like this the daily administration. The early side effects like that all can be significantly benefited by that strong interaction.

The international markets, this international markets are an incredibly important part, of our whole story.

In the international markets International markets are incredibly important part of our whole story spin and then talk a little bit about.

I'll spend, I'm going to talk a little bit about that, more about that in the next slides coming up.

More about that in the next slides coming up but suffice it to say that as we look at Europe . We've highlighted this many times.

But suffice it to say that as we look at Europe, we've highlighted this many times, for all rare diseases, and it's certainly the case in the areas that we're working, Europe is better organized, single payer healthcare system, patients get referred, center of excellence gets set up, true KOLs, thought leaders emerge out of that. They have the opportunity to see many patients.

We're all rare diseases and it's certainly the case in the areas that we're working Europe is better organized single payer healthcare system patients get referred center of excellence get set up Kols thought leaders emerge out of that they have the opportunity to see many patients that can do research and so again.

They can do research.

And so again, the end result of that is as a starting point, there tend to be many more patients identified.

Result of that as a starting point that tend to be many more patients identified and once you do get approval through the health care system for access the process of then getting patients onto therapy is much more street.

And once you do get approval through the healthcare system for access, the process of then getting patients on to therapy is much more straight.

And then in our third bucket, we have a broad clinical development program, and it's amazing. We put in a tremendous amount of work to get these trials up and running, and they're now, running.

Sure.

And then in that third bucket, we have a broad clinical development program and it's a thing we put in a tremendous amount of work to get these trials up and running and they're now running M&A DAYBREAK hyperkalemia obesity trial, pediatrics weeds weekly formulation trials ongoing for.

M&A, Daybreak, the hypothalamic obesity trial, pediatrics, weeds, weekly formulation trials, all ongoing.

We're generating a lot of data, and we're publishing that data, and we just had abstracts, released at PEAS, Pediatric Endocrine Society, over the weekend, and we announced on Monday new additional abstracts, which will be presented at ENDO, and Linda will highlight those in more detail.

We're generating a lot of data and we're publishing that data and we've just had.

Abstracts released it is pediatric and its print society over the weekend and we announced.

On Monday, New additional abstracts will be presented at Endo and Linda will highlight goes in more detail and finally as you know we're very much looking forward to providing updates.

And finally, as you know, we're very much looking forward to providing updates, the, results on our hypothalamic study and our MC4R rescuable interim data, and that will happen mid-year.

The results on a hyperkalemia study in RMC for our rescue Bowl interim data and that will happen midyear.

So, next slide, number seven.

So next slide.

Kevin.

So, internationally, and as I said, we've highlighted that first commercial patients, started in March in France, and we're underway in their early access program, and with that early access program, we're about a year ahead of where we would be if we did not have that in France.

So internationally and as I've said, we've highlighted the first commercial patients started in March in France were underway and their early access program and with that early access program or about a year ahead of where we would be if we do not have that in France, and Germany. All along has been a real education in a very.

Germany all along has been a real education and a very positive development here.

Positive development here.

These products, weight loss drugs in general, are viewed as lifestyle products and restricted.

These products weight loss drugs in general are viewed as lifestyle products and restricted we were able through to get an exemption from annex too.

We were able to get an exemption from Annex II, and that was just published in the past, couple of days in the National Gazette, so that's confirmed.

And that was just published in the past couple of days in the National gift set. So that's confirmed reimbursement dossiers now are being submitted and we look forward to having our first patients commercial patients in the next couple of months in Germany.

Reimbursement dossier is now being submitted, and we look forward to having our first patients, commercial patients, in the next couple of months in Germany.

In the UK, a nice recommendation expected in June, and we will get it.

In the UK nice recommendation expected in June and we will get it. This is not one where are we going to be approved enable to go forward in the U K, we're going to go forward final details to be worked out but.

This is not one where, you know, are we going to be approved and able to go forward in the, UK.

No, we're going to go forward.

Final details can be worked out, but that, you know, we progress to that stage where, we can be extremely confident.

Progressed to that stage, where we can be extremely confident similarly in Italy final stages of price negotiation.

Similarly, in Italy, final stages of price negotiation, feel remarkably good about that.

Remarkably good about that.

That's evolved perhaps even more favorably than we had hoped.

That's evolved perhaps even more favorably than we had hoped Netherlands earlier, but active in Spain, and Sweden, where in the process of associated so we're working our way through Europe .

Netherlands earlier, but active, and then Spain and Sweden were in the process of submitting, those dossiers.

So we're working our way through Europe with, you know, a team of about 20 people, highly, experienced and young on the phone.

<unk> of about 20 people highly experienced and beyond on the phone again, if there's additional questions. We'd go there.

Again, if there's additional questions, we can go there.

Thanks.

And so on the clinical side, as you know, we've updated our M&A and daybreak strategies, slightly, and Linda will dive into that in greater detail, but I'll just say up front, we feel that the adjustments we've made to M&A, we have a flat-out better trial with a higher probability of success, and I'll remind you that we're working in an area where we continue to learn.

And so.

On the clinical side as you know, we've updated our M&A and DAYBREAK strategy slightly and Linda will dive into that in greater detail, but I'll, just say upfront we feel that the adjustments. We've made to M&A, we have a flat out better trial with a higher probability of success and I'll remind you that we're working in an area where we.

To learn.

We continue to learn more about not just us, but us and our partners, the world at large, more about individual variants, and allows us to think about classifying them, looking at ones that were in that boost category, but now maybe with a little better understanding, you could categorize them as more likely to be toward the pathogenic, likely pathogenic end of the spectrum.

To learn more about not just us, but our us and our partners the world at large more about into the deal with variance and allows us to think about classifying them.

Looking at ones that were in that boosts category, but now maybe with a little better understanding you could categorize them as more likely to be towards the pathogenic or likely pathogenic end of the spectrum and so as we've redesigned it again narrowing it down focusing on those it does give us that.

And so as we've redesigned it, again, narrowing it down, focusing on those, it does give us, that better trial.

Better trial.

The numbers, so from a total market opportunity, the numbers have decreased, but I'll remind, you here, so no change to the SH2B1, SRC1 numbers, and the heterozygous POMC and leptin receptor numbers at about 10,000 puts us at an aggregate opportunity, U.S. only, of 50,000-plus.

The numbers so from a total market opportunity the numbers have decreased but I'll remind you here. So no change to the <unk> numbers in the heterozygous palm seeing leptin receptor numbers at about 10000 puts us at an aggregate opportunity.

U S only.

Of 50000 plus.

The HET, LEPT, and Receptor and POMC worlds will in fact be a less confusing commercial, opportunity.

And.

The leptin receptor and policy worlds.

We will in fact be less confusing commercial opportunity. These patients that are better and more clearly defined based on their genetics, and therefore will be easier to manage through the overall process. So net net feel really good about where we are with M&A.

These patients are better and more clearly defined based on their genetics and therefore, will be easier to manage through the overall process.

So net-net feel really good about where we are with M&A and Daybreak.

Britt.

So with that, I'll turn it over to Jennifer.

So with that.

Ill turn it over to Jennifer.

Thank you, David.

Thank you David.

So beginning on slide 11 here, we last shared details of our BBS commercial readiness efforts, in February.

This is a cartoon of our biology.

Beginning on slide 11 here.

Lastly, our details if RBS commercial readiness efforts in February and with producer and launch coming June 16th we aimed today to provide some more detail on the tremendous progress our teams have been making.

And with PDUFA and launch coming June 16th, we aim today to provide some more details, on the tremendous progress our teams have been making.

Many of you know this slide well.

And as we all know, it's been a particularly difficult moment in the markets generally, and it's been particularly difficult for small and mid-cap biotechnology companies.

As we outlined before, the estimated prevalence of BBS in the U.S. is 1,500 to 2,500 patients. And we know approximately 70 to 90 percent of these patients have obesity.

But for the estimated prevalence of Bbs and <unk> 1500 to 25 patients and we now have approximately 70% to 90% of these patients have obesity.

We consider these patients in four distinct categories.

We consider these patients in four distinct category, the first or does that remain undiagnosed.

The first are those that remain undiagnosed.

Similar to other rare genetic diseases, the vast majority of patients remain under the, care of ACPs who have not yet suspected or clinically diagnosed the patient.

Similar to other rare genetic diseases.

Majority of patients to remain under the care of HCP is not yet suspected or clinically diagnosed the paycheck.

This remains a large opportunity.

The second category are those patients under the care of ACPs who have suspected BBS but, may not have yet definitively diagnosed them. Physicians may continue with additional evaluation before verifying a clinical diagnosis.

The second category are those patients under the care of HCP.

Bbs, but may not have yet definitively diagnose.

Physicians may continue with additional evaluation before verifying in clinical diagnostics.

In disease states where there is no approved therapy, there may be less urgency to come, to a specific diagnosis. Providing an approved therapy often aids awareness of the disease and some urgency, towards making a diagnosis.

And disease States, where there is no approved therapy, there may be less urgency to come to you with specific diagnosis.

Having an approved therapy, often AIDS away awareness of the disease and some urgency towards making a diagnosis.

In the last two segments of patients who have been diagnosed, the territory managers have, validated more than 150 physicians who are managing over 350 BBS patients under their care. And we continue to find additional BBS patients through our efforts.

And the last two segments of patients who have been diagnosed the territory managers have validate it more than 150 physician <unk>.

Managing over 350, Bbs patients under their care.

And we continue to find additional Bbs patients there are efforts.

Next slide.

As we prepare for the upcoming potential approval of MCIFRI, the priority focus of the territory, managers remain on engaging with physicians with already identified BBS patients under their care. For this group, we have a baseline – they all have a baseline understanding of BBS, but we are continuing to educate on the underlying impairment to MC4 pathway function and the impact of the resulting hyperphagia and severe obesity on patients.

And I think at moments like these, it's worth looking at fundamentals.

As we prepare for the upcoming potential approval 11th defray the priority focus of the territory managers remain on engaging with physicians with already identified Bbs patients under their care.

They're always important, but particularly so at these kind of moments.

Third, we have a precision medicine, a solution to this problem.

The 7-lanotide is an analog for alpha MSH, and when it engages the receptor, you get all those benefits.

And we are essentially a replacement therapy.

For this group, we have a baseline they all have a baseline understanding of Bbs, but we're continuing to educate on the underlying impairment to emcee for pathway function and the impact of the resulting hyperphagia and severe obesity on pacer.

It's very simple, conceptually and biologically.

In addition to this group, our second set of priority physician targets remain our focus, in terms of speeding the diagnosis of BBS.

In addition to that group.

<unk> set a priority physician targets remain our focus.

Terms of speeding the diagnosis of Bbs.

Here our outreach, engagement, and educational efforts center on BBS disease state awareness, so physicians can suspect BBS and better understand the path to diagnosis.

And we're working in a world where other approaches to try to manage this problem have not been reliably successful.

Here, our outreach engagement and educational efforts center on DVS disease state awareness, so physicians suspect Bbs and better understand the path to diagnosis.

Bariatric surgery, you can get weight loss, but do you get it reliably and sustainably?

And that's the same for other approaches to weight loss management.

Four, we're de-risked.

Most things fail in this industry, and we've been fortunate enough to get 7-lanotide through the regulatory process in both FDA and EMEA.

Rhythm is coming to know these physicians through our Uncovering Rare Obesity genetic, testing program.

Rhythm is coming to know these physicians there are uncovering where obesity genetic testing program.

In the long term, URO may prove to be a rich source of BBS patient identification as these, patients have some degree of severe obesity in order to qualify for the test.

And the long term euro may prove to be a rich source of Bbs patient identification as these patients have some degree of severe obesity in order to qualify for the test.

If there is a hit for BBS, we are able to work with the physician to consider a clinical, diagnosis.

If there is a hit for Biolife Bvs, we are able to then work with the physician to consider a clinical diagnosis.

We have talked in the past about our machine learning approach.

We have an approved drug with another one or two indications imminent coming up.

We've talked in the past also about our machine learning approach.

We have developed a targeted list of physicians associated with certain ICD-10 codes that, are relevant to BBS. The work of our territory managers also supports the building of care teams and broadening, referral networks. As we know, BBS has a constellation of symptoms.

And so, from a secure, no-risk standpoint, this is a company that's passed one of the very major hurdles that we all aspire to.

<unk> developed a targeted list of physicians associated with certain ICD 10 codes that are relevant to Bbs.

Five, and it's not an endless list here, we know what we need to do commercially.

We know what we need to do clinically, and we know what we need to do financially. And we have the team to do it.

So, what you're going to hear as we continue to update you, we're executing, and as I said, I feel really good about the fundamentals that we're standing on.

Next slide.

The work of our territory managers also support the building of care teams and broadening referral network.

We now Bbs has a constellation of symptoms, while hyperphagia and obesity are among the most prevalent and pressing at the symptoms, we know patients with Bbs suffer from retinal disease and vision loss.

While hyperphagia and obesity are among the most prevalent and pressing of the symptoms, we know patients with BBS suffer from retinal disease and vision loss, renal impairments, and other health-related issues. Therefore, a critical factor affecting optimal care of patients with BBS, where they suffer, from various disease manifestations, is the accessibility of a multidisciplinary care network.

Renal impairment and other health related issues. Therefore, a critical factor affecting optimal care of patients with Bbs, where they suffer from various disease manifestation is the accessibility of our multidisciplinary care network.

The Marshall Clinic in Wisconsin serves as a gold standard of holistic, multidisciplinary, care for BBS patients. This clinic started with Dr. Haas, an interested pediatric nephrologist who connected with, an ophthalmologist and expanded their network from there.

The Marshfield clinic in Wisconsin serves as a gold standard of holistic multi disciplinary care for Bbs patient.

This clinic started with Dr. Hards.

Interested pediatric nephrologist, who connected with an ophthalmologist and expanded their network from there.

Interestingly, we are seeing more and more of this type of approach. For example, this last quarter, one of our territory managers called on an inherited, retinal disease specialist at a sizable health center here in the Northeast. This specialist had an interest in BBS and had diagnosed patients under his care, but, he was really focused on the vision issues for these patients, not their obesity or hyperphagia.

Interestingly, we are seeing more and more of this type of approach.

So, with that, let's go to the quarter.

For example, this last quarter one of our territory managers call on an inherited retinal disease specialists as sizable health center here in the northeast the.

So, slide six.

We're on track.

With specialists had an interest in DBS and had diagnosed patients under care, but he was really focused on the vision issues for these patients not their obesity or hyperphagia.

Let's talk about the U.S. first.

Our territory manager identified and connected with a nearby pediatrician with a focus on, obesity and a pediatric cardiologist who had expressed interest in BBS and fostered introductions. These introductions have set in motion the development of a pediatric obesity clinic, with a special focus on BBS.

Our territory manager identified and connected with a nearby pediatrician with a focus on obesity and a pediatric cardiologist, who had expressed interest in DBS and foster introductions.

These introductions have set in motion the development of a pediatric obesity clinic with a special focus on DVS.

We know these connections are also happening in other parts of the nation.

Building out these care teams is important. It helps gain traction in diagnosing patients earlier in their journey, and more importantly, it helps provide these patients with a more complete care team.

Building out these care teams, it's important it helps gain traction and diagnosing patients earlier in their journey and more importantly, it helps provide these patients with a more complete care team.

Next slide.

Just as Rhythm territory managers are working to help build our physician network and care, teams, we have a separate customer engagement team designed to support patients along their journeys.

Just as with him territory managers are working to help build our physician network and care teams.

Have a separate customer engagement team designed to support patients along their journeys.

As David mentioned, Rhythm Intune is a patient support program designed to help overcome, challenges and empower patients and caregivers by providing education and resources tailored to fit the unique needs of each patient. We match patient and caregivers with a dedicated patient education manager as a single point, of contact for a personalized experience.

As David mentioned rhythm and sharing is a patient support program designed to help overcome challenges and empower patients and caregivers by providing education and resources tailored to fit the unique needs of each patient.

We matched patient and caregivers with a dedicated patient education manager at a single point of contact for a personalized experience.

We have really learned from our initial approval in patients with POMC, PCSK1, and leprary, mutations and have fine-tuned our support offerings in preparation for the BBS launch.

We have really learned from our initial approval in patients with Tom CPC SK, One library mutations and had fine tuned our support offering and preparation for the Bbs launch.

For our initial approval, the main focus was on supporting patients through the reimbursement, process. Now, as we finalize our preparations for the BBS launch, we have supplemented this support, with proactive engagement of our customer service team to help patients go from prescription receipt through reimbursement approval to maintenance on therapy. And we have a robust action plan to stay in contact with patients and caregivers, whether, by phone, video call, or even simple checking in emails throughout the course of therapy.

For initial approval the main focus was on supporting patients through the reimbursement process.

Next slide.

Now as we finalize our preparations for the Bbs launch we have supplemented the support with proactive engagement of our customer service team to help patients go from prescription receipt through reimbursement of peripheral to maintenance on therapy.

And we have a robust action plan to stay in contact with patients and caregivers whether by phone video call.

Simple checking an e-mail throughout the course of therapy.

Next slide.

We are ready to launch on day one, June 16th, or earlier. Upon approval, the teams are prepared to engage directly with prioritized physicians with, identified BBS patients, along with consented BBS patients and caregivers.

We're very much looking forward to our PDUFA date on June 16th. We've used the time well, as you can imagine.

We are ready to launch on day, one June 16th or earlier.

Upon approval. The teams are prepared to engage directly with prioritize physicians with identified Bbs patients along with consensus Bbs patients and caregivers.

We have several healthcare providers, as well as BBS patient and caregiver speaker, programs planned, and we are ready to supplement these moving forward.

We've continued active patient identification and disease education efforts, and Jennifer will highlight and provide a little more color around that effort.

We have several health care providers as well as well as Bbs patient and caregiver speaker programs planned.

And we are ready to supplement these moving forward.

In addition, we continue to maintain close relationships with patient advocacy organizations, which are looking forward to sharing the potential news of approval with their membership.

We know there are patients awaiting for a BBS therapy, and we are ready to deliver.

We know there are patients are waiting for Bbs therapy, and we are ready to deliver.

With that, let me hand it over to Linda Shapiro to provide a regulatory and clinical update.

The current commercial opportunity is playing out exactly as we had hoped.

With that.

Let me hand, it over to Linda Shapiro to provide a regulatory and clinical update.

Thank you, Jennifer.

We have tens of patients on therapy.

Thank you Jennifer.

We're now on slide 16 to discuss a brief update on our regulatory progress. Our PDUCA goal date for Bardet-Beetle and Alstrom syndrome is about six weeks away on, June 16th, and label discussions are anticipated to begin in the coming weeks, leading to the final step.

We continue to learn more about the market access situation.

Now on slide 16 to discuss a brief update on our regulatory progress.

We are able to educate payers, and those interactions are laying a strong foundation for our BBS launch.

Our Paducah goal date for BARDA and Ahlstrom syndrome is about six weeks away on June 16. The label discussions are anticipated to begin in the coming weeks, leading to the final step.

And really importantly, as we've highlighted in the past, we continue to get to interact with patients who have consented in to our patient services group, now called Intune, and that's hugely valuable insights as we think about how we can provide the best service for that patient, how we can help them manage through the early part of beginning a therapy like this, the daily administration, the early side effects, and the like, that all can be significantly benefited by that strong interaction.

And the international markets, this, international markets are an incredibly important part of, our whole story.

In Europe, we anticipate the CHMP will make its recommendation on our type 2 amendment, for BBS this summer, with a full decision to come from the European Commission in the fall.

In Europe , we anticipate the <unk> will make a recommendation on our type two amendment for Bbs. This summer with a full decision to come from the European Commission in the fall.

And we do have a recent update to report that last week, the CHMP provided a positive opinion, for a modification to the SMPC, the EU label, with recommendations to expand the use of IMSA-BRE in patients with moderate and severe renal impairment and biallelic POMC, PCSK1, or leptin receptor deficiency.

So we do have a recent update to report that last week.

<unk> provided a positive opinion for a modification to the SMP see EU label with.

With recommendations to expand the use of <unk> in patients with moderate and severe renal impairment.

<unk> receptor deficiency.

The final EC decision on this amendment is anticipated in July, and the same amendment, modification request is being considered as part of the scheduled review for BBS.

Final PUC.

A decision on this amendment is anticipated July and the same amendment modification request is being considered as part of the scheduled review from UBS.

Now on to slide 17.

I'll spend, I'm going to talk a little bit about that, more about that in the next slides, coming up, but suffice it to say that as we look at Europe, we've highlighted this many times, for all rare diseases, and it's certainly the case in the areas that we're working, Europe is better organized, single payer healthcare system, patients get referred, center of excellence, gets set up, true KOLs, thought leaders emerge out of that, they have the opportunity to see many patients, they can do research, and so again, the end result of that is as a starting point, there tend to be many more patients identified, and once you do get approval through the healthcare system for access, the process of then getting patients onto therapy is much more straightforward.

Now on to slide 17.

I'll focus brief remarks on our several ongoing trials evaluating fentanyl antidote in rare, genetic and now also acquired diseases of obesity.

I'll focus brief remarks on our several ongoing trials evaluating several appetite in rare genetic and now also acquired diseases of obesity.

Before providing updates on MNA Daybreak and our phase 2 trial in acquired hypothalamic, obesity, let me mention briefly our phase 3 weekly formulation switch trial and our phase 3 pediatrics trial for young children between the ages of 2 and less than 6 years.

And then in our third bucket, we have a broad clinical development program, and it's a thing, we put in a tremendous amount of work to get these trials up and running, and they're now running, M&A Daybreak, the hypothalamic obesity trial, pediatrics leads, weekly formulation trials, all ongoing, we're generating a lot of data, and we're publishing that data, and we just had abstracts released at PEAS, Pediatric Endocrine Society over the weekend, and we announced on Monday, new additional abstracts, which will be presented at ENDO, and Linda will highlight those in more detail, and finally, as you know, we're very much looking forward to providing updates, the results on our hypothalamic study, and our MC4-R rescuable interim data, and that will happen mid-year.

Before providing updates on M&A DAYBREAK on our phase II trial in acquired Hypothalamic obesity, let me mention briefly our phase III weekly formulation switch trial, and our phase III pediatric trial for young children between the ages of two and less than six years.

So next slide, number seven, so internationally, and as I said, we've highlighted that first, commercial patient started in March in France, and we're underway in their early access program, and with that early access program, we're about a year ahead of where we would be if we did not have that in France.

Germany all along has been a real education and a very positive development here.

These products, weight loss drugs in general, are viewed as lifestyle products and restricted.

We were able to get an exemption from Annex II, and that was just published in the past, couple of days in the National Gazette, so that's confirmed.

These trials are both important elements of our strategy, as we know very well that in, BBS and genetic obesity, the hyperphagia and severe obesity begin very early in life and, We believe it will make quite a difference for them and their caregivers and overall long-term treatment adherence.

These trials are both important elements of our strategy as we know very well that in Bbs genetic obesity.

Hyperplasia in severe obesity began very early in life have a devastating effect on these patients and their families.

We can bring something Willamette tied to these patients earlier in their lives.

More convenient and user friendly weekly dosing regimen, we believe it will make quite a difference for them and their caregivers and overall long term treatment and Terry.

As a reminder, the pediatrics trial is a multi-center, multi-national, one-year, open-label, Phase III trial, enrolling patients with biallelic, POMC, PCSK1, or leptin receptor deficiency obesity, or a clinical diagnosis of BBS with genetic confirmation. As we announced last quarter, we enrolled our first patient in February.

As a reminder, the pediatrics pediatrics trial is a multicenter multinational one year open label Phase III trial is enrolling patients with <unk> <unk>, one our leptin receptor deficiency obesity.

A clinical diagnosis of Bbs with genetic confirmation.

Reimbursement dossier is now being submitted, and we look forward to having our first patients, commercial patients, in the next couple of months in Germany.

As we announced last quarter, we enrolled our first patient in February .

The Phase III SWISH trial evaluates a weekly formulation of setmelanotide in comparison to the daily formulation in patients six years and older, with a rare genetic disease of obesity who are currently in our long-term extension trial and taking a stable dose of the daily formulation of setmelanotide. First patients were dosed with the weekly formulation in January, and enrollment is progressing.

In the UK, a nice recommendation expected in June, and we will get it.

This is not one where, you know, are we going to be approved and able to go forward in the, UK.

Phase III switch trial evaluates a weekly formulation of <unk> in comparison to the daily formulation in patients six years and older with the rare genetic disease of obesity.

Currently in our long term extension trial, taking a stable dose of the daily formulations that will amortize.

No, we're going to go forward.

Patients were dosed.

With the weekly formulations January January and enrollment is progressing.

Now we'll go into a little bit more detail on our hypoglycemic obesity trial, Daybreak and Emanate, beginning with Emanate on slide 18. Emanate now includes four independent sub-studies evaluating setmelanotide in patients with severe obesity due to one of four genetic subtypes.

Now I will go into a little bit more detail on our hydrocodone with obesity trials DAYBREAK and M&A beginning with M&A.

Emanate now includes four independent sub studies evaluating certain Atlanta tied to patients with severe obesity due to one of four genetic subtypes.

There remains a significant unmet need for people living with these rare genetic diseases of obesity that are unresponsive to other treatment interventions. These patients are living with hyperphagia, that pathological insatiable hunger, and severe obesity, which has a significant impact on all aspects of their lives. We are committed to bringing these patients a much-needed safe and effective therapy. As for many of them, we know lifestyle interventions of physical activity and nutrition changes do not work, nor do bariatric surgery or other pharmacotherapies, as they do not address the underlying impairment to the MC4R pathway that is the root cause of the hyperphagia and severe obesity.

There remains a significant unmet need for people living with these routes genetic disease. Several facility that are unresponsive to other treatment interventions.

These patients are living with hyperphagia that pathological insatiable hunger.

Severe obesity, which has a significant impact on all aspects of their lives.

We are committed to bringing these patients a much needed safe and effective therapy as are many of them. We know lifestyle interventions of disco activity and nutrition changes do not work, nor dewberry ethic surgery or other pharmacotherapy as they should not address the underlying impairment to the empty for a pathway that is the root cause of the hyperphagia.

It's fairly steady.

We announced last month we have implemented modifications to optimize both Emanate and Daybreak to focus on the rare patient populations which we believe have the highest likelihood of success.

Final details to be worked out, but that, you know, we've progressed to that stage where, we can be extremely confident.

We announced last month, we have implemented modifications to optimize both M&A and debris focused on the rare patient population, which we believe have the highest likelihood of success.

Similarly in Italy, final stages of price negotiation, feel remarkably good about that.

We initiated the trial with the first patient enrolled in April.

That's evolved perhaps even more favorably than we had hoped.

The trial with the first patient enrolled in April .

Now on to slide 19.

Netherlands earlier, but active, and then Spain and Sweden were in the process of being, associated.

Now on to slide 19.

So we're working our way through Europe, you know, a team of about 20 people, highly, experienced, and Jan's on the phone.

A little more detail on the design for this trial.

Again, if there's additional questions, we can go there.

A little more detail on the design for this trial.

Emanate includes four independent sub-studies evaluating setmelanotide compared to placebo over 52 weeks. Patients six years of age and older with hyperphagia and obesity due to a heterozygous variant of the POMCY PCSK1 genes, leptin receptor gene, SRC1 gene, and the SH2B1 gene.

Next.

M&A includes four independent sub studies evaluating certain Atlanta.

Compared to placebo over 52 weeks.

And so on the clinical side, as you know, we've updated our M&A and daybreak strategy, slightly, and Linda will dive into that in greater detail.

It's six years of age and older with hyperphagia and obesity due to a heterozygous variant of the <unk> leptin receptor gene Src, one gene and the message to be launching.

But I'll just say up front, we feel that the adjustments we've made to M&A, we have a flat, out better trial with a higher probability of success.

As we announced last month, the POMCY PCSK1 and leptin receptor sub-studies, we are focusing enrollment on variants classified following the framework established by the American College of Medical Genetics as pathogenic and likely pathogenic, as initially planned.

And I'll remind you that we're working in an area where we continue to learn. We continue to learn more about not just us, but us and our partners, the world at large, more about individual variants, and allows us to think about classifying them, looking at ones that were in that boost category, but now maybe with a little better understanding, you could categorize them as more likely to be toward the pathogenic, likely pathogenic end of the spectrum.

As we announced last month the <unk> one receptor sub studies, we are focusing enrollment on variance classified following the framework established by the American College of medical genetics, as pathogenic and likely pathogenic as initially planned.

And we have modified to include a narrower sub-population of variants of uncertain significance for BOOS.

And so as we've redesigned it, again, narrowing it down, focusing on those, it does give us, that better trial.

We have modified to include a narrower subpopulation of variants of uncertain significance our booth.

Now only include the BOOS subset with variants that are suspected to be pathogenic and most likely to impair the MC4 pathway function. Based on this rationale and our phase two basket trial data, also most likely to respond to setmelanotide.

These patients are, better and more clearly defined based on their genetics and, therefore, will be easier to manage through the overall process.

Now only include the boost subset with variance that are suspected to be pathogenic and most likely to impair the FC for pathway function based on this rationale in our phase II basket trial data off the most likely to respond to several advertising.

So that and that feel really good about where we are with M&A and Daybreak.

And so with that, I'll turn it over to, Jennifer.

Primary endpoint in this trial is a difference in mean percent change in BMI compared to placebo for each sub study and BMI is well suited measure for this patient population that includes both adults and children.

This trial design allows for independent data readouts, submission, and registration of, each of the genes in sub-studies.

Thank you, David.

This trial design allows for independent data Readouts submission in registration.

Each of the chains.

Upsetting.

Next slide.

We also recently modified our Phase 2 Daybreak Trial to focus initially on rare variants, associated with 10 prioritized MC4R-relevant genes, which we and several key opinion leaders believe have the highest probability of responses at melanotypes. For the remaining genes, we paused enrollment, and we will evaluate expansion of daybreak, to these genes based on the early clinical data from the prioritized genes. Daybreak has an efficient design that allows for quickly achieving signals of proof of concept, for each genetic cohort independently during an initial open-label run-in period.

We also recently modified our phase II <unk> trial to focus initially on rare variance associated with 10 prioritized since before our relevant genes, which we at several key opinion leaders believe have the highest probability of responses.

For the remaining genes, we paused enrollment and we will evaluate expansion in day rates for these teams based on the early critical data from the prioritize.

Fabric has an efficient design that allows for complete achieving signals a proof of concept for each genetic cohort independently during an initial open label run in period.

This could provide signals of potential efficacy in certain gene cohorts by the end of this year, in patients who demonstrate a clinically meaningful response to that melanotype. This is then followed by a randomized placebo-controlled second stage.

This could provide signals of potential efficacy uncertainties cohorts by the end of this year and patients to demonstrate a clinically meaningful response several advertise.

This is followed by a randomized placebo controlled second stage.

Daybreak enrollment began in January of this year.

So beginning on slide 11 here, we last shared details of our BBS commercial readiness efforts in February, and, with PDUFA and launch coming June 16th, we aim today to provide some more details on the tremendous progress our teams have been making.

As we outlined before, the estimated prevalence of BBS in the U.S. is 1,500 to 2,500 patients, and we know approximately 70 to 90% of these patients have obesity.

Fabric enrollment began in January of this year.

Next slide.

Hypothalamic obesity is a rare acquired form of obesity that develops following structural injury, to the hypothalamic region of the brain that contains the MC4 pathway neurons responsible for controlling physiologic functions such as food intake, energy expenditure, and body weight regulation. This disease is most commonly associated with craniopharyngioma, a rare brain tumor, or the associated treatment by surgery or radiation. Approximately half of patients with craniopharyngioma experience rapid onset acute weight gain, and hyperphagia shortly after tumor treatment.

We consider these patients in four distinct categories.

Hypothalamic obesity is a rare acquired form of obesity that develops following structural injury to the Hyperscale <unk> region of the brain that contains the emcee for pathway neurons responsible for controlling physiological functions such as.

The first are those that remain undiagnosed. Similar to other rare genetic diseases, the vast majority of patients remain under the care of ACPs who have not yet suspected or clinically diagnosed the patient.

This remains a large opportunity.

The second category are, those patients under the care of ACPs who have suspected BBS but may not have yet definitively diagnosed them. Physicians may continue with additional evaluation before verifying a clinical diagnosis.

Food intake energy expenditure and body weight regulations.

In disease states where there is no approved therapy, there may be less urgency to come to a specific diagnosis. Having an approved therapy often aids awareness of the disease and some urgency towards making a diagnosis.

This disease is most commonly associated with cranial French Guiana career brain tumor.

In the last two segments of patients who have been diagnosed, the territory managers have validated more than 150 physicians who are managing over 350 BBS patients under their care, and we continue to find additional BBS patients through our efforts.

Next slide.

Or the associated treatment by surgery or radiation.

As we prepare for the upcoming potential approval of MCIFRI, the priority focus of the territory managers remain on engaging with physicians with already identified BBS patients under their care.

For this group, we have a baseline, they all have a baseline understanding of BBS, but we are continuing to educate on the underlying impairment to MC4 pathway function and the impact of the resulting hyperphagia and severe obesity on patients.

Approximately half of patients with cranial pharyngeal experienced rapid onset acute weight gain and hyperphagia shortly after tumor treatments.

While treatment does exist to replace many of the hormones controlled by the pituitary gland, that is also injured during tumor treatment, there are no safe and effective therapeutic options for the hyperphagia and obesity that result from injury to the hypothalamus, and this can be the most devastating and disruptive for patients and their families.

While treatment does exist to replace many of the hormone controlled by the pituitary gland that is also ensured very tumor treatment. There are no safe and effective therapeutic options for the hyperphagia and obesity that result from injury to the hypothalamus and this can be the most devastating and disruptive for patients and their families.

The community around hypothalamic obesity is well-established and well-organized, with the Raymond A.

The community around Hypothermic obesity is well established and well organized with the Raymond <unk> Foundation founded in 2016 to empower hypothermic pituitary brain tumor survivors for improved quality of life by providing access to education technology is evolving treatment.

Wood Foundation founded in 2016 to empower hypothalamic pituitary brain tumor survivors for improved quality of life by providing access to education, technology, and evolving treatments. In October 2021, this group hosted a patient listening session with the Food and Drug Administration, where several patients and caregivers provided testimony on the insurmountable challenges of hypothalamic obesity.

In addition to this group, our second set of priority physician targets remain our focus in terms of speeding the diagnosis of BBS.

In October 2021, this group posted a patient listening sessions with the food and drug administration.

Here, our outreach, engagement, and educational efforts center on BBS disease state awareness, so physicians can suspect BBS and better understand the path to diagnosis.

Rhythm is coming to know these physicians through our Uncovering Rare Obesity genetic testing program.

For several patients and caregivers provided testimony on the interim optical challenges challenges.

Parameter obesity.

I have a sample of quotes here.

Upon returning home from the hospital, he foraged at night.

Upon returning home from the hospital before it at night.

Hyperphagia is the biggest cause of low quality of life.

Hyperplasia is the biggest cause of low quality of life.

Within six months, I gained 30 pounds.

Within six months I gained 30 pounds.

It's clear there's a significant unmet need, and this patient community is desperate for safe and effective therapy.

In the long term, URO may prove to be a rich source of BBS patient identification, as these patients have some degree of severe obesity in order to qualify for the test.

It's clear there is a significant unmet need in this patient community is desperate for safe and effective therapy.

Now to slide 22 for a brief overview of our Phase 2 trial in patients with hypothalamic obesity.

If there is a hit for biallelic BBS, we are able to then work with the physician to consider a clinical diagnosis.

Now to slide 22 for a brief review for a brief overview of our phase II trial in patients with type of landmark obesity.

This is a phase two open label proof of concept trial evaluating certain Atlanta.

This is a Phase 2 open-label, proof-of-concept trial evaluating set melanocytes in individuals with hypothalamic obesity.

We've talked in the past also about our machine learning approach.

And individuals with pipeline with obesity.

Enrollment is complete with 18 patients aged 6 years or older in this open-label, 16-week treatment period.

We have developed a targeted list of physicians associated with certain ICD-10 codes that are relevant to BBS.

<unk> is complete with 18 patients aged six years with older. In this open label 16 week treatment period.

We look forward to sharing preliminary data this summer, so please stay tuned.

Next slide.

The work of our territory managers also supports the building of care teams and broadening referral networks.

Look forward to sharing preliminary data this summer so please stay tuned.

We have a busy spring planned when it comes to presentations at medical conferences. These presentations afford us an excellent opportunity to engage with top key opinion leaders in treating healthcare providers on rare genetic diseases of obesity and the severity of hyperphagia and obesity these patients and their families live with. Importantly, it also gives us the opportunity to discuss with them the efficacy and safety of setmelanotide, and we are pleased to have tremendous support of leading key opinion leaders who are delivering these presentations.

Now to slide 23.

We have a busy spring plans when it comes to presentations at medical conferences.

These presentations before us with excellent opportunities to engage with top key opinion leaders and treating health care providers and rare genetic disease, <unk> and the severity of hyperphagia and obesity in these patients and their families.

Importantly, it also gives us the opportunity to discuss with them the efficacy and safety of certain Atlanta right. Now we're pleased to have tremendous support of leading key opinion leaders who are delivering these presentations.

At the Pediatric Endocrine Society 2022 virtual annual meeting this past weekend, we presented new data supporting the potential for setmelanotide to treat the early onset obesity, hyperphagia, and metabolic impairments associated with Vardic beetle syndrome. In addition, we announced cumulative safety data from across the setmelanotide clinical development program, demonstrating that treatment is generally safe and well-tolerated.

As we know, BBS has a constellation of symptoms. While hyperphagia and obesity are among the most prevalent and pressing of the symptoms, we know patients with BBS suffer from retinal disease and vision loss, renal impairments, and other health-related issues. Therefore, a critical factor affecting optimal care of patients with BBS, where they suffer from various disease manifestations, is the accessibility of a multidisciplinary care network.

The Marshfield Clinic in Wisconsin serves as a gold standard of holistic multidisciplinary care for BBS patients. This clinic started with Dr. Haas, an interested pediatric nephrologist, who connected with an ophthalmologist and expanded their network from there.

At the pediatric Endocrine Society 2022 virtual annual meeting this past weekend.

Presented new data supporting the potential for certain Atlanta tried to treat the early onset obesity hyperphagia and metabolic impairment associated with <unk> syndrome.

Interestingly, we are seeing more and more of this type of approach.

For example, this last quarter, one of our territory managers called on an inherited retinal disease specialist, at a sizable health center here in the Northeast. This specialist had an interest in BBS and had diagnosed patients under his care, but he was really focused on the vision issues for these patients, not their obesity or hyperphagia.

In addition, we announced cumulative safety data from across that will amortize clinical development program demonstrated that treatment is generally safe and well tolerated.

Our territory manager identified and connected with a nearby pediatrician with a focus on obesity, and a pediatric cardiologist who had expressed interest in BBS and fostered introductions. These introductions have set in motion the development of a pediatric obesity clinic with a special focus on BBS.

And as we announced today, six abstracts of new data were accepted for presentation at the Endocrine Society annual meeting and expo in June of this year. Highlights here will include one-year BMI data in SRC1, SH2B1, and heterozygous POMC PCSK1 electron receptor, along with longer-term data in BBS and biallelic POMC PCSK1 electron receptor.

We know these connections are also happening in other parts of the nation.

And as we announced today six abstracts of new data were accepted for presentation at the endocrine Society annual meeting.

<unk>.

In June of this year.

Highlights share will include one year BMI data and Src, one assets should be one heterozygous prop 65 tier one leptin receptor.

<unk> with longer term data in Bbs and <unk> receptor.

We're thrilled to have the support of an all-star cast of key opinion leaders as listed on this slide.

Next slide.

Just as Rhythm territory managers are working to help build our physician network and care teams, we have a separate customer engagement team designed to support patients along their journeys.

We're thrilled to have the support of all star cast of key opinion leaders as listed on this slide.

These conferences provide us with a great opportunity to communicate and disseminate data about setmelanotide and genetic diseases of obesity to support recruitment in our ongoing trials, as well as raise awareness and educate the healthcare community about POMC PCSK1 electron receptor and BBS.

These conferences provide us with a great opportunity to communicated disseminate data about set melanocyte genetic diseases of obesity support recruitment in our ongoing trials as well as raise awareness and educate the health care community about proxy.

The first chapter of Bbs.

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

With that I will turn the call over.

Thank you, Dr. Shapiro.

Thank you Dr Shapiro turning.

Turning to slide 25, as David mentioned at the start of the call, we're pleased to report product revenue of $1.5 million in the first quarter of 2022, as compared to approximately $35,000 in the first quarter of 2021. While sales during the quarter included our first sales from outside the U.S., sales volumes did not significantly affect the quarter's results, given how late they occurred during the quarter and the limited number of initial prescriptions involved.

As David mentioned, Rhythm in Tune is a patient support program designed to help overcome, challenges and empower patients and caregivers by providing education and resources tailored to fit the unique needs of each patient. We match patient and caregivers with a dedicated patient education manager as a single point, of contact for a personalized experience.

Turning to slide 25, as David mentioned at the start of the call. We're pleased to report product revenue of $1 5 million for the first quarter of 2022 as compared to approximately 35000.

In the first quarter of 2021.

We have really learned from our initial approval in patients with POMC, PCSK1, leprary mutations, and have fine-tuned our support offerings in preparation for the BBS launch.

Sales during the quarter included our first sales from outside the U S sales volumes did not significantly affect the quarter's results given how late they occurred during the quarter and the limited number of initial prescriptions involved.

Net sales in Q1 2022 were down sequentially versus Q4 2021. This decrease was largely due to a decrease in orders from our specialty pharmacy versus prior quarter.

Next slide.

We are ready to launch on day one, June 16th, or earlier. Upon approval, the teams are prepared to engage directly with prioritized physicians, with identified BBS patients, along with consented BBS patients and caregivers.

In Q1, 2022 was down sequentially versus Q4 2021. This decrease was largely due to a decrease in orders from our specialty pharmacy versus prior quarter vial shipped from the SP patients were largely unchanged.

We have several healthcare providers, as well as BBS patient and caregiver speaker programs, planned, and we are ready to supplement these moving forward.

In addition, we continue to maintain close relationships with patient advocacy organizations, which are looking forward to sharing the potential news of approval with their membership.

We know there are patients awaiting for a BBS therapy, and we are ready to deliver.

Files shipped from the SP to patients were largely unchanged.

Cost of goods sold was $230,000 in Q1.

Cost of goods sold was 230000 in Q1, the largest portion of this figure was amortization of sales milestones.

The largest portion of this figure was amortization of sales milestones paid to Ipsen. Rhythm previously paid Ipsen a milestone of $5 million for the first U.S. sale, and during Q1 paid a $4 million milestone covering the first sale in Europe. These milestones will be amortized quarterly. COGS also include the 5% royalty payable to Ipsen.

Rhythm previously paid absent a milestone of $5 million for the first U S sale and during Q1 paid a $4 million milestone covering the per sale in Europe .

Milestones will be amortized quarterly costs also include the 5% royalty payments payable to us.

Loss from operations was $52.7 million in the quarter, an increase of $18.3 million over the first quarter of 2021. R&D expense increased by $12.6 million to $32.5 million. The increase was primarily due to higher clinical trial expense involving the startup of our M&A Daybreak weekly formulation switch studies. In addition, Rhythm purchased $3.8 million of clinical supply material during the quarter.

Loss from operations was $52 7 million in the quarter, an increase of $18 3 million over the first quarter of 2021 R&D expense expense increased by $12 6 million to $32 5 million. The increase was primarily due to higher clinical trial expense involving the startup of our M&A DAYBREAK weekly formulation.

With that, let me hand it over to Linda Shapiro to provide a regulatory and clinical update.

<unk> switch studies. In addition, rhythm purchased $3 8 million of clinical supply materials during the quarter.

At G&A expense was $21.4 million in Q1, an increase of $6.9 million versus the first quarter of 2021. The increase was largely the result of increased headcount costs in our U.S. and international commercial organizations, as well as increased marketing spend.

G&A expense was $20 $21 4 million in Q1, an increase of $6 $9 million versus the first quarter of 2021.

The increase was largely the result of increased head count costs in our U S and international commercial organizations as well as increased marketing expense.

Consistent with the results in Q1, we expect our full year 2022 operating expenses to increase over 2021 due to increased clinical development activities. As is typical of large clinical trials, there are significant upfront costs during study startup. In addition, we anticipate higher commercialization activities related to the potential launch of inobsidian BBS in the U.S., as well as ongoing efforts across Europe.

Consistent with the results in Q1, we expect our full year 2022 operating expenses to increase over 2021 due to the increased clinical development activities.

As is typical of large clinical trials there are significant upfront costs during the study startup.

In addition, we anticipate higher commercialization activities related to the potential launch of <unk> Bbs and <unk>.

S as well as ongoing efforts across Europe .

Our share count was 50.3 million basic and diluted shares, and loss per common share was $1.05.

Share count was $50 3 million basic and diluted shares in loss per common share was $1 and $5.

We concluded the quarter in a strong financial position with cash and cash equivalents and short-term investments of $241 million, which we believe will be sufficient to fund Rhythm's operations in the fourth quarter of 2023.

We concluded the quarter in a strong financial position with cash and cash equivalents and short term investments of 241 billion, which we believe will be sufficient to fund rhythms operations in the fourth quarter of 2023.

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

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

Thank you.

Thank you, Jennifer.

Thank you Hunter.

We're now on slide 16 to discuss a brief update on our regulatory progress. Our PDUCA goal date for Bartlett-Beetle and Alstrom syndrome is about six weeks away on, June 16th, and label discussions are anticipated to begin in the coming weeks, leading to the final step.

As you've all heard.

I have a lot underway.

<unk> on the left.

I think what's most noteworthy as well.

Had a very daunting at one level task of getting all of these clinical trials up and running and they are all up.

In Europe, we anticipate the CHMP will make its recommendation on our type 2 amendment, for BBS this summer, with a full decision to come from the European Commission in the fall.

It'll be up and running and so when we look forward to going forward lots of head producer date, EMEA approval and as you've heard lots of data on that.

And we do have a recent update to report that last week, the CHMP provided a positive opinion, for a modification to the FMPC, the EU label, with recommendations to expand the use of IMSA-BRE in patients with moderate and severe renal impairment and biallelic POMC, PCSK1, or leptin receptor deficiency.

The final EC decision on this amendment is anticipated in July, and the same amendment, modification request is being considered as part of the scheduled review for BBS.

Now on to slide 17.

Reporting out.

With that in the first half launching in Europe started in France, Germany, UK, Italy, all to come in.

I'll focus brief remarks on our several ongoing trials evaluating fentanylanotide in rare, genetic and now also acquired diseases of a rare disease.

Before providing updates on MNA Daybreak and our Phase 2 trial in Acquired Hypothalamic, Obesity, let me mention briefly our Phase 3 Weekly Formulation Switch Trial and our, Phase 3 Pediatrics Trial for young children between the ages of 2 and less than 6 years.

These trials are both important elements of our strategy, as we know very well that in, BDS and genetic obesities, the hyperphagia and severe obesity begin very early in life and have a devastating effect on these patients and their families.

So we'll be getting that last de Novo study as part of our weekly.

We can bring setmelanotide to these patients earlier in their lives, and in a more convenient, and user-friendly weekly dosing regimen, we believe it will make quite a difference for them and their caregivers and overall long-term treatment adherence.

Overall development plan in the second half so again very much looking forward to those events and a very important year for rhythm.

Thank you, Hunter.

We welcome your questions so with that operator, we can go to Q&A. Thank you.

So I think, as you've all heard, we have a lot underway in the box on the left.

As a reminder, the Pediatrics Trial is a multi-center, multi-national, one-year, open-label, Phase, 3 trial enrolling patients with bioallelic, POMC, PCSK1, or left-of-receptor deficiency obesity, or a clinical diagnosis of BDS with genetic confirmation. As we announced last quarter, we enrolled our first patient in February.

I think, you know, what's most noteworthy is we had a very daunting at one level task of getting all these clinical trials up and running, and they're all up and running.

Thank you we will now begin the question and answer session. If you have a question. Please press <unk> one on your Touchtone phone.

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<unk>.

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And so what we look forward to going forward, lots ahead.

Phase 3 Switch Trial evaluates a weekly formulation of setmelanotide in comparison to the daily, formulation in patients 6 years and older with a rare genetic disease of obesity who are currently in our long-term extension trial and taking a stable dose of the daily formulation of setmelanotide.

And we have a question from Phil Nadeau from Cowen and company. Please go ahead.

Purdue for date, EMA approval, as you've heard, lots of data that we're reporting out.

First, patients were dosed with the weekly formulation in January, and enrollment is, progressing.

Some of that in the first half, launching in Europe, started in France, Germany, UK, Italy, all to come.

Now, we'll go into a little bit more detail on our hypoglycemic obesity trial, Daybreak, and M&AID, beginning with M&AID on slide 18.

And we'll also be getting that last de novo study as part of our weekly overall development plan in the second half.

M&AID now includes four independent sub-studies evaluating setmelanotide in patients with severe, obesity due to one of four genetic subtypes. There remains a significant unmet need for people living with these rare genetic diseases, of obesity that are unresponsive to other treatment interventions. These patients are living with hyperphagia, that pathological insatiable hunger, and severe, obesity, which has a significant impact on all aspects of their lives.

We are committed to bringing these patients a much-needed safe and effective therapy.

So, again, very much looking forward to those events and a very important year for Rhythm.

Hi, This is Tyler on for Phil. Thank you so much for taking my question and congrats on the progress.

As for many of them, we know lifestyle interventions of physical activity and nutrition changes, do not work, nor do bariatric surgery or other pharmacotherapies, as they do not address the underlying impairment to the MC4R pathway that is the root cause of the hyperphagia and severe obesity.

Maybe really quickly on the phase two data.

Hyperbola Nikko BCD.

We announced last month we have implemented modifications to optimize both M&AID and Daybreak, to focus on the rare patient populations which we believe have the highest likelihood of success.

We initiated the trial with the first patient enrolled in April.

Can you maybe just give a brief overview of what you might consider for this concept darrin in terms of the proportion of patients achieving a reduction in BMI or would you need to see the progress development. Thank you.

Now on to slide 19.

And we now welcome your questions.

So with that uprated, we can go to Q&A.

A little more detail on the design for this trial.

Linda you want to sure. So the endpoints are focused on changes in body weight and BMI and other BMI related measures in the pediatric population as well as our hunger and hyperphagia scores.

Thank you.

M&AID includes four independent sub-studies evaluating setmelanotide compared to placebo, over 52 weeks. Patients 6 years of age and older with hyperphagia and obesity due to a heterozygous variant, of the POMC PCSK1 genes, leptin receptor gene, SRC1 gene, and the SH2B1 gene.

As we announced last month, the POMC PCSK1 and leptin receptor sub-studies, we are focusing, enrollment on variants classified following the framework established by the American, College of Medical Genetics as pathogenic and likely pathogenic as initiated.

And we have modified to include a narrower sub-population of variants of uncertain significance for BOOS. We now only include the BOOS subset with variants that are suspected to be pathogenic, and most likely to impair the MC4 pathway function.

Based on this rationale and our Phase 2 BASCA trial data, also most likely to respond to separal amortized.

The primary endpoint in this trial is the difference in mean percent change in BMI compared to placebo for each sub-study, and BMI is a well-suited measure for this patient population that includes both adults and children.

This trial design allows for independent data readout, submission, and registration of each of the genes in sub-studies.

Thank you.

Next slide.

We also recently modified our Phase 2 Daybreak trial to focus initially on rare variants associated with 10 prioritized MC4R-relevant genes, which we and several key opinion leaders believe have the highest probability of response to separal amortized.

Don't think at this time, we can comment on what we would need to progress, but middle of the year, how we will be announcing the data plans.

For the remaining genes, we paused enrollment and we will evaluate expansion of Daybreak to these genes, based on the early clinical data from the prioritized genes. Daybreak has an efficient design that allows for quickly achieving signals of proof of concept for each genetic cohort independently, during an initial open-label run-in period.

This could provide signals of potential efficacy in certain gene cohorts by the end of this year, in patients who demonstrate a clinically meaningful response to separal amortized. This is then followed by a randomized placebo-controlled second stage.

Daybreak enrollment began in January of this year.

Plans if appropriate thereafter.

And the only thing I would add to that is.

The FDA is very clearly outlined at 5% threshold for weight loss BMI changes clinically significant significant from a regulatory standpoint, needless to say, we would need to see at least that.

I also think.

We're looking to make a meaningful difference and so as Linda said, when we evaluate that data will not be looking to just barely cleared that hurdle. So to speak come. So again I'd be looking for something north of that 5% kind of improvement.

That's very helpful. Thank you so much.

Thank you.

We will now begin the question and answer session.

Next slide.

Our next question comes from Derek <unk> from Wells Fargo. Please go ahead.

Hypothalamic obesity is a rare acquired form of obesity that develops following structural injury to the hypothalamic region of the brain, that contains the MC4 pathway neurons responsible for controlling physiologic functions, such as food intake, energy expenditure, and body weight regulation. This disease is most commonly associated with craniopharyngioma, a rare brain tumor, or the associated treatment by surgery or radiation. Approximately half of patients with craniopharyngioma experience rapid onset acute weight gain and hyperphagia, shortly after tumor treatment.

While treatment does exist to replace many of the hormones controlled by the pituitary gland that is also injured during tumor treatment, there are no safe and effective therapeutic options for the hyperphagia and obesity that result from injury to the hypothalamus, and this can be the most devastating and disruptive for patients and their families.

The community around hypothalamic obesity is well-established and well-organized, with the Raymond A.

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Hey, good morning, guys and congrats on the progress just a couple of questions from us.

First on the Bbs launch.

I would love to just kind of get a sense of how you think the trajectory could go and if theres any good analogs you can point to is this something where we expect more of a slow trickle or is there a bolus of patients.

Given the outreach you've done.

Second I would ask just in terms of the Germany soon.

I guess now that you are ramping are you starting to sell there how many patients have you actually identified in that country.

Once again, if you have a question, please press 01 on your touchtone phone.

I have a sample of quotes here.

And when I go to Jennifer <unk>.

The U S launch and then beyond I'll turn to you for some comments on Germany.

Thanks for the question.

And we have a question from Phil Nadeau from Cohen and Company.

Please go ahead.

I think in.

Any rare disease, especially when there is no therapy available.

Difficult to really accurately project a trajectory of any bonds.

With that said I think that the Bbs launch will be completely different in terms of expectations versus what we saw with the PPL approval.

We feel.

Very very good in terms of the strong number of patients that have already been identified to date I think once again in an area, where there is no therapy available the starting point and where we are is quite strong.

It's clear there is a significant unmet need and this patient community is desperate for a safe and effective therapy.

Now to slide 22 for a brief overview of our Phase 2 trial in patients with hypoglammic obesity. This is a Phase 2 open-label proof-of-concept trial evaluating set melanocytes in individuals with hypoglammic obesity.

With the territory managers in the field, we have also the corporate accounts team in place.

As I outlined rhythm into NN actively setting expectations.

And we have a team in place that is really quite anxious and ready to go in terms of the launch and helping to get patients on drug and stay on <unk> and <unk>.

So we are very confident in terms of having a successful launch here and there is a lot of excitement that we hear also from.

The community from patients caregivers as well as physician.

And any analogs.

Think of them.

Hi, this is Lila on for Phil.

Maybe I'll just start off I mean, this is a challenge in the rare disease space. Obviously, there's some similarities in the sense that rare disease drug some price that.

Thank you so much for taking the question and congrats on the progress.

Price point, they tend to be priced add often working with physicians, who have never written a prescription for a rare disease drug never gone through the approval process, which was a bit more cumbersome than cumbersome than writing a prescription for your local Cvs obviously.

So all that is part of it but that said theres not really a good analog for this but ill reinforce where general percent starting point with the number of patients. We've identified the level of the organization of the community at this point, it's incredibly positive. So I think in a relative sense. We feel good very good about where we will start in that.

Enrollment is complete with 18 patients aged 6 years and older in this open-label 16-week treatment period.

We look forward to sharing preliminary data this summer, so please stay tuned.

Now to slide 23.

First six months as you know Derek we've tried to guide people away from this idea that there is a specific expectation whatever it is I don't know if were going to come out of the gate fast whatever that means are a bit more slowly.

But.

Over time, meaning the six to 12 12 to 18 month period, that's the period, where I would really look at to get a better sense for what this opportunity is going to look like.

Maybe really quickly on the phase two data expected in hypothalamic obesity.

Certainly.

Importantly, it also gives us the opportunity to discuss with them the efficacy and safety of set melanocytes and we are pleased to have tremendous support of leading key opinion leaders who are delivering these presentations.

Im sorry, John Germany.

Yes, so I will start maybe with Europe .

In Europe , you focus your key.

We have more than 100 patients already identified.

Patients in Germany represents.

B malls under one sale of December .

Can you maybe just give a brief overview of what you might consider proof of concept there?

At the Pediatric Endocrine Society 2022 virtual annual meeting this past weekend, we presented new data supporting the potential for set melanocytes to treat the early onset obesity, hyperphagia, and metabolic impairments associated with Bardet-Biedl syndrome. In addition, we announced cumulative safety data from across set melanocytes clinical development programs demonstrating that treatment is generally safe and well-tolerated.

And as we announced today, six abstracts of new data were accepted for presentations at the Endocrine Society Annual Meeting and Expo in June of this year. Highlights here will include one-year BMI data in SRC1, SH2B1, and heterozygous PONCY-PCSK1-11 receptors, along with longer-term data in BBS and biallelic PONCY-PCSK1-11 receptors.

Okay.

We're thrilled to have the support of an all-star cast of key opinion leaders as listed on this slide.

These conferences provide us with a great opportunity to communicate and disseminate data about set melanocytes and genetic diseases of obesity to support recruitment in our ongoing trials, as well as raise awareness and educate the healthcare community about PONCY-PCSK1-11 receptor and BBS.

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

Got it bottomline.

Okay great.

No no I was not saying reinforcing again Europe is well organized thank you.

And in terms of the proportion of patients that achieving a reduction in BMI, what would you need to see to progress development?

Got it and maybe just one follow up if I can squeeze it in just in terms of the U S and the <unk>.

Moving parts around kind of paying a payer and reimbursement for Bbs I know like <unk>.

<unk> had some discussions but any update there in terms of just making sure that the indication we will get paid for it.

Thank you.

Thank you, Dr. Shapiro.

Jennifer.

Yes, so I think that this is like one of the areas, where we have certainly learned from the initial PCL experience.

That sales in Q1 2022 were down sequentially versus Q4 2021. This decrease was largely due to a decrease in orders from our specialty pharmacy versus prior quarter. Vials shipped from the SP to patients were largely unchanged.

Cost of goods sold was $230,000 in Q1.

The largest portion of this figure was amortization of sales milestones paid to Ipsos. Rhythm previously paid Ipsin a milestone of $5 million for the first U.S. sale, and during, Q1 paid a $4 million milestone covering the first sale in Europe. These milestones will be amortized quarterly. Cogs also include the 5% royalty payable to Ipsin.

Loss from operations was $52.7 million in the quarter, an increase of $18.3 million, over the first quarter of 2021. R&D expense increased by $12.6 million to $32.5 million. The increase was primarily due to higher clinical trial expense, involving the startup, of our M&A Daybreak weekly formulation switch studies. In addition, Rhythm purchased $3.8 million of clinical supply material during the quarter.

That G&A expense was $21.4 million in Q1, an increase of $6.9 million versus the first, quarter of 2021. The increase was largely the result of increased headcount costs in our U.S. and international, commercial organizations, as well as increased marketing expense.

Consistent with the results in Q1, we expect our full year 2022 operating expenses to increase, over 2021 due to increased clinical development activities. As is typical of large clinical trials, there are significant upfront costs during study, startup. In addition, we anticipate higher commercialization activities related to the potential launch, of Invisible BBS in the U.S., as well as ongoing efforts across Europe.

Our share count was 50.3 million basic and diluted shares, and loss per common share, was $1.05.

We concluded the quarter in a strong financial position with cash and cash equivalents and, short-term investments of $241 million, which we believe will be sufficient to fund Rhythm's operations in the fourth quarter of 2023.

I'll start off and say that from a commercial payer perspective, we have had very strong reimbursement.

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

The board.

Just in terms of coverage of Jeffrey.

There are a couple of different plans that have not made decisions and our opportunities for our corporate accounts tend to just go ahead and educate a follow up as they move forward in terms of their dialogues with various different pairs.

From a Medicare perspective.

Because of the CMS statute or weight loss medications.

We expect that we're not going to be successful in terms of coverage there at this point of time.

I will outline that one piece to remember, though is similar in terms of our Biallelic PPL patient population, what we saw.

The Bbs patients that we've identified also because of our focus in terms of where we do disease education. They are primarily younger and more likely to have commercial and or Medicaid coverage.

On the Medicaid side, what we're seeing is it.

It's Mick.

We certainly see today that are covering in February .

And those that have also not yet made a decision and those that have weight loss exclusion decided not a pepper sifry and once again I think that with a team on ground. The latter two buckets really are opportunities for our teams to go.

And educate and differentiate our target populations from the broad obesity population.

I think in terms of expectations.

We are not expecting to get 100% coverage across the board.

But I do feel.

Positive just in terms of our ability to change the current landscape.

We are already seeing positive reception to our value story and in fact, even in certain states that have outlined from a Medicaid perspective, there excluding <unk>, we've been able to get patients through the process on drug. So it's an evolving process, where there is a lot of opportunities to.

They will continue to dialogue and educate.

Sure.

Thank you.

Thanks, Jennifer.

Did we answer your.

Derek.

So the endpoints are focused on changes in body weight, BMI, and other BMI related measures in the pediatric population, as well as hunger and hyperphagia scores.

Thank you, Hunter.

Yes. Thank you so much Greg congrats on the progress thanks.

I don't think at this time we can comment on what we would need to progress, but middle of the year we will be announcing the data and plans if appropriate thereafter.

Thank you next question.

And the only thing I would add to that is the FDA has very clearly outlined that 5% threshold for weight loss BMI change is clinically significant, significant from a regulatory standpoint.

So I think, as you've all heard, we have a lot underway in the box on the left.

Thank you. The next question comes from Dae Gon Ha from Stifel. Please go ahead.

Needless to say, we would need to see at least that.

I think, you know, what's most noteworthy is we had a very daunting at one level task, of getting all these clinical trials up and running, and they're all basically up and running.

I also think, you know, we're looking to make a meaningful difference here.

And so, what we look forward to going forward, lots ahead.

Yes. Good morning, Thanks for taking my questions as well I'll piggyback off of some of Eric's questions on Bbs.

And so, as Linda said, when we evaluate that data, we'll not be looking to just barely, clear the hurdle, so to speak.

So, again, I'd be looking for something north of that 5% kind of improvement.

Purdue for date, EMEA approval, as you've heard, lots of data that we're reporting out, some of that in the first half, launching in Europe, started in France, Germany, UK, Italy, all to come.

Are you able to comment on whether you've already started engaging the FDA on the labeling discussions for Bbs and secondly, when we think about the launch trajectory I guess, the slide with regards to 350 patients or more being identified I think the commentary today was more than 150 physicians.

That's very helpful.

And we'll also be beginning that last de novo study as part of our weekly overall development, plan in the second half.

So again, very much looking forward to those events and a very important year for Rhythm, and we now welcome your questions.

That take care of those identified patients. So how much of an overlap is there between those physicians that take care of Bbs versus the Biola like PPL, just wondering about the COVID-19 impact we've heard certain kols at institutions still restricting in person sales Rep meeting and I've got a follow up thanks.

Okay, I'll give that one to Jennifer on the engaging with the FDA.

We've said previously we expect that engagement.

Some point roughly a month or so ahead of time and Thats all.

We've had there's no further update there.

To your question just in terms of ACP overlap.

For the PPL pace.

Patient population in terms of the scripts.

The volume is outlined from an expectation perspective was well however.

However.

<unk>.

The majority of these physicians coming in we're already in our rhythm CRM were similar patients or physicians that we were also already engaging with.

Hence there is some overlap with the Bbs physician Paul.

But theres also physicians that have not yet prescribed from a PCL perspective.

We are actively engaging with as we went forward.

So with that uprated, we can go to Q&A.

Great. Okay. Thanks for that Oh.

Im sorry, David.

Thank you.

Hello. Thanks.

Okay, well so the other question is just shifting gears a little bit to DAYBREAK.

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Following the amendment you spoke about how within the 10, such studies or the genotype. So youre looking at two are actually going to have some broader implications as it is part of <unk> Tianjin pathway network. So can you maybe talk a little bit about those two genes what led you to identifying those two versus the other 11.

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We have a question from Phil Nadeau from Cohen and Company.

Please go ahead.

Hi.

And how much of a derisking can we anticipate based on those two changes with respect to sort of what their protium products do in that MSC for our pathway.

This is Lila on for Phil.

Yes, that's a great question. Thank you very much. So we came to identify the genes by working with our key opinion leaders, who are experts in the field as well as looking into our own preclinical data to.

Thank you so much for taking the question, and congrats on this progress.

To identify those that.

R&D risks and most likely do have the greatest potential impact of impairing the pathway and therefore being responsive to set melanocyte.

So those two genes that are part of the SMS three family of genes.

We're looking both at the flex and <unk> for as well as the Sistema three G.

So two different angles into that family. So we really do feel this will give us the greatest opportunity to be able to identify the impact that that all of those associated genes have as well as.

The impact that the other genes have based on the science. It does support that they do have a strong relevance to the empty for our pathway.

Maybe really quickly on the phase two data expected in hypothalamic obesity, can you, maybe just give a brief overview of what you might consider proof of concept there, and in terms of the proportion of patients that achieving a reduction in BMI, what would you need to see to progress development?

Thank you.

The endpoints are focused on changes in body weight, BMI, and other BMI-related measures, in the pediatric population, as well as hunger and hyperphagia scores.

I don't think at this time we can comment on what we would need to progress, but middle, of the year we will be announcing the data and plans, if appropriate, thereafter.

Okay alright, thank you.

And the only thing I would add to that is the FDA has very clearly outlined that 5% threshold for weight loss BMI change is clinically significant.

Needless to say, we would need to see at least that.

It's significant from a regulatory standpoint.

I also think we're looking to make a meaningful difference here.

And so, as Linda said, when we evaluate that data, we'll not be looking to just barely, clear the hurdle, so to speak.

Yes, Yes, I guess I guess I was just kind of curious how much of a derisking can we really anticipate given that it is part of like a complex for example that functions as a single unit versus multiple different proteins being engaged at different portions of the pathway.

Again, I'd be looking for something north of that 5% kind of improvement.

That's kind of what I was trying to get at but we can we can certainly catch up offline or talk later after the data is out.

Hey, maybe we can leave it.

As Linda said those two were.

Based on looking at the group and figuring that those two are the highest.

The highest probability.

<unk>.

Responding if neither one of those show any effect then we're done with the pathway.

If we see a significant effect and of course, we'll dive more deeply into the pathway. So the derisking will occur through that I think your question is how quickly those two are linked to all the others.

There is not a short answer to that question.

Got it okay. Thank you very much.

Thank you. The next question comes from Joseph Stringer from Needham <unk> Company.

Thank you so much.

That's very helpful.

Thank you.

Thank you so much.

Our next question comes from Derek Archila from Wells Fargo.

Thank you.

Please go ahead.

Our next question comes from Derek Archula from Wells Fargo.

Hi, good morning, Thanks for taking my questions supervised first one is.

Hey.

On the.

CVR gallstone.

Did the FDA require any additional.

Data.

Excuse me.

The FDA requested any.

Additional data analysis.

Yes.

Since you initially announced an update in February of this year.

Then.

Second question is on.

On M&A do you anticipate the SRT one <unk> one.

But in general faster just given the.

Higher prevalence relative to the.

Sub studies.

Thanks for taking my questions.

Sure Great question I'll start with the M&A because that is the easier answer. So so yes, we do anticipate just via the higher prevalence that there will be a faster enrollment of Src Wyman FH, Jimmy one for Glenn.

The others as far as the FDA and no additional requests for data other than that that we spoke about previously.

Other than we did submit our periodic benefit risk evaluation referred firm that's part of our regular requirements. So they just had some follow ups after that.

Part of it too but.

But otherwise we are on track.

No additional requests have been received to date.

Next question.

Yes.

Thank you.

Our next question comes from Michael Higgins from Ladenburg Thalmann. Please go ahead.

Please go ahead.

Good morning, guys.

Hey, good morning, guys, and congrats on the progress.

Good morning, guys. Thanks for taking the questions.

Just wanted to follow up on the comments you have.

<unk> made an announcement press release.

The modification to the summary product characteristics and Europe following.

Making adjustments to the moderate and severe renal impairment on the adjustment for dose escalation lower Max dose what led to that.

Does that post marketing is that something thats on the data and how is that affecting.

And congrats on the progress.

Just a couple questions from us.

The FDA review.

Sure Great question. So we conducted a trial in patients with renal impairment mild moderate and severe renal impairment and reassess the pharmacokinetics and based on the data from that trial data came out of it.

Just a couple of questions from us.

Submitted this data both to the FDA and EMA slightly different pathways by which those regulatory approvals go through but they are both kind of tied to our GBS submission and in essence. The data showed that there was no need for any dose adjustments in the mild to moderate renal impairment.

Purchase with severe renal impairment.

Data suggests starting at a lower dose and dose escalating slower the Max target dose can still be the same.

Jim.

But it will be dose escalated based on response clinic.

Clinical response efficacy and safety.

So just a follow up to that would you look for the same type of language.

From the FDA.

Yes, yes, we anticipate that it would be quite similar.

Okay Super helpful. And then just a follow up on the ABS market.

You've discussed the 350 patients.

<unk>.

There are 750, <unk> Bbs group as it has.

Your steps that you're taking to close that gap, obviously, theres some patient confidentiality, but.

Youre working so closely with that group also wondering how that is coming together.

And the last part of that would be.

Mentioned identifying patients through ICD 10 codes.

I don't think its for Bbs. So if you could expand on what that is you're finding in those codes.

Okay.

So.

Just in terms of effort so for all in engagements the relationship we have with the Marshalls clinic is extremely strong.

Of course, they are the one to one.

The registry you outlined there are some restrictions just in terms of our ability to access and such but I think.

Based off of their interest also in terms of treatment of the patient population and also.

Interest in the drug that may be one opportunity also in terms of the play through.

You know how things are communicated with patients that they are also in touch with.

I think moving on to the question in terms of the ICD 10 code.

There are there is a benefit like I said this is a very different loss from the initial indication because bbs syndromic indications and.

Based off what the various different symptoms where its involvement.

Good day.

Things around.

Sure.

Renal impairment et cetera.

There is the ability to sort of triangulate to try to understand which physicians have patients that may be at the ABS paycheck, particularly if you start with one code.

<unk> hundred 80, 786 were Bbs actually resides there may be an ability to tease out out out of that tens of thousands under that code, which physician may have diagnosed that bbs patient versus the 10 other plus.

Indications that fall within that category. So we're just trying to be smart in terms of targeted efforts of how we go about disease educating.

And Jennifer maybe one clarification, the 350 plus patients that your teams have identified are not necessarily all in the registry right. We at this point in time, we don't really know the overlap in terms of.

350, plus patients versus the one that are in the Marshfield.

Registry right now there may be.

I assume that there is not 100% overlap.

Our teams have been a ground educating and targeting various different physicians throughout the nation.

Andrew very helpful. Yes.

Yes. It does thank you thanks guys.

Thank you.

As a reminder, if you have any questions please spread zero one or.

Our next question comes from Jeff Hung from Morgan Stanley . Please go ahead.

I just want to first, on the BDS launch, would love to just kind of get a sense of how you, think the trajectory could go, and if there's any good analogs you could point to.

Thanks for taking my questions.

Central Bbs launch do you have a sense for what percentage of the 350 patients would be interested in being treated like what kind of pre screening have you done through the physicians.

Is this something where we expect more of a slow trickle, or is there a bolus of patients, given the outreach you've done?

Second, I would ask, just in terms of the Germany sales, I guess now that you're ramping, or you're starting to sell there, how many patients have you actually identified in that country?

Thanks.

And then as we look towards the potential approval, how often should we expect updates for the number of identified and treated patients.

What kind of metrics might you could provide regular updates on thanks.

Yeah.

Sure.

I'll go to Jennifer first on the U.S. launch, and then Jan, I'll turn to you for some comments, on Germany.

I'll go to Jennifer first on the U.S. launch and then Jan.

In terms of the patient.

Like I said, it's very difficult to really come up with an estimate just in terms of exact percentage that will be expected to go on therapy, maybe if I could also caveat things in certain ways.

I'll turn to you for some comments on Germany.

When you think of the physician population that we are targeting.

A lot of our efforts have been in the past also around the pediatric endocrinologist endocrinologist and from that perspective, they are having issues that theyre going to this specific physician populations.

To address and hence they may be more motivated population in terms of wanting to really.

Seek out treatment for their <unk> and hyperphagia components. So that's a positive factor just in terms of.

<unk> desire to find a new Austin.

I think.

In terms of the second question was related in terms of updates so.

And maybe just one additional point Don Jeff Fund on terms of the percentage as Jennifer said, it's impossible to estimate, but I think thats. The point that you made is the critical one which is these patients that we are confirming in that 350 plus are engaged in the system. They are engaged in the system, they're seeking health and so they're going to get on therapy would be the prediction.

It's a question how long when will they see good I mean, there's a lot of factors.

And how much time, it takes maybe to get them on therapy, but they have already signaled that they are out there looking for help and so word will get around.

In terms of metrics again, I'll just say, we're very early in terms of.

The obvious things as patient numbers, there's prescriptions written theres number of doctors, who are writing prescriptions and the like and what we'll do is we'll begin to get more experience. Here is if you look at things that we feel provide the most meaningful insight and we'll clear though.

At this point, we're not going to tell you exactly what metrics would always will be.

Alright, great. Thank you.

Thanks Rich.

Thank you last question.

Our next question comes from Karen Jenkins, Karen Jenkins from Goldman Sachs. Please go ahead.

Yes.

Everybody.

So maybe totally different pack here, but as you expand these emanate and the DAYBREAK basket studies Im curious if youre seeing any change in dynamics with respect to the receptivity or utilization of the euro.

Test just given there is a higher.

Yield on being able to do something about the genetic screening test as they come back.

Okay.

It's a very good question.

Very much in a sense controlled that.

It's broadly available people can just sign up for it and be shipped to kit.

That said, we are very much we've shifted our strategy from the beginning it was basically wide open. We are just trying to understand the epidemiology. We've now become much more focused our field teams around encouraging screening at those sites either as a clinical trial sites themselves or clinics that are in some radius around our clinical trial sites so that when they.

Accretion is quite quick diagnosis, they have a reasonable chance of being eligible are able to get into emanate DAYBREAK. So it's not a good number.

Screening has gone up somewhat from our northern numbers, but it is governed by a restricted if you will by pepper.

Kurt.

Okay. Thanks, that's helpful.

Yeah.

Thank you Greg.

With that I think.

At the end here and.

I want to thank all of you for tuning in and if there any questions that we did not get to can you. Please.

Dave Kang.

To respond to those individually.

With that thank you all for tuning in.

Okay. Thank you ladies and gentlemen. This concludes today's conference. Thank you for participating you may now disconnect.

Goodbye.

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Okay.

Welcome to the rhythm Pharmaceuticals first quarter 2022 earnings Conference call. My name is Hilda and I will be your operator for today's call.

Thanks for the question.

I think in any rare disease, especially when there's no therapy available, it's difficult, to really accurately project the trajectory of any launch.

At this time all participants are in a listen only mode. Later, we will conduct a question and answer session.

During the question and answer session and at anytime if you have a question. Please press <unk> one on your Touchtone phone.

I will now turn the call over to Mr. David Connolly Investor Relations and corporate Communications you may begin.

With that said, I think that the BDS launch will be completely different in terms of expectations, versus what we saw with the PPL approval.

Thank you and good morning, everybody I'm, Dave constantly head of IR and corporate communications here 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 the investors page on our website at IR Dot rhythm TX Dot com.

We feel, first, very, very good in terms of the strong number of patients that have, already been identified to date.

This morning, we issued a press release that provides our.

First quarter, and first quarter 2022 financial results and business update which is available on our website.

And as listed on slide two.

Today here with me in Boston for the conference call are David Meeker Chair, President and Chief Executive Officer of rhythm.

Jennifer Chen Executive Vice President head of North America, Linda Shapiro, our Chief Medical Officer Hunter Smith, our Chief Financial Officer, and Jan massive Rowe Executive Vice President head of International is on the phone joining us from France.

On slide three I'll remind you this call contains.

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

I think, once again, in an area where there's no therapy available, the starting point and, where we are is quite strong.

Thank you, Dave and good morning, everyone. Thank you for tuning in this morning, and we look forward to updating you on the progress we've made in quarter one.

I do that I'd like to start on slide slide five with a bit of an unusual start here.

Cartoon of our biology, many of you know this.

With the territory managers in the field, we have also the corporate accounts team in, place.

Well.

And as we all know it's been a particularly difficult moment in the market generally and it's been particularly difficult for small and mid cap biotechnology companies.

Moments like these it's so it's worth looking at fundamentals are always important but particularly so at these kind of moments. So I wanted to spend a couple of minutes just reviewing rhythms fundamentals.

So number one there is a clear unmet medical need.

Pursuing here patients who have a genetic variant that compares the <unk> pathways suffered from hyperphagia.

Decreased energy expenditure and consequent early onset obesity and all of the comorbidities associated with that.

The biology's incredibly strong as highlighted on this slide it's been well studied.

The pathway that we're pursuing the <unk> pathway the endogenous ligand.

The alpha MSH, which interacts with EMC for receptor when it engages with decreases the appetite increases energy expenditure and you get a reduction in weight.

And we've shown and again multiple trials that that's associated with other benefits as well.

Third.

We have a precision medicine solution to this problem the <unk> as an analog for alpha MSH someone engages the receptor you got all of those benefits and we are essentially a replacement therapy.

Three simple conceptually and biologically and were working in a world where other approaches to try to manage this problem have not been reliably successful bariatric surgery, you can get weight loss, but you get it reliably and sustainably and that's the same for other approaches to weight loss management.

Or we are de risked.

Most things fail in this industry.

Unfortunately, not to get <unk> through the regulatory process in both FDA and EMEA you have an approved drug with another one or two indications imminent coming up and so from a.

Sure No risk standpoint. This is a company that is perhaps one of the very major hurdles that we all aspire to.

It's not.

And enlist this year.

No we need to do commercially.

We need to do clinically and we know what we need to do financially and we have the team to do it so what youre going to year as we continue to update you.

We're executing and as I said I feel really good about the fundamentals that we're standing on top.

As I outlined, rhythm and tune, actively setting expectations, and we have a team in place, that is really quite anxious and ready to go in terms of the launch and helping to get patients on drug and stay on syphilis.

As I outlined, rhythm and tune, actively setting expectations.

We are very confident in terms of having a successful launch here, and there is a lot, of excitement that we hear also from the community, from patients, caregivers, as well as physicians.

So with that let's go to the quarter So slide six.

We're on track.

Talk about the U S. First we're very much looking forward to our <unk> date on June 16th.

Used the time well as you can imagine with continued active patient identification and disease education efforts and Jennifer will highlight.

A little more color around that effort.

Any analogs that you think of?

We have a team in place that is really quite anxious and ready to go in terms of the launch, and helping to get patients on drug and stay on syphilis.

The current commercial.

Opportunity.

Is playing out exactly as we had hoped we have tens of patients on therapy. We continue to learn more about the market access situation. We are able to educate payers in those interactions are laying a strong foundation for our Bbs launch and really importantly, as we've highlighted in the past we continue to get to interact with patients.

We are very confident in terms of having a successful launch here.

Consented into our patient services group now called in June and that.

It's usually valuable insights as we think about how we can provide the best service for that patient how we can help them manage through the early part of getting a therapy like this the daily administration. The early side effects like that all can be significantly benefited by that strong interaction.

There is a lot of excitement that we hear also from the community, from patients, caregivers, as well as physicians.

The international markets International markets are incredibly important part of our whole story spin and then talk a little bit.

Maybe I'll just start.

Any analogs that you think of?

More about that in the next slides coming up but suffice it to say that as we look at Europe . We've highlighted this many times.

This is a challenge in the rare disease space.

Maybe I'll just stop.

Obviously, there's some similarities in the sense that rare disease drugs, at price point, they tend to be priced at, often working with physicians who have never written a prescription for a rare disease drug and never gone through the approval process, which is a bit more cumbersome than writing a prescription for your local CVS, obviously.

This is a challenge in the rare disease space.

For all rare diseases, and it's certainly the case in the areas that we're working Europe is better organized single payer healthcare system patients get refers center of excellence get set up to Kols. Some thought leaders emerge out of that they have the opportunity to see many patients that can do research and so again.

All that is part of it.

Result of that as a starting point that tend to be many more patients identified and once you do get approval through the health care system for access.

So then getting patients onto therapy is much more straight forward.

And then in that third bucket, we have a broad clinical development program and it's.

Put in a tremendous amount of work to get these trials up and running and they're now running M&A DAYBREAK hyperkalemia obesity trial, pediatrics weeds weekly formulation trials ongoing.

We're generating a lot of data and we're publishing that data and we've just had.

Abstracts released it is pediatric and its print society over the weekend and we announced.

On Monday, New additional abstracts will be presented at Endo and Linda will highlight those in more detail.

And as you know, we're very much looking forward to providing updates.

The results on a hyperkalemia study in our <unk>, our rescue Bill interim data and that will happen mid year.

So next slide.

Kevin.

So internationally and as I've said, we've highlighted the first commercial patients started in March in France and were underway and their early access program with that early access ran for about a year ahead of where we would be if we did not have that in France, and Germany. All along has been a real education in a very positive.

<unk> development here.

These products weight loss drugs in general are viewed as lifestyle products and restricted we were able through to get an exemption from annex too.

Was just published.

Last couple of days in the National gift set so thats confirmed reimbursement dossier is now being submitted and we look forward to having our first patients commercial patients for the next couple of months in Germany.

Progress to that stage, where we can be extremely confident similarly in Italy final stages the price negotiation.

Remarkably good about that.

That's evolved perhaps even more favorably than we had hoped Netherlands earlier, but active in Spain, and Sweden, where in the processes associated so we're working our way through Europe .

<unk> of about 20 people highly experienced in loans on the phone again, if there's additional questions. We'd go there.

Okay.

So on the clinical side as you know, we've updated our M&A and DAYBREAK strategies slightly and Linda will dive into that in greater detail, but I'll just say upfront.

We feel that the adjustments we've made to M&A, we have a flat out better trial with a higher probability of success and I'll remind you that we're working in an area, where we continue to learn.

To learn more about not just us, but our thoughts and our partners the world at large more about into the deal with variance and allows us to think about classifying them.

Looking at ones that were in that boosts category, but now maybe a little better understanding you could categorize them as more likely to be towards the pathogenic or likely pathogenic end of the spectrum and so as we've redesigned it again narrowing it down focusing on does it does.

Does it give us.

Better trial.

The numbers so from a total market opportunity the numbers have decreased but I'll remind you here. So no change to the message to be when Src on numbers in the heterozygous pharmacy in leptin receptor numbers at about 10000.

At an aggregate opportunity U S only.

50000, plus.

And.

The leptin receptor in Palm Sea World.

We will in fact be a less confusing commercial opportunity. These patients are better and more clearly defined based on their genetics, and therefore will be easier to manage through the overall process. So net net.

Feel really good about where we are with M&A fabric.

With that ill turn it over to Jennifer.

All that is part of it, but that said, there's not really a good analog for this, but I'll, reinforce what Jennifer said.

That said, there's not really a good analog for this, but I'll reinforce what Jennifer said.

The starting point, with the number of patients we've identified, the level of organization, of that community at this point is incredibly positive, so I think, in a relative sense, we feel good, very good about where we'll start.

Thank you David.

And that first six months, as you know, Derek, we try to guide people away from this idea, that there's a specific expectation, whatever it is, I don't know if we're going to come out of the gate fast, whatever that means, or a bit more slowly.

So beginning on slide 11 here, we last shared details of our Bbs commercial readiness efforts in February and with producer and launch coming June 16th we aimed today to provide some more details on the tremendous progress our teams have been making.

But over time, meaning the 6-12, 12-18 month period, that's the period where I would really, look at to get a better sense for what this opportunity is going to look like.

Oh, sorry, Yann, Germany.

The starting point with the number of patients we've identified, the level of organization of, that community at this point is incredibly positive.

I think in a relative sense, we feel good, very good about where we'll start.

That first six months, as you know, Derek, we try to guide people away from this idea that, there's a specific expectation.

As we outlined before the estimated prevalence of Bbs and the U S is 500 to 2500 patients and we now have approximately 70% to 90% of these patients have obesity.

Whatever it is, I don't know if we're going to come out of the gate fast, whatever that means, or a bit more slowly.

But over time, meaning the 6-12, 12-18 month period, that's the period where I would really look, at to get a better sense for what this opportunity is going to look like.

Yes, so I will start maybe with Europe.

Oh sorry, Yann, Germany.

We consider these patients in four distinct categories. The first are those that remain undiagnosed.

So in Europe, U4 plus UK, we have more than 100 patients already identified by LDL-PPL patients, and Germany represents roughly more than one-third of this number.

Yes, so I will start maybe with Europe.

There are two other rare genetic diseases. The vast majority of patients remain under the care of ACP, who have not yet suspected or clinically diagnosed the patients.

Got it.

So in Europe, you focus UK, we have more than 100 patients already identified by LDL-PPL patients and Germany represents roughly more than one third of this number.

This remains a large opportunity.

The second category are those patients under the care of Hcp's co packed with Bbs.

Oh, go ahead.

Got it.

<unk> may not have yet definitively diagnosed.

Thank you.

<unk> may continue with additional evaluation before verifying a clinical diagnosis.

And disease States, where there is no approved therapy, there may be less urgency to come to a specific diagnosis.

And maybe just one follow-up, if I can squeeze it in, just in terms of the U.S. and the moving parts around kind of paying a payer and reimbursement for BDS.

Having an approved therapy, often AIDS away awareness of the gcs and some urgency towards making a diagnosis.

And the last two segments of patients who have been diagnosed.

Territory managers have validated more than 150 physicians, who are managing over 350 Bbs patients under their care.

And we continue to find additional Bbs patients there are efforts.

No, no, reinforcing again, Europe is well-organized.

I mean, I know I think you've had some discussions, but any update there in terms of just making sure the indication will get paid for?

Next slide.

As we prepare for the upcoming potential approval of <unk>. The priority focus of the territory managers remain on engaging with physicians with already identified Bbs patients under their care.

Thank you.

Thanks.

Got it.

Jennifer?

In addition to this group our second set of priority physician targets remain our focus in terms of speeding the diagnosis of Bbs.

And maybe just one follow-up, if I can squeeze it in.

Yeah, so I think that this is like one of the areas where we have certainly learned from the initial PPL experience.

Just in terms of the U.S. and the moving parts around kind of paying a payer and reimbursement for BBS, I mean, I know I think you've had some discussions, but any update there in terms of just making sure the indication will get paid for?

I would start off and say that from a commercial payer perspective, we have had very strong reimbursement across the board, just in terms of coverage of emceefery.

Here, our outreach engagement and educational efforts center on DBS disease state awareness, so physicians can suspect Bbs and better understand the path to diagnosis.

There's a couple of different plans that have not made decisions and there are opportunities for our corporate accounts team to just go ahead and educate and follow up as they move forward in terms of their dialogues with various different payers.

Thanks.

From a Medicare perspective, you know, because of the CMS statute on weight loss medications, we expect that we're not going to be successful in terms of coverage there at this point of time.

Jennifer?

I will outline that one piece to remember, though, is similar in terms of our bioallelic PPL patient population and what we saw.

Rhythm is coming to know these physicians there are uncovering where obesity genetic testing program.

In the long term euro may prove to be a rich source of Bbs patient identification as these patients have some degree of severe obesity in order to qualify for the test.

If there is a hit for Biolife Bvs, we are able to then work with the physician to consider a clinical diagnosis.

Yeah, so I think that this is like one of the areas where we have certainly learned from the initial PPL experience.

I would start off and say that from a commercial payer perspective, we have had very strong reimbursement across the board, just in terms of coverage of emcifery.

We've talked in the past also about our machine learning approach.

From a Medicare perspective, you know, because of the CMS statute on weight loss medications, we expect that we're not going to be successful in terms of coverage there at this point of time.

The BDS patients that we've identified, also because of our focus in terms of where we do disease education, they are primarily younger and more likely to have commercial and or Medicaid coverage.

On the Medicaid side, what we're seeing is it is mixed.

Have developed a targeted list of physicians associated with certain ICD 10 codes that are relevant to Bbs.

We certainly see states that are covering emceefery, those that have also not yet made a decision, and those that have weight loss exclusions and decided not to cover emceefery.

And once again, I think that with a team on ground, the latter two buckets really are opportunities for our teams to go and educate and differentiate our target populations from the broad obesity population.

Next slide.

I think in terms of expectations, we are not expecting to get 100% coverage across the board, but I do, feel positive just in terms of our ability to change the current landscape.

We are already seeing positive reception to our value story, and in fact, even in certain states that have outlined from Medicaid perspective, they are excluding emceefery.

The work of our territory managers also support the building of care teams and broadening referral network as.

I will outline that one piece to remember, though, is similar in terms of our biallelic PPL patient population and what we saw.

We now Bbs has a constellation of symptoms.

While hyperphagia and obesity are among the most prevalent and pressing of the symptoms.

No patients with Bbs suffer from retinal disease, and vision loss renal impairments and other health related issues. Therefore, a critical factor affecting optimal care of patients with Bbs, where they suffer from various disease manifestation is the accessibility of our multi disciplinary.

The BBS patients that we've identified, also because of our focus in terms of where we do disease education, they are primarily younger and more likely to have commercial and or Medicaid coverage.

On the Medicaid side, what we're seeing is it is mixed.

We certainly see states that are covering emcifery, those that have also not yet made a decision, and those that have weight loss exclusions and have decided not to cover emcifery.

Once again, I think that with a team on ground, the latter two buckets really are opportunities for our teams to go and educate and differentiate our target populations from the broad obesity population.

I think in terms of expectations, we are not expecting to get 100% coverage across the board, but I do feel positive just in terms of our ability to change the current landscape.

Carrier network.

The Marshfield clinic in Wisconsin serves as a gold standard of holistic multi disciplinary care for Bbs patients.

This clinic started with Dr Hards, and interested pediatric nephrologist, who connected with an ophthalmologist and expanded their network from there.

We are already seeing positive reception to our value story.

In fact, even in certain states that have outlined from a Medicaid perspective, they are excluding emcifery.

Interestingly, we are seeing more and more of this type of approach.

We've been able to get patients through the process on drugs.

For example, this last quarter one of our territory managers call on an inherited retinal disease specialists.

Is that a sizable health center here in the northeast.

The specialists had an interest in DBS and had diagnosed patients under care, but he was really focused on the vision issues for these patients not their obesity or hyperphagia.

It's an evolving process where there's a lot of opportunities to still continue to dialogue and educate.

Our territory manager identified and connected with a nearby pediatrician with a focus on obesity and a pediatric cardiologist, who had expressed interest in DBS and fostered introductions.

Thanks, Jennifer.

These introductions have been in motion the development of a pediatric obesity clinic with a special focus on Bbs.

We know these connections are also happening in other parts of the nation.

Building out these care teams. It's important it helps gained traction and diagnosing patients earlier in their journey and more importantly, it helps provide these patients with a more complete care team.

Next slide.

Just as with him territory managers are working to help build our physician network and care teams, we have a separate customer engagement team designed to support patients along their journeys.

We've been able to get patients through the, process on drugs.

So it's an evolving process where there's a lot of opportunities to still continue to dialogue and educate.

Thanks, Jennifer.

Did we answer your question, Derek, that we sent?

We matched patient and caregivers with a dedicated patient education manager at a single point of contact for a personalized experience.

Yeah, all good.

Thank you so much.

We have really learned from our initial approval in patients with <unk> mutations and have fine tuned our support offering and preparation for the Bbs launch.

Great.

Congrats on the progress.

For initial approval the main focus was on supporting patients through the reimbursement process.

Thanks.

Okay.

Thank you.

Next question.

Thank you.

And we have a robust action plan to stay in contact with patients and caregivers, whether by phone video call or even simple checking an e-mail throughout the course of therapy.

The next question comes from Dae Gona from CFO.

Please go ahead.

Next slide.

We are ready to launch on day, one June 16th or earlier.

<unk>. The teams are prepared to engage directly with prioritize physicians with identified Bbs patients along with consensus Bbs patients and caregivers.

We have several health care providers as well as well as Bbs patient and caregiver speaker programs planned.

And we are ready to supplement these moving forward.

In addition, we continue to maintain close relationships with patient advocacy organizations, which are looking forward to sharing the potential news of approval with their membership.

We know there are patients awaiting for Bbs therapy, and we are ready to deliver.

Yeah, good morning.

With that.

Let me hand, it over to Linda Shapiro to provide a regulatory and clinical update.

Did we answer your question, Derek?

Thanks for taking my questions as well.

Thank you Jennifer.

Did we get everything you sent?

I'll piggyback off of some of Derek's questions on BBS.

Now on slide 16 to discuss a brief update on our regulatory progress.

Yeah, all good.

Are you able to comment on whether you've already started engaging the FDA on labeling discussions for BBS?

Our Paducah goal date for <unk> and Ahlstrom syndrome is about six weeks away on June 16th the label discussions are anticipated to begin in the coming weeks, leading to the final step.

Thank you so much.

Great.

Congrats on the progress.

In Europe , we anticipate the see HMP will make a recommendation on our type two amendment for Bbs. This summer with a full decision to come from the European Commission in the fall.

Thanks.

So we do have a recent update to report that last week. The HMP provided a positive opinion for a modification to the SMP SEC.

Label with recommendations to expand the use of <unk> in patients with moderate and severe renal impairment and <unk>.

Our lesson receptor deficiency.

The final decision on this amendment is anticipated July .

And the same amendment modification request is being considered as part of the scheduled review from UBS.

Thank you.

And secondly, when we think about the launch trajectory, I guess the slide with regards to 350 patients or more being identified, I think the commentary today was more than 150 physicians that take care of those identified patients.

Now on to slide 17.

Next question.

So how much of an overlap is there between those physicians that take care of BBS versus the biallelic PPL?

I'll focus brief remarks on our several ongoing trials evaluating <unk> appetite and rare genetic and now also acquired diseases of obesity.

Thank you.

The next question comes from Dae Conner from CFO.

Just wondering about the COVID impact.

Before providing updates at emanate day break in our phase II trial in acquired Hypothalamic obesity, Let me mentioned briefly our phase III weekly formulation switch trial, and our phase III pediatric trial for young children between the ages of two and less than six years.

Please go ahead.

We've heard certain KOLs at institutions still restricting in-person sales rep meetings.

Yeah, good morning.

And I've got a follow-up.

These trials are both important elements of our strategy as we know very well that in Bbs genetic obesity and hyperphagia and severe obesity again very early in life have a devastating effect on these patients and their families.

We can bring certain parameters to these patients earlier in their lives in a more convenient and user friendly weekly dosing regimen. We believe it will make quite a difference for them and their caregivers and overall long term treatment adherence.

Thanks for taking my questions as well.

Thanks.

As a reminder, the pediatrics pediatrics trial is a multicenter multinational one year open label Phase III trial enrolling patients with <unk> <unk>, one our leptin receptor deficiency obesity or a clinical diagnosis of Bbs with genetic confirmation.

I'll piggyback off of some of Derek's questions on BBS.

Are you able to comment on whether you've already started engaging the FDA on labeling discussions for BBS?

I'll give that one to Jennifer.

As we announced last quarter, we enrolled our first patient in February .

Phase III switch trial evaluates a weekly formulation of <unk> in comparison to the daily formulation in patients six years and older with the rare genetic disease or obesity.

Currently in our long term extension trial, taking a stable dose of the daily formulations that will amortize.

On the engagement with the FDA, as we've said previously, we expect that engagement at some point roughly a month or so ahead of time.

First patients per dose.

With the weekly formulations January January and enrollment is progressing.

So how much of an overlap is there between those physicians that take care of BBS versus the biallelic PPL?

And that's all we've had as a further update there.

Now I will go into a little bit more detail on our hypoglycemic obesity trials DAYBREAK and M&A, beginning with M&A on slide 15.

Just wondering about the COVID impact.

To your question just in terms of ACP overlap, for the PPL patient population in terms of the scripts, the volume as outlined from an expectation perspective was low.

We've heard certain KOLs that institutions still restricting in-person sales rep meetings.

However, the majority of these physicians coming in were already in our rhythm CRM, so were patients or physicians that we were also already engaging with. Hence, there is some overlap with the BBS physician pool.

Emanate now includes four independent sub studies evaluating certain Atlanta tied to patients with severe obesity due to one of four genetic subtypes.

And I've got a follow up.

But there's also physicians that have not yet prescribed from a PPL perspective.

And, you know, we are actively engaging with as we move forward.

Thanks.

Okay.

There remains a significant unmet need for people living with these routes genetic disease. Several facility that are unresponsive to other treatment interventions.

I'll give that one to Jennifer.

Thanks for that.

On the engagement with the FDA, as we've said previously, we expect that engagement at some point, roughly a month or so ahead of time.

Oh, sorry, David.

These patients are living with hyperplasia that pathological insatiable hunger and severe obesity, which has a significant impact on all aspects of their lives.

And that's all we've had for further update there.

Okay.

To your question, just in terms of ACP overlap, for the PPL patient population in terms of the scripts, the volume as outlined from an expectation perspective was low.

However, the majority of these physicians coming in were already in our rhythm CRM.

We are committed to bringing these patients a much needed safe and effective therapy as are many of them. We know lifestyle interventions of disco activity and nutrition changes do not work, nor dewberry ethic surgery or other pharmacotherapy as they do not address the underlying impairment to the empty for a pathway that is the root cause of the hyperphagia.

So we're patients or physicians that we were also already engaging with.

Hence, there is some overlap with the BBS physician pool.

But there's also physicians that have not yet prescribed from a PPL perspective.

And, you know, we are actively engaging with as we move forward.

It's variability.

Well, so the other question is just shifting gears a little bit to Daybreak.

We announced last month, we have implemented modifications to optimize both M&A and debris focus on the rare patient population, which we believe have the highest likelihood of success.

Okay, thanks for that.

Following the amendment, you spoke about how within the 10 sub-studies or the genotypes that you're looking at, two are actually going to have some broader implications as it is part of 13 gene pathway network.

Initiated the trial with the first patient enrolled in April .

I'm sorry, David.

So can you maybe talk a little bit about those two genes?

Now on to slide 19.

Okay.

What led you to identifying those two versus the other 11?

A little more detail on the design for this trial.

Well, so the other question is just shifting gears a little bit to daybreak.

M&A includes four independent sub studies evaluating step in Atlanta.

Third to placebo over 52 weeks.

Following the amendment, you spoke about how within the 10 sub studies or the genotypes that you're looking at, two are actually going to have some broader implications as it is part of 13 gene pathway network.

And how much of a de-risking can we anticipate based on those two genes with respect to sort of what their protein products do in that MC4R pathway?

Patients six years of age and older with hyperphagia and obesity due to a heterozygous variant of the <unk> leptin receptor gene Src, one Jean <unk>.

So can you maybe talk a little bit about those two genes?

What led you to identifying those two versus the other 11?

Yes.

As we announced last month the <unk> one method receptor sub studies, we are focusing enrollment on variance classified following the framework established by the American College of medical genetics, as pathogenic and likely pathogenic as initially planned.

That's a great question.

Thank you very much.

And we have modified to include a narrower subpopulation of variants of uncertain significance our booth.

This trial design allows for independent data Readouts submission and registration of each of the James.

Upsetting.

Next slide.

And how much of a de-risking can we anticipate based on those two genes with respect to sort of what their protein products do in that MC4R pathway?

So we came to identify the genes by working with the key opinion leaders who are, you know, experts in this field, as well as looking to our own preclinical data to identify those that are de-risked and most likely do have the greatest potential impact of impairing the pathway and therefore being responsive to set melanotype.

We also recently modified our phase II DAYBREAK trial to focus initially on rare variance associated with 10 prioritize FQ4 are relevant genes, which we at several key opinion leaders believe have the highest probability of response to separately.

For the remaining James we paused enrollment.

We'll evaluate expansion in day rates for these changes based on the early clinical data from the prioritizing.

Fabric has an efficient design that allows for quickly achieving signals a proof of concept for genetic cohort independently during an initial open label run in period.

This could provide signals of potential efficacy uncertainties cohorts by the end of this year and patients to demonstrate a clinically meaningful response several advertise.

This is Doug followed by a randomized placebo controlled second stage.

That's a great question.

So those two genes that are part of the Sema3 family of genes, we're looking both at the Plexin A4 as well as the Sema3G.

Fabric enrollment began in January of this year.

Thank you very much.

So two different angles into that family.

Okay.

So we came to identify the genes by working with the key opinion leaders who are experts in this field, as well as looking to our own preclinical data to identify those that are de-risked and most likely do have the greatest potential impact of impairing the pathway and therefore being responsive to set melanotype.

So we really do feel this will give us the greatest opportunity to be able to identify, the impact that all of those associated genes have, as well as the impact that the other genes have, based on the science that does support that they do have a strong relevance to the MC4 pathway.

Hyperscale Amrok obesity is a rare acquired form of obesity that develops following structural injury to the hyper <unk> region of the brain that contains the emcee for pathway neurons responsible for controlling the geologic functions such as food intake energy expenditure and body weight Rachel.

So those two genes that are part of the Cisema 3 family of genes, we're looking both at the Flexin A4 as well as the Cisema 3G.

So two different angles into that family.

Okay.

So we really do feel this will give us the greatest opportunity to be able to identify, the impact that all of those associated genes have, as well as the impact that the other genes have based on the science that does support that they do have a strong relevance to the MC4 pathway.

Okay.

All right.

<unk>.

All right.

Well, thank you.

This disease is most commonly associated with cranial pharyngeal not a rare brain tumor or the associated treatment by surgery or radiation.

Well, thank you.

Did that answer your question?

Do you have another question?

Yeah.

Approximately half of patients with cranial pharyngeal experienced rapid onset acute weight gain and hyperphagia shortly after tumor treatments.

Yeah.

I guess I was just kind of curious, how much of a de-risking can we really anticipate, given that if it's part of like a complex, for example, that functions as a single unit versus multiple different proteins being engaged at different portions of the pathway?

I was just kind of curious, how much of a de-risking can we really anticipate given, that if it's part of like a complex, for example, that functions as a single unit versus multiple different proteins being engaged at different portions of the pathway?

While treatment does exist to replace many of the hormone controlled by the pituitary gland that has also endured very tumor treatment. There are no safe and effective therapeutic options for the hyperphagia and obesity that result from injury to the hypothalamus and this can be the most devastating and disruptive for patients and their families.

I guess that's kind of what I was trying to get at, but we can certainly catch up offline, or talk later after the data is out.

The community around Hypothermic obesity is well established and well organized with the Raymond <unk> Foundation founded in 2016.

Empower hypothermic pituitary brain tumor survivors for improved quality of life by providing access to education technology is evolving treatments.

Yeah.

In October 2021, this group posted a patient listening session with the food and drug administration for.

Maybe we can leave it.

For several patients and caregivers provided testimony on the interim optical challenges challenges.

But raymond obesity.

As Linda said, those two were picked based on looking at the group and figuring that, those two had the highest probability of responding.

Obviously folks here.

Upon returning home from the hospital before it at night.

Hyperphagia is the biggest cause of low quality of life.

Within six months I gained 30 pounds.

It's clear there's a significant unmet need in this patient community is desperate for safe and effective therapy.

If neither one of those show any effect, then we're done with the pathway.

I guess that's kind of what I was trying to get at, but we can certainly catch up offline, or talk later after the data is out.

Now to slide 22 for a brief review for a brief overview of our phase II trial in patients with type of landmark obesity.

If we see a significant effect, then of course we'll dive more deeply into the pathway. So the de-risking will occur through that.

Yeah.

This is a phase two open label proof of concept trial evaluating certain Atlanta and individuals with pipeline macro basically.

Maybe we can leave it.

<unk> is complete with 18 patients aged six years with older. In this open label 16 week treatment period.

As Linda said, those two were picked based on looking at the group and figuring that, those two had the highest probability of responding.

Look forward to sharing preliminary data this summer so please stay tuned.

If neither one of those show any effect, then we're done with the pathway.

If we see a significant effect, then of course we'll dive more deeply into the pathway. So the de-risking will occur through that.

Now to slide 23.

I think your question is how tightly those two are linked to all the others, and I think, there's not a short answer to that question.

We have a busy spring plans when it comes to presentations at medical conferences.

These presentations are for us with excellent opportunities to engage with top key opinion leaders and treating health care providers on rare genetic disease severity and the severity of hyperphagia and obesity in these patients and their families.

Got it.

Importantly, it also gives us the opportunity to discuss with them the efficacy and safety of certain Atlanta site and we are pleased to have tremendous support of leading key opinion leaders who are delivering these presentations.

Okay.

At the pediatric Endocrine Society 2022 virtual annual meeting this past weekend.

Presented new data supporting the potential for certain Atlanta trying to treat the early onset obesity hyperplasia and metabolic impairment associated with BARDA fetal syndrome.

Thank you very much.

In addition, we announced cumulative safety data from across the <unk> clinical development program demonstrated that treatment is generally safe and well tolerated.

Thank you.

And as we announced today six abstracts of new data were accepted for presentation at the endocrine Society annual meeting.

<unk>.

In June of this year.

Highlights share will include one year PMI data is Src, one updates should be one in heterozygous proxy.

The receptor.

With longer term data in Bbs and <unk> wanted to lesser sector.

The next question comes from Joseph Stringer from Needham and Company.

We're thrilled to have the support of all star cast of key opinion leaders as listed on this slide.

Hi.

These conferences provide us with a great opportunity to communicate to disseminate data about separately enterprise.

In genetic diseases of obesity support recruitment in our ongoing trials as well as raise awareness and educate the health care community about proxy.

First after EBITDA.

I think your question is how tightly those two are linked to all the others, and I think, there's not a short answer to that question.

With that I will turn the call over to us.

Got it.

Good morning.

Thank you Dr Shapiro.

Okay.

Thanks for taking our questions.

Turning to slide 25, as David mentioned at the start of the call. We are pleased to report product revenue of $1 5 million for the first quarter of 2022 as compared to approximately 35000.

In the first quarter of 2021, while sales during the quarter included our first sales from outside the U S sales volumes did not significantly affect the quarter's results given how late they occurred during the quarter and the limited number of initial prescriptions involved.

Thank you very much.

Two from us.

Thank you.

The first one is on the CVS Alstrom.

Net sales in Q1 2022 was down sequentially versus Q4 2021. This decrease was largely due to a decrease in orders from our specialty pharmacy versus prior quarter vial shipped from ESP patients were largely unchanged.

Did FDA request any additional data analysis since you initially announced an update in, February of this year?

And then second question is on M&A, do you anticipate the SRC1 and the SH2B1 sub-studies, to enroll faster just given the higher prevalence relative to the HES sub-studies?

The next question comes from Joseph Stringer from Needham and Company.

Hi.

Good morning.

Cost of goods sold was 230000 in Q1, the largest portion of this figure was amortization of sales milestones.

Thanks for taking our questions.

Two from us.

Rhythm previously paid absent a milestone of $5 million for the first U S sale and during Q1 paid a $4 million milestone covering the first sale in Europe . These milestones will be amortized quarterly costs also include the 5% royalty payments payable to us.

The first one is on the CVS Alstrom.

Did FDA request any additional data analysis since you initially announced an update in, February of this year?

And then second question is on M&A, do you anticipate the SRC1 and the SH2B1 sub-studies, to enroll faster just given the higher prevalence relative to the HES sub-studies?

Thanks for taking our questions.

Loss from operations was $52 7 million in the quarter, an increase of $18 $3 million over the first quarter of 2021.

Great question.

I'll start with the M&A because that is the easier answer.

Randy expense expense increased by $12 6 million to $32 5 million. The increase was primarily due to higher clinical trial expense involving the startup of our M&A DAYBREAK weekly formulation switch studies. In addition, rhythm purchased $3 8 million of clinical supply material during the quarter.

So yes, we do anticipate just via the higher prevalence that there will be a faster enrollment, of the SRC1 and the SH2B1 compared to the others.

As far as the FDA, no additional request for data other than that that we spoke about previously.

Other than we did submit our periodic benefit risk evaluation report, that's part of our, regular requirements, and they just had some follow-ups that we have responded to.

But otherwise, we're on track, and no additional requests have been received to date.

Next question.

Thank you.

Our next question comes from Michael Higgins from Lattinburg-Tulman.

SG&A expense was 20 $21 4 million in Q1, an increase of $6 9 million versus the first quarter of 2021.

Please go ahead.

The increase was largely the result of increased head count costs in our U S and international commercial organizations as well as increased marketing expense.

Consistent with the results in Q1, we expect our full year 2022 operating expenses to increase over 2021 due to increased clinical development activities.

As is typical of large clinical trials there are significant upfront costs during study startup.

In addition, we anticipate higher commercialization activities related to the potential launch of <unk> Bbs and the U S as well as ongoing efforts across Europe .

Share count was $50 3 million basic and diluted shares and a loss per common share was $1 and $5.

We concluded the quarter in a strong financial position with cash and cash equivalents and short term investments of $241 million, which we believe will be sufficient to fund rhythms operations in the fourth quarter of 2023.

Good morning, guys.

Thanks for taking our questions.

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

Thank you for taking the questions.

Great question.

Thank you, Eric So I think as you've all heard.

First, I just want to follow up, on the comments you've made and also impressively swearing the modification to the summary product characteristics in Europe following making adjustments to the moderate and severe renal impairment on a adjustment for dose escalation in a lower max dose.

I have a lot underway.

The box on the left.

What led to that?

What's most noteworthy is we had a very daunting at one level task of getting all these clinical trials up and running and they are all up.

And so when we look forward to going forward lots ahead Paducah date.

Is that post-marketing?

Is that something that's on the data?

<unk> approval as you've heard lots of data that we'll be reporting out some of that in the first half launching in Europe started in France, Germany, UK, Italy all to come.

And.

We will also be beginning that last de Novo study as part of our weekly.

Overall development plan in the second half so again very much looking forward to those events and a very important year for rhythm.

And how is that affecting the FDA review?

Yes.

We welcome your questions so with that operator, we can go to Q&A. Thank you.

Thank you.

Thanks.

I'll start with the M&A because that is the easier answer.

We will now begin the question and answer session. If you have a question. Please press <unk> one on you touched on phones.

Great question.

So yes, we do anticipate just via the higher prevalence that there will be a faster enrollment, of the SRC1 and the SH2B1 compared to the others.

So we conducted a trial in patients with renal impairment, mild, moderate, and severe renal impairment, and we assessed the pharmacokinetics.

As far as the FDA, no additional requests for data other than that that we spoke about, previously, other than we did submit our periodic benefit risk evaluation report.

You wish to be removed from the queue. Please press zero two.

If you are using a speakerphone you may need to pick up the handset first before pressing the numbers.

And based on the data from that trial, that is what came out of it.

That's part of our regular requirements, and they just had some follow-ups that we have, responded to.

So we have submitted this data both to the FDA and to the EMA.

But otherwise, we're on track, and no additional requests have been received to date.

Once again, if you have a question. Please press <unk> one on your Touchtone phone.

Slightly different pathways by which those regulatory approvals go through, but they are both, kind of tied to our BBS submission.

Next question.

And we have a question from Phil Nadeau from Cowen and company. Please go ahead.

And in essence, the data shows that there was no need for any dose adjustments in the mild and moderate renal impairment. But in patients with severe renal impairment, the data suggests starting at a lower dose and dose escalating slower.

The max target dose can still be the same, but it will be dose escalated based on response, you know, clinical response efficacy and safety.

So just to follow up to that, would you look for the same type of language from the FDA?

Thank you.

Hi, This is <unk> on for Phil. Thank you so much for taking my question and congrats on the progress.

Yes, yes.

Our next question comes from Michael Higgins from Lattinburg-Tulman.

We anticipate they would be quite similar.

Okay, super helpful.

Please go ahead.

Really quickly on the phase III data expected in hypersonic obesity can you maybe just give a brief overview of what you might consider proof of concept Darrin in terms of the quick question of patients achieving a reduction in BMI, what would you need to feed it progressed development. Thank you.

And then just a follow up on the BBS market.

Good morning, guys.

You've discussed the 350 patients that have been identified.

There are 750 that the BBS group has.

What are your steps that you're taking to close that gap?

Thanks for taking the questions.

Obviously, there's some patient confidentiality, but you're working so closely with that group also, wondering how that is coming together.

Linda you want them sure so.

Our focus on changes in body weight, BMI and other BMI related measures in the pediatric population as.

As well as our hunger and hyperphagia scores.

I don't think at this time, we can comment on what we would need to progress by the middle of the year and we will be announcing the data.

If appropriate thereafter.

And the only thing I would add to that is.

The FDA is very clearly outlined that 5% threshold for weight loss BMI changes clinically significant significant from a regulatory standpoint, needless to say, we would need to see at least that.

I also think.

We're looking to make a meaningful difference and so as Linda said, when we evaluate that data will not be looking to just barely clear the hurdle so to speak come so again I'd be looking for something north of that 5% kind of improvement.

That's very helpful. Thank you so much.

Thank you.

And the last part of that would be, you mentioned identifying patients through ICD-10 codes.

Our next question comes from Derek <unk> from Wells Fargo. Please go ahead.

I don't think it's for BBS.

Hey, good morning, guys and congrats on the progress just a couple of questions from us.

So if you could expand on what that is you're finding in those codes.

First on the Bbs launch.

I would love to just kind of get a sense of how you think the trajectory could go and if there is any good analogs you can point to is this something where we expect more of a slow trickle or is there a bolus of patients, but given the outreach you've done.

Secondly, I would ask just in terms of the Germany.

Just now that you are ramping are you starting to sell there how many patients have you actually identified in that country.

And well go to Jennifer <unk>.

U S launch and then beyond I'll turn to you for some comments on Germany.

Thanks.

Thanks for the question.

So, you know, I think that just in terms of efforts overall and engagement, the relationship we have, with the Marshall Clinic is extremely strong.

And as you outlined, there are some restrictions just in terms of our ability to access and such.

What led to that?

You know, of course, they are the ones who own the registry.

But I think, you know, based off of their interest also in terms of treatment of the patient population and also interest in the drug, that may be one opportunity also in terms of the play through of, you know, how things are communicated with patients that they are also in touch with.

I think in any rare disease, especially when there is no therapy available.

Difficult to really accurately project the trajectory of any launch.

I think moving on to the question in terms of the ICD-10 code, you know, there is a benefit.

Is that post-marketing?

Is that something that's on the data?

With that said I think that the Bbs launch.

Will be completely different in terms of expectations versus what we saw with the PPL approval.

Like I said, this is a very different launch from the initial indication because BBS is a syndromic, indication.

We feel very very good in terms of the strong number of patients that have already been identified to date I think once again in an area, where there is no therapy available the starting point and where we are is quite strong.

With the territory managers in the field, we have also the corporate accounts team in place.

As I outlined rhythm into actively setting expectations.

And we have a team in place that is really quite anxious and ready to go in terms of the launch and helping to get patients on drug and stay on <unk> and surgery.

We are very confident in terms of having a successful launch here and there is a lot of excitement that we hear also from.

The community from patients caregivers as well as physician.

And any analogs.

Think of them.

Maybe I'll just start off I mean, this is a challenge in the rare disease space. Obviously, there's some similarities in the sense that rare disease drug some price.

Price point, they tend to be priced add often working with physicians, who have never written a prescription for a rare disease drug never gone through the approval process.

More cumbersome and cumbersome than writing a prescription for your local Cvs obviously.

All of that is part of it but that said theres not really a good analog for this but ill reinforce with general percent starting point with the number of patients we've identified the level of organization of that community.

And based off of the various different symptoms where it's eye involvement, you know, obesity, things around renal impairments, etc.

There is an ability to sort of triangulate systems to try to understand which, physicians have patients that may be a BABS patient.

Particularly, if you start with one code, a Q87-86 where BBS actually resides, there may be an ability to tease out out of the tens of thousands under that code which physician may have diagnosed a BBS patient versus, you know, the 10 other plus indications that fall within that category.

I was incredibly positive so I think in a relative sense, we feel good very good about where we will start in that first six months as you know Derek we try to guide people away from this idea that there's a specific expectation whatever it is I don't know if were going to come out of the gate fast whatever that means a bit more slowly.

So we're just trying to be smart in terms of targeted efforts of how we go about, disease educating.

Over time, meaning the six to 12 12 to 18 month period to period, where I would really look at to get a better sense for what this opportunity is going to look like.

Certainly.

All right Jan Germany.

Yes, so I will start with Europe .

In Europe , you focus your key.

We have more than 100 patients already identified.

PPL patients.

Many represents.

Roughly more than one third of December .

Got it.

Okay great.

No no I was going to say.

Reinforcing again Europe is well organized.

Got it and maybe just one follow up if I could squeeze it in just in terms of the U S and the.

Moving parts around kind of paying a payer and reimbursement for Bbs I mean, I know I think you've got some discussions but any update there in terms of just making sure that the indication.

We'll get paid for.

Jennifer.

Yes, so I think that this is like one of the areas, where we have certainly learned from the initial PCL experience.

And how is that affecting, the FDA review?

I'll start off and say that from a commercial payer perspective, we have had very strong reimbursement.

Across the board.

In terms of coverage of the free.

Just a couple of different plans that have not made decisions and our opportunities for our corporate account team to just go ahead and educate a follow up.

As they move forward in terms of their dialogues with various different pairs.

From a Medicare perspective.

Because of the CMS statute or weight loss medications.

We expect that we're not going to be successful in terms of coverage there at this point of time.

I will outline that one piece to remember, though is similar in terms of our Biallelic PPL patient population and what we saw.

The Bbs patients that we've identified also because of our focus in terms of where we do disease education. They are primarily younger and more likely to have commercial and or Medicaid coverage.

On the Medicaid side, what we're seeing is it.

Is mix.

We certainly see states that are covering their free.

And those that have also not yet made a decision and those that have weight loss exclusion decided not a tougher sifry and once again I think that with a team on ground. The latter two buckets really are opportunities for our teams to go.

And educate and differentiate our target populations from the broad obesity population.

I think in terms of expectations.

We are not expecting to get 100% coverage across the board.

But I do feel.

Positive just in terms of our ability to change the current landscape.

They'll continue to dialogue and educate.

And Jennifer, maybe one clarification, the 350 plus patients that your teams have identified are not necessarily all in the registry.

Thanks.

Thanks, Jennifer.

Did we answer your question Derrick.

Right.

Sure.

Yeah, all good. Thank you so much Greg congrats on the progress thanks.

Great question.

Thank you next question.

Thank you. The next question comes from Dae Gon Ha from Stifel. Please go ahead.

Yes. Good morning, Thanks for taking my questions as well I'll piggyback off of some of Eric's questions on Bbs.

Are you able to comment on whether you've already started engaging the FDA on the labeling discussions for Bbs and secondly, when we think about that.

The launch trajectory.

The slide with regards to 350 patients or more being identified I think the commentary today was more than 150 physicians.

That take care of those identified patients. So how much of an overlap is there between those physicians that take care of Bbs versus the Biola like PPL, just wondering about the COVID-19 impact we've heard certain kols that institutions still restricting in person sales rep meetings and I've got a follow up thanks.

Okay.

That went to Jennifer on the engaging with the FDA.

We've said previously we expect that engagement.

Some point roughly a month or so ahead of time and Thats all.

We have no further update there.

We, we, at this point in time, we don't really know the overlap in terms of the 350 plus patients versus the ones that are in the Marshfields, the CRIBS registry right now.

To your question just in terms of ACP overlap.

For the PPL pace.

Patient population in terms of the scripts.

The volume is outlined from an expectation perspective was well however.

There may be, I would assume that there's not a hundred percent overlap as you know, our teams have been on ground educating and targeting various different physicians throughout the nation.

However.

<unk>.

The majority of these physicians coming in we're already in our rhythm CRM, where similar patients or physicians that we were also already engaging with.

Hence there is some overlap with the Bbs physician Paul.

But theres also physicians that have not yet prescribed from a PCL perspective.

We are actively engaging with as we move forward.

Did we answer it?

Okay. Thanks for that I.

Im sorry, David.

Hello. Thanks.

Very helpful.

Okay, well so the other question is just shifting gears a little bit to DAYBREAK.

Yes, it does.

Following the amendment you spoke about how within the 10 sub studies or the genotype. So youre looking at two are actually going to have some broader implications as it is part of <unk> Tianjin pathway network. So can you maybe talk a little bit about those two genes what led you to identifying those two versus the other 11.

And how much of a derisking can we anticipate based on those two changes with respect to sort of what their protium products do in that MSC for our pathway.

Yes, that's a great question. Thank you very much. So we came to identify the genes by working with our key opinion leaders, who are experts in the field as well as looking to our own preclinical data.

To identify those that.

R&D risks and most likely do have the greatest potential impact of impairing the pathway and therefore being responsive to central Antitype. So those two genes that are part of the SMS three family of genes.

We're looking both at the flex and <unk> for as well as the Sistema III G.

So two different angles into that family. So we really do feel this will give us the greatest opportunity to be able to identify the impact that that all of those associated gene tab as well as.

The impact of the other genes.

Based on the science it does support that they do have a strong relevance to the empty for a pathway.

Okay alright, thank you.

Yes, Yes, I guess I guess I was just kind of curious how much of a derisking can we really anticipate given that if it is part of like a complex for example that functions.

Well unit versus multiple different proteins being engaged at different portions of the pathway.

That's kind of what I was trying to get at but we can we can certainly catch up offline or talk later after the data is out.

Hey, maybe we can leave it.

As Linda said those two were based.

Based on looking at the group and figuring that those two are the highest.

The highest probability.

<unk>.

Responding.

Neither one of those show any effect then we're done with the pathway if.

If we see a significant effect then of course, we'll dive deeply into the pathways. So the derisking will occur through that I think your question is how tightly those two are linked to all the others.

I think theres not a short answer to that question.

Got it okay. Thank you very much.

Thank you. The next question comes from Joseph Stringer from Needham <unk> Company.

Thank you.

Thank you guys.

Thank you.

That's a reminder.

Hi, good morning, Thanks for taking my questions supervised first one is.

On the <unk>.

<unk>.

Did the FDA require any additional data.

Excuse me.

Good afternoon reflect any.

Additional data analysis.

Steve.

Since you initially announced.

In February of this year.

Second question is on.

On M&A do you anticipate the SRT one <unk>.

<unk> one.

Favorable faster just given.

The higher prevalence relative to the sub studies.

Thanks for taking my questions.

Sure Great question I'll start with the M&A because that is the easier answer. So so yes, we do anticipate.

Via the higher prevalence that there will be a faster enrollment of Src women FH, Jimmy one for Glenn.

The other as far as the FDA and no additional requests for data other than that that we spoke about previously.

Other than we did submit our periodic benefit risk evaluation report firm that's part of our regular requirements. So they just had some follow ups.

Market too but.

But otherwise we're on track.

No additional requests separate been received to date.

Next question.

Yes.

Thank you.

Our next question comes from Michael Higgins from Ladenburg Thalmann. Please go ahead.

Good morning, guys. Thanks for taking the questions.

Just wanted to follow up on the comments you've made and also in the press release for the modification to the summary product characteristics in Europe following.

Making adjustments in moderate and severe renal impairment.

Adjustments for dose escalation and the lower Max dose what led to that.

Is that post marketing is that something that's on the data and how is that affecting the.

So we conducted a trial in patients with renal impairment, mild, moderate, and severe renal impairment, and we assessed the pharmacokinetics and based on the data from that trial, that is what came out of it.

The FDA review.

Sure Great question. So we conducted a trial in patients with renal impairment mild moderate and severe renal impairment and we assess the pharmacokinetics and based on the data from that trial data came out of it. So we have submitted this data both to the FDA and the EMA slightly different.

So we have submitted this data both to the FDA and to the EMA. Slightly different pathways by which those regulatory approvals go through, but they are both kind of tied to our BBS submission. And in essence, the data shows that there was no need for any dose adjustments in the mild and moderate renal impairment.

Pathways by which those regulatory approvals go through but they are both kind of tied to our Bbs submission and in essence. The data show that there was no need for any dose adjustments in the mild and moderate renal impairment.

But in patients with severe renal impairment, the data suggests starting at a lower dose and dose escalating slower. The max target dose can still be the same, but it will be dose escalated based on clinical response efficacy and safety.

With severe renal impairment.

<unk> suggest starting at a lower dose and dose escalating slower the Max target dose can still be the same.

So just to follow up to that, would you look for the same type of language from the FDA?

It will be dose escalated based on response.

Clinical response efficacy and safety.

So just a follow up to that would you look for the same type of language.

Yes.

From the FDA.

Yes, yes, we anticipate that it would be quite similar.

We anticipate they would be quite similar.

Okay Super helpful. And then just a follow up on the DBS market.

You've discussed the 350 patients identified.

Okay.

There are 750 that the Bbs group as it has.

What are your steps that you're taking to close that gap, obviously, theres some patient confidentiality, but.

Youre working so closely with that group also wondering how that is coming together in.

And the last part of that would be.

Mentioned identifying patients through ICD 10 codes.

I don't think its for Bbs. So if you could expand on what that is you're finding in those codes.

Okay.

So.

Just in terms of efforts over all in engagements the relationship we have with the Marshalls clinic is extremely strong.

Of course, they are the one two.

On the registry and Matthew outlined there are some restrictions just in terms of our ability to access their thoughts, but I think base.

Based off of their interest also in terms of treatment of the patient population and also.

Interest in the drug that may be one opportunity also in terms of the blade through us.

You know how things are communicated with patients that they are also in touch with.

I think moving on to the question in terms of the ICD 10 code.

There are there is a benefit like I said this is a very different loss from the initial indication because bbs syndromic indication and.

Based off with at various different symptoms, where its involvement.

<unk>.

Things around.

<unk>.

Renal impairments et cetera, there is the ability to sort of triangulate to try to understand which physicians have patients that may be at the ABS paycheck, particularly if you start with one code.

<unk> hundred 80, 786 were Bbs actually resides there may be an ability to tease out out out of that tens of thousands under that code.

Physician may have diagnosed at Bbs patient versus the <unk>.

10, other plus <unk>.

Indications that fall within that category. So we're just trying to be smart in terms of targeted efforts of how we go about disease educating.

50, plus patients versus the one that are in the Marseille.

Chris Registry right now there may be I would assume that there is not 100% overlap.

Our teams have been a ground educating and targeting various different physicians throughout the nation.

Very helpful.

Yes. It does thank you thanks guys.

Thank you.

If you have any questions, please press zero one.

Super helpful.

As a reminder, if you have any questions please spread zero one or.

Our next question comes from Jeff Hunk from Morgan Stanley.

Our next question comes from Jeff Hung from Morgan Stanley . Please go ahead.

Please go ahead.

And then just a follow-up on the BBS market.

Thanks for taking my questions ahead of the potential Bds launch do you have a sense for what percentage of the 350 patients would be interested in being treated like what kind of pre screening have you done through the physicians.

You've discussed the 350 patients that have been identified.

There are 750 that the BBS group has.

What are your steps that you're taking to close that gap?

Thanks for taking my questions.

Obviously, there's some patient confidentiality, but you're working so closely with that group also.

And then as we look towards the potential approval, how often should we expect updates for the number of identified and treated patients.

Wondering how that is coming together.

What kind of metrics might you can provide regular updates on thanks.

Yeah.

Sure.

Ahead of the potential BBS launch, do you have a sense for what percentage of the 350 patients would be interested in being treated?

And the last part of that would be, you mentioned identifying patients through ICD-10 codes.

In terms of the patient.

Like what kind of pre-screening have you done through the physicians?

Like I said, it's very difficult to really come up with an estimate just in terms of exact percentage that will be expected to go on therapy, maybe if I could also caveat things in certain ways.

And then as we look towards the potential approval, how often should we expect updates for the number of identified and treated patients or what kind of metrics might you provide regular updates on?

When you think of the physician population that we are targeting.

Thanks.

In terms of the patients, you know, like I said, it's very difficult to really come up with an estimate just in terms of exact percentage that will be expected to go on therapy.

Maybe if I could also caveat things in certain ways, when you think of the physician populations that we are targeting a lot of our efforts have been in the past also around the pediatric endocrinologist endocrinologist.

And from that perspective, they are having issues that they are going to this, these specific physician populations to address and hence they may be a more motivated population in terms of wanting to really seek out a treatment for their, their obesity and hyperphagia components.

To address and hence they may be more motivated population in terms of wanting to really.

Seek out treatment for their therapies today and hyperphagia components. So that's a positive factor just in terms of native tree desire to find a new option.

So that's a positive factor just in terms of need to treat a desire to find a, new option.

I think in terms of the second question was related.

I think.

Yeah.

In terms of the second question was related in terms of updates so.

And maybe just one additional point, Jeff fund in terms of the percentage as Jennifer said, it's impossible to estimate, but I think thats. The point that you made is the critical one which is these patients that we are confirming in that 350 plus are engaged in the system. They're engaged in the system. They are seeking health so they're going to get on therapy would be the prediction.

It's a question how long when will they see good I mean, there's a lot of factors will dictate how much time. It takes maybe to get them on therapy, but they have already signaled that they are out there looking for help and so word will get around.

In terms of updates.

In terms of metrics again, I'll just say, we're very early in terms of.

The obvious things as patient numbers, there's prescriptions written theres number of doctors, who are writing prescriptions and the like and what we'll do as we begin to get more experience here has tried to look at things that we feel provide the most meaningful insight and we'll clear though.

At this point we're not.

And I can tell you exactly what metrics with those will be.

Alright, great. Thank you.

Yes.

Thanks Rich.

Thank you last question.

Our next question comes from Karen Jenkins, Karen Jenkins from Goldman Sachs. Please go ahead.

So maybe just one additional point on Jeff on, on terms of the percentage, as Jennifer said, it's impossible to estimate, but I think that the point that she made is the critical one, which is these patients that we are confirming and that 350 plus are engaged in the system. They're engaged in the system, they're seeking help.

So they're going to get on therapy with the prediction.

Yes.

It's the question, how long, when will they seek it?

Everybody.

I mean, there's a lot of factors will dictate how much time it takes maybe to get them on therapy, but they've already signaled that they're, they're out there looking for help.

So maybe totally different tack here, but as you expand these emanate and the DAYBREAK basket studies Im curious if youre seeing any change in dynamics with respect to the receptivity or utilization of the euro.

And so word will get around in terms of metrics.

Again, I'll just say we're very early in terms of you know, they're the obvious things.

There's patient numbers, there's prescriptions written, there's a number of doctors who are writing prescriptions and the like.

Test just given there is a higher.

Yield on being able to do something about the genetic screening test as they come back.

And what we'll do as we begin to get more experience here is try to look at, things that we feel provide the most meaningful insight and we'll share those.

But at this point, we're not going to tell you exactly what, what metrics for those will be.

Okay.

I agree.

It's a very good question.

Very much in a sense controlled that.

Broadly available people can just sign up for it and be shipped a kit that said we are very much we've shifted our strategy from the beginning it was basically wide open. We are just trying to understand the epidemiology. We've now become much more focused our field teams around encouraging screening at those sites needed the clinical trial sites themselves.

Thank you.

Our next question comes from Karen Jenkins.

Karen Jenkins from Goldman Sachs.

Please go, ahead.

Yes.

Good morning, everybody.

Or clinics that are in some radius around our clinical trial sites.

Accretion is quote unquote diagnosed they have a reasonable chance of being eligible are able to get into emanated DAYBREAK. So it's not a good number the malware screening has gone up somewhat from our no other numbers, but it is governed by a restricted if you will by that.

So maybe totally different tack here, but as you expand these, M&A and the Daybreak Basket studies, I'm curious if you're seeing any change in dynamics with respect to the receptivity or utilization of the URO test, just given there's a higher yield on being able to do something about the genetic screening test as they come back?

It's a very good question.

We very much in a sense control that.

It's broadly available. People can just sign up for it and be shipped a kit.

That said, we are very much, we've, shifted our strategy from in the beginning it was basically wide open.

We are just trying to understand the epidemiology.

The amount we're screening has gone up somewhat, from our other numbers, but it's governed by a restrictive, if you will, by that effort.

We've now become much more focused, our field teams around encouraging screening at those sites, either the clinical trial sites themselves or clinics that are in some radius around a clinical trial site so that when a patient is quote unquote diagnosed, they have a reasonable chance of being eligible, able to get into M&A or Daybreak.

Okay, thanks.

So it's not a good number.

That's helpful.

Right.

Okay. Thanks, that's helpful.

Thank you.

Thank you great well with that I think.

With that, I think we're at the end here and I want to thank all of you for tuning in.

I don't think it's for BBS, so if you could expand on what that is you're finding in those codes.

Great.

So I think that just in terms of efforts overall and engagement, the relationship we have with the Marshall Clinic is extremely strong.

Of course, they are the ones who own the registry.

At the end here.

I want to thank all of you for tuning in and if there any questions that we did not get to can you. Please.

And if there are any questions that we did not get to, can you please submit those to, Dave Connolly and we'll work to respond to those individually.

And as you outlined, there are some restrictions just in terms of our ability to access and such.

But I think based off of their interest also in terms of treatment of the patient population and also interest in the drug, that may be one opportunity also in terms of the playthrough of how things are communicated with patients that they are also in touch with.

I think moving on to the question in terms of the ICD-10 code, there is a benefit.

Like I said, this is a very different launch from the initial indication because BBS is a, syndromic indication.

And Jennifer, maybe one clarification.

And based off of the various different symptoms where it's eye involvement, you know, obesity, things around renal impairments, etc.

Dave Kang and we'll work to respond to those individually.

The 350 plus patients that your teams have identified are not necessarily all in the registry.

There is an ability to sort of triangulate systems to try to understand which, physicians have patients that may be a BABS patient.

Particularly, if you start with one code, Q87-86, where BBS actually resides, there may be an ability to tease out of the tens of thousands under that code which physician may have diagnosed a BBS patient versus, you know, the ten other plus indications that fall within that category.

So we're just trying to be smart in terms of targeted efforts of how we go about disease educating.

And with that, thank you all for tuning in.

Right.

But I think the opportunity.

We, at this point in time, we don't really know the overlap in terms of the 350 plus patients, versus the ones that are in the Marshfield, the CRIBS registry right now.

There may be, I would assume that there's not a hundred percent overlap as, you know, our teams have been on ground educating and targeting various different physicians throughout the nation.

Did we answer it?

Thank you.

Okay. Thank you ladies and gentlemen. This concludes today's conference. Thank you for participating you may now disconnect.

Very helpful.

Ladies and gentlemen, this concludes today's conference.

As a reminder, if you have any questions, please press 01.

Yes, it does.

Our next question comes from Jeff Hong from Morgan Stanley.

Thanks, David.

Please go ahead.

Thank you for participating.

Thanks, guys.

Thanks for taking my question.

You may now disconnect.

Ahead of the potential BBS launch, do you have a sense for what percentage of the 350 patients would be interested in being treated?

Goodbye.

Like what kind of pre-screening have you done through the physicians?

And then as we look towards the potential approval, how often should we expect updates for the number of identified and treated patients?

Or what kind of metrics might you provide regular updates on?

Thanks.

Sure.

In terms of the patients, you know, like I said, it's very difficult to really come up with an estimate just in terms of exact percentage that will be expected to go on therapy.

Maybe if I could also caveat things in certain ways.

When you think of the physician populations that we are targeting, a lot of our efforts have been in the past also around the pediatric endocrinologist. And from that perspective, they are having issues that they are going to these specific physician populations to address.

And hence, they may be a more motivated population in terms of wanting to really seek out a treatment for their obesity and hyperphagia components. So that's a positive factor just in terms of need to treat, desire to, find a new option.

I think, in terms of the second question was related.

Yeah, in terms of updates.

So maybe just one additional point, Jeff, on terms of the percentage.

Jennifer said it's impossible to estimate.

But I think that the point that she made is the critical one, which is these patients that we are, confirming in that 350 plus are engaged in the system. They're engaged in the system.

They're seeking help.

So they're going to get on therapy with the prediction.

It's the question, how long, when will they seek it?

I mean, a lot of factors will dictate how much time it takes maybe to get them on therapy.

But they have already signaled that they're out there looking for help. And so word will get around.

In terms of metrics, again, I'll just say we're very early in terms of, the obvious things.

There's patient numbers.

There's prescriptions written.

There's a number of doctors who are writing prescriptions and the like.

And what we'll do as we begin to get more experience here, is try to look at things that we feel provide the most meaningful insight, and we'll share those.

But at this point, we're not going to tell you exactly what metrics those will be.

Great.

Thank you.

Our next question comes from Karen Jenkins.

Karen Jenkins from Goldman Sachs.

Please go, ahead.

Yes.

Good morning, everybody.

So maybe totally different tack here, but as you expand these, M&A and the Daybreak Basket studies, I'm curious if you're seeing any change in dynamics with respect to the reciprocity or utilization of the URO test, just given there's a higher yield on being able to do something about the genetic screening test as they come back?

It's a very good question.

We very much in a sense control that.

It's broadly available. People can just sign up for it and be shipped a kit.

That said, we are very much, we've, shifted our strategy from the beginning.

It was basically wide open.

We are just trying to understand the epidemiology.

So it's not a good number.

The amount we're screening has gone up somewhat, from our other numbers, but it's governed by or restricted, if you will, by that effort.

Okay, thanks.

That's helpful.

Thank you.

Great.

With that, I think we're at the end here and I want to thank all of you for tuning in.

And if there are any questions that we did not get to, can you please submit those to, Dave Connolly and we'll work to respond to those individually.

And with that, thank you all for tuning in.

Thank you.

Ladies and gentlemen, this concludes today's conference.

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