Q3 2021 Rhythm Pharmaceuticals Inc Earnings Call

November 2, 2021

[music].

Operator: Good day, and thank you for standing by. Welcome to the Rhythm Pharmaceuticals third quarter financial results conference call. At this time, all participants are in listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question, you will need to press star 1 on your telephone. Please be advised that today's conference is being recorded. If you require deferred assistance, please press star 0. I would now like to hand the conference over to your speaker today, David Connolly, with Rithin. and pharmaceuticals, Please go ahead.

Good day and thank you for standing by welcome to the rhythm Pharmaceuticals third quarter financial results Conference call. At this time, all participants are in a listen only mode.

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

That's a question you will need to press star one on your telephone. Please be advised today's conference is being recorded if you require any further assistance. Please press star zero I would now like to hand, the conference over to your speaker today, David Connolly with receiving Pharmaceuticals. Please go ahead.

Thank you and good morning, I'm, David Connolly 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.

This morning, we issued a press release that provides our third quarter <unk> third quarter 2021 financial results and business update which is available on our website.

David Connolly: As listed on slide two, with me today here in Boston for the conference caller are David Demethe, Chair, President, and Chief Executive Officer of Rhythm, Linda Shapiro, our Chief Medical Officer, Jennifer Chen, Executive Vice President, Head of North America, and Hunter Smith, our Chief Financial Officer.

As listed on slide two.

With me today here in Boston Bullish conference call are David <unk>, Chairman, President and Chief Executive Officer of rhythm.

Linda Shapiro, our Chief Medical Officer, Jennifer Chen Executive Vice President head of North America, and Hunter Smith, our Chief Financial Officer with Slide three I'll remind you that this call contains remarks concerning future expectations plans and prospects, which constitute forward looking statements actual results may differ materially.

David Connolly: Slide three, I'll remind you that this call contains remarks concerning future expectations, plans, and prospects, which constitute forward-looking statements. However, actual results may differ materially from those indicated by these forward-looking statements as a result of various factors, including those discussed in our most recent annual 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. 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.

Curiously from those indicated by these forward looking statements as a result of various factors, including those discussed in our most recent annual 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 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.

David P. Meeker: Thank you, Dave, and good morning, everyone. We're very pleased to report another strong quarter of execution for rhythm, and I'll remind you that we're building rhythm piece by piece, gene by gene, and are, like I said, very pleased with the progress to date. The first slide is to highlight four areas of high focus for us. One is, of course, the commercial experience with Encivary. Second, we are looking forward to the anticipated Barton Beetle and Allstrom's launch in 2022.

Thank you, Dave and good morning, everyone.

Im very pleased to report another strong quarter of execution for rhythms and I'll remind you that we're building rhythms piece by piece gene by gene and like I said very pleased with the progress to date. The first slide is to highlight four areas of high focus for US one is of course the commercial experience.

With and Sebree second is looking forward to the anticipated BARDA beetle and all Stearns launch in 2022.

David P. Meeker: Third is to build out our global presence, working with healthcare systems, first and foremost in Europe, but we will increasingly look beyond there. And fourth, to continue to advance a robust clinical development process, which has the ability to meaningfully increase the addressable patient population. Now, quarter three is a quarter with multiple highlights, again, with continued execution.

Third is to build out our global presence working with health care systems, first and probably foremost in Europe, but we will increasingly look beyond there.

Fourth to continue to advance a robust clinical development program, which has the ability to meaningfully increase the addressable patient population.

Now quarter three is a quarter with multiple highlights again with continued execution.

David P. Meeker: First, the U.S. and Sivry launch is progressing and meeting expectations. As we said, we expected to have tens of patients on treatment, and that view of the world has continued to hold. We were pleased with the net sales, clearing $1 million for the quarter, but more importantly, we're really happy about the learnings that we're beginning to accumulate from this initial commercial experience, which will lay the foundation for our subsequent Barton-Bed Beetle launch.

First the U S and Sebree launch is progressing and meeting expectations. As we said we expected to have tens of patients on treatment and that's.

Our view of the World has continued to hold me, we're pleased with that sales clearing 1 million for the quarter, but more importantly, we're really happy about the learnings that we're beginning to accumulate from this initial commercial experience, which will lay the foundation for a subsequent BARDA beetle lunch and then the international markets Europe specifically.

David P. Meeker: And in international markets, Europe specifically, reimbursement dossiers have been filed in major markets and some of the smaller markets as well. And we're in advanced discussions with the three major markets, Germany, France, and the UK. Second, as we advance toward BBS launch in mid-2020, as you know, the regulatory submissions have been filed in both the U.S. and Europe. We've fully hired a highly experienced field team, and Jennifer will provide you with more color around that. So a year ahead of anticipated launch, we feel like we are in a good place, so I'm looking forward to that event.

Reimbursement dossiers have been filed in major markets and some of the smaller markets as well and we're in advanced discussions with the three major markets, Germany, France and the UK.

Second as we advance towards Bbs launch in mid 2022 as you know the regulatory submissions have been filed in both the U S and Europe and the U S and we are.

Fully hired a highly experienced Uh huh.

Field team and Jennifer will provide you with more color around that so a year ahead of anticipated launch we feel like we are in a good place I'm looking forward to that event.

David P. Meeker: Third, we had a very strong presence at medical meetings with 22 presentations at three major medical conferences. Positive data was presented from a variety of different clinical data sets, with world-renowned KOLs presenting supplemental antitide data. And in a noteworthy category, we have our first data on health-related quality of life and additional data on hunger and weight scores across a number of different genetic diseases. Linda will provide a little more color on that in her presentation. And finally, the clinical development programs remain on track with many favorite psychiatric and easeaseat trials advancing to first patient.

Third we had a very strong presence at medical meetings with 22 presentations at the three major medical conferences positive data was presented from a variety of different clinical data sets with world renowned kols presenting several anti data and there are no really.

Noteworthy category, we have our first data on health related quality of life and additional data on hunger and weight scores across a number of different genetic diseases, Linda will provide a little more color on that in her presentation and finally, the clinical the clinical development programs remain on track with M&A DAYBREAK Yatra.

Yeah.

Trials advancing two first patient in and I will provide a little more color on our testing program.

David P. Meeker: And I will provide a little more color on our testing program here in a slide, too. But before we get to that on the next slide, slide number seven, just want to remind you there's efficiency to a rare disease community building, which we are taking advantage of. And in the bare disease setting, you often have a limited number of centers of excellence, a limited number of KOLs, and they serve multiple purposes. And so you can focus your efforts very much around these sites.

<unk> two.

Before we get to that on the next slide slide number seven I just want to remind you there is an efficiency.

Rare disease community building, which we are taking advantage of and in the rare disease setting you often you have a limited number of centers of excellence a limited number of Kols and they serve multiple purposes and so you can focus your efforts very much around these sites and not only do they run the trials.

Serve as key opinion leaders and they're also the same physicians health care providers, who diagnose and actually treat these patients and what we're doing is pursuing a hub and spoke model where that center of excellence a clinical trial site is at the center and then we will work with.

David P. Meeker: Not only do they run the trials and serve as key opinion leaders, but they're also the same physicians and health care providers who diagnose and actually treat these patients. And what we're doing is pursuing a hub-and-spoke model where that Center of Excellence, the Clinical Trial Site, is at the center, and then we will work with a surrounding set of providers, interested parties who are potential referral sites, referring patients into that site, and over time, some will become their own Centers of Excellence, depending on the level of injury.

Surrounding set of treaters.

Interested parties, who are potential referral sites I'm, referring into that site and over time, some will become their own center of excellence, depending on the level of interest.

Moving to slide eight here's a brief update on our testing program. We've had several generations of our screening genetic screening panel in May we went from a 40 gene panel that we reported out on to reporting out on an 80 gene panel.

And that panel includes all the genes of interest to rhythm in terms of genes. We believe are closely linked to the M. C. Four pathway, but it also includes the number of genes that would be of interest to the.

David P. Meeker: Moving to slide eight, here's a brief update on our testing program. We have had several generations of our genetic screening panel. In May, we went from a 40 gene panel that we reported out on to reporting out on an 80 gene panel, and that panel includes all the genes of interest to rhythm in terms of genes we believe are closely linked to the MC4 pathway. But it also includes a number of genes that would be a lot of genes.

<unk>.

Obesity treater at large meaning other genes that might help inform what is the underlying driver of that patients obesity.

But what this pie graph shows is on the order of 55% of patients who present with a history of early onset obesity and hunger are likely to test positive for one of the genes of interest, meaning a gene that would qualify that patient for entry into the M&A trial or the DAYBREAK try.

Bill, which is an additional 31 genes we've yet to explore but have some reason to believe they may be related to the pathway or b potentially eligible for a commercial therapy with an SIB Murray now of note in that 55% or $1 96, almost 2% of the population who are biallelic for BARDA.

David P. Meeker: of interest to the Obesity Treater at large, meaning other genes that might help inform what is the underlying driver of that patient's obesity. So what this pie graph shows is that on the order of 55% of patients who present with a history of early-onset obesity and hunger are likely to test positive for one of the genes of interest, meaning a gene that would qualify that patient for entry into the MNate trial or the daybreak trial, which is an additional 31 genes we've yet to explore, but have some reason to believe they may be related to the pathway or be potentially eligible for commercial therapy within Si

Beetle or the arms, one gene, which is the gene that is responsible for alstom syndrome, so that percentage of them as a noteworthy percentage there's much more to be learned we don't know that all of those patients.

Their genetic defect is driving their underlying obesity or that they will even go on to develop BARDA beetle, but it opens up a whole another avenue for better understanding of this disease and rhythms going to play a leading role in driving that exploration.

David P. Meeker: Now, of note, in that 55% are 1.96, almost 2% of the population who are biolelic for Bardett Beetle or the Alms 1 gene, which is the gene that is responsible for Alstrom's syndrome. So that percentage is a noteworthy percentage. There's much more to be learned. We don't know that all of those patients have the genetic defect driving their underlying obesity or that they will even go on to develop Bart at Beetle, but it opens up a whole other avenue for better understanding this disease, and Rhythm is going to play a leading role in driving that exploration.

With that we'll move on to slide nine slide nine inside just to remind you again that we do have a broad pipeline and underscores. The fact that I think we have a legitimate pipeline in a product and Linda will provide a little more color on our progress across this portfolio and her search.

And with that I'll turn it over to Linda.

Thank you David.

This is an exciting time for wisdom and start.

First around the Barnett shale are coming together on many fronts.

That's in a position to bring to patients the first ever therapy to address the unmet needs of hyperphagia and severe obesity that affect the lives of patients and families living with this disease.

David P. Meeker: With that, we'll move on to slide nine. Slide nine is just to remind you again that we do have a broad pipeline, and it underscores the fact that I think we have a legitimate pipeline for a product, and Linda will provide a little more color on our progress across this portfolio in her section. And with that, I'll turn it over to Linda.

<unk> syndrome, our DBS is a clinical syndrome with many features including severe obesity from an early age and an insatiable hunger hyperphagia, which impact the health and quality of life for parents.

Our patients their families and caregivers.

Linda Shapiro: This is an exciting time for rhythm as our efforts around Bartlett-Bedal Syndrome are coming together on many fronts, putting us in a position to bring to patients the first ever therapy to address the unmet needs of hyperphasia and severe obesity that affect the lives of patients and families living with this disease. Bart at Beetle Syndrome, or BBS, is a clinical syndrome with many features, including severe obesity from an early age and an insatiable hunger or hyperphasia, which impacts the health and quality of life for parents, for patients, their families, and caregivers.

There is currently no effective treatment.

We know from interviews and our work on health related quality of life and patients and families with Bbs presented this week for the first time, just how dire need is to control hunger and to stop thinking about food all the time.

This quarter as David said, we are one step closer to delivering a transformative new treatment option to patients having completed our regulatory submissions in the U S and EU.

That will amortize its demonstrated clinical efficacy and safety as well as meaningful improvements for patients and their families caregivers and health care providers and we look forward to reviewing some of these data today.

Linda Shapiro: There is currently no effective treatment, and we know from interviews and our work on health-related quality of life in patients and families with BBS, which was presented this week for the first time, just how dire the need is to control hunger and stop thinking about food all the time. This quarter, as David said, we are one step closer to delivering a transformative new treatment option to patients, having completed our regulatory submissions in the U.S. and EU.

Bye.

The severe impact that.

D. S has on the lives of patients and families is significant and.

And we've made tremendous strides this quarter in documenting qualifying.

Quantify this impact.

But the patients caregivers and families clearly speak for themselves.

Eric quote on this slide in depth qualitative interviews that we conducted with patients with a b S. Android their caregivers.

I want to stress and guilt denying food to children with hyperplasia and point to how the world.

We're all around.

Okay.

Linda Shapiro: Setmalanatide has demonstrated clinical efficacy and safety, as well as meaningful improvements for patients and their families, caregivers, and health care providers. And we look forward to reviewing some of these data, for certain. The severe impact that BBS has on the lives of patients and families is significant, and we've made tremendous strides this quarter in documenting, qualifying, and quantifying this impact. But the patient's caregivers and families clearly speak best for themselves. As there are quotes on this slide from in-depth qualitative interviews that we conducted with patients with BBS and or their caregivers, point to the stress and guilt of denying food to children with hyperphasia and point to how the world revolves around food, which limits their focus on anything else. Pause here for an opportunity for you to read through some of these closed questions.

Anything else.

Pause here.

For your chance.

Thanks.

During a company all hands meeting we heard last night from the mother of a child with park Central and her story reinforced our understanding of the impact be SaaS on families and underscore the unmet need that exists in this community.

He told us about the significant weight gain evidenced by two years old that continued.

The charts right of weight growth.

And the challenges she faced in school with weight gain including physical as well as social difficulties.

He told US it was very tough.

These firsthand accounts reinforce our understanding of the impact EPS has on families.

Alright.

Yes.

Yeah.

Slide 14.

This quarter, we completed regulatory submissions for <unk> syndrome, and Ahlstrom syndrome in both the United States as well as the European Union.

In September we submitted a supplemental new drug application to the FDA for ancillary and branded name it separately on our side for the treatment of obesity and control of hunger and adult and pediatric patients six years of age and older with Bbs or ultra syndrome.

Linda Shapiro: Last month, at an all-hands meeting, we heard from the mother of a child with Bartapedal syndrome, and her story reinforced our understanding of the impact BBS has on families and underscored the unmet need that exists in this community. She told us about the significant weight gain evident by two years old that continued at an off the charts rate of weight growth, and the challenges she faced in school with weight gain, including physical as well as social difficulties. She told us it was very, These firsthand accounts reinforce our understanding of the impact BBS has on families and underscore the unmet need that exists, by 14. This quarter, we completed regulatory submissions for Bartlett Beetle Syndrome and Ulstrom Syndrome in both the United States and your K&U.

We requested priority review from the FDA as part of the application.

Based on FDA timelines, we will know in November if our supplemental NDA has been accepted with priority review.

If granted that would mean a target FDA review period of six months from that date.

In October we submitted a type two variation application to the European medicines agency premiums debris for the treatment of obesity and telephone Barrett in adult and pediatric patients six years of age and older with Bbs for all sorts of things.

Joe.

There were a few timeline in Europe, it's calendar base.

Would expect a decision from the European Commission in the second half of 2020.

We are confident in these submissions is fair based on data from the pivotal phase III trial in which that will amortize achieved clinically meaningful and statistically significant reduction in body weight.

The unrelenting pressure associated with the syndrome.

Linda Shapiro: In September, we submitted a supplemental new drug application to the FDA for Imsevary, the branded name of setmalanitide, for the treatment of obesity and control of hunger in adult and pediatric patients six years of age and older with BBS or Alzheimer's syndrome. We requested priority review from the FDA as part of the application. Based on FDA timelines, we will know in November if our supplemental NDA has been accepted for priority review. And if granted, that would mean a target FDA review period of six months from that date of acceptance.

And these submissions include a series of comprehensive narrative, just individual patient supporting our belief that <unk> has the potential to offer the first therapeutic option for the early onset severe obesity and unrealized.

Okay.

Yes.

Yeah.

On slide 15.

Here's a reminder of the trial design of a phase III trial evaluating certain Atlanta type therapy in patients as part of <unk> and gentlemen, Ahlstrom syndrome.

This trial began with a one to one randomization in a double blind placebo controlled period of 14 weeks as highlighted in the light blue area.

Then progressed or a minimum of 52 weeks to Atlanta type therapy.

All patients were titrated on Atlanta tight at the beginning of the open label portion and proceeded to complete at least 52 weeks on therapy for those who began to placebo and a total of 66 weeks on therapy for those who began separately appetite.

Linda Shapiro: In October, we submitted a type two variation application to the European Medicines Agency for IMSABRI for the treatment of obesity and control of hunger and adult and pediatric patients six years of age and older with BBS or Alzheimer's syndrome. The review timeline in Europe is calendar-based, and we would expect a decision from the European Commission in the second half of 2020.

Patients were evaluated for the primary and key secondary endpoint at 52 weeks on therapy as shown here in the red boxes.

Slide 16.

Data from the 14th week double blind.

The CFO control period.

Linda Shapiro: We are confident in these submissions as they are based on data from the Pivotal Phase 3 trial in which septmal anatide achieved clinically meaningful and statistically significant reductions in body weight and in the unresolving hunger associated with these syndromes. And these submissions include a series of comprehensive narratives for each individual patient, supporting our belief that insub-free has the potential to offer the first therapeutic option for the early onset, severe obesity, and unrelated to hunger that characterize these children.

Significant BMI reductions in patients with Bbs on several anti therapy versus placebo.

Patients in the placebo group had negligible weight loss or be BMI reduction at 14 weeks.

Patients in the treatment group, who reduced their BMI by an average of four 3%.

This translates to a statistically significant placebo corrected certain Atlanta type treatment effect of three 8% reduction in 14 weeks.

Slide 17.

This trial achieved all primary and key secondary endpoints were statistically significant and clinically meaningful reductions in body weight and hunger.

Linda Shapiro: On slide 15, here's a reminder of the trial design of our Phase 3 trial, evaluating set melanotide therapy in patients with Bart at Biedel syndrome and Alzheimer's. This trial began with a one-to-one randomization to a double-blind placebo-controlled period of 14 weeks, as highlighted in the light blue area, and then progressed through a minimum of 52 weeks on set melanotide therapy. All patients were titrated on setmalanitide at the beginning of the open label portion and proceeded to complete at least 52 weeks on therapy for those who began on placebo and a total of 66 weeks on therapy for those who began on setmalanitide. Patients were evaluated for the primary and key secondary endpoints at 52 weeks on therapy, as shown here in the red box. Slide 16.

These data on patients with Bbs from the Phase III trial are presented this week at the obesity week conference in a symposium by Dr. Robert Haws, Marshfield clinic, the leading part of it all syndrome key opinion leader in the United States.

As you can see we saw clinically significant reduction in body mass index across all 31 patients with EPS in this trial with a mean reduction of greater than 9% in both adults as well as children and adolescence at 52 weeks of therapy.

Right.

Slide 18.

Seven Atlanta tide achieved clinically meaningful reductions in hyperphagia that insatiable hunger that dramatically affects the lives of patients with <unk> syndrome and their families.

As we saw these data in both the initial 14 week double blind period of set here and the light blue blocks and out to 52 weeks.

At 14 weeks to these data showed that patients in the placebo group had a modest reduction in hunger scores compared to the nearly 35% reduction achieved by the treatment group.

Linda Shapiro: The data from the 14-week double-blind receivocal control period are shown. Significant BMI reductions in patients with BBS on septimal anitide therapy versus placebo. Patients in the placebo group had negligible weight loss or BMI reduction at 14 weeks, compared to patients in the treatment group who reduced their BMI by an average of 4.3%. This translates to a statistically significant placebo-corrected set melanatide treatment effects of 3.8% BMI reduction in 14. As 17, at CPS previously, this trial achieved all primary and key secondary endpoints with statistically significant and clinically meaningful reductions in body weight and hunger at 615.

Interestingly when we compare the data trends over 52 weeks there is a clear separation of hunger during the double blind placebo controlled period.

Highlight didn't like Blue box, followed by the placebo group, reaching treatment levels rapidly after crossover to open label setting Atlanta type treatment.

Period.

The white background.

Also after the placebo controlled double blind period at week 14, you can see a brief rebound at hunker when patients are set in Atlanta tight or retreat re titrated onto the drag.

This speaks to the sensitivity of hunger and bark beetle syndrome patients as well as the sensitivity of the central advertiser spots.

Slide.

It's really week conference. This week, we're also presenting the first ever health related quality of life results to measure the impact of certain Atlanta type therapy of patients with Bbs.

This is particularly important in this ultra rare disease as a research underscores the need to adjust our health related quality of life burden experienced by patients.

Linda Shapiro: These data on patients with BBS from the Phase 3 trial will be presented this week at the Obesity Week Conference in a symposium by Dr. Robert Haas from the Marshville Clinic, the leading Bartlett-Betle Syndrome key opinion leader in the United States. As you can see, we saw clinically significant reductions in body mass index across all 31 patients with BBS in a trial, with a mean reduction of greater than 9% in both adults as well as children and adolescents at 52 weeks of therapy on set in the land. Slide 18.

The data show after one year of treatment with certain Atlanta tight 85% of patients reported clinically meaningful improvements in our preserve their unimpaired health related quality of life status.

For adult patients changes to their impact quality of life score from impact of quality of life score from baseline to 52 weeks, what's clinically meaningful with a mean increase of 12 point.

For pediatric patients, we saw clinically meaningful increased at the pace quality of life score from baseline to 52 weeks of 11.2 points.

Linda Shapiro: Semilamilamatide achieved clinically meaningful reductions in hyperphasia, that insatiable hunger that dramatically affects the lives of patients with Bartat Beetle syndrome and their, As we saw, these data in both the initial 14-week double-blind period set here in the light blue blocks and out to 52. At 14 weeks, these data showed that patients in the placebo group had a modest reduction in hunger scores compared to the nearly 35% reduction achieved by the treatment.

Clinically meaningful improvements in clinical outcomes, such as body mass index, and hunker also weird improvements and health related quality of life.

Importantly at the patient level improvements were sustained over the 52 week trial period.

With slide 21, I'd like to shift gears from CBS to our robust clinical development programs to treat more patients with obesity and hyperphagia due to genetically impaired Atlantic <unk> four receptor pathways.

Linda Shapiro: Interestingly, when we compare the data trends over 52 weeks, there is a clear separation of hunger during the double blind placebo-controlled period, highlighted in the Light Blue Box, followed by the placebo group reaching treatment levels rapidly after crossover to the open label, set melanotide treatment period with the white background. Also, after the placebo-controlled double-blind period at week 14, you can see a brief rebound of hunger when patients on set melanotide were retitrated onto the drug. This speaks to the sensitivity of hunger in Bartlett-Biedel syndrome patients, as well as the sensitivity of the septimian. Slide 19.

I want to begin by touching on a recent publication that illustrates the severity of disease.

For patients with <unk>.

Several of pricing.

Separately <unk> growing body of evidence in these indications.

Then I'll summarize for that short update on our next wave of clinical trials.

On slide 20 shale.

Article titled Implications of heterozygous variant and the changed at the left and the Atlantic Horton pathway and severe obesity by Dr. Stuffy Court barge and the team in the lab of Dr. Occurring so much Sorbonne University in Paris was published online this summer in the journal of clinical endocrinology and metabolism.

This article details for the first time, the phenotypes of patients with early onset severe obesity and hyperphagia.

Linda Shapiro: At the obesity week conference this week, we're also presenting the first ever health-related quality of life results to measure the impact of sent melanotide therapy in patients with BBS. This is particularly important in this ultra rare disease, as our research underscores the need to adjust the health-related quality of life burden experienced by patients. The data show that after one year of treatment with set melanotide, 85% of patients reported clinically meaningful improvements in or maintained their non-impaired health-related quality of life status.

Heterozygous variant in Atlanta for receptor pathway, including leptin receptor <unk> genes.

Hum.

Comparatively to patients with homozygous for Biomarin looks very good.

Importantly, the comparison shows similarly severe obesity with similar early onset and sugar hyperphagia all.

All of which underscore the genetics and the effect of the impaired pathway.

It's hard enough to rare genetic disease for obesity and the need for it.

Yes.

This research underscore the effects of a genetically inherited emcee for our pathway and the burden of rare genetic diseases of obesity and the need for therapy.

Linda Shapiro: For adult patients, changes to their impact of quality of life score from impact of weight quality of life score from baseline to 52 weeks were clinically meaningful, with a mean increase of 12. For pediatric patients, we saw a clinically meaningful increase in the P's quality of life score from baseline to 52 weeks of 11.2. Clinically meaningful improvements in clinical outcomes, such as body mass index and hunger, have also mirrored improvements in health-related quality of life.

On Slide 23 in addition to doctors for Boston. So much we are grateful for the support of the world's leading key opinion leaders and genetic obesity.

Between the European Society for Paediatric Endocrinology, the obesity Medical Association and the Obesity Society Congress. This week 22 presentations at certain Atlanta tight at uncovering where obviously data had been presented by physicians, including Dr. Martin <unk> at the University of Dr.

Dr. Peter Cuneo of Humboldt University in Berlin, Dr. Jesus are hinting at the Autonoma University in Madrid, Dr. <unk> from the University of Cambridge, Dr. Elizabeth four sites in the University College, London and Dr. Robert caused from Nashville, Phoenix, where I mentioned previously.

Linda Shapiro: Importantly, at the patient level, improvements were sustained over the 52-week trial period. Now, with slide 21, I'd like to shift gears from BPS to our robust clinical development programs to treat more patients with obesity and hyperphasia due to genetically impaired melanocorin-4 receptor tests. I want to begin by touching on a recent publication that illustrates the severity of disease, patients with other than psychic variance in several of our Sentimal Anitides growing body of evidence in these indications, And then I'll summarize with a short update on our next wave of clinical trials.

We've covered nearly everything today.

These efficacy results from complete topline analysis of our phase II basket study, which are protected at SP in September.

These data show weight loss and hunger reduction at three months on therapy in patients with Src, one or stage two be one change efficiencies as well as a clear separation between patients who responded to second line treatment at three months and those who did not.

All of these presentations are available on our website.

Lastly on slide 24, our clinical development programs are on track, most notably the DAYBREAK and MH studies, which aim to address severe obesity and hyperphagia across 36 genes with strong or very strong relevance to the Atlantic market for receptor pathway.

Linda Shapiro: On slide 22, there is an article titled Implication of Heterozygous Variance in the genes of the Leopardin-Corton Pathway in Severe Obes, by Dr. Sophie Courage and the team in the lab of Dr. Karin-Clamant at Sorbonne University in Paris, published online this summer in the Journal of Clinical Endocrinology and Metabolism. This article details for the first time the phenotype of patients with early onset, severe obesity, and hyperphasia due to the heterozygous variance in the melanocortin-4 receptor pathways, including lepton receptor, pom C, and PCSK1, Um, comparatively to patients with homozygous or biolus very. Importantly, the comparison shows similarly severe obesity with similarly early onset and severe hyperphasia, all The burden of the rare genetic disease and the need for This research underscores the effect of a genetically inherent MC4R pathway and the burden of rare genetic diseases of obesity.

Site initiations are underway with investigator meetings planned for this month or next month and first patient in.

Anticipated in the fourth quarter.

There's a tremendous amount of activity outgoing.

A lot of excitement.

That's helpful.

Jennifer Thank you.

Thank you Linda.

I'll start on slide 26.

Our strategy is making an FID for a commercially available in the U S. It's meeting our expectations through the first two full quarters.

As David said in the third quarter, we reached $1 million in net sales and we are pleased to report that patients are getting access Tim sifry with positive coverage decisions and reimbursement.

We remain focused on HCP engagement and walking them through the process from start form an authorization and if needed support throughout the appeals process.

Our corporate accounts and patient service teams, which are new this past quarter are making a significant difference.

And most importantly in communications with patients on them separate we are hearing positive feedback.

Linda Shapiro: On slide 23, in addition to Dr. Courvage and Quermont, we are grateful for the support of the world's leading key opinion leaders in genetic obesity. Between the European Society for Pediatric Endocrinology, the Obesity Medical Association, and the Obesity Society Congress this week, 22 presentations of set melanotide and uncovering rare obesity data have been presented by physicians, including Dr. Martin Wabish of the University of Ulm, Dr. Peter Kuhn of Humboldt University in Berlin, Dr. Hes-Arhente of the Autonomic University in Madrid, Dr. Saddam-Beruki from the University of Cambridge, Dr. Elizabeth Forsyte from the University College of London, and Dr. Robert Haas from Marshall Clynex, who I mentioned previously.

And adult man, who was constantly distracted by hunger for as long as he can remember now forget to eat.

And the snacks report really speak to what we're providing.

A mom who told US. It's every therapy resulted in weight loss and reduced her daughter's obsession in constant drive to eat.

He was able to tell her 11 year old daughter.

This is not your fault.

On slide 27.

Looking to Bbs.

Linda shared some details and how devastating Bbs is for patients and families who have no approved therapy.

Separately as we have previously communicated.

<unk> estimates for Bbs are 2500 in the U S and the same in Europe.

The community has come together around the need for a therapy and relative to patients with bio <unk> Tom C. P. C. S. K, one or leopard deficiencies. They are known to the health care system.

Linda Shapiro: We've covered nearly everything today, except these efficacy results from complete topline analyses of our Phase 2 basket study, which were presented at SP in September. These data show weight loss and hunger reduction at three months on therapy in patients with SRC1 or SH2B1 gene deficiency, as well as a clear separation between patients who responded to melanotide treatment at three months and those who did not. All these presentations are available on our website.

We know there are more than 600 patients in the U S based cribbs registry.

And then the EU four and the U K, we estimate there are a total of 1500 diagnosed bbs patients.

As we know from experience in rare disease.

Initial prevalence estimates are usually low and we consider them a starting point as we actively engage with the community to diagnose and find more.

Linda Shapiro: Lastly, on slide 24, our clinical development programs are on track, most notably the daybreak and emanate studies, which aim to address severe obesity and hyperphasia across 36 genes with strong or very strong relevance to the melanocort and 4 receptor path. Flight initiations are underway, with investigator meetings planned for this month and next month, and first patients will participate in the fourth quarter. There's a tremendous amount of activity ongoing and a lot of excitement. And with that, also, generally, Gem.

On slide 28.

Our U S commercial availability strategy for Pompe fee Pcf's keep one and leopard deficiency obesity enabled us to put the infrastructure in place that allows for access to <unk> now.

It also lays the groundwork to set up for success for the Bbs launch.

Looking ahead, our near term priorities are clear.

Establishing access by patient support and payer engagement.

Elevate the need to treat the hyperphagia and severe obesity that comes with Bbs.

And accelerate emphasis facilitate diagnosis.

Jennifer L. Chien: Thank you, Linda. I will start on slide 26. Our strategy of making SIFRI commercially available in the U.S. is meeting our expectations through these first two full quarters. As David said, in the third quarter, we reached $1 million in net sales, and we are pleased to report that patients are getting access to MCFRI with positive coverage decisions and reimbursement. Remain focused on HCP engagement and walking them through the process from Start Forms and authorizations, and, if needed, support throughout the appeals process.

Next slide.

There are patient support team we are.

We're making direct contact with consented patients or their caregivers.

Hcp's prescribed and separately for them.

Our team provides comprehensive case management.

<unk> education, and coordination of treatment access activities to help identify and resolve barrier to therapy.

We also provide support to prescribers as they navigate the prior authorization process to facilitate timely payer coverage.

Our continued support and engagement of key milestones in the patient journey are designed to ensure inherent.

Jennifer L. Chien: Our corporate accounts and patient service teams, which are new this past quarter, are making a significant difference. And most importantly, in our communications with patients on emcephry, we are hearing positive feedback. An adult man who was constantly distracted by hunger for as long as he can remember now forgets to eat.

Next slide.

In addition to having high touch patient services established now we have fully hired trained and deployed in the field our team of Bbs territory managers.

Our our highly engaged and experienced team with more than 20 years of farmer sales experience on average on top of rare disease and launch experience.

Jennifer L. Chien: And this next report really speaks to what we are providing. A mom who told us that emcivery therapy resulted in weight loss and reduced her daughter's obsession and constant drive to eat. She was able to tell her 11-year-old daughter, "see, this is not your fault."

And with experience in ophthalmology, Nephrology and endocrinology, we are seeing results.

These territory managers are engaging physicians and focused on identifying bbs patients and expanding care network for Bbs patient.

Their focus on physician engagement starts with ongoing engagement of top tier targets of approximately 125, hcp's with Bbs patients in their care.

Jennifer L. Chien: On slide 27, Looking to BBS, Linda shared some details on how devastating BBS is for patients and families who have no approved therapy. As we have previously communicated, President Obama's estimates for BBS are 2,500 in the U.S. and the same in Europe.

In addition, we have tiered targets. We believe are likely to have Bbs patients that have been identified through machine learning as well as follow up as ACP with Biola like Bbs genes identified through our Euro program.

Jennifer L. Chien: The community has come together around the need for a therapy, and relative to patients with biololic Palm C, PCSK1, or leperer deficiencies, they are known to the health care system. We know there are more than 600 patients in the U.S.-based Crips Registry, and in the EU4 and the UK, we estimate there are a total of 1,500 diagnosed BBS patients. As we know from experience in rare diseases, these initial prevalence estimates are usually low, and we consider them a starting point as we actively engage with the community to diagnose and find more. See slide 28.

Next slide.

Armed with the full data from the phase III Bbs trial, we recently completed double blinded qualitative primary market research with 30 U S. ACP is to treat patients with Bartleby they'll spend got.

It is clear that obesity is universally viewed as a serious health concern and individuals with Bbs with no treatment options.

When presented with the product profile is set free <unk>.

<unk>, 5% of them said, they would prescribe <unk> Atlanta tied as a first line therapy for Bbs patients to treat obesity.

This is due to the mechanism of action are expected age range of fixed plus and weight loss efficacy.

Jennifer L. Chien: Our U.S. commercial availability strategy for POMC, PCF1, and leper deficiency, obesity, enabled us to put the infrastructure in place that allows for access to MCFRI now. It also lays the groundwork to set up for success for the BBS flanks. Looking ahead, our near-term priorities are clear.

Moving to slide 32.

And lastly, I just wanted to touch on the work of our area development managers, who are charged with executing a targeted strategy to drive genetic testing and individuals with early onset severe obesity.

Jennifer L. Chien: Establish access via patient support and payer engagement. Elevate the need to treat the hyperphasia and severe obesity that comes with BBS, and accelerate and facilitate diagnosis. Next slide.

This of course will help drive enrollment for M&A and DAYBREAK.

Also we know this will help us find patients with Biola like Palm C. P. C S K, one or a leper.

Jennifer L. Chien: Through our patient support team, we are making direct contact with consented patients or their caregivers as HCPs prescribe and consult for them. Our team provides comprehensive case management, offering education and coordination of treatment access activities to help identify and resolve barriers to therapy. We also provide support to prescribers as they navigate the prior authorization process to facilitate timely para-coverage. Our continued support and engagement at key milestones in the patient journey are designed to ensure adherence. Next slide.

And as David mentioned earlier, we are also finding ACP with patients who have genetic variance associated with Bbs, who may or may not have the clinical diagnosis of bvs.

In these cases, the ADM will hand, these ACP to the bvs territory managers for follow up hence a very nice collaboration has seen amongst the field team.

I'd now like to turn the call over to Hunter to review, our third quarter financial results.

Thank you Jennifer.

On slide 34.

During the third quarter rhythm reported product revenue of 1 million $1 million. All revenue came from the United States. There were no revenues during the comparable quarter of 2020.

Jennifer L. Chien: In addition to having high-touch patient services established now, we have fully hired, trained, and deployed in the field our team of BBS Territory Managers. They are a highly engaged and experienced team with more than 20 years of farmer sales experience on average, on top of their rare disease and launch experience. And with experience in ophthalmology, nephrology, and endocrinology, we are seeing results. These territory managers are engaging physicians and focused on identifying BBS patients and expanding the care network for BBS patients.

Loss from operations was $44 million, an increase of $10 million over the comparable quarter in 2020 due to increases.

And both clinical trial activity as well as higher head count in our research and development commercial and general and administrative functions.

Operating loss was offset by approximately $9 million tax benefit reducing the tax provision we made in the first quarter due to our sale of the priority Review review voucher.

Our share count was $50 2 million basic and diluted shares in loss per common share was <unk> 70 a.

The decrease of <unk> <unk> versus the third quarter of 2020.

We concluded this quarter with cash cash equivalents and short term investments of $328 million, which we believe to be sufficient to fund rhythms operations into the second half of 2023.

Jennifer L. Chien: Their focus on physician engagement starts with ongoing engagement of top-tier targets of approximately 125 ACPs with BBS patients in their care. In addition, we have tiered targets that we believe are likely to have BBS patients that have been identified through machine learning, as well as follow-up of HCPs with biolilic BBS genes identified through our URO program. Next slide.

And now I will turn the Mike back over to David So he can conclude thank you.

Thank you Hunter.

As I think you've heard and we had a really good quarter in quarter three Linda highlighted the significant progress we've made across our clinical development program and look forward to that continuing for the balance.

Jennifer L. Chien: Armed with the full data from the Phase 3 BBS trial, we recently completed double-blinded qualitative primary market research with 30 U.S. ACPs who treat patients with Bartle Beetle syndrome. It is clear that obesity is universally viewed as a serious health concern in individuals with BBS, with no treatment options. When presented with the product profile of emcivary, 75% of them said they would prescribe set melanotide as a first-line therapy for BBS patients to treat obesity. This is due to the mechanism of action, our expected age range of 6 plus, and weight loss efficacy. Moving to slide 32.

Four and into 2022.

A large presence that we've had in medical meetings and it's obviously important to share new data and you've heard some of that also.

A critical component in increasing awareness drawing further attention to the problem of rare genetic diseases of obesity.

And as you heard from Jennifer we are continuing to make good.

Good progress in preparing for a very meaningful opportunity.

And I have to say.

Here's a experience.

In the area of rare diseases I think the team that has built in the process of being built because experience.

And so we have a good challenge in front of us, but we certainly have the team and the capabilities.

Jennifer L. Chien: And lastly, I just want to touch on the work of our area development managers, who are charged with executing a targeted strategy to drive genetic testing of individuals with early-onset severe obesity. This, of course, will help drive enrollment for Eminate and daybreak. But also, we know this will help us find patients with biolilic POMC, PCSK1, or leper. And as David mentioned earlier, we are also finding ACPs with patients who have genetic variants associated with BBS who may or may not have the clinical diagnosis of BBS. In these cases, the ADMs will hand these ACPs to the BBSs Territory managers for follow-up. Hence, very nice collaboration is seen amongst the field team.

We have the ability to execute on that.

So the last slide is just again trying to put in perspective rhythm in the opportunity in front of us as we've talked about the initial approval for palm CPC SK, one and left bar Biallelic deficiencies.

Believe they're on the order of 600 2500.

The data around that and we're still learning and beginning to explore it but over time that number will grow.

It's small and again, we're meeting expectations nothing's changed in our <unk>.

Castro guidance, there if you will but the opportunities ahead of us some are much more significant part of.

Jennifer L. Chien: I'd like to turn the call over to Hunter to review our third quarter financial results.

<unk> and <unk>, because as a syndrome. They are more easily identified and therefore, we start with a much larger number of patients who have been diagnosed based on their clinical presentation. We project on the order of 2000 to 3000, but this is a group where again based on past experience epidemiology can often underestimate.

Hunter C. Smith: Thank you, Jennifer. I'm on slide 34.

Hunter C. Smith: During the third quarter, Rhythm reported product revenue of net of $1 million. All revenue came from the United States. There were no revenues during the comparable quarter of 2020. Loss from operations was $44 million, an increase of $10 million over the comparable quarter of 2020 due to increases in both clinical trial activity, as well as a higher head count in our research and development, commercial, and general administrative functions. The operating loss was offset by approximately $9 million in tax benefits, reducing the tax provision we made in the first quarter due to our sale of the priority review vouchers.

The number of patients that may be out there the work that we're doing with the euro testing the genetic screening where patients are presenting.

The history of early onset obesity, and hunger and not insignificant number of them.

Genetic defects biallelic defects for <unk> in Australia.

Said, whether they will ultimately go on to full blown presentation remains to be seen but it does provide a bit of a window into perhaps the fact that yes for sure there have to be more patients out there who have yet to come to diagnosis. So we'll continue to push on that.

And finally, just reminds you M&A trial its five sub studies in each one of them will readout independently. They are independently powered and any one of them offers a very meaningful increase over our current opportunity and you can see the numbers projected here. So theyre all 20000 individuals.

Hunter C. Smith: Our share count was 50.2 million basic and diluted shares, and the loss for the common share was 70 cents, a decrease of seven cents versus the third quarter of 2020. We concluded this quarter with cash, cash equivalents, and short-term investments of $328 million, which we believed to be sufficient to fund Rhythms operations into the second half of 2023. Now I'll turn the mic back over to David so he can conclude. Thank you

U S only opportunities and then DAYBREAK trial, which is very efficient as we've explained in the past.

Looking at the additional 31 genes, we believe are linked to the pathway and we.

Sure.

Relatively.

Rapid way I hope.

Get insights into a number of these teams as to whether they in fact are driving that underlying early.

David P. Meeker: Hunter, and hopefully, as I think you've heard, we had a really good quarter in quarter three. Linda highlighted the significant progress we've made across our clinical development programs, and we look forward to that continuing for the balance of before and into 2022. The large presence that we've had at medical meetings, and it's obviously important to share new data, and you've heard some of that, but it's also a critical component in increasing awareness and drawing further attention to the problem of rare generic diseases of obesity.

Severe obesity presentation, so with that I'll turn it back to the operator and open it up for Q&A. Thank you.

Thank you.

Minder chassis question, you will need to press star one on your telephone to withdraw your question press the pound key please standby, while we compile the Q&A roster.

Our first question comes from the line of Phil Nadeau with Cowen and co. Your line is open.

Good morning, Thanks for taking our questions and congrats on all the progress.

Just a few from US first on the DBS Salesforce already being deployed are their goals for the sales force in terms of number of Hcp's contacted or a number of Bbs patients engaged by the time of the approval midyear next year.

David P. Meeker: And as you heard from Jennifer, we are continuing to make good progress in preparing for a very meaningful opportunity, which we believe, is a part of the Bato St. L launch. And I have to say, in my years of experience, working in the area where diseases are found, I think the team that has been built, and is in the process of being built, has experience with, and so we have a good challenge in front of us, but we certainly have the team and the capabilities who have the ability to execute. on that.

Jennifer.

So they current Bbs territory managers are provided with.

Different targets.

The first number of targets starts with the approximately 125 HCP that were already within our sphere.

That have Bbs patients.

David P. Meeker: So the last slide is just again trying to put in perspective the rhythm and the opportunity in front of us. As we've talked about, the initial approval for Palm C, PCSK1 and Lepar, biolilic deficiencies. We believe they're on the order of 600 to 2,500, that the data around that we're still, you know, learning and beginning to explore. But over time, that number will grow. It starts small, and again, we're meeting expectations. Nothing's changed in our... forecast or guidance there, if you will.

So the engagement of those initial positions will remain a key target for them in addition to that.

We outlined on the call there's an opportunity in terms of disease educating a broader set of physicians, who may have bbs patients.

This includes follow up.

Physician to have Biallelic.

Ah patients through and discovered through our <unk> program.

There are in addition, we have been working.

Through machine learning to also learn about the history and journeys of patients who have avs and through these learnings we are able to do.

David P. Meeker: But the opportunities ahead of us are much more significant, for parted beetle and ulstroms, because as a syndrome, they are more easily identified, and therefore we start with a much larger number of patients who have been diagnosed based on their clinical presentation. We project on the order of 2,000 to 3,000. But, you know, this is a group where, again, based on past experience, epidemiology can often underestimate the number of patients that may be out there.

More accurately identify hcp's, who may have babies.

Bbs patients within their care that can also be a target for follow up so they do have a tiered list of physicians that they are following up with already identified Bbs patients as well as potentially having bbs patients that they can educate and get to a clinical diagnosis.

Perfect. That's very helpful. And then second on the quality of life data.

David P. Meeker: The work that we're doing with URO testing, the genetic screening, where patients are presenting with that history of early onset, obesity, and hunger, a not insignificant number of them have genetic defects, biallelic defects, for Barton also. As I said, whether they will ultimately go on to full-blown presentation remains to be seen, but it does provide a bit of a window into perhaps this fact that, yeah, for sure, there have to be more patients out there who have yet to come to diagnosis, so we'll continue to push on.

What drove the improvements.

Quality of life for Bbs patients was it the hyperphagia, specifically PMI PMI changes or.

Or some combination of the two.

Yes, Thanks, Linda sure.

That's a great question and the way the questionnaires are designed it does not drive down into that detail, but to your point it likely is a combination of both.

And the weight specifically the adult question here the impact of weight of quality of life is designed about weight, but there is a component where the hyperphagia on it for the hyperphagia.

Improved.

I do quite as well.

Perfect and then last question.

Sure Greg.

No I was just going to say about half of the.

Your question is could only be done by those patients who did not have cognitive impairment and then the Bbs world. There are some number of those and so in that smaller subset, where we could link the hunger to the quality of life benefit that didn't mirror.

David P. Meeker: And finally, just reminds you about the M&A trial. It's five sub-studies, and each one of them will read out independently. They're independently powered, and any one of them offers a very meaningful increase over our current opportunity, and you can see the numbers projected here. So they're all 20,000 individuals, U.S. only opportunities. And then the daybreak trial, which is a very efficient, as we've explained in the past, way of looking at the additional 31-Js. genes, we believe, are linked to the pathway, and we should, in a relatively rapid way, I hope, you're going to get insights into a number of these genes as to whether they, in fact, are driving that underlying early severe obesity presentation.

Perfect Okay.

And then last question for Us in terms of the M&A and DAYBREAK trials, what's limiting to getting those first patients in the door is it finding the patients are there other startup activities.

At the sites that are treating.

Yeah, great questions. So we're going through the standard process of startup so where.

We're completely aligned to our timelines.

On track so there is no limitation.

Per se, we're just following through the steps we have actually a number of patients lined up at the site. So once we turn on the green light that they'll be ready to go and we anticipate quite a bullish that in the beginning for those patients who are already lined up.

Operator: So with that, I'll turn it back to the operator and open it up for a Q&A.

Perfect. Thanks for taking my questions and congrats again on premise.

Operator: Thank you. As a reminder, to ask a question, you will need to press the star key on your telephone. To draw your question, press the pound key. Please stand by when we compile the Covaney. Our first question comes from the line of Phil Nato, with Cohen and Coe. Your line is open.

Thank you.

Our next question comes from the line of Joseph Stringer from Needham and company. Your line is open.

Hi, good morning, everyone. Thanks for taking my questions.

First one just a general question on comparing the relative launches.

From <unk> and.

Sebree.

Initial launch.

Operator: Good morning, thanks for taking our questions and congratulations on all the progress. Just a few from us. First, on the BBS Salesforce already being deployed, are there goals for

Policy left bar versus Barney Vito and potential launch for <unk>.

What are the do you expect to sort of hit the ground running in terms of.

If the approval does come.

In second quarter of next year would you be ready to sort of launch commercially.

Operator: Already being deployed, are there goals for Salesforce in terms of the number of HCPs contacted or the number of VBS patients engaged by the time of the approval in mid-year next year?

Soon thereafter.

Are there any gating factors around that and the second question is around.

Jennifer Lee: So the current BBS territory managers are provided with different targets. The first number of targets starts with the approximately 125 ACPs that are already within our sphere and have BBS patients. So the engagement of those initial physicians will remain a key target for them. In addition to that, as we outlined on the call, there's an opportunity, in terms of disease education, to reach a broader set of physicians who may have BBS patients. This includes follow-up of physicians who have biolilic patients through and discovered through our Euro program.

The potential contribution ex U S versus U S.

Terms of sales for <unk> and <unk> it seems like.

The patients are a little bit there's more identified patients ex U S. It seems like there is.

Maybe a little bit better.

Infrastructure around patient I'd.

Things like that so just curious if you could compare and.

Contrast, U S versus ex U S.

Relative contributions.

Jennifer Lee: In addition, we have been working through machine learning to also learn about the histories and journeys of patients who have BBS. And through these learnings, we are able to do so more accurately. Identify ACPs who may have BBSs within their care that can also be a target for follow-up. So they do have a tier list of physicians that they are following up with already identified BBS patients, as well as potentially having BBS patients that they can educate and get to a clinical diagnosis.

Thank you.

Okay.

Thanks for the question.

So we think that there are for sure different centers just in terms of the initial launch events and set free for the PPL indication.

One of the biggest differences is just in terms of the teams that were in place to really start the process of educating.

And also.

Great thing with our customers.

Operator: Perfect, that's very helpful. And then, on the quality of life data,

We didn't really have teams in place for the initial launch.

Operator: What drove the improvements in quality of life for BBS patients? Was it the hyperphagia, specifically BMI?

Based off of a very low number of PPL <unk> that were also diagnosed.

Linda Shapiro: specifically BMI changes, or some combination of the two.

And our expectations in terms of sales as outlined in the past has been.

Operator: Linda? Sure. That's a great question. The way the questionnaires are designed, they do not drive down into that detail, but to your point, it likely is a combination of both, and the weight, specifically the adult questionnaire, the impact of weight on quality of life, is designed to measure weight, but there is a component where the hyperphacian could have improved the quality of life.

And in the first couple of years.

Things are very different for the Bbs launch we have hired.

And the team that will be in place to really position us or being able to hit the ground running once we get their peripheral within the Bbs indication.

<unk> mentioned on this call as well.

There are a significant more number of Bbs patients because.

Linda Shapiro: Perfect, and then last question for us: sorry, go ahead.

The fact that there are certain duramax and more easily identified.

Linda Shapiro: I was just going to say about half of the hunger questionnaires could only be done by those patients who did not have cognitive impairment, and in the BBS world, there are some number of those. And so in that smaller subset where we could link the hunger to the quality of life benefit, it did mirror.

That we would be able to catch back to being able to get on the drug.

If we were to peripheral next year.

As it relates to ticket numbers, and let's say that in terms of our Trs.

They are.

More well organized persistence term genetic and getting.

Operator: Okay. Then last question for us, in terms of the M&A and daybarry trials, what's limiting to getting those first patients in the door?

Patients who are suspected of genetic diseases to specific specialty.

Enters to get genetically diagnosed with also speak to the volume of patients that have been identified as Bbs and Europe.

Operator: patients in the door, is it finding the patients, or are there other startup activities, particularly

Linda Shapiro: Yeah, great question. So we're going through the standard process of startup. So we're completely aligned with our timelines and on track, so there is no limitation per se. We're just following through the steps. We actually have a number of patients lined up at the site, so once we turn on the green light, they'll be ready to go, and we anticipate quite a bolus in the beginning for those patients who are already lined up. Perfect.

Or any free cash flow versus the U S.

<unk> also shifted over to David to provide a bit of more color on that perspective, yes. Thanks, Andrea enjoy I think just to maybe add one more thing on the U S is.

We unlike the first.

<unk>.

Our world.

Where we had almost no patients in the U S. A significant number of the patients in the development program did come from the U S and so there'll be available.

Operator: Perfect. Thanks for taking our questions and congratulations on the exam.

Easier to transition second is that the products in the channel.

Operator: Our next question comes from the line of Joseph Stringer from Needham and Company. Your line is open.

Unlike the initial launch whether there was.

Usual startup just given supply chain established until so.

Operator: Hi, good morning everyone, thanks for taking our questions.

That's the U S. Europe as Jennifer said is absolutely more well better organized larger number of patients we've talked about 1500 patients being available across the EU for in the U K, meaning these are patients that are well identified and sitting with us in centers of excellence the gating factor for Europe as we all know as you work country by.

Operator: One is just a general question about comparing the relative launches from, for Incivri, the initial launch from Pomsi, Pomsi, Lepar,

Countries in terms of getting reimbursement and establishing pricing.

Operator: versus Barre Vito and the potential launch for Bar de Vito

Yes.

It may come early in some country and there may be quite delayed and the others. So the big issue there will be just the timing of reimbursement.

Operator: on Alstroms. What are the, do you expect to sort of hit the ground running in terms of

I hadn't mentioned it but we expect first sales on our first approved indication over there in the first half of 2022.

Operator: If the approval does come in the second quarter of next year, would you be ready to sort of launch commercially soon thereafter, or are there any gaining factors around that? And the second question is:

The Bbs and Aaas filing is running in parallel.

FDA filing a claim is it.

Great. Thanks for taking my question.

Okay. Thanks, Ron.

Operator: the potential contribution of XUS versus U.

Again to ask a question you will need to press star one on your telephone.

Operator: in terms of sales for Barney Beetle and Alstroms, it seems like the patients are a little bit smaller, but there's more

Our next question comes from the line of Corinne Jenkins with Goldman Sachs. Your line is open.

Operator: or identified patients XUS, seems like there's maybe a little bit better infrastructure around patient ID and

Yes, good morning, everybody.

Just curious as you've engaged in various medical conferences. You've attended this fall what did you learn specifically from the community with respect to the Bbs either on the clinical need or with respect to the physician's view of the South Atlanta type profile.

Operator: and things like that, XUS. So I was just curious if you could compare and contrast.

Operator: U.S. versus XUS relative contributions to that. Thank you. Okay, Jennifer Lee, thank you.

Jennifer Lee: Thanks for the question. So I think that there are, for sure, differences, just in terms of the initial launch around MSIFRI for the PPL indication. One of the biggest differences is just in terms of the teams that were in place to really start the process of educating and also interfacing with our customers. We didn't really have the teams in place for the initial. launch, also based on the very low number of PPL bilalilics that were also diagnosed

Thanks Karim.

I'll lead off and then I'll, let Jennifer Linda.

And.

What's really interesting to me is you do clinical trials and they're driven by P values in the topline data are aware, but that doesn't really tell you. The whole story and I think it's become absolutely clear it doesn't tell us the whole story here for Bbs and <unk> and what's been most enlightening and the recent data sets have been the interviews.

We had exit interviews done and that will be coming out as a <unk>.

Jennifer Lee: And our expectations in terms of stills, as outlined in the past, have been 10 in the first couple of years. Things are very different for the BBS launch. We have hired the team that will be in place to really position us for being able to hit the ground once we get the approval within the BBS indication.

The case in the not too distant future and I think has been one of the posters and if you look at the quotes in the quote that I think you really begin to understand the devastating impact of this disease. I mean, you heard a couple of today from both Linda and Jennifer.

That stands out in my mind and that is and I think it is in the poster presented the publication but.

Jennifer Lee: And as was mentioned on this call as well, there are a significantly more number of BBS patients because of the fact that they're syndromic and more easily identified that we would be able to expect to be able to get on to the drug if we were to get approval next year. As it relates to patient numbers, I will say that, in terms of Europe. They are, you know, more well organized just in terms of genetics and getting patients who are suspected of genetic diseases to specific specialty centers to get genetically diagnosed.

Young child at the age of four who has taken away from his family because the family was viewed by the social services is over feeding their child and essentially abusing their child and has put in a facility for a year and a half.

For something that was absolutely not.

So those are that's where the nuances coming in and Jennifer did report out the market research data, where physicians prevent presented with the profile of this drug 75% of them said they would prescribe it first line and I think in an area where disease awareness is relatively low and you're educating on both the disease at the same.

Jennifer Lee: We've also spoken to the volume of patients that have been identified as BBS in Europe or international versus the U.S. But I'm going to also shift it over to David to provide a bit of more color on that perspective. Yeah, thanks, and Joy, I think just to

Educating on the drug and that's a pretty remarkable recognition again.

This is an emerging area and the unmet need is absolutely clear.

If that helps but that's the kind of thing.

We're learning today that we didn't have last time, we spoke.

Yes, that's helpful.

Go ahead.

I'll just quickly check on <unk> and <unk>.

David P. Meeker: Yeah, thanks, and Joy, I think just to maybe have one more thing about the U.S., is that unlike the first Palm C. LepR world, where we had almost no patients in the U.S., a significant number of the patients in the development program did come from the U.S., and so they'll be available and easier to transition. Second, the products in the channel, unlike the initial launch where there was the usual startup problem of just getting the supply chain. established and filled

Support that whether it's through <unk>.

Market insights from physicians or patients are the interactions with physicians themselves.

The aspect of the obesity and hyperphagia, even in the Syndromic indication really pops up in terms of being one of the key priority.

Dressing within this particular patient population simply because of the impact that it had not only on the patients, but as well as the caregiver family.

David P. Meeker: So that's the U.S. Europe, as Jennifer said, is absolutely more, well, better organized, and has a larger number of patients. We've talked about 1,500 patients being available across the EU4 and the U.K., meaning these are patients that are well identified and sitting with incentives of excellence. The gating factor for Europe, as we all know, is that you work country by country in terms of getting reimbursement and establishing pricing. Access, you know, may come early in some countries, but it may be quite delayed in the other.

So it is.

Definitely a need out there where physicians.

Our waiting to have something to be able to specifically address.

The needs of the patient population.

Thanks, and then as we think about the growth in the U R. U R. O testing can you help us understand whether that's primarily driven and how you expect it to be driven on the forward.

Of new H Gpus, or just existing hcp's that are already doing testing testing more and more patients.

So in.

In addition to.

The territory managers that are on grounds, which our team. That's also supporting the ongoing efforts that were put in place through our MSL.

David P. Meeker: So the big issue there will be just the timing of reimbursement. I hadn't mentioned it, but we expect first sales on our first approved indication over there in the first half of 2022. Obviously, the BBS and AAS filing is running in parallel to the FDA filing, as Linda said.

We also have our <unk>.

Our area development managers and in terms of testing initiatives.

Outlined in the last.

Operator: Great, thanks for taking our question. Okay, thanks, Roy.

Earnings call, we have been in place efficiencies around our <unk> program that should make it easier for physicians to be able to order kits and tests and see the results.

Operator: Again, to ask a question, you will need to press Star 1 on your telephone. Our next question comes from the line of Corrine Jenkins with Goldman Sachs. Your line is open. Yeah, good morning, everybody. I'm just curious as to what you've engaged in.

So the initial target will definitely be educating physicians, who are already testing.

See if there is interest in terms of increasing the volume through the efficiencies.

Operator: medical conferences you've attended this fall. What did you learn specifically from the community with respect to BBS, either on the clinical need or with respect to physicians?

But certainly they also have additional targets that Archie just in terms of increasing awareness around RJ Dio and general suspecting and then testing as well.

David P. Meeker: Thanks, Karine. I think, you know, I'll lead off and then let Jennifer or Linda jump in.

Let me just add one other thing Theres a poster in the most recent posters that just went up on our website, which speaks to our euro testing program and we described in there the number of kits that have been requested physicians and healthcare providers requesting kits and the number of returns. So on the order of 1400 health care providers have rich.

David P. Meeker: You know, what's really interesting to me is that you do clinical trials, and they're driven by P values and, you know, the top line data where, but that doesn't really tell you the whole story, and I think it's become absolutely clear that it doesn't tell us the whole story here for BBS and Allstroms. And what's been most enlightening in the recent data sets have been the interviews. So we had exit interviews done, and that will be coming out as a publication in the not too distant future, and I think it's on one of the posters.

<unk> kits. So for me, that's just a fabulous starting point in terms of <unk>.

Physicians health care providers, who are clearly indicating.

Interest recognizing that genetics may be driving it.

The vast majority of the majority if you will or Pete Zendo Peds in medical genetics again all of this is in the poster and the other piece, which.

And in the top 10.

Again back to your question on Jennifer's answer.

Hi utilizes today are driving the bulk and the real opportunity are those health care providers, who sent in one test.

David P. Meeker: And if you look at the quotes, it's in the quote that I think you really begin to understand the devastating impact of this disease. I mean, you heard a couple today from both Linda and Jennifer, one that stands out of my mind, and that is in the, and I think it's in the poster if it's not in the publication, but, you know, a young child at the age of four who is taken away from his family because the family was viewed by the social services as overfeeding their child and essentially abusing their child and has put in a facility for a year and a half for something that was absolutely not his fault.

They've signaled that interests they've already done it once and so the ability to scale from there is.

Is good.

And then lastly, I just wanted to.

What's also really interesting in that poster since I'm talking about is the <unk>.

The number of.

The age of the patients who are being tested and.

Fully 20% of less than six years old and another 30% or between.

The ages of seven and 12, 50% our children and for a genetic disease not a surprise.

You would expect these kids to be presenting early the problem essentially arises at birth.

Parents notice it and they seek help so I want to be learned there but.

David P. Meeker: So that's where the nuances come in. Jennifer did report out the market research data where, you know, physicians were presented with the profile of this drug. 75% of them said they would prescribe at first line. And I think in an area where disease awareness is relatively low, and you're educating people on both the disease and the drug at the same time you're educating them on the drug. That's a pretty remarkable recognition, again, that this is an emerging area and the unmet need is absolutely clear. So I don't know if that helps, but that's the kind of thing that we're learning today that we didn't have last time we. Yeah, that's helpful.

Like I said I think we have a lot of optimism around the opportunity and the role that.

<unk> testing is going to play in this overall development.

Great. Thank you.

That's correct.

Next question there are no further questions at this time now I will turn the call back over to David Meeker.

Okay, well, thanks to all of you.

For tuning in this morning.

Look forward to talk to you again in three months time and for the fourth quarter update.

Hey, good morning, Thanks, everyone.

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

Jennifer L. Chien: I'll just quickly add to and support that, whether it's through market insights from physicians or patients or the interactions with physicians themselves. You know, the aspects of obesity and hyperfasia, even in the syndromic indication, really pop up in terms of being one of the key priorities for addressing within this particular patient population, simply because of the impact that it has. not only on the patient but also on the caregiver in the family. So there is definitely a need out there where physicians are waiting to have something to be able to specifically address the needs of the patient population. Thanks.

Okay.

[music].

Okay.

[music].

Operator: And then as we think about the growth in URO testing, can you help us understand whether that's primarily driven by and how you expect it to be driven forward by new HTPs or just existing HDPs that are already doing testing, testing more and more patients? So in addition to the territory managers that are on the ground, which are a team that's also supporting the ongoing efforts that were put in place through our MSL, we also have our ADMs, or area development managers.

Operator: And in terms of testing initiatives, as I outlined in the last earnings call, we, we, we, we, have, we, we, we, put in place efficiencies around your own program that should make it easier for physicians to be able to order kits and tests and see the results. So the initial target will definitely be educating physicians who are already testing to see if there is interest in terms of increasing the volume through efficiency. But certainly, they also have additional targets that are key just in terms of increasing awareness around RGDO in general, suspecting, and then testing as well. And Karina, let me just add one more thing.

Operator: There's a poster in the

David P. Meeker: And Karina, let me just add one other thing. There's a poster in the most recent posters that just went up on our website, which speaks to our URO testing program. And we describe there the number of kits that have been requested, physicians, and health care providers requesting kits, and the number of returns. So on the order of 1,400 health care providers have returned kits.

[music].

David P. Meeker: So, you know, for me, that's just a fabulous starting point in terms of physicians and health care providers who are clearly indicating an interest and recognizing the genetics may be driving it. The vast majority, or the majority, if you will, are peds endo, peds, and medical genetics. Again, all of this is on the poster. And the other piece, which, in the top 10, you know, again, back to your question and Jennifer's answer, the high utilizers today are driving the bulk, and the real opportunity are those health care providers who sent in one test. They've signaled an interest. They've already done it once, so they have the ability to scale from there.

Operator: Is, uh, is good. And then last, I just want to, what's also really interesting in that poster since I'm talking about the number of the age of the patients who are being tested. And, you know, fully 20% are less than six years old, and another 30% are between the ages of 7 and 12. So 50% are children. And for a genetic disease, not a surprise. You know, you would expect these kids to be coming up early.

Operator: The problem, essentially, arises at birth, and parents notice it, and they seek help. So a lot to be learned there, but as I said, I think we have a lot of optimism around the opportunity and the role that URL testing is going to play in this overall development.

David P. Meeker: Next question. Claire, for the questions at this time. Now I turn to call back over to David Meeker.

Operator: Great, well, thanks to all of you for tuning in this morning, and we look forward to talking again in three months' time. It's the fourth quarter update.

Operator: That'll take goodbye. Thanks, everyone. This concludes today's conference call. Thank you for participating. You may now disconnect. Bres.

Operator: This concludes today's conference call. Thank you for participating. You may now disconnect. Theeerner,

Operator: Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you, Bhopin.

Operator: Thank you. Thank you. Thank you. Thank you, and so on the end up.

Operator: Thank you. Thank you. Thank you. Thank you. Thank you. Thank you.

Operator: Good day, and thank you for standing by. Welcome to Rhythm Pharmaceuticals' third quarter financial results conference call. At this time, all participants are in listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question, you need to press star 1 on your telephone. Please be advised that today's conference is being recorded. If you require deferred assistance, please press Star Zero. I would now like to hand the conference over to your speaker today, David Connolly, from Rithms. information goals, Please go ahead.

David Connolly: Thank you, and good morning. I'm David Conley, head of IR and Corporate Communications here at Rhythm Pharmaceuticals. For those of you participating via 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. This morning, we issued a press release that provides our third quarter, 2021 financial results and business update, which is available on our website, as listed on slide two. With me today here in Boston for the conference call, David Meeker, Chairman, President, and Chief Executive Officer of Rhythm, Linda Shapiro, our Chief Medical Officer, Jennifer Chen, Executive Vice President, Head of North America, and Hunter Smith, our Chief Financial Officer.

[music].

David P. Meeker: Thirdly, to build out our global presence, working with healthcare systems, first and foremost in Europe, but we will increasingly look beyond there. And fourth, to continue to advance robust clinical development which has the ability to meaningfully increase the addressable patient population. Now, quarter three is a quarter with multiple highlights.

David P. Meeker: Again, we've continued execution. First, the U.S. and Sivry launch is progressing and meeting expectations. As we said, we expected to have tens of patients on treatment, and that view of the world has continued to hold. We were pleased with the net sales, clearing one million for the quarter, but more importantly, we're really happy about the learnings that we're beginning to accumulate from this initial commercial experience, which will lay the foundation for our subsequent Barton at Beetle One.

Good day, and thank you for standing by welcome to the rhythm Pharmaceuticals third quarter financial results Conference call.

At this time all participants are in a listen only mode. After the speaker's presentation. There will be a question and answer session. Jaffe question, you will need to press star one on your telephone. Please be advised today's conference is being recorded if you require any further assistance. Please press star zero I would now like to hand, the conference over to your speaker today.

David P. Meeker: Third, we had a very strong presence at medical meetings with 22 presentations at three major medical conferences. Positive data was presented from a variety of different clinical data sets, with world-renowned KOLs presenting subal antitide data. And in a noteworthy category, we have our first data on health-related quality of life and additional data on hunger and weight scores across a number of different genetic diseases. Linda will provide a little more color on that in her presentation.

David Connolly with within Pharmaceuticals. Please go ahead.

Thank you and good morning, I'm, David Connolly 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.

David P. Meeker: And finally, the clinical development programs remain on track with MNA FAPD, pediatric, and EECD trials advancing to first patient, and I will provide a little more color on our testing program here on the slide, too. But before we get to that, on the next slide, slide number seven, I just want to remind you there's efficiency in rare disease community building, which we are taking advantage of. And in the bare disease setting, you often have a limited number of centers of excellence, a limited number of KOLs, and they serve multiple purposes. And so you can focus your efforts very much around these sites.

This morning, we issued a press release that provides our third quarter to a third quarter 2021 financial results and business update which is available on our website.

As listed on slide two.

With me today here in Boston for the conference call are David Meeker Chair, President and Chief Executive Officer of Rhythm Linda Shapiro, Our Chief Medical Officer, Jennifer Chen Executive Vice President head of North America, and Hunter Smith, our Chief Financial Officer.

Slide three I'll remind you that this call contains remarks concerning future expectations plans and prospects, which constitute forward looking statements actual results may differ materially from those indicated by these forward looking statements as a result of various factors, including those discussed in our most recent annual report on file with the SEC.

David P. Meeker: Not only do they run the trials, serve as key opinion leaders, but they're also the same physicians, and health care providers who diagnose and actually treat these patients. And what we're doing is pursuing a hub-and-spoke model where that Center of Excellence, the Clinical Trial site, is at the center, and then we will work with a surrounding set of treaters, interested parties who are potential referral sites, referring patients into that site, and over time, some will become their own Centers of Excellence depending on the level of injury.

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

Thank you, Dave and good morning, everyone.

I'm very pleased to report another strong quarter of execution for rhythms.

David P. Meeker: Moving to slide eight, here's a brief update on our testing program. We have had several generations of our genetic screening panel. In May, we went from a 40 gene panel that was reported out on to reporting out on an 80 gene panel, and that panel includes all the genes of interest to rhythm in terms of genes we believe are closely linked to the MC4 pathway. But it also includes a number of genes that would be of interest to the Obesity Treater at large, meaning other genes that might help inform what the underlying driver of that patient's obesity is.

And I'll remind you that we're building rhythms piece by piece gene by gene and like I said I'm very pleased with the progress to date. The first slide is to highlight four areas of high focus for US. One is of course, the commercial experience with and Savory second is looking forward to the anticipated BARDA beetle in Ulster.

<unk> launch in 2022 third is to build out our global presence.

King with health care systems, first and prominently foremost in Europe, but we will increasingly look beyond there.

And fourth to continue to advance a robust clinical development program, which has the ability to meaningfully increase the addressable patient population.

David P. Meeker: So what this pie graph shows is that on the order of 55% of patients who present with a history of early onset obesity and hunger are likely to test positive for one of the genes of interest, meaning a gene that would qualify that patient for entry into the MNate trial or the daybreak trial, which is an additional 31 genes we've yet to explore, but have some reason to believe they may be related to the pathway, or be potentially eligible for commercial tests. therapy with Incivious.

Now quarter three is a quarter with multiple highlights again with continued execution.

First the U S. <unk> launch is progressing and meeting expectations. As we said we expected to have tens of patients on treatment and thats.

That view of the World has continued to hold.

We're pleased with that sales clearing 1 million for the quarter, but more importantly, we're.

I'm happy about the learnings that we're beginning to accumulate from this initial commercial experience, which will lay the foundation for our subsequent BARDA beta launch and in the international markets Europe, specifically reimbursement dossiers have been filed in major markets and some of the smaller markets as well and we're in advanced discussions with the three.

David P. Meeker: Now, of note, in that 55% are 1.96, almost 2% of the population who are bilalic for Bartet Beetle or the alms 1 gene, which is the gene that is responsible for Alstrom's syndrome. So that percentage is a noteworthy percentage. There's much more to be learned. We don't know in all of those patients that their genetic defect is driving their underlying obesity. or that they will even go on to develop Bart at Beetle, but it opens up a whole new avenue for better understanding this disease, and rhythm is going to play a leading role in driving that exploration.

Major markets, Germany, France, and the UK.

Second as we advance towards Bbs launch in mid 2022, as you know the regulatory submissions have been filed in both the us and Europe and the U S.

<unk> fully hired a highly experienced.

Our field team and Jennifer will provide you with more color around that so a year ahead of anticipated launch we feel like we are in a good place. So I'm looking forward to that event.

Third we had a very strong presence at medical meetings with 22 presentations at three major medical conferences positive data was presented from a variety of different clinical data sets with world renowned kols presenting <unk> data in our no really.

Noteworthy category, we have our first data on health related quality of life and additional data on hunger and weight scores across a number of different genetic diseases, Linda will provide a little more color on that in her presentation and finally, the clinical and clinical development programs remain on track M&A favorites theatrics in mutual.

Linda Shapiro: This is an exciting time for rhythm as our efforts around Bartlett-Beedl syndrome are coming together on many fronts, putting us in a position to bring to patients the first ever therapy to address the unmet needs of hyperphasia and severe obesity that affect the lives of patients and families living with this disease. Art of Beetle syndrome, or BBS, is a clinical syndrome with many features, including severe obesity from an early age and an insatiable hunger or hyperphasia, which impacts the health and quality of life for parents, patients, their families, and caregivers.

Trials advancing two first patient in and I'll provide a little more color on our testing program.

<unk> two.

And before we get to that on the next slide slide number seven I just want to remind you there is an efficiency.

Mayor disease community building, which we are taking advantage of and in the fair disease setting you often have a limited number of centers of excellence for limited number of Kols and they serve multiple purposes and so you can focus your efforts very much around these sites not only do they run the trials.

Service key opinion leaders and they are also the same physicians health care providers, who diagnose and actually treat these patients and what we're doing is pursuing a hub and spoke model where that center of excellence a clinical trial site is at the center and then we will work with <unk>.

Surrounding set of treaters.

Interested parties, who are potential referral sites, referring into that site and over time, some will become their own center of excellence, depending on the level of interest.

Linda Shapiro: Setmalanatide has demonstrated clinical efficacy and safety, as well as meaningful improvements for patients and their families, caregivers, and health care providers, and we look forward to reviewing some of these data. The severe impact that BBS has on the lives of patients and their families is significant. And we've made tremendous strides this quarter in documenting, qualifying, and quantifying this impact. But the patient's caregivers and families clearly speak best for themselves. As there are quotes on this slide from in-depth qualitative interviews that we conducted with patients with BBS and or their caregivers, they point to the stress and guilt of denying food to children with hyperphasia and point to how the world revolves around food, which limits their focus on anything else. Pause here for an opportunity for you to read through some of these quotes.

And that panel includes all the genes of interest to rhythm in terms of genes. We believe are closely linked to the <unk> pathway, but it also includes the number of genes that would be of interest to the.

The.

Obesity treater at large meaning other genes that might help inform what is the underlying driver of that patients won't be sitting.

So what this pie graph shows is on the order of 55% of patients who present with a history of early onset obesity and hunger are likely to test positive for one of the genes of interest, meaning a gene that would qualify that patient for entry into the M&A trial or the DAYBREAK try.

Linda Shapiro: Last month, at an all-hands meeting, we heard from the mother of a child with Bartapedal syndrome, and her story reinforced our understanding of the impact BBS has on families and underscored the unmet need that exists in this community. She told us about the significant weight gain evident by two years old that continued at an off the charts rate of weight growth, and the challenges she faced in school with weight gain, including physical as well as social difficulties. She told us that it was very important. These firsthand accounts reinforce our understanding of the impact BBS has on families and underscore the unmet need that exists. This quarter, we completed regulatory submissions for Bartlett Beetle Syndrome and Ulstrom Syndrome in both the United States and the European Union.

Bill, which is an additional 31 genes we've yet to explore but have some reason to believe they may be related to the pathway or b potentially eligible for commercial therapy with ancillary now of note in that 55% or $1 96, almost 2% of the population who are bio link for BARDA.

Beetle or the arms, one gene, which is the gene that is responsible for all <unk> syndrome, so that percentage them as a noteworthy percentage there's much more to be learned we don't know that all of those patients that those their genetic defect is driving their underlying obesity or that they will even.

Go on to develop BARDA Bureau, but it opens up a whole another avenue for better understanding of this disease and rhythms going to play a leading role in driving that exploration.

And with that I'll turn it over to Linda.

Thank you David.

This is an exciting time for Wyndham Srs.

That's our efforts surround Barnet Bill Wilson Jones, our coming together on many fronts, putting us in a position to bring to patients the first ever therapy to address unmet needs of hyperphagia and severe obesity that affect the lives of patients and families living with this disease.

Linda Shapiro: In October, we submitted a type 2 variation application to the European Medicines Agency for IMSABRI for the treatment of obesity and control of hunger and adult and pediatric patients six years of age and older with BBS or Alzheimer's syndrome. The review timeline in Europe is calendar-based, and we would expect a decision from the European Commission in the second half of 2015.

<unk> syndrome, our Bbs is a clinical syndrome with many features including severe obesity from an early age and an insatiable hunger hyperphagia, which impact the health and quality of life for parents for.

For patients their families and caregivers.

There is currently no effective treatment and we know from interviews and our work on health related quality of life and patients and families with Bbs and was presented this week for the first time.

Linda Shapiro: We are confident in these submissions as they are based on data from the Piddle Phase 3 trial in which Cetmul Anitide achieved clinically meaningful and statistically significant reductions in body weight and in the unrequited hunger associated with these syndromes. And these submissions include a series of comprehensive narratives for each individual patient, supporting our belief that insub-free has the potential to offer the first therapeutic option for the early onset, severe obesity, and unrelenting hunger that characterize these children.

Just how dire need is to control hunger and to stop thinking about food all the time.

This quarter as David said, we are one step closer to delivering a transformative new treatment option to patients having completed our regulatory submissions in the U S and EU.

<unk> has demonstrated clinical efficacy and safety as well as meaningful improvements for patients and their families caregivers and health care providers and we look forward to reviewing some of these data today.

Slide 13.

Linda Shapiro: On slide 15, here's a reminder of the trial design of our Phase 3 trial, evaluating set melanotide therapy in patients with Bart at Biedel syndrome and also. This trial began with a one-to-one randomization to a double-blind placebo-controlled period of 14 weeks, as highlighted in the light blue area, and then progressed through a minimum of 52 weeks on set melanotide therapy. All patients were titrated on setmalanitide at the beginning of the open label portion and proceeded to complete at least 52 weeks on therapy for those who began on placebo and a total of 66 weeks on therapy for those who began on setmalanitide. Patients were evaluated for the primary and key secondary endpoints at 52 weeks on therapy, as shown here in the red box. Slide 16.

The severe impact that.

UBS has on the lives of patients and families is significant and.

And we've made tremendous strides this quarter in documenting qualifying.

To quantify this impact.

But the patients caregivers and families clearly speak for themselves.

Eric quote on this slide from in depth qualitative interviews that we conducted with patients with Bbs and or their caregivers.

0.2, the stress and guilt of denying food to children with hyperplasia.

To how the world.

Revolve around.

<unk> limits their focus on anything else.

Pause here.

That opportunity for you to read through some of these wells.

During a company all hands meeting we heard last month from the mother of a child with BARDA fetal syndrome.

Story reinforced our understanding of the impact PBS has on families and underscoring the unmet need that exists in this community.

Linda Shapiro: The data from the 14-week double-blind receivocontrol period are shown. Significant BMI reductions in patients with BBS on Stemol Anitide Therapy versus Placeto. Patients in the placebo group had negligible weight loss or BMI reduction at 14 weeks, compared to patients in the treatment group who reduced their BMI by an average of 4.3%. This translates to a statistically significant placebo-corrected set of melanotide treatment effects of 3.8% BMI reduction in 14. And slide 17, as before, this trial achieved all primary and key secondary endpoints with statistically significant and clinically meaningful reductions in body weight and hunger at 65%.

She told us about the significant weight gain evidenced by two years old that continued is off the charts right of weight growth.

And the challenges faced in school with weight gain including physical as well as social difficulties.

Told us it was very tough.

These firsthand accounts reinforce our understanding of the impact DBS has on families and underscore the unmet need that exists.

<unk>.

Slide 14.

This quarter, we completed regulatory submissions for <unk> syndrome, and Ahlstrom syndrome in both the United States as well as the European Union.

In September we submitted a supplemental new drug application to the FDA for <unk>.

Brand name of SAP melanocyte for the treatment of obesity and control of hunger and adult and pediatric patients six years of age and older with Bbs are ahlstrom syndrome.

Linda Shapiro: These data on patients with BBS from the Phase 3 trial will be presented this week at the Obesity Week Conference in a symposium by Dr. Robert Haas of the Marshfield Clinic, the leading Bartlett-Betle Syndrome key opinion leader in the United States. As you can see, we saw clinically significant reductions in body mass index across all 31 patients with BBS in the trial, with a mean reduction of greater than 9% in both adults, as well as children and adolescents, at 52 weeks of therapy on set malamination. Slide 18.

We requested priority review from the FDA as part of the application.

Based on FDA timelines, we will know in November if our supplemental NDA has been accepted with priority review.

If granted that would mean a target FDA review period of six months from that date of acceptance.

In October we submitted a type two variation application to the European medicines agency premiums debris for the treatment of obesity and control of hunger in adult and pediatric patients six years of age and older with bvs for Ahlstrom syndrome.

The review timeline in Europe as calendar base, and we would expect a decision from the European Commission in the second half of 2022.

We are confident in these submissions as they are based on data from the pivotal phase III trial in which that will amortize achieved clinically meaningful and statistically significant reductions in body weight and in the unreluctant associated with <unk> syndrome.

Linda Shapiro: Semalamalatide achieved clinically meaningful reductions in hyperphasia, that insatiable hunger that dramatically affects the lives of patients with Bartat Beetle syndrome and their, As we saw, these data in both the initial 14-week double-blind period set here in the light blue blocks and out to 52. At 14 weeks, these data showed that patients in the placebo group had a modest reduction in hunger scores compared to the nearly 35% reduction achieved by the treatment.

Okay.

On slide 15 here.

Linda Shapiro: Interestingly, when we compare the data trends over 52 weeks, there is a clear separation of hunger during the double blind placebo-controlled period, highlighted in the Light Blue Box, followed by the placebo group reaching treatment levels rapidly after crossover to the open label, Semalanatide Treatment Period, with the white background. Also, after the placebo control double-blind period at week 14, you can see a brief rebound of hunger when patients on set melanotide were retitrated onto the drug. This speaks to the sensitivity of hunger in Bartlett-Biedel syndrome patients, as well as the sensitivity of the September, Slide 19.

Here's a reminder of the trial design of our phase III trial evaluating <unk> in Atlanta type therapy in patients with BARDA <unk> Olsen gentlemen, ahlstrom syndrome.

This trial began with a one to one randomization in a double blind placebo controlled period of 14 weeks as highlighted in the light Blue area, and then progressed or a minimum of 52 weeks on Atlanta type therapy.

All patients were titrated offset Willamette tight at the beginning of the open label portion and proceeded to complete at least 52 weeks on therapy for those who began on placebo and a total of 66 weeks of therapy for those who began at that mill appetite.

Patients were evaluated for the primary and key secondary endpoint at 52 weeks on therapy as shown here in the red boxes.

Linda Shapiro: At the obesity week conference this week, we're also presenting the first ever health-related quality of life results to measure the impact of Stent melanotide therapy on patients with BBI. This is particularly important in this ultra rare disease, as our research underscores the need to adjust the health-related quality of life burden experienced by patients. The data show that after one year of treatment with set melanotide, 85% of patients reported clinically meaningful improvements in or preserved their non-impaired health-related quality of life status.

Slide 16.

The data from the 14th week double blind.

The CTO control period or Sean.

Significant BMI reductions in patients with Bbs on several anti therapy versus placebo.

Patients in the placebo group had negligible weight loss or BMI reduction at 14 weeks.

Care to patients in the treatment group, who reduced their BMI by an average of four 3%.

This translates to a statistically significant placebo corrected certain Atlanta type treatment effect of three 8% reduction in 14 weeks.

Linda Shapiro: For adult patients, changes to their impact of quality of life score from impact of weight, quality of life score, from baseline five to 52 weeks were clinically meaningful with a mean increase of 12. For pediatric patients, we saw a clinically meaningful increase in the P's quality of life score from baseline to 52 weeks of 11.5. Clinically meaningful improvements and clinical outcomes such as body mass index and hunger also mirrored improvements in health-related quality of life. Importantly, at the patient level, improvements were sustained over the 52-week trial period. Thank you.

On slide 17.

This trial achieved all primary and key secondary endpoints were statistically significant and clinically meaningful reductions in body weight and hunger at 52 weeks.

These data on patients with Bbs from the Phase III trial are presented this week at the obesity week conference in a symposium by Dr. Robert Haws, Marshfield clinic, the leading part of beetle syndrome key opinion leader in the United States.

As you can see we saw clinically significant reductions in body mass index across all 31 patients with EPS in this trial with a mean reduction of greater than 9% in both adults as well as children adolescence at 52 weeks of therapy.

Linda Shapiro: With slide 21, I'd like to shift gears from BPS to our robust clinical development programs to treat more patients with obesity and hyperphasia due to genetically impaired melanocorin-4 receptor tests. I want to begin by touching on a recent publication that illustrates the severity of disease, patients with any like experience in several of our Similar Anitides, Growing Body Bevenous in these indications, And then I'll summarize with a short update on our next wave appointment.

Right.

Slide 18.

Atlanta tide achieved clinically meaningful reductions in hyperphagia that insatiable hunger that dramatically affected the lives of patients with <unk> syndrome and their families.

As we saw these data in both the initial 14 week double blind period of set here the light blue blocks and out to 52 weeks.

At 14 weeks to these data showed that patients in the placebo group had a modest reduction in Congress as far as compared to the nearly 35% reduction achieved by the treatment group.

Linda Shapiro: On slide 22, there's an article titled Implication of Heterozygous Variation in the genes of the Leptin-Milanticorten pathway in severe obesity, by Dr. Sophie Courage and the team in the lab of Dr. Karin-Clamant at Sorbonne University in Paris, published online this summer in the Journal of Clinical Endocrinology and Metabolic. This article details for the first time the phenotype of patients with early onset, severe obesity, and hyperphasia due to heterozygous variance in the melanocortin-4 receptor pathway, including left-end receptor, POMC, and PCSK1, can comparatively to patients with homozygous or biolus very, Importantly, the comparison shows similarly severe obesity with similarly early onset and severe hyperfasia, all of which underscore the The burden of the rare genetic disease and the need for This research underscores the effect of a genetically inherent MC4R pathway and the burden of rare genetic diseases of obesity.

Interestingly when we compare the data trends over 52 weeks there is a clear separation of hunger during the double blind placebo controlled period.

Highlighted in light Blue box, followed by the placebo group, reaching treatment levels rapidly after crossover to open label setting Atlanta type treatment period.

The white background.

Also after the placebo controlled double blind period at week 14.

You'll see a brief rebound of hunger when patients are set in Atlanta tight or re.

Re titrated onto the drug.

This speaks to the sensitivity of hunger and heartbeat, Austin jump patients as well as the sensitivity of the central Advertiser spots.

Slide 19.

Yes.

It's really week conference. This week, we're also presenting the first ever health related quality of life results to measure the impact of <unk> therapy patients with Bbs.

This is particularly important in this ultra rare disease as a research underscores the need to adjust the health related quality of life verdict experienced by patients.

Linda Shapiro: On slide 23, in addition to Dr. Courvage and Quermont, we are grateful for the support of the world's leading key opinion leaders in genetic obesity. Between the European Society for Pediatric Endocrinology, the Obesity Medical Association, and the Obesity Society Congress this week, 22 presentations of set melanotide and uncovering rare obesity data have been presented by physicians, including Dr. Martin Wabish of the University of Ulm, Dr. Peter Kuhn of Humboldt University in Berlin, Dr. Jesus Arhente of the Autonomic University in Madrid, Dr. Saddameruki from the University of Cambridge, Dr. Elizabeth Forsyte from the University College of London, and Dr. Robert Haas from Marshall Seneca, who I mentioned previously.

The data show after one year of treatment with certain Atlanta tight.

85% of patients reported clinically meaningful improvements in our preserve their unimpaired health related quality of life status.

For adult patients changes to their impact quality of life score from impacted quality of life score from baseline to 52 weeks with clinically meaningful with a mean increase of 12 point.

For pediatric patients, we saw clinically meaningful increase of the peace quality of life score from baseline to 52 weeks of 11 two points.

Clinically meaningful improvements in clinical outcomes, such as body mass index and hunger also mirrored improvements and health related quality of life.

Importantly at the patient level improvements were sustained over the 52 week trial period.

Yeah.

Linda Shapiro: We've covered nearly everything today, except these efficacy results from complete top-line analyses of our Phase 2 basket study, which were presented at SB in September. These data show weight loss and hunger reduction at three months on therapy in patients with SRC1 or SH2B1 gene deficiency, as well as a clear separation between patients who responded to melanotide treatment at three months and those who did not. All these presentations are available on our website.

I want to begin by touching on a recent publication that illustrates the severity of disease.

For patients with heterozygous variant and several of our chain.

That <unk> growing body of evidence in these indications and then I'll summarize for that short update on our next wave of clinical trials.

On slide 20 shale.

Article titled Implication of heterozygous variant and the change that the leptin Melinda important pathway in severe obesity by Dr. Sofia <unk> and the <unk> in the lab of Dr. Recurring to the launch of Star Bond University at Paris was published online. This summer in the journal of clinical endocrinology and metabolism.

Linda Shapiro: Lastly, on slide 24, our clinical development programs are on track, most notably the daybreak and emanate studies, which aim to address severe obesity and hyperphasia across 36 genes with strong or very strong relevance to the melanocort and four receptor path. Flight initiations are underway, with investigator meetings planned for this month and next month, and first patients will participate in the fourth quarter. There's a tremendous amount of activity going on and a lot of excitement. And with that, also, all of the general, Thank you, Linda.

This article details for the first time, the phenotypes of patients with early onset severe obesity and hyperphagia.

Heterozygous variant in Atlanta, exporting four receptor pathway, including leptin receptor <unk> James.

Kim.

Comparatively to patients with homozygous for Biomarin looked very good.

Importantly, the comparison shows similarly severe obesity with similar early onset severe hyperplasia.

Jennifer L. Chien: I start on slide 26. Our strategy of making SIFRI commercially available in the U.S. is meeting our expectations through these first two full quarters. As David said, in the third quarter, we reached $1 million in net sales, and we are pleased to report that patients are getting access to MCFRI with positive coverage decisions and reimbursement. Remain focused on HCP engagement and walking them through the process from Start Forms and authorizations, and, if needed, support throughout the appeals process.

All of which underscore the genetics and the effect of the impaired pathway.

The burden of the rare genetic disease for obesity and the need for that.

This research underscore this after the genetically inherit etsy for our pathway and the burden of rare genetic diseases of obesity and the need for therapy.

On Slide 23 in addition to doctors for Boston four months, we are grateful for the support of the world's leading key opinion leaders and genetic obesity.

Between the European Society for Paediatric, Endocrinology, Ubicity Medical Association and the Obesity Society Congress. This week 22 presentations of certain Atlanta tight and uncovering where obviously data had been presented by physicians, including Dr. Martin <unk> of the University of Dr.

Dr. Peter Cuneo of Humboldt University in Berlin, Dr. Jesus are Henry at the Autonoma University and Madrid, Dr. <unk> from the University of Cambridge, Dr. Elizabeth Foresight, and the University College of London, and Dr. Robert Haws from Nashville, Phoenix I mentioned previously.

We have covered nearly everything today.

These efficacy results from complete topline analysis of our phase II basket study, which are protected at Sps September these.

These data show weight loss and hunger reduction at three months on therapy in patients with Src, one or stage two be one change efficiencies as well as a clear separation between patients who responded to central antitype treatment at three months, a dose who say boss al.

All of these presentations are available on our website.

Lastly on slide 24, our clinical development programs are on track, most notably the DAYBREAK and Maa's studies, which aim to address severe obesity and hyperphagia across 36 genes with strong or very strong relevance to the Atlantic market for receptor pathway.

Site initiations are underway with investigator meetings planned for this month and next month and first patient.

Anticipated in the fourth quarter.

There's a tremendous amount of activity ongoing and a lot of excitement.

That's helpful.

Jennifer Thank you.

Thank you Linda.

I'll start on slide 26.

Our strategy is making an FID for a commercially available in the U S is meeting our expectations through the first two full quarters.

As David said in the third quarter, we reached $1 million in net sales and we are pleased to report that patients are getting access to separate with positive coverage decisions and reimbursement.

Jennifer L. Chien: Our U.S. commercial availability strategy for POMC, PCF1, and leopard deficiency, obesity, enabled us to put the infrastructure in place that allows for access to MCFRI now. It also lays the groundwork to set up for success for the BBS flanks. Looking ahead, our near-term priorities are clear.

We remained focus on HCP engagement and walking them through the process from start form and authorizations and if needed support throughout the appeals process.

Our corporate accounts and patient service teams, which are new this past quarter are making a significant difference.

And most importantly in communications with patients on <unk>, we are hearing positive feedback.

And adult man, who was constantly distracted by hunger for as long as he can remember now for guests to eight.

And the snacks report really speaks to what we're providing.

Amar who told US in February therapy resulted in weight loss and reduced her daughters obsession in constant drive to eight.

He was able to tell her 11 year old daughter.

This is not your fault.

On slide 27.

Looking to Bbs.

Linda shared some details on how devastating Bbs is for patients and families who have no approved therapy.

As we have previously communicated.

<unk> estimates for Bbs are 2500 in the U S and the same in Europe.

The community has come together around the need for a therapy and relative to patients with <unk>, Tom Z, Pts K, one or leopard deficiencies. They are known to the healthcare system.

We know there are more than 600 patients in the U S based cribbs registry.

And then the EU four and the U K, we estimate there are a total of 1500 diagnosed bbs patients.

As we know from experience in rare disease. This initial prevalence estimates are usually low and we consider them a starting point as we actively engage with the community to diagnose and find more.

On slide 28.

Our U S commercial availability strategy for Pompe fee Pcs keep one and leopard deficiency obesity enabled us to put the infrastructure in place that allows for access to <unk> now.

Jennifer L. Chien: Their focus on physician engagement starts with ongoing engagement of top-tier targets of approximately 125 ACPs with BBS patients in their care. In addition, we have tiered targets that we believe are likely to have BBS patients that have been identified through machine learning, as well as follow-up of HCPs with biololic BBS genes identified through our URO program. Next slide.

It also lays the groundwork to set up for success for the Bbs launch.

Looking ahead, our near term priorities are clear.

Establishing access.

Patient support and payer engagement.

Elevate the need to treat the hyperphagia and severe obesity that comes with Bbs.

And accelerate emphasis facilitate diagnosis.

Next slide.

They're our patient support team we are.

We're making direct contact with consented patients or their caregivers.

Hcp's prescribed and separately for them.

Our team provides comprehensive case management.

<unk> education, and coordination of treatment access activities to help identify and resolve barriers to therapy.

We also provide support to prescribers as they navigate the prior authorization process to facilitate timely payer coverage.

Our continued support and engagement are key milestones in the patient journey are designed to ensure and Harris.

Next slide.

In addition to having high touch patient services established now we have fully hired trained and deployed in the field our team of Bbs territory managers.

Jennifer L. Chien: And lastly, I just want to touch on the work of our area development managers, who are charged with executing a targeted strategy to drive genetic testing of individuals with early-onset severe obesity. This, of course, will help drive enrollment for Eminate and daybreak. But also, we know this will help us find patients with biololic POMC, PCSK1, or leper. And as David mentioned earlier, we are also finding ACPs with patients who have genetic variants associated with BBS who may or may not have the clinical diagnosis of BBS. In these cases, the ADMs will hand these ACPs to the BBSs for follow-up. Hence, very nice collaboration is seen amongst the field team.

Our our highly engaged and experienced team with more than 20 years of farmer sales experience on average on top of rare disease and launch experience.

And with experience in ophthalmology, Nephrology and endocrinology, we're seeing results of.

These territory managers are engaging physicians and focused on identifying bbs patients and expanding care network for Bbs patient.

The focus on physician engagement starts with ongoing engagement of top tier targets of approximately 125, hcp's with Bbs patients in their care.

In addition, we have tier targets, we believe are likely to have Bbs patients that have been identified through machine learning as well as follow up hep's with <unk> Bbs genes identified through our Euro program.

Hunter C. Smith: I'd like to turn the call over to Hunter to review our third quarter financial results.

Hunter C. Smith: Thank you, Jennifer. I'm on slide 34.

Hunter C. Smith: During the third quarter, Rhythm reported product revenue of net of $1 million. All revenue came from the United States. There were no revenues during the comparable quarter of 2020. Loss from operations was 44 million, an increase of 10 million over the comparable quarter of 2020 due to increases in both clinical trial activity, as well as a higher head count in our research and development, commercial, and general administrative functions. The operating loss was offset by approximately $9 million in tax benefits, reducing the tax provision we made in the first quarter due to our sale of the priority review vouchers.

Next slide.

Armed with a full data from the phase III Bbs trial, we recently completed double blinded qualitative primary market research with <unk> U S ACP to treat patients with <unk> syndrome.

It is clear that obesity is universally viewed as a serious health concern and individuals with Bbs with no treatment options.

When presented with the product profile of <unk>, 75% of them said, they would prescribe <unk> <unk> as a first line therapy for Bbs patients to treat obesity.

This is due to the mechanism of action are expected age range of six plus and weight loss efficacy.

Moving to slide 32.

Hunter C. Smith: Our share count was 50.2 million basic and diluted shares, and the loss for the common share was 70 cents, a decrease of seven cents versus the third quarter of 2020. We concluded this quarter with cash, cash equivalents, and short-term investments of $328 million, which we believe to be sufficient to fund rhythms operations into the second half of 2023. Now I'll turn the mic back over to David so he can conclude. Thank you.

This of course will help drive enrollment for M&A and DAYBREAK, but.

Also we know this will help us find patients with <unk> <unk>, one or a leper.

And as David mentioned earlier, we are also finding ACP with patients who have genetic variance associated with Bbs, who may or may not have the clinical diagnosis of bvs.

In these cases, the ADM will hand, these ACP to the Bbs territory managers for follow up hence a very nice collaboration has seen amongst the field teams.

David P. Meeker: Thank you, Hunter. And hopefully, as I think you've heard, we had a really good quarter in quarter three. Linda highlighted the significant progress we've made across our clinical development program and look forward to that continuing with the balance of before and into 2022. The large presence that we've had in medical meetings, and it's obviously important to share new data, and you've heard some of that. It's also a critical component in increasing awareness and drawing further attention to the problem of rare genetic diseases of obesity.

I'd now like to turn the call over to Hunter to review, our third quarter financial results.

Thank you Jennifer.

On slide 34.

During the third quarter rhythm reported product revenue of 1 million $1 million. All revenue came from the United States. There were no revenues during the comparable quarter of 2020.

Loss from operations was $44 million, an increase of $10 million over the comparable quarter in 2020 due to increases.

In both clinical trial activity as well as higher head count.

In our research and development commercial and general and administrative functions.

Operating loss was offset by approximately $9 million tax benefit reducing the tax provision we made in the first quarter due to our sale of the priority reviews review voucher.

David P. Meeker: And as you heard from Jennifer, we are continuing to make good progress in preparing for a very meaningful opportunity, we believe, is a part of the Bato St. L launch. And I have to say, in my years of experience working in the area of weird diseases, I think the team that has been built, or is in the process of being built, he has experienced the only team that I've worked with. And so we have a good challenge in front of us, but we certainly have the team and the capabilities who have the ability to execute on that.

Our share count was $50 2 million basic and diluted shares in loss per common share was <unk> 70.

The decrease of <unk> versus the third quarter of 2020.

We concluded this quarter with cash cash equivalents and short term investments of $328 million, which we believe to be sufficient to fund rhythms operations into the second half of 2023.

And now I will turn the Mike back over to David. So you can conclude thank you.

Thank you Hunter.

Hopefully as you've heard we had a really good quarter in quarter three Linda highlighted the significant progress we've made across our clinical development programs and look forward to that continuing for the balance.

David P. Meeker: So the last slide is just again trying to put in perspective the rhythm and the opportunity in front of us. As we've talked about, the initial approval for Palm C, PCSK1 and LEPR, biolilic deficiencies. We believe they're on the order of 600 to 2,500, that the data around that we're still, you know, learning and beginning to explore. But over time, that number will grow. It starts small, and again, we're meeting expectations. Nothing's changed in our... forecast or guidance there, if you will.

Four and into 2022.

A large presence that we've had in medical meetings and it's obviously important to share new data and you've heard some of that also.

A critical component in increasing awareness and drawing further attention to the problem of rare genetic diseases of obesity.

And as you heard from Jennifer we are continuing to make good.

Good progress in <unk>.

Bearing floor, a very meaningful opportunity.

And I have to say.

Here's a experience.

In the area of rare diseases.

<unk> team that has been built in the process of being built because experience.

And so.

Have a good challenge in front of us, but we certainly have the team and the capabilities correct throughout.

We have the ability to execute on that.

So the last slide is just again trying to put in perspective for rhythm in the opportunity in front of us as we've talked about the initial approval for palm CPC SK, one in lip or Biallelic deficiencies.

David P. Meeker: The work that we're doing with URO testing, the genetic screening, where patients are presenting with that history of early onset, obesity, and hunger, a not insignificant number of them have genetic defects, biallelic defects, for Bartlett, Bidol, and ulcer. As I said, whether they will ultimately go on to full-blown presentation remains to be seen, but it does provide a bit of a window into perhaps the fact that, yeah, for sure, there have to be more patients out there who have yet to come to diagnosis.

And believe there is on the order of 600 2500.

The data around that and we're still learning and beginning to explore but over time that number will grow.

It's small and again, we're meeting expectations nothing's changed in our <unk>.

<unk> guidance there if you will but the opportunities ahead of us some are much more significant beetle in all streams because is a syndrome. They are more easily identified and therefore, we start with a much larger number of patients who have been diagnosed based on their clinical presentation. We project on the order of 2000 to 3000, but.

David P. Meeker: So we'll continue to push on. And finally, just reminds you about the M&A trial: it's five sub-studies, and each one of them will read out independently. They're independently powered, and any one of them offers a very meaningful increase over our current opportunity, and you can see the numbers projected here. So they're all 20,000 individuals, U.S.-only opportunities. And then the daybreak trial, which is a very efficient way, as we've explained in the past, of looking at the additional 31-G, which we believe are linked to the pathway, and we should, in a relatively rapid way, I hope, begin to get insights into a number of these genes as to whether they, in fact, are driving that underlying early severe obesity presentation. So with that, I'll turn it back to the operator and open

This is a group where again based on past experience epidemiology can often underestimate the number of patients that may be out there. The work that we're doing with the euro testing the genetic screening where patients are presenting.

History of early onset obesity, and hunger and not insignificant number of them.

Genetic defects Biallelic defects provided in Australia and.

As I said, whether they will ultimately go on to full blown presentation remains to be seen but it does provide a bit of a window into perhaps the fact that yes for sure there has to be a more patients out there who have yet to come to to diagnosis. So we'll continue to push on that.

Operator: Thank you. As a reminder, to ask a question, you will need to press the star one on your telephone. For your question, press the pound key. Please stand by while we compile the cleaning. Our first question comes from the line of Afil Nato, with Cohen and Coe. Your line is open.

<unk> only opportunities and then DAYBREAK trial, which is very efficient as we've explained in the past the way of looking at the additional 31 genes. We believe are linked to the pathway.

We should in a relatively.

Rapid way I hope.

Operator: Good morning, thanks for taking our questions and congratulations on all the progress. Just a few from us. First, on the BBS Salesforce already being deployed, are there goals for the Salesforce in terms of the number of HCP content?

Let me get insights into a number of these teams as to whether they in fact are driving that underlying early.

Severe obesity presentation, so with that I'll turn it back to the operator and open it up for Q&A. Thank you.

Thank you as a reminder to ask a question you will need to press star one on your telephone to withdraw your question press the pound key please standby, while we compile the Q&A roster.

Operator: in terms of the number of HCPs contacted or the number of VBS patients engaged by the time of the approval in mid-year next year.

Our first question comes from the line of Phil Nadeau with Cowen and co. Your line is open.

Good morning, Thanks for taking our questions and congrats on all the progress.

Jennifer.

So they current Bbs territory managers are provided with <unk>.

Different targets.

The first number of target starts with the approximately 125 HCP that were already within our sphere that have Cvs patients.

Jennifer Lee: In addition, we have been working through machine learning to also learn about the histories and journeys of patients who have BBS. And through these learnings, we are able to do so more accurately. Identify ACPs who may have BBSs within their care that can also be a target for follow-up. So they do have a tiered list of physicians that they are following up with already identified BBS patients, as well as potentially having BBS patients that they can educate and get to a clinical diagnosis.

The engagement of those initial physicians will remain a key target for them. In addition to that as we outlined on the call. There is an opportunity in terms of disease educating a broader set of physicians, who may have bbs patients.

This includes follow up physician to have finally lick.

Ah patients through and discovered through our <unk> program.

There are in addition, we have been working.

Through machine learning to also learn about the history and journeys of patient to have Bbs and through these learnings we are able to do.

Operator: Perfect, that's very helpful. And then, on the quality of life data,

Operator: What drove the improvements in quality of life for BBS patients? Was it the hyperphagia, specifically BMI changes, or some combination of the two?

More accurately identify acp's, who may have been.

Patients within their care that can also be a target for follow up so they do have a tiered list of physicians that they are following up with already identified Bbs patients as well as potentially having bbs patients that they can educate and get to a clinical diagnosis.

Linda Shapiro: Linda? Sure. That's a great question. The way the questionnaires are designed, they do not drive down into that detail, but to your point, it likely is a combination of both and weight. Specifically, the adult questionnaire, the impact of weight and quality of life is designed to measure weight, but there is a component where the hyperphacian could have improved the quality of life.

Perfect. That's very helpful. And then second on the quality of life data.

What drove the improvements.

Oh boy for Bbs patients was it the hyperphagia, specifically PMI PMI changes or some combination of the two.

Yes, Thanks, Linda sure.

Operator: Perfect, and then the last question for Buzz: sorry, go ahead.

That's a great question and the way the questionnaires are designed it does not drive down into that detail, but to your point it likely is a combination of both.

Linda Shapiro: I was just going to say about half of the hunger questionnaires could only be done by those patients who did not have cognitive impairment, and in the BBS world, there are some number of those, and so in that smaller subset where we could link the hunger to the quality of life benefit, it did, it did mirror.

And the weight of specifically the adult question here the impact of way of quality of life is designed about weight, but there is a component where the hyperphagia on it where the hyperphagia.

Operator: Okay. Then last question for us, in terms of the M&A and daybreak trials, what's limiting to getting those first patients in the door? Is it finding the patients, or are there other startup activities at the sites that are lagging?

Proved.

The quality of life as well.

Perfect and then last question.

Sure Greg.

I was just going to say about half of the.

Hunger question is could only be done by those patients who did not have cognitive impairment and then the Bbs world. There are some number of those and so in that smaller subset, where we could link the hunger to the quality of life benefit that didn't mirror.

Perfect Okay.

And then last question for Us in terms of the M&A and DAYBREAK trials, what's limiting to getting those first patients in the door is it finding the patients are there other startup activities, particularly at the sites that are treating.

Yes, great questions. So we're going through the standard process of startup so we're.

We're completely aligned to our timeline.

On track so there is no limitation.

First they were just following through the steps we have actually a number of patients lined up at the site. So once we turn off the green might that they'll be ready to go and we anticipate quite a bullish something at the beginning for those patients who are already Linda.

Operator: Perfect. Thanks for taking our questions and congratulations.

Perfect. Thanks for taking my questions and congrats again on brokers.

Operator: Our next question comes from the line of Joseph Stringer from Needham and Company. The line is open.

Thank you.

Our next question comes from the line of Joseph Stringer from Needham and company. Your line is open.

Operator: Hi, good morning everyone, thanks for taking our questions.

Hi, good morning, everyone. Thanks for taking my questions.

Operator: One is just a general question about comparing the relative launches from For Encivri, initially.

First one is just a general question on comparing the relative launches.

From <unk> and.

Operator: to launch, Pomsy, Lepar,

Sebree.

Operator: versus Barre Vito and potential launch for Barre Vidal and Alstroms. What are the, do you expect to sort of hit the ground running?

Initial launch.

Possibly left bar versus.

Potential launch for a party beat on all terms.

What are the when do you expect to sort of hit the ground running in terms of.

Operator: in terms of

Operator: You know, if the approval does come.

If the approval does come.

Operator: In the second quarter of next year, would you be ready to sort of launch?

And the second quarter of next year would you be ready to sort of launch commercially.

Operator: Commercially, soon thereafter, or are there any gaining factors around that and the

Soon thereafter.

Are there any gating factors around that and the second question is around.

Operator: And the second question is around:

Operator: the potential contribution of XUS versus U.

The potential contribution ex U S versus U S.

Operator: in terms of sales for Barney Beatle and Alstroms, it seems like the patients are a little bit more identified patients XUS. It seems like there's maybe a little bit better infrastructure around patient ID,

Terms of sales for <unk> and <unk> it seems like.

The patients are a little bit there's more identified patients ex U S. It seems like there is.

Operator: patient ID and things like that, XU.S. So I was just curious if you could compare and contrast.

Maybe a little bit better infra.

Infrastructure around patient I'd.

Things like that so just curious if you could compare and.

Jennifer Lee: versus XUS's relative contributions to that. Thank you. Okay, Jennifer Lee, yeah.

Contrast, U S versus ex U S.

Relative contributions.

Thank you.

Thanks, Jennifer and thanks for the question.

Jennifer Lee: Thanks for the question. I think that there are, for sure, differences just in terms of the initial launch around MSIFRI for the PPL indication. One of the biggest differences is just in terms of the teams that were in place to really start the process of educating and also interfacing with our customers. We didn't really have the teams in place for the initial. launch also based off of the very low number of PPL bilalilics that were also diagnosed. And our expectations in terms of stills, as outlined in the past, have been 10 in the first couple of years.

So I think that there are for sure different centers just in terms of the initial launch around <unk> for the PPL indication.

One of the biggest differentiators just in terms of the teams that were in place to really start the process of educating.

And also.

Great thank with our customers.

We didn't really have six teams in place for the initial launch also based off of a very low number of PPL <unk> that were also diagnosed.

And our expectations in terms of sales as outlined in the past has been.

Jennifer Lee: Things were very different for the BBS launch. We have hired the team that will be in place to really position us for being able to hit the ground once we get the approval within the BBS indication, and as was mentioned on this call, there are a significantly more number of BBS patients because of the fact that they're syndromic and more easily identified that we would be able to expect to be able to get on to the drug if we were to get approval next year.

And in the first couple of years.

Thanks are very different for the Bbs launch we have hired.

And the team that will be in place to really position us or being able to hit the ground running once we get their peripheral within the Bbs indication.

As <unk> mentioned on this call as well.

There are a significant more number of Bbs patients because.

The fact that there are certain duramax and more easily identified.

Jennifer Lee: As it relates to patient numbers, I will say that in terms of Europe, they are, you know, more well organized just in terms of genetics and getting patients who are suspected of genetic diseases to specific specialty centers to get genetically diagnosed. We also have to speak to the volume of patients that have been identified as BBS in Europe or internationally versus the U.S., but I'm going to do that now. I'm also going to shift it over to David to provide a bit of more color on that perspective. Yeah, thanks, and Joy, I think just to

That we would be able to expect to help us to get on the drug.

If we were to peripheral next year.

As it relates to patient numbers, and let's say that in terms of Trs.

They are.

More well organized persistence term genetic and getting.

Patients who are suspected of genetic diseases to specific specialty.

Enters to get genetically diagnosed with also speak to the volume of patients that have been identified as Bbs and Europe.

Jennifer Lee: Yeah, thanks, and Joy, I think just do, maybe I have one more thing on the U.S. We, unlike the first Palm Sea, our world, where we had almost no patients in the U.S., a significant number of the patients in the development program did come from the U.S., and so they'll be available and easier to transition. Second, the products in the channel, unlike the initial launch where there was the usual startup problem of just getting the supply chain. established and filled

Or entered cash loans versus the U S, but im going to also shifted over to David to provide a bit of more color on that perspective, yes, Thanks, Ed Brian and John I think just to maybe add one more thing on the U S is.

Unlike the first.

<unk>.

World.

Where we had almost no patients in the U S. A significant number of the patients in the development program did come from the U S and so there'll be available.

Easier to transition second is that the products in the channel.

David P. Meeker: So that's the U.S. Europe, as Jennifer said, is absolutely more, well, better organized, and has a larger number of patients. We've talked about 1,500 patients being available across the EU4 and the U.K., meaning these are patients that are well identified and sitting in centers of excellence. The gaining factor for Europe, as we all know, is that you work country by country in terms of getting reimbursement and establishing pricing. Access, you know, may come early in some countries.

Unlike the initial launch where there was huge.

Actual startup just given supply chain established and so so.

That's the U S. Europe as Jennifer said is absolutely more well that are organized larger number of patients. We've talked about 1500 patients being available across the EU for in the UK, meaning these are patients that are well identified and sitting with us in centers of excellence the gating factor for Europe as we all know as you work country by.

Country in terms of getting reimbursement and establishing pricing.

Yes.

It may come early in some country, and then may be quite delayed and the others. So the big issue there will be just the timing of reimbursement.

David P. Meeker: may be quite delayed in the other. So the big issue there will be just the timing of reimbursement. I hadn't mentioned it, but you know, we expect first sales on our first approved indication over there in the first half of 2022. Obviously, the BBS and AAS filing is running in parallel to the FDA filing, as Linda said.

I haven't mentioned it but we expect first sales on our first approved indication over there in the first half of 2022.

The Bbs and Aaas filing is running in parallel to the FDA filing is limited.

Operator: Clint, thanks for taking a question.

Great. Thanks for taking the question.

Operator: Again, to ask a question, you will need to press Star 1 on your telephone. Our next question comes from the line of Karin Jenkins with Goldman Sachs. Your line is open. Yeah, good morning, everybody.

Okay. Thanks, Ron.

Again to ask a question you will need to press star one on your telephone.

Our next question comes from the line of Corinne Jenkins with Goldman Sachs. Your line is open.

Operator: Yeah, good morning, everybody. I'm just curious, as you engaged in the various medical conferences you attended this fall, what have you learned specifically from the community with respect to BBS, either on the clinical need or with respect to the physician's view of the set malanatide profile?

Yes, good morning, everybody.

Just curious as you've engaged in various medical conferences. You've attended this fall what did you learn specifically from the community with respect to Bbs either on the clinical need or with respect to the physician's view of the South Atlanta type profile.

David P. Meeker: Thanks, Karine. I think, you know, I'll lead off and then let Jennifer or Linda jump in.

Thanks Karim.

I'll lead off and then let Jennifer Linda.

And you know what.

It's really interesting to me is you do clinical trials and they're driven by P values in the topline data where would that doesn't really tell you. The whole story and I think it's become absolutely clear it doesn't tell us the whole story here for Bbs and <unk>.

It's been most in lightning and the recent data sets have been the interviews.

We had exit interviews done and that will be coming out is a publication.

Too distant future.

And one of the posters and if you look at the quotes it's in the quote that I think you really begin to understand the devastating impact of this disease. I mean, you heard a couple of today from both Linda and Jennifer.

David P. Meeker: And if you look at the quotes, it's in the quote that I think you really begin to understand the devastating impact of this disease. I mean, you heard a couple today from both Linda and Jennifer, one that stands out in my mind, and that is in the, and I think it's in the poster if it's not in the publication, but, you know, a young child at the age of four who is taken away from his family because the family was viewed by the social services as overfeeding their child and essentially abusing their child and it was put in a facility for a year and a half for something that was absolutely not his fault.

And that stands out in my mind and that is and I think it is in the poster publication, but.

Young child at the age of four who has taken away from his family because the family was viewed by the social services is over feeding their child and essentially abusing their trial and it was put in a facility for a year and a half.

For something that was absolutely not useful.

David P. Meeker: So that's where the nuance is coming in. Jennifer did report out the market research data where, you know, physicians were presented with the profile of this drug. 75% of them said they were prescribed at first line. And I think in an area where disease awareness is relatively low, and you're educating people on both the disease and the drug at the same time you're educating them on the drug. That's a pretty remarkable recognition, again, that this is an emerging area and the unmet need is absolutely clear. So I don't know if that helps, but that's the kind of thing that we're learning today that we didn't have last time we. Yeah, that's helpful.

So those are that's where the nuances coming in general report out the market research data, where physicians prevent presented with the profile of this drug 75% of them said they would prescribe it first line and I think in an area where disease awareness is relatively low and you're educating on both the disease at the same.

Educating on the drug and that's a pretty remarkable recognition again.

This is an emerging area and the unmet need is absolutely clear.

If that helps but that's the kind of thing.

We're learning today that we didn't have last time, we spoke.

That's helpful.

Jennifer L. Chien: I'll just quickly add to and support that, whether it's through market insights from physicians or patients or the interactions with physicians themselves. You know, the aspects of obesity and hyperfasia, even in the syndromic indication, really pop up in terms of being one of the key priorities for addressing within this particular patient population, simply because of the impact that it has. not only on the patient but also on the caregiver and family. So there is definitely a need out there where physicians are waiting to have something to be able to specifically address the needs of the patient population. Thanks.

Go ahead.

I'll just quickly back on and <unk>.

Support that whether it's through a market insights from physicians or patients are the interactions with physicians themselves.

The aspects of <unk> and hyperphagia, even in the Syndromic indication really pops up.

In terms of being one of the key priority.

Resting within this particular patient population simply because of the impact that it had not only on the patients, but as well as the caregiver family.

It is.

Definitely a need out there where physicians.

Our waiting to have something to build to specifically address.

The needs of the patient population.

Thanks, and then as we think about the growth in the U R. U R. O testing can you help us understand whether that's primarily driven and how you expect it to be driven on the forward.

Of new <unk> or just existing each of us that are already doing testing testing more and more patients.

So yes.

In addition to.

They.

Territory managers that are on grounds, which our team. That's also supporting the ongoing efforts that were put in place through our MSL.

We also have our 88.

Our area development managers and in terms of testing initiatives.

Operator: And in terms of testing initiatives, as I outlined in the last earnings call, we, we, we, we, we, we, you know, have put in place efficiencies around your Rove program that should make it easier for physicians to be able to order kits and tests and see the results. So the initial target will definitely be educating physicians who are already testing to see if there is interest in terms of increasing the volume through efficiency. But certainly, they also have additional targets that are key just in terms of increasing awareness around RGDO in general, suspecting, and then testing as well. And Karina, let me just add one more thing.

Lined in the last.

Earnings call, we have been in play efficiencies around our <unk> program that should make it easier for physicians to be able to order kits and paas and <unk> results.

So the initial target we will definitely be educating physicians who are already testing.

See if there is interest in terms of increasing the volume through the efficiencies.

But certainly they also have additional targets that are key to us in terms of increasing awareness around our GTO and general suspecting and then testing as well.

Operator: There's a poster in the...

David P. Meeker: And Karina, let me just add one other thing. There's a poster in the most recent posters that just went up on our website, which speaks to our URO testing program, and we describe there the number of kits that have been requested, positions, health care providers requesting kits, and the number of returns. So, you know, for me, that's just a fabulous starting point in terms of physicians and health care providers who are clearly indicating an interest.

And let me.

Just to add one other thing Theres a poster in the most recent posters that just went up on our website, which speaks to our euro testing program and we described in there the number of kits that have been a request physicians and health care providers requesting kits and the number of returns. So on the order of 1400 health care providers have returned kits.

For me, that's just a fabulous starting point in terms of.

Physicians health care providers, who are clearly indicating.

David P. Meeker: recognizing that genetics may be driving it. The vast majority, or the majority, if you will, are peds endo, peds, and medical genetics. Again, all of this is in the poster. And the other piece, which, in the top 10, you know, again, back to your question and Jennifer's answer, the high utilizers today are driving the bulk, and the real opportunity is those health care providers who send in one test. They've signaled an interest. They've already done it once, and so the ability to scale from there is, uh, is good.

Interest recognizing the genetics may be driving the vast majority or the majority if you will our peds Endo peds in medical genetics again all of this is in the poster and the other piece, which.

In the top 10.

Again back to your question on Jennifer's answer the high utilizes today are driving the bulk and the real opportunity are those health care providers, who sent in one test.

The signal of interest they've already done it once and so the ability to scale from there is.

David P. Meeker: And then last, I just want to say what's also really interesting in that poster since what I'm talking about is the number of patients who are being tested. And, you know, fully 20% are less than six years old, and another 30% are between the ages of 7 and 12. So 50% are children. And for a genetic disease, that's not a surprise. You know, you would expect these kids to be presenting early.

<unk> is good.

And then lastly, I just wanted to.

What's also really interesting that posters have been talking about is the <unk>.

The number of the age of the patients who are being tested and.

Fully 20% or less than six years old and another 30% or between.

The ages of seven and 12, so 50% our children and for a genetic disease not a surprise.

You would expect these kids to be presenting early.

David P. Meeker: The problem, essentially, arises at birth, and parents notice it, and they seek help. So a lot to be learned there, but as I said, I think we have a lot of optimism around the opportunity and the role that URL testing is going to play in this overall development.

Essentially arises at birth.

<unk> noticed it and they seek help so lots to be learned there but.

I said I think we have a lot of optimism around the opportunity and the role that <unk> testing is going to play in this overall development.

Great. Thank you.

Operator: Next question. Clearly, for the questions at this time. Now I turn to call back over to David Meeker.

That's correct.

Next question clearly no further questions at this time now I will turn the call back over to David Meeker.

David P. Meeker: Great, well, thanks to all of you for tuning in this morning, and we look forward to talking to you again in three months' time at the fourth quarter update. That'll be my goodbye. Thanks, everyone.

Great well, thanks to all of you.

For tuning in this morning.

Look forward to talk to you again in three months time at sea fourth quarter update.

Hey, good morning, Thanks, everyone.

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

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

Q3 2021 Rhythm Pharmaceuticals Inc Earnings Call

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