Q4 2022 Rhythm Pharmaceuticals Inc Earnings Call
Speaker 4: The conference will begin shortly. To raise and lower your hand during Q&A, you can dial star 1-1.
Operator: Good day, and thank you for standing by. Welcome to the Rhythm Pharmaceuticals fourth quarter and full year 2022 earnings conference call.
Speaker 5: Thank you.
Speaker 6: Good day, and thank you for standing by. Welcome to the RISM Pharmaceuticals Fourth Quarter and Full Year 2022 Earnings Conference Call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question-and-answer session.
Operator: At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you will need to press store 1-1 on your telephone. You will then hear an automated message advising you whether your hand is right. To withdraw your question, please press star 1-again. Please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker today, Dave Connolly, Executive Director of Investor Relations and Corporate Communications. Please go ahead. Thank you, Michelle.
Speaker 7: To ask a question during this session, you will need to press star 11 on your telephone. You will then hear an automated message advising your hand is raised.
Speaker 8: To withdraw your question, please press star 11 again. Please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker today, Dave Connolly, Executive Director of Investor Relations and Corporate Communications. Please go ahead. Dave Connolly, Executive Director of Investor Relations and Corporate Communications
David Connolly: Thank you, Michelle. I'm Dave Connolly.
David Connolly: We are here at Rhythm Pharmaceuticals. For those of you participating in the conference call, our slides can be accessed and controlled by going to the investor section on the investors page of our website at ir.rhythmpx.com. And this morning, we issued a press release that provides our fourth quarter and year-end 2020 financial results and business update, which is available on our website and as listed on the slides. Thank you.
Speaker 9: Thank you, Michelle. I'm Dave Connolly, IR here at RYTHM Pharmaceuticals. For those of you participating on the conference call, our slides can be accessed and controlled by going to the investors section on the investors page of our website at ir.rythmtx.com. And this morning we issued a press release that provides our fourth quarter...
David Connolly: And as listed on slide two is our agenda. Here with me today in Boston are David Meeker, Chair, Chief Executive Officer, and President of Rhythm Pharmaceuticals; Jennifer Chen, Executive Vice President, Head of North America; Hunter Smith, our Chief Financial Officer; and Jan Mazabro, Executive Vice President, Head of International, is on the line joining us from Europe. And I'll remind you that this call contains remarks concerning future expectations, plans, and prospects, which constitute forward-looking statements.
Speaker 10: pharmaceuticals, Jennifer Chen, Executive Vice President, Executive Vice President, Head of North America, Hunter Smith, our Chief Financial Officer, and Jan Massebro, Executive Vice President, Head of International, is on the line joining us from Europe . And I'll remind you that this call contains...
David Connolly: Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in our most recent annual or quarterly reports on file with the SEC. In addition, any forward-looking statements represent our views only as of today, and they should not be relied upon as representing our views as of any subject.
Speaker 11: contains remarks concerning future expectations, plans, and prospects which constitute forward-looking statements. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors including those discussed on our most recent annual or quarterly reports on file with the FCC.
Speaker 12: In addition, any forward-looking statements represent our views only as of today. It should not be relied upon as representing our views as of any subject at date. We specifically disclaim any obligation to update such statements.
David P. Meeker: We specifically just claim any obligation to update such state, With that, I'll turn the call over to David, who will begin on 5. Thank you, Dave, and good morning, everyone. Thank you for joining the fourth quarter earnings call, and we are going to talk about earnings, which worked good, and this week's announced acquisition of Zinvento. However, before we do that, I wanted to reflect for a moment on this company's, There's almost a decade ago when we published the first case reports in the Newman Journal of Medicine describing the remarkable effect of the septmal antide in two patients with palm seed efficient Since then, we have learned so much about the MC4 receptor pathway, the associated genetic deficiencies, the importance of hypersia and energy expenditure in the development of, At the same time, we started to learn about what it means to live with one of these rare diseases.
Speaker 13: With that, I'll turn the call over to David, who will begin on slide five.
Speaker 14: Thank you, Dave, and good morning, everyone. Thank you for joining the fourth quarter earnings call, and we are going to talk about earnings, which worked good in this week's announced acquisition of Zindento. However, before we do that, I want to reflect for a moment on this company's journey.
Speaker 15: It was almost a decade ago when we published the first case reports in the Newman Journal of Medicine describing the remarkable effect of the fentanyl anetide in two patients with on-seat efficiency.
Speaker 16: Since then, we have learned so much about the MC4 receptor pathway, the associated genetic deficiencies, the importance of hyperphasia, and energy expenditure in the development of obesity.
David P. Meeker: Complete lack of awareness on the part of the health care system, the relative shortage of experts, the almost complete lack of genetic testing, all compounded by societal and medical bias which confronts the individual and family living with DBS. As a mother of one child with DBS said, when asked, how bad can the hyperphasia and obesity be when your child may be losing their sight? A response? People are kind to blind people.
Speaker 17: At the same time, we started to learn about what it means to live with one of these rare diseases. Complete lack of awareness on the part of the healthcare system, the relative shortage of experts, the almost complete lack of genetic testing, all compounded by the societal and medical bias which confronts the individual and family living with obesity.
Speaker 18: As the mother of one child with BBS said when asked, how bad can the hyperplasia and obesity be when your child may be losing their sight?
David P. Meeker: So slide five, the challenges of living with a rare disease were further highlighted this week as we mark Rare Disease Day with the rhythm of a guest speaker, a mother of two children with BBS, who described the incredible challenges of living with the hypoly. This severe preoccupation with food and the associated abnormal food-seeking behaviors and how her child and her family's life has been changed since starting in Cipari, and Rare Disease Day reads into Obesity Care Week and World Obesity Day on March 4th, which brings obesity to the forefront as a disease that requires a new way of thinking and new therapeutic options at work. Rhythm is at the center of these awareness events. As we know, obesity is not just one disease but many diseases, some of them rare, and each disease deserves a careful evaluation and the right treatment. Find six.
Speaker 19: The response? People are kind to blind people.
Speaker 20: So slide five, the challenges of living with a rare disease were further highlighted this week as we mark Rare Disease Day at rhythm of the guest speaker, a mother of two children with BBS who describe the incredible challenges of living with the hyperphagia.
Speaker 21: This severe preoccupation with food and the associated abnormal food seeking behaviors and how her child and her family's life has been changed since starting in sivari. And rare disease day leads into obesity care week and world obesity day on March 4th, which brings obesity to the forefront as a disease that requires a new way of thinking and new therapeutic options at work.
Speaker 22: Rhythm is at the center of these awareness events. As we know, obesity is not just one disease, but many diseases, some of them rare. Each disease deserves a careful evaluation.
Speaker 23: at the center of these awareness events, as we know obesity is not just one disease but many diseases, some of them rare, and each disease deserves a careful evaluation and the right treatment.
David P. Meeker: 2022 is a transformative year for rhythm as we now embark on our next chapter as an established commercial stage company expanding geographically and now further diversifying our pipeline. The DBS launch, as you will hear from Jennifer and Yon, continues to go extremely well. Since FDA approval in June through the end of the year in the U.S., we have received more than 200 new prescriptions from 125 prescribing physicians, with more than 100 patients approved for reimbursement. Our confidence in this opportunity continues to grow. Internationally, Sivry is now available in eight XUS markets for POMC and LepR. France also includes BBS through paid early access.
Speaker 24: Slide six.
Speaker 25: The 2022 is a transformative year for RYTHM as we now embark on our next chapter as an established commercial stage company expanding geographically and now further diversifying our pipeline.
Speaker 26: The DBS launch, as you will hear from Jennifer and Jan, continues to go extremely well.
Speaker 27: Since FDA approval in June through the end of the year in the U.S., we have received more than 200 new prescriptions from 125 prescribing physicians, with more than 100 patients approved for reimbursement.
Speaker 28: Our confidence in this opportunity continues to grow.
Speaker 29: Internationally, in Sivri is now available in eight ex-US markets for POMC and LEPAR. France also includes BBS through paid early access.
David P. Meeker: The success to date in both regions speaks to the quality of the team's leadership, and we're continuing to execute on our strategy to expand the overall opportunity for septimal antide. With strong proof of concept data in our phase two hypoklamic obesity trial in 2022, phase three trial sites are now being initiated, and we have begun screening patients. This year, we'll also have data readouts in our Phase 3 Pediatrics trial and Phase 3 switch study, evaluating the weekly formulation of several antidepressants, and preliminary data from the Open Label, stage one portion of the Phase 2 daybreak trial.
Speaker 30: The success to date in both regions speaks to the quality of the teams we have.
Speaker 31: And we are continuing to execute on our strategy to expand the overall opportunity for set planet type.
Speaker 32: With strong proof of concept data in our phase two hypokalemic obesity trial in 2022, phase three trial sites are now being initiated and we have begun screening patients.
This year, we'll also have data readouts in our Phase III pediatrics trial and Phase III switch study evaluating the weekly formulation of sepalanotide and preliminary data from open-label Stage I portion of the Phase II daybreak trial.
David P. Meeker: On Monday, we were excited to announce the acquisition of Zimvento, a pre-clinical Dutch company with a suite of drug candidates for congenital hyperinsic, which we believe represents an outstanding fit with rhythm and our expanded focus looking at where this fits perfectly with our concentration of pediatric endocrinologists, and we've already heard from some of them how they are excited about this development and look forward to working with us to develop those companies. We're targeting being in the clinic in 2024, and as noted, we are well capitalized into 2025, and the Sunvental acquisition will have no impact on that fourth. Slide 7.
Monday, we were excited to announce the acquisition of Zindento, a preclinical Dutch company with a suite of drug candidates for congenital hyperinsulinism, which we believe represents an outstanding fit with rhythm in our expanded focus looking at rare endocrinology. This fits perfectly with our concentration of pediatric endocrinologists, and we've already heard from some of our patients who have been working on this.
forecast. Slide 7.
So CHI is a disease where the available treatments are suboptimal, both in terms of safety, tolerability and importantly effectiveness.
The unmet need is clear. I had the opportunity to get to know Claudine Demasande, the CEO , and Pete Wigginink, the CFO , as one of their scientific advisors. I was incredibly impressed by Claudine's personal story, the thoughtful way she has pursued her mission, and the great progress she and Pete have made in a short period of time. The fit with rhythm was obvious.
David P. Meeker: So CHI is a disease where the available treatments are suboptimal, both in terms of safety, tolerability, and importantly, effectiveness. The unmet need is clear. I had the opportunity to get to know Claudine, the CEO, and Pete Wigernink, the C-S-O, as one of their scientific advisors. I was incredibly impressed by Clodine's personal story, the thoughtful way she has pursued her mission, and the great progress she and Pete have made in a short period of time. The fit with the rhythm was off.
CHI is a genetic disease with patients presenting during the neonatal period with hypoglycemic episodes which may trigger seizures, loss of consciousness, and with repetitive insults, brain damage, and death. Thank you for your attention. Thank you for your attention. Thank you for your attention. Thank you for your attention.
Biologically, in a normally functioning beta cell, an increase in glucose levels triggers insulin release, and as glucose levels drop, insulin release is suppressed. In CHI, this process malfunctions, and insulin release continues in the presence of low glucose levels, resulting in further lowering of the blood glucose for life-threatening levels. The emergency treatment is dextrose and glucose infused.
David P. Meeker: CHI is a genetic disease, with patients presenting during the neonatal period with hypoglycemic episodes, which may trigger seizures, loss of consciousness, and with repetitive insults, brain damage, and death. Biologically, in the normally functioning beta cell, an increase in glucose levels triggers insulin release, and as glucose levels drop, insulin release is suppressed. In CHI, this process malfunctions, and insulin release continues in the presence of low glucose levels, resulting in further lowering of blood glucose to life-threatening levels.
We know from patient and family surveys conducted by the International Patient Organization that these hypoglycemic low blood sugar levels are occurring one or more times per day in 25% and one or more times per week in an additional 20% of patients despite being on standard care.
This is an ultra rare disease with an incidence of approximately 1 in 30,000 individuals in the US and Japan respectively. Approximately 70 to 80% of these patients need medical treatment.
In addition to patients with chronic hyperinfluenism, there's another population of patients potentially twice as large with transient hyperinfluenism in the neonatal period, who we will potentially target as well. In addition to the number of patients with chronic hyperinfluenism, there's another population
David P. Meeker: The emergency treatment is dextrose and glucose. We know from patient and family surveys conducted by the International Patient Organization that these hypoglycemic low blood sugar levels occur one or more times per day in 25% and one or more times for a week in an additional 20% of patients despite being on standard of care. This is an ultra rare disease with an incidence of approximately 1 in 30,000 individuals in the US, EU, and Japan, respectively.
We look forward to providing a more in-depth presentation on the science and our development plans later this year.
This is slide 8. Base retrial for HO is actively screening patients. This is a double-blind randomized controlled trial of 120 patients randomized two to one to set melanotype or placebo. Patients will be dose escalated over eight weeks and then followed for an additional 52 weeks. The primary endpoint is percent change in BMI. For deserves square footage, check Guide 2 beforebie.
We expect it will take six to 12 months to enroll, probably skewing closer to the 12-month timeframe.
Slide 10, as you know, this is a fundamentally different opportunity for rhythm with an estimated 5 to 10,000 patients in the US and the EU, respectively, largely already identified based on their history of injury to the hypothalamus with associated impairment of the MC4 pathway and their need for ongoing hormonal replacement related to pituitary injury.
David P. Meeker: Approximately 70 to 80% of these patients need medical treatment. In addition to patients with chronic hyperinsulinism, there's another population of patients, potentially twice as large, with transient hyperinsulinism in the neonatal period, who we will potentially target as well. We look forward to providing a more in-depth presentation on the science and our development plans later this year. Friday.
We look forward to providing an update on the patients in the long-term extension before the end of the year and anticipate that will be tied to an abstract presentation at a fall meeting.
David P. Meeker: The Baseery trial for H.O. is actively screening patients. This is a double-blind, randomized controlled trial of 120 patients, randomized 2-1 to melanotide or placebo. Patients will be dose escalated over eight weeks and then followed for an additional 52 weeks. The primary endpoint is percent change in BMI. We expect it will take six to 12 months to enroll, probably skewing closer to the 12-month time.
Slide 11. Multiple trials ongoing. These other programs are progressing well. Both the PEDS and weekly switch trials, as noted, will read out top-line data in the second half of this year. We'll provide an initial look at the phase two daybreak open-label portion in the second half of this year. And EMANATE is enrolling patients to report independent sub-studies.
Slide 12, before I turn it over to Jennifer, we are formally updating our BDS prevalence numbers, which we talked about previously, as we have described.
David P. Meeker: Slide 10, as you know, this is a fundamentally different opportunity for rhythm with an estimated 5 to 10,000 patients in the U.S. and EU, respectively, largely already identified based on their history of injury to the hypothalamus with associated impairment of the MC4 pathway and their need for ongoing hormonal replacement related to pituitary. We look forward to providing an update on the patients in the long-term extension before the end of the year. Anticipates that it will be tied to an abstract presentation at a fall conference. 2012.
When we look at the identified patient numbers in Europe , where the diagnostic was created ahead of the US. We look at the identified patient numbers in Europe , where the diagnostic was created
and extrapolate that to the U.S. population, combined with the frequency of patients with a biallelic pathogenic variant for BDS being identified in our URO testing program.
and our initial experience with LAUNCH, all of this gives us increased confidence that the target population is larger than originally anticipated. It's on the order of 4 to 5,000 patients in the US and similarly in Europe .
And with that, I'll turn it over to Jeff.
Thank you, David.
I'm going to be starting on slide 13 today. We are excited about the current status of our U.S. Encephri BBS launch. We remain focused on our efforts to see the diagnosis of patients with BBS and educate them on the availability of Encephri, the only FDA-approved therapy that targets the current MC4 pathway.
David P. Meeker: Multiple trials ongoing. These other programs are progressing well. Both the PEDs and weekly switch trials are noted. We'll read out top-line data in the second half of this year. We'll provide an initial look at the Phase 2 daybreak, open-label portion in the second half of this year, and M&A is enrolling patients in each of its four independent sub-studies. Slide 12.
a root cause of hunger and obesity in people living with BBS. Through all the efforts of our cross-functional team, we have seen continued progress and success across the journey from diagnosis of BBS patients through to securing access and maintaining patients on therapy due to the benefits they received.
living with BBS. Through all the efforts of our cross-functional team, we have seen continued progress and success across the journey from diagnosis of BBS patients through to securing access and maintaining patients on therapy due to the benefits they receive. Next slide.
David P. Meeker: Before I turn it over to Jennifer, we are formally updating our BDS prevalence numbers, which we talked about previously. As we have described, When we look at the identified patient numbers in Europe, where the diagnostic rated ahead of extrapolating that to the U.S. population, combined with the frequency of patients with a bilialic pathogenic variant for BDS being identified in our URO testing process, and our initial experience with launch, all of this gives us increased confidence that the target population is larger than originally anticipated. It's on the order of 4,000 to 5,000 patients in the U.S. and, similarly, in Europe.
We are pleased with the progress and achievements made in the second full quarter of launch. As we did last quarter, we will share with you today key metrics we believe reflect the progress of our launch, focusing on prescriptions, prescribers, and care approval for reimbursement.
Since delivery was approved for BBS by the FDA on June 16, 2022, and through the end of the fourth quarter of 2022, we have received more than 200 new prescriptions for BBS patients.
coming from more than 125 physicians.
This breaks down to more than 120 new prescriptions between June and the end of September and more than 80 in the fourth quarter. Given that 20 focal trial patients have converted to commercial prescriptions during the third quarter, we are pleased to see the continued growth in quarter-over-quarter prescriptions.
David P. Meeker: With that, I'll turn it over to John. Thank you, David.
Jennifer L. Chien: I'm going to be starting on slide 13 today. We are excited about the current status of our U.S. Encivary BBS launch. We remain focused on our efforts to diagnose patients with BDS and educate them on the availability of idivry. The only FDA of P2, which is charged in the United MC4 pathway, a root cause of hunger and obesity in people living with BBS. Through all the efforts of our cross-functional team, we have seen continued progress and success across the journey, from diagnosis of VBS patients through to securing access to and maintaining patients on therapy due to the benefits they receive. Next slide.
Importantly, we have received payer approval for more than 100 of these prescriptions since launch. The demand for emceevery is strong. Physicians are writing the prescriptions and patients are experiencing benefit on drugs. On the next slide, we'll take a closer look at emceevery prescribers since launch.
Jennifer L. Chien: We are pleased with the progress and achievements made in the second full quarter of launch. As we did last quarter, we will share with you today key metrics that we believe reflect the progress of our launch, focusing on prescriptions, prescribers, and payer approvals for reimbursement. Symptens Civry was approved for BDS by the FDA on June 16, 2022, and through the end of the fourth quarter of 2022, we have received more than 200 new prescriptions for BBS patients, coming in for more than 125 positions.
a subscriber.
On the small pie chart on the right, you can see that approximately 22% of all emissive represcribers since launch are new to rhythm. By this we mean they had not been called on by a rhythm territory manager prior to writing a prescription. alethria. consecutive st
Interestingly, these neuter rhythm prescribers view towards primary care or general pediatrics.
We believe this speaks to the success of our non-circles promotion efforts, which has to take some broader physician and patient populations, as well as motivated patients who likely became aware and separate their own relationship with the DBS Foundation.
Next slide. Getting more than 100 payer approvals for reimbursement is quite a meaningful milestone for us at the end of the fourth quarter. Our payer mix for BDS prescriptions still remains with the vast majority coming from commercial plans and Medicaid.
Jennifer L. Chien: This breaks down to more than 100 new prescriptions, 120 new prescriptions between June and the end of September and more than 80 in the fourth quarter. Given that 20 clinical trial patients have converted to commercial prescriptions during the third quarter, we are pleased to see the continued growth in quarter-over-quarter prescriptions. Importantly, we have received pair approval for more than 100 of these prescriptions since long. The demand for impsvery is strong.
and a small portion for 9% coming from Medicare.
Time to payer approval remains approximately one to three months. There are certainly outliers, but this range represents the average, and we are starting to see subsequent prescriptions submitted to payers that have already approved reimbursement for emissivity move faster to approvals. While the majority of the remaining prescriptions are in the prior authorization, the majority
Jennifer L. Chien: Physicians are writing the prescriptions, and patients are experiencing benefit from the drugs. On the next slide, we'll take a closer look at Incivious Prescribers for a long time. Not surprisingly, endocrinology, both pediatric and adult, remains the top specialty amongst our prescribers at a combined 47%. Pediatricians remain second, accounting for 24% of prescribers.
self-insured plants that are not providing coverage from zippering.
Finally, Medicaid continues to be a mixed bag as some states offer coverage for empsivirate and others will make a decision on a case-by-case basis through the appeals process. Both of these categories make up the majority of Medicaid's plan. There are, however, some states that currently outline they will not cover empsivirate and have not covered empsivirate.
Jennifer L. Chien: On the small pie chart on the right, you can see that approximately 22% of all insulin prescribers since launch are new to rhythm. By this, we mean they had not been called on by a rhythm territory manager prior to writing a prescription. Interestingly, these new to written prescribers skewed towards primary care or general pediatrics. We believe this speaks to the success of our non-personal promotion efforts, which educates a broader physician audience in patient populations, as well as motivated patients who likely became aware of uspiry through our relationship with the BBS Foundation. Next slide.
our payer education and outreach efforts to help them recognize CVS as a distinct disease that requires a targeted therapeutic approach.
education and outreach efforts to help them recognize CVS as a distinct disease that requires a targeted therapeutic approach. Next slide.
On this slide, we show the age breakdown of BDF patients for whom we have prescriptions enhanced and splashed. This slide shows the age breakdown of BDF patients for whom we have prescriptions enhanced and
Jennifer L. Chien: Getting more than 100 payer approval for reimbursement is quite a meaningful while-term for us at the end of the fourth quarter. Our pair mix for BDS prescriptions still remains with a vast majority coming from commercial plans and Medicaid, and a small portion of 9% coming from Medicare. Tides to Pair approval remain approximately one to three months.
Adults account for 46% of prescriptions received, while prescriptions for children and adolescents account for over half the prescriptions received.
In the vast majority, 95% of patients with prescriptions have consented to receiving direct connection and education from our patient services team, which we call Rhythm in Tune.
Jennifer L. Chien: There are certainly outliers, but this range represents the average, and we are starting to see subsequent prescriptions submitted to payers that have already approved reimbursement for MCIvery move faster to approvals. While the majority of the remaining prescriptions are in the prior authorization and appeal stage, we have moved patients to free drugs or PAC, our patient assistance program. By statute, Medicare does not cover anti-abucity medication, so those patients are transitioned to pass. Similar to other rare diseases, there are patients with small self-insured plants that are not providing coverage firms different.
We are proud to offer this program. Our teams work side by side with patients and their families to help them gain insurance coverage and to support them through our education efforts from initiation and maintenance on therapy.
We are so pleased and inspired by the overwhelmingly positive feedback from patients and their practitioners of rhythm and tune.
and inspired by the overwhelmingly positive feedback from patients and their physicians of rhythm and tune. Next slide.
While we are happy with the results of the launch to date, we still have more opportunity ahead of us and we are focused on optimizing our execution moving forward. Last month, we held our 2023 North America team meeting in Dallas to align on our strategy for this year. We are also working on the launch of the 2023 North America team to align on our strategy for this year. We are also working on the launch of the 2023 North America team to align on our strategy for this year.
Jennifer L. Chien: Finally, Medicaid continues to be a mixed bag, as some states offer coverage for insifery, and others will make a decision on a case-by-case basis through the appeals process. Both of these categories make up the majority of Medicaid plans. There are, however, some states that currently state they will not cover insifery, and hence we do also have some Medicaid patients on free drugs.
We have a great foundation in place to build on as 2022 really set the stage for patient identification, prescriptions, and therapy initiation and maintenance as exhibited by the results from the first two quarters of commercial launch.
And this year, we remain focused on accelerating hope for patients and their families by continuing to engage with our customers around the need to treat hyperphagia and severe early onset obesity caused by an impaired NC4 pathway.
Jennifer L. Chien: We continue to work this system persistently and explore alternative venues for reimbursement for all of our patients, and we have experienced early success transitioning patients off of attack. We remain committed to our payer education and outreach efforts to help them recognize CBS as a distinct disease that requires a targeted therapeutic approach. Next slide. On this slide, we show the age breakdown of BDS patients for whom we had prescriptions in hands and swine. Adults account for 46% of prescriptions received, while prescriptions for children and adolescents account for over half of all prescriptions received.
educate that emsifery is the right treatment option for patients with BBS. With a tremendous team in place with deep experience in rare diseases, we are focused on ensuring our engagement with customers cultivates a positive experience with rhythm and emsifery. And lastly...
With the conviction we have of the benefits that patients are receiving on therapy, we remain focused on expediting the identification of more patients with VBS who may benefit from incivory. With that, let me hand it over to Jan.
Jennifer L. Chien: And the vast majority, 95% of patients with prescriptions, have consented to receiving direct connection and education from our patient services team, which we call Rhythm in Tune. We are proud to offer this program. Our teams work side by side with patients and their families to help them gain insurance coverage and to support them through our education efforts from initiation to maintenance of therapy. We are so pleased and inspired by the overwhelmingly positive feedback from patients and their provision of rhythm in tune.
Thank you, Jennifer, and good morning. I will start with the slide 20. So in the international region, we had a very strong year and a very strong fourth quarter as well, making significant progress in securing access for in-serve for POMC and LITAR indications and in parallel working intensely at market access execution for Bardet-Lille syndrome.
In-Siber is now available in eight countries outside the United States and we are looking forward to continued execution this year. As you can see on the picture, the international team came together mid-January to kick off the year with the focus of market access, patient identification, launch plans and operational excellence.
countries outside the United States and we are looking forward to continued execution this year. As you can see in the picture the international team came together mid-January to kick off the year with a focus of market access, patient identification, launch plans and operational excellence. Next slide.
For POMC, PCSK1 and NIPA patients, we have identified approximately 100 patients being cared for in medical centers in EU4 and the UK, and the estimated prevalence is approximately 600 to 2500 patients in Europe .
Jennifer L. Chien: Next slide. While we are happy with the results of the launch to date, we still have more opportunity ahead of us, and we are focused on optimizing our execution moving forward. Last month, we held our 2003 North America team meeting in Dallas to align on our strategy for this year.
For Pomsian-Lipar, we are now fully launched in the UK, in Germany, in the Netherlands and in Italy. We achieved paid early access in France, same in Austria and Turkey, and we also have an early access program in Argentina in place. Compared to the United States, we know that the community and referral networks in Europe are better organized for these patients.
Jennifer L. Chien: We have a great foundation in place to build on as 2022 really sets the stage for patient identification, prescriptions, and therapy initiation and maintenance, as demonstrated by the results from the first two quarters of commercial launch. And this year, we remained focused on accelerating hope for patients and their families by continuing to engage with our customers around the need to treat hyperphasia and severe early-onset obesity caused by an impaired NC4 pathway, and educate that emstivary is the right treatment option for patients with BBS.
the numbers are too small we are in positions to leverage that existing radiated infrastructure and we are
For BBS we have made significant progress since we received the marketing authorization from the UC in September last year.
like for policy and legal indications we are in positions to leverage the existing
DDS is a larger population, we believe the EU prevalence estimate of 4,000 to 5,000 patients, as David has detailed. We know of approximately 1,500 patients who are diagnosed and being cared for in EU4 in the UK.
Jennifer L. Chien: With a tremendous team in place, with deep experience in rare diseases, we are focused on ensuring our engagement with customers cultivates a positive experience with rhythm and Insipfrey. And lastly, with the conviction we have of the benefits that patients are receiving on therapy, we remain focused on expediting the identification of more patients with BBS who may benefit from miscivary. With that, let me hand it over to Yon.
In France, we achieved paid early access for BBS last year. This paid early access program called AP1 allows reimbursed early access for therapies where a positive risk-benefit balance is recognized and when no other therapeutic antibodies are available. With approximately 700 patients with BBS diagnosed in France, there is a clear and met medical need there.
In Germany we are progressing in our discussion with the Joint Federal Committee, the GBA, with very positive interaction so far. We are seeking the exemption from the lifestyle drugs reimbursement exclusion list as we successfully did for POMC and LIPA.
and we are looking forward to launching in the second quarter of 2023. In addition, we look forward to launching in the Netherlands in Q4 of 2023, in Italy and in Spain in the first half of 2024, and in the UK in the second half of 2024.
Yann Mazabraud: Good morning. I will start with slide 20.
Yann Mazabraud: So in the international regions, we had a very strong year and a very strong force quarter as well, making significant progress in securing access to InSivari for POMC and Lipar indications and, in parallel, working intensely at market access execution for Bardi Vidal syndrome. InSivry is now available in eight countries outside the United States, and we are looking for work to continue market access execution this year. As you can see in the picture, the international team came together mid-January to kick off the year, with the focus on market access, patient identification, launch plans, and operational excellence. Next slide.
We are very excited about all the progresses we are making in Europe . We are making steady progress with Policy and Le Par and with BBS we are making tremendous strides.
with securing access.
We look forward to launching in Germany this year and bringing several other countries online in 2024 like for example Belgium and some Nordic countries.
With that, I will pass the baton to Hunter.
Thank you so much, Jan. Turning to slide 24.
And it begins 2023 well capitalized with $333 million in cash on hand, sufficient to fund all planned operations into 2025 as we continue to grow as a global commercial stage by a pharmaceutical company.
This cash guidance includes the impact of projected milestones and R&D spending associated with the Shinvento acquisition. We recorded $8.8 million in net product revenue from SIVRI in the fourth quarter and $16.9 for the calendar year 2022.
Yann Mazabraud: For POMCPCSK1 and NIPAR patients, we have identified approximately 100 patients being cared for in medical centers in EU4 in the UK, and the estimated prevalence is approximately 600 to 2,500 patients in Europe. For Pontian Lippar, we are now fully launched in the UK, in Germany, in the Netherlands, and in Italy. We achieved paid early access in France, the same in Australia and Turkey, and we also have an early access program in Argentina. Compared to the United States, we know that the community and referral networks in Europe are better organized for these patients.
Quarterly revenue marked an increase of 4.5 million or 105% over the third quarter of 2022, driven primarily by in-sibri sales for BBS in the United States.
as well as increased POMC and LEPR sales in our international region.
US sales represented 84% of total Q4 net product sales and 85% for the full year.
Cost of goods sold for the fourth quarter was 1 million or about 11.7% of product revenue.
Yann Mazabraud: While the numbers are still small, we are in positions to leverage that existing rare disease infrastructure, and we are already doing so. For BBS, we have made significant progress since we received the marketing authorization from the UC in September last. And like for POMC and Lipar Indications, we are in positions to leverage the existing rare disease healthcare structure. DDS is a larger population.
Cost of goods sold consisted of 440,000 royalties due to Ibsen under original licensing agreement, 400,000 product costs related to commercial sales and product distributed under patient assistance programs, and about 200,000 related to the amortization of our previously capitalized sales-based milestones. Our D expenses were 23.5 million.
and $108.6 million for the fourth quarter and calendar year 22, respectively, on a quarter-over-quarter basis, R&D expenses decreased by $8 million.
Yann Mazabraud: We believe the EU prevalence estimate of 4,000 to 5,000 patients, as David has detailed. We know of approximately 1,500 patients who were diagnosed and being cared for in EU 4 and the UK. In France, we achieved paid early access for BBS last year. This paid early access program called AP1 allows reimbursed early access for therapies where a positive risk-benefit balance is recognized and when no other therapeutic alternatives are available. With approximately 700 patients with BBS diagnosed in France, there is a clear and unmet medical need.
On a sequential quarterly basis, this represented an increase of $2.4 million as compared to the third quarter of 2022, primarily driven by increased spending on clinical supply materials. Clinical trial costs remained largely unchanged as decreases in older studies offset increases in costs associated with the ramp-up of activity for our pivotal Phase III hypothalamic obesity and M&A studies. SGA expenses were $26.3 million for the quarter and $92 million for the year.
Compared to Q4 2021, STNA increased by 5.3 million, sequential quarterly basis versus Q3 2022, the increase was 4.4. The latter increase is primarily due to increased marketing costs related to BBS, increased special fees.
Yann Mazabraud: In Germany, we are progressing in our discussion with the joint federal committee, the GBA, with very positive interaction so far. We are seeking an exemption from the Lifestyle Drugs Reimbursement Exclusion List, as we successfully did for POMC and LIP, and we are looking forward to launching in the second quarter of 2023. In addition, we look forward to launching in the Netherlands in Q4, Italy and Spain in the first half of 2024, and in the UK in the second half of 2020.
related to commercial, regulatory, and international operations.
For the fourth quarter weighted average common shares outstanding were $56.3 million and quarterly net loss per share was $0.75.
For the full year, average common share is $50.3 million. So, 3.47 per common share.
Turning to slide 25 for some comments about the outlook for the coming year.
We enter the year well capitalized and we are executing our global strategy.
Yann Mazabraud: We are very excited about all the progress we are making in Europe; we are making steady progress with POMC and IPA, and with BBS, we are making tremendous strides with securing our capacity. We look forward to launching in Germany this year and bringing several other countries online in 2024, like, for example, Belgium and some Nordic countries. Zap, I would pass the baton to Hunter.
with disciplined investments in our programs designed to maximize benefits for patients while delivering shareholder value.
That was our strategy. That was the example we set in 2022. And we expect 2023 to be no different.
We have not offered revenue guidance in the past. We have no plans to do so in the future. Projecting rare disease launches is a challenging exercise, and we don't expect quarterly growth to be linear.
Hunter C. Smith: Thank you so much, Jan. Turning to slide 24, and it begins in 2023, well capitalized, with 333 million in cash and enhanced fission to fund all planned operations into 2025 as we continue to grow as a global commercial stage biopharmaceutical company. This cash guidance includes the impact of projective milestones and R&D spending associated with the Shinvento Act.
We expect long-term success based on Rynum's ability to bring potential and civvy patients to diagnosis.
Our success to date increases our confidence in the long-term opportunity in DBS and other potential indications. As such, we remain focused on commercial execution to maximize the opportunity for VSEVERI globally. Having said that, I will offer a few comments and some context for how to think about the drivers of revenue growth in the coming year.
PBS is the primary driver of M-SIBRI revenue, so it's worth re-emphasizing that PalmSea left our bioelic sites and so on drug in the first few years we'll number in the tens.
Hunter C. Smith: We recorded 8.8 million in net product revenue from Sivry in the fourth quarter and 16.9 million for the calendar year 2022. Quarterly revenue marked an increase of 4.5 million, or 105%, over the third quarter of 2022, driven primarily by MCBRI sales for BBS in the United States, as well as increased POMC and LEPR sales in our international region. U.S. sales represented 84% of total Q4 net product sales and 85% for the full year.
In the last full quarter prior to the DDS launch, for example, the first quarter of 2022, net sales in the delivery totaled 1.5 million, reflecting the ultra rarity of POMC and LEP-R patients. We expect the percentage contribution from our international region to increase over time, but the timing of this increase is largely dependent upon country-level reimbursement decisions associated with the increase in the number of patients in the DDS. We expect the percentage contribution from our international region to increase over time, but the timing of this increase is largely dependent upon country-level reimbursement decisions associated with the increase in the number of patients in the DDS.
Hunter C. Smith: Cost of goods sold for the fourth quarter was $1 million, or about 11.7% of product revenue. Cost of goods sold consisted of $440,000 royalties due to Ibson under the original licensing agreement, $400,000 product costs related to commercial sales, and product distributed under patient assistance programs, and about $200,000 related to the amortization of our previously capitalized sales-based files. R&D expenses were $23.5 million and 108.6 million for the fourth quarter of calendar year 22, respectively. On a quarter over quarter basis, R&D expenses decreased by $8.
Spain, Italy and the UK are expected in 2024. We will plan to keep you up to date on the projected timing of these reimbursement decisions as our visibility increases.
Excluding the German BBS launch, therefore, the POMC and LEPR indication will remain the main driver of revenue in our international region in 2023.
We also thought it would be helpful to give you more perspective about our forecast for operating costs given all the activity going on at rhythm. We expect approximately 200 to 220 million.
and non-GAAP operating expenses in 2023. This projection includes 120 to 130 million for R&D expenses and 80 to 90 million for SG&A. Both projections exclude stock-based compensation. R&D will represent an increase of approximately 22% over 2022 using the midpoint of the range. This increase is driven primarily by our pivotal phase 3.
Hunter C. Smith: On a sequential quarterly basis, this represented an increase of $2.4 million as compared to the third quarter of 22, primarily driven by increased spending on clinical supply materials. Clinical trial costs remain largely unchanged, as decreases in older studies offset increases in costs associated with the ramp-up of activity for our pivotal phase three, hypothalamic obesity, and emanate studies. SG&A expenses were $26.3 million for the quarter and $92 million for the year.
trial in hypothalamic obesity, a global trial for which we expect to open more than 20 sites. Enrollments in our phase 3 M&A trial, as we anticipate the vast majority of patients entering the trial this year, and costs related to our phase 3 de novo trial for the weekly formulation of set melanotype. On the FGNA side, we expect an increase in the number of patients in the M&A trial.
Hunter C. Smith: Compared to Q4 2021, SG&A increased by 5.3 million, on a sequential quarterly basis versus Q32. The increase is 4.4. The latter increase is primarily due to increased marketing costs related to BBS, increased professional fees related to commercial, regulatory, and international operations. For the fourth quarter, weighted average common shares outstanding were 56.3 million, and the quarterly net loss per share was 75 cents.
we expect expenses between $80 and $90 million for an increase of about 9% over 2022, again using the bid point of the range.
Our US commercial operations are now at full strength, so the increase is driven primarily by annualization of these costs as they were growing during 2022, or the headcount was growing during 2022, as well as headcount increases in the international region and other support functions.
All of these non-GAAP estimates include non-cash stock compensation, which totaled $20 million in 2022. Lastly, we are very excited about the shavental opportunity.
Hunter C. Smith: For the full year, average common share is 50.3 million, for that loss of 3.47 per common share. Turning to slide 25 for some comments about the outlook for the coming year, we enter the year well capitalized, and we are executing our global strategy with disciplined investments in our programs designed to maximize benefits with patients by delivering shareholder value. That was our strategy.
Rhythm is paying a $5 million upfront fee and taking over development costs for the company's portfolio of preclinical assets. In addition to the upfront, we agreed to pay $6 million in preclinical development milestones. There are no near-term clinical milestones. The remaining milestones payable to Shinvento shareholders are based largely upon FDA and EC regulatory approval.
Hunter C. Smith: That was the example we said in 2022, and we expect 2023 to be no different. We have not offered revenue guidance in the past, and we have no plans to do so in the future.
Hunter C. Smith: Projecting rare disease launches is a challenging exercise, and we don't expect quarterly growth to be linear; we expect long-term success based on Rhydom's ability to bring potential insivary patients to diagnose. Our success to date increases our confidence in the long-term opportunity for BBS and other potential indications. As such, we remain focused on commercial execution to maximize the opportunity for Mississippi globally.
and Pete join us on this high impact opportunity in a disease with a high on medical need. Now I will return the call over to David. Thank you. Thank you, Hunter. So I'll quickly share these last two sides before moving to questions. So slide 27, slide 26, slide 27, slide 29, slide 30, slide 31, slide 32, slide 33, slide 34, slide 35, slide 36, slide 37,
Hunter C. Smith: Having said that, I will offer a few comments and some context for how to think about the drivers of revenue growth in the coming year. BBS is the primary driver of e-commerce revenue. So it's worth reemphasizing that POMC-N-LEPR Bialic stations on the drug in the first two years will number in the 10s. In the last full quarter prior to the DBS launch, for example, the first quarter of 22, net sales in the civvary totaled 1.5 million, reflecting the ultra rarity of POMCC and Lepar patients.
As noted, we have several trial starts and top line data readouts this year, which we'll talk about, as well as several market access milestones and a number of ex-US markets, which we'll talk about in detail. Slide 28, just reminding you, we have three main FOSI areas for this year, maximizing the PBS and BBS commercial opportunity globally.
executing on our phase three trial in hypokalemic obesity and continued expansion through clinical development for set-malinotide in these other trials. And now our assets from the SimPento acquisition, which again we look forward to moving forward as rapidly as possible. And with that, we'll open it up for questions and a few operators. As a reminder, to ask a question, please press star 1-1 on your telephone. Thanks for your time.
Hunter C. Smith: We expect the percentage contribution from our international region to increase over time, but the timing of this increase is largely dependent upon country-level reimbursement decisions associated with the BBS indication. Jan outlined this timeline earlier in the call. At present, the only country in which we expect full reimbursement for BDS for a significant portion of this year is Germany. The Netherlands and potentially Canada will come in the second half of the year.
and wait for your name to be announced. To withdraw your question, please press star 1-1 again. Please stand by while we compile the Q&A roster. Our first question comes from Phil Nadeau with Cohen. Your line is now open.
Hunter C. Smith: Full reimbursement in other major markets such as France, Spain, Italy, and the UK is expected in 2024. We will plan to keep you up to date on the projected timing of these reimbursement decisions as our visibility increases. Excluding the German BBS launch, therefore, the POMC fee and Lepar Indications will remain the main driver of revenue in our international region in 2023. We also thought it would be helpful to give you more perspective about our forecasts for operating costs, given all the activity going on at Rhythm. We expect approximately 200 to 220 million and non-gap operating expenses in 2023. This projection includes 120 to 130 million for R&D expenses and 80 to 90 million for SG&A. Both projections exclude stock-based compensation.
Thanks for taking our questions and congrats on a successful quarter.
The first question is on the BBS launch. The pace at which you're adding prescriptions is impressive.
with 200 a year end and adding 80 a quarter, the simple math would say you'd be over 500 by the end of 2023, which is.
the vast majority of people who are in the BBS registry. Can you tell, one, whether you're adding new patients to the prescriptions, are you giving patients prescriptions who are not currently in the registry? And two, can you talk about new patient identification more broadly, is it possible for this rate of prescriptions to continue even beyond?
registry. Can you tell one whether you're adding new patients to the prescriptions, are you giving patients prescriptions who are not currently in the registry? And two, can you talk about new patient identification more broadly? Is it possible for this rate of prescriptions to continue even beyond 2023?
Hunter C. Smith: R&D will represent an increase of approximately 22% over 2022, using the midpoint of the range. This increase is driven primarily by our pivotal phase three trial in hypothalamic obesity, a global trial for which we expect to open more than 20 sites. Enrollment in our phase three M&A trial, as we anticipate the vast majority of patients entering the trial this year, and costs related to our phase three de novo trial for the weekly formulation of setmalanatide.
Thanks, Joe. Thanks for the question. So, you asked about the Crips Registry. And one, we have great relationships with the folks at the Marshall Clinic. They are incredibly dedicated to the BBS patients and their care. When we think about the Crips Registry, however, there are privacy policies in place. So, we...
at this point really don't have any visibility in terms of the overlap of the patients that are in the registry versus the patients and the HEPs that we have within our view at rhythm. So that's one piece. To your point in terms of the prescriptions, I will say that we've been very happy with the level of the demand for this product. It speaks to the need and the differential.
Hunter C. Smith: On the FTNA side, we expect expenses between 80 and 90 million for an increase of about 9% over 20, 22, again, using the midpoint of the rate. Our U.S. commercial operations are now at full strength. So the increase is driven primarily by annualization of these costs, as they were growing during 2022, or the headcount was growing during 2022, as well as headcount increases in the international region and other support functions. All of these non-gap estimates include non-cash stock compensation, which totaled 20 million in 2022.
in terms of the hyperphasia on the patient population, for them to be seeking treatment, and not only for their obesity, but the underlying hyperphasia itself. And so we are very much focused in terms of school through of opportunities. There still remains opportunity in terms of the physicians that we already have identified with patients that they are treating with BBS, and pulling through those patients onto therapy through our interactions and education efforts.
Hunter C. Smith: Lastly, we're very excited about the Shadvental opportunity. Rhythm is paying a $5 million upfront fee and taking over development costs for the company's portfolio preclinical asset. In addition to the upfront, we agree to pay $6 million in preclinical development milestones. There are no near-term clinical milestones.
And to your point, we continue to be ultra-focused in terms of identifying additional patients to add to our view. These include patients that are already diagnosed with CDS that are lost in the system, and we have different mechanisms that we're going about in terms of defining those patients.
Hunter C. Smith: The remaining milestones pay off-full to Shinvento shareholders are based largely upon FDA and EC regulatory approval and successful future commercialization, totaling up to $125 million. There's a potential for an additional $75 million in the event that the second molecule would select a development route. The economics of this transaction are success-based, and we at Rhythm are very excited to have Claudine, Pete, and Pete join us on this high-impact opportunity in a disease with a high level of medical need. Now I will return the call to David. Thank you. Thank you, Hunter.
as well as educating both potential patients out there as well as ACPs on the differential diagnosis of EDS so that we can get an expedite additional patients to get to a proper diagnosis. So there just remains a lot of opportunity out there. Is there any sense
David P. Meeker: So I'll quickly share these last two sides. We'll move into place. So, Sight 27, as noted, we have several trial starts and top line data readouts this year, which we talked about, as well as several market access milestones and a number of XUS markets with yon and details, slide 28, just reminding you, we have three main FOSI areas for this year, maximizing the PBS, BBS commercial opportunity globally, executing on our phase three trial in hypolomal obesity and continued expansion through clinical development for set melanotide in these other trials. And now, our assets from the Simento acquisition, which again, we look forward to moving forward as rapidly as possible. For that, we'll open it up for questions. A few operators.
of my head's up demand, you know, for any disease area where there's no therapy that's available for years and years and years. When something becomes available, it's quite interesting for a patient who were, you know, really trying to find a therapeutic option.
And as we move forward, we can.
have continued conviction about the needs and what's again our focus is just around getting those patients to a quicker diagnosis as the journey or diagnostic journey up and times it so along for these patients. So Phil just to reinforce a couple things that you know first shed there. I want to remind one of our common themes can read a G's world.
Operator: As a reminder, to ask the question, please press Star 1-1 on your telephone and wait for your name to be announced. To withdraw your question, please press Star 1-1 again. Please stand by while we compile the Q&A roster. Our first question comes from Phil Nato with Cohen. Your line is now open. Good morning, thanks for taking our questions.
don't trend it in a linear fashion. So that certainly goes for revenues and it early on and it also goes for the script. So whether it'll be 80 per quarter and the like, almost for sure or not, it will continue. That will also be lumpy. But as Jennifer said, we remain incredibly encouraged by the strength of the man here. And the one of the people I refer you to, which she, Jennifer highlighted, was the 22% of physicians who were not engaged with
Philip M. Nadeau: Good morning, thanks for taking our questions, and congratulations on a successful quarter. The first question is on the BBS launch. The pace at which you're adding prescriptions is impressive; with 200 at year end and adding 80 a quarter, the simple math would say you'd be over 500 by the end of 2023, which is the vast majority of people who are in the BBS registry. Can you tell me whether you're adding new patients to the prescriptions, or are you giving patients prescriptions who are not currently in the registry? Can you talk about new patient identification more broadly? Is it possible for this rate of prescriptions to continue even beyond?
to release results from all the gene types in the study, or will it be...
a snapshot as to the most mature data that you have at that time? Probably a blend of that answer in the sense that, as you know, remember we start off looking at 30 genes and then during the course of the trial, we amended that based on some early results of a gene not being so interesting and also some of the genes were just so rare that we really couldn't enroll them, so we stopped looking.
Jennifer L. Chien: Which other question? So you asked about the Cribs Registry. And one, we have great relationships with the folks at the Marshall Clinic. They are incredibly dedicated to the BBS patients and their care. When we think about the CRIPS registry, however, there are privacy policies in place. So, at this point, we really don't have any visibility in terms of the OECDGRES registry. overlap of the patients that are in the registry versus the patients and the ATP that we have within our view at Rhythm. So that's one piece.
Jennifer L. Chien: To your point in terms of prescriptions, I will say that we've been very happy with the level of demand for this product. It speaks to the need and the differential impact in terms of hyperfasia on the patient population for them to be seeking treatment, not only for their obesity but the underlying hyperfasia itself. And so we are very much focused on full through of opportunities. There still remains opportunities in terms of the positions that we already have identified with patients that they are treating with BBS and pulling through those patients onto therapy through our interactions and education efforts.
the expectation that'll be probably on the order of five plus or minus maybe as much as ten, but that's going to be the kind of data and the focus you'll hear. That's very helpful. Thanks again for taking our questions.
Please stand by for our next question. Our next question comes from Derek or Chila with Wells Fargo. Your line is now open. Good morning everyone and thanks.
for taking the questions, congrats on all the progress here. Just a couple of questions from us. I guess 81st as we are now in 2023, just any commentary on more recent trends for scripts and particularly around BBS patients. And is there any seasonality as we should think about this first quarter?
Jennifer L. Chien: And to your point, we continue to be ultra-focused in terms of identifying additional patients to add to our view. These include patients that are already diagnosed with me. that are lost in the system. And we have different mechanisms that we're going about in terms of finding those patients, as well as educating potential patients out there, as well as ACPs, on the differential diagnosis of BDS, so that we can get an exudite additional patients to get to a proper diagnosis. So there just remains a lot of opportunity out there.
you know, relative to the rest of the year. And then second question is given that you have 100 reimbursed scripts, I guess, you know, simple math, is that kind of imply like a 30 million, you know, kind of annual rate here in terms of all those patients stay on therapy. And I guess if that's true, I guess how does that, you know, you know, impact your thinking on where current consensus is, which is like 35 to 66 million for 2023. Thanks.
I'll have it. Thanks, Jack. Thanks, Jack. So what we'll do is I'll let Hunter take the consensus question just to. Yeah, I don't think we want to get into the this of commenting on consensus. It's inconsistent with our not giving guidance. Having said that spread is spread is quite wide and we expect as we as we continue to as we continue to execute I do expect the range of estimates to narrow.
Jennifer L. Chien: And is there any sense? Any sense internally, whether what we saw in the second half of last year was Ebola, or do you think that rate of prescriptions could continue actually through 2023 given its impressive rate?
Jennifer L. Chien: I mean, I would say that there is certainly an upsurge in demand, you know, for any disease area where there's no therapy that's available for years and years and years, when something becomes available, it's quite interesting for a patient who is really trying to find a therapeutic option. We also had about 20 clinical trial patients that were converted to commercial scripts, but that was born in Q3. But with that said, I think, you know, the growth that we saw in Q4 was quite exciting for us.
So what is interesting is for this particular therapy, oftentimes those family gatherings are surrounded by food. And it's also a potential opportunity as you know, token are out of school for patients who...
Jennifer L. Chien: And as we moved forward, we just continued conviction about the needs, and once again, our focus is just around getting those patients to a quicker diagnosis, as the journey, the diagnostic journey, oftentimes, is so long for these patients.
He initiated on therapy during a period where they are on break. And so we just see some of that happening as well, or heard some of those parents who wanted to actually initiate therapy during this time, that may happen a downtime in other areas.
David P. Meeker: So, Phil, just to reinforce a couple things that Jennifer said there, I want to remind you one of our common themes, again, the rare disease world doesn't trend in a linear fashion, so that certainly goes for revenues in it early on, and it also goes for the script. So whether it'll be 80 per quarter and the like, almost for sure or not, it will continue, that will also be lumpy.
David P. Meeker: But, as Jennifer said, we remain incredibly encouraged by the strength and demand here, and one of the pieces I'll refer you to, which she highlighted, was the 22% of physicians who were not engaged with who were writing. These are, you know, patients who are not on our radar. So back to the different ways patients are coming into the system, you know, A, we may find them, or B, they may find us. So, again, a lot of convictions.
I know you guys are prepping for launch, so maybe you can kind of discuss what you're doing there. And then I think you said there's 1,500 BBS patients that are identified in Europe . I guess how many of those are in Germany?
Yeah, I'll take that. Sure. So I will not miss the exact number because first we don't know it exactly, but of course it's a significant portion of it. And as often in Europe , I would say that these patients are...
Philip M. Nadeau: That's very helpful. And one last question on the pipeline. On the daybreak data that we're going to get in the second half of the year, Do you think you'll be in a position to release results from all the gene types in the study or will it be a snapshot as to the most mature data that you have at that Probably a blend of that answer in the sense that, as you know, remember we start off, you know, we're looking at 30 genes, and then during the course of the trial, we amended that based on some early results of a genes not being so interesting, and also some of the genes were just so rare that we really couldn't enroll them, so we stopped looking for them, which doesn't mean they're not out there, it's just that they'll not be part of daybreak.
localized in centers of excellence. So many centers with a lot of patients in each. Thank you very much. I think, yeah, I mean, we're optimists about Germany and I probably sleep.
I think just to reinforce Hunter's comments, part of our goal in trying to give you a little more insight in terms of the breakdown between US and Europe is, as we learn and we try to help you understand how Europe evolves, is you do a tremendous amount of groundwork to get through the market access, get pricing established and the like. You have the advantage of better organized patient communities and centers of excellence, if you will.
Philip M. Nadeau: So we'll try to give you a sense of the larger landscape and how we narrowed it down, but the area of interest will be those genes for which, focused down on, we're able to enroll enough patients to draw some conclusions, which will be a number much smaller than 30. That's the expectation that it'll probably be on the order of five plus or minus, maybe as much as 10. But that's going to be the kind of data and the focus still here. That's very helpful. Thanks again for taking our question. Thank you.
But there is this steady gradual startup. So it's not a world where you tend to get a large bolus and you have a very big quarter. We expect this to build very steadily over time and Germany leading us as we get approval for BPS here.
steady gradual startup. So it's not a world where you tend to get a large bolus and you have a very big quarter. We expect this to build very steadily over time with Germany leading us as we get approval for BPS here. Got it. Cool.
Thank you, Tara. Please stand by for our next question. Our next question comes from Corinne Jenkins with Goldman Sachs. Your line is now open. Good morning, everyone. You mentioned this earlier, but can you just expand on the degree of white space that remains among those 125 current prescribers from every baseline?
Operator: Please stand by for our next question. Our next question comes from Derek Archela with Wells Fargo. Your line is now open. Hey, good morning.
Derek Christian Archila: Hey, good morning everyone, and thanks for taking the questions. Congratulations on all the progress here.
Derek Christian Archila: Just a couple of questions from us. I guess, first, as we are now in 2023, maybe just any commentary on recent trends for scripts and particularly around, you know, BBS patients. And is there any seasonality, as we should think about, you know, kind of this, you know, first quarter, you know, relative to the rest of the year? And then second question, you know, given that you have 100 reimbursed.
Maybe the additional patients are under their care and might be appropriate for the drug. So Jennifer, so the 125 physicians who written prescription, how many do you think are holding other patients that they may be acting on or going to be acting on?
So, of the subscribers, I would say approximately a quarter of them or so have written, sorry, around 20% or so that have written more than one script. So, we...
Hunter C. Smith: scripts, I guess, you know, simple math, does that kind of imply like a 30 million, you know, kind of annual rate here in terms of if all those patients stay on therapy? And I guess if that's true, how does that impact your thinking on where the current consensus is, which is like 35 to 66 million for 2023. Thanks. I'll have it, thanks Derek, thanks, so what we'll do is I'll let Hunter take the consensus question. Yeah, I don't think we want to get into the business of commenting on consensus.
You have already positioned to have written more than once for within the area of rare disease. I would say that you know a lot of physicians only have one patient so it's not as normal that it would only have one patient at this point in time.
But there's still, once again, remains opportunity within other physicians who have yet to prescribe for various different reasons, just in terms of going through and, once again, identifying additional physicians who have patients as well.
Okay. And then maybe on the, is it Genvento acquisition? Should we expect that asset to be developed in a distinct mechanism of action, or are you looking to develop more of like a best in class against what are some of the known targets in that disease?
Hunter C. Smith: It's inconsistent with our not giving guidance. Having said that, the spread is quite wide, and we expect, as we continue to..., as we continue to execute, I do expect the range of estimates to narrow. Jennifer, several questions there, one on just the overall trend again in seasonality, quarter on quarter in a rare disease world, this one specifically.
Yeah, I think we'll, I could send that, we have said an appress release when I commented and we'll provide an in-depth greater in-depth presentation of where that program is and what we're going after. So we're not going to reveal the target today, but I will say, and I'm going to say a little bit, just great if you will here.
Jennifer L. Chien: Just speaking to seasonality, I think it's not unusual for the fourth quarter to potentially be light. If there are, you know, November holidays as well as, you know, seasonal holidays in general. What is interesting is that for this particular therapy, sometimes those family gatherings are surrounded by food. And it's also a potential opportunity.
The biology was incredibly compelling. Why was this a good opportunity for us? As with all things, you start with, is there an unmet medical need? Is the biology and the approach to the problem, does it make sense? Is the progress that they've made sufficient to give you confidence that you could have a reasonable probability of success here? Genvento checked all three of those boxes.
Jennifer L. Chien: as, you know, children are out of school, so patients can be initiated on therapy during a period where, you know, they are on break. And so, you know, we did see some of that happening as well or heard some of the parents who wanted to actually initiate therapy during this time that may have been a downtime in other areas. But with that said, I don't think that there's going to be much, like, seasonality. I think it's really more based in terms of the physician, when they see the patients, and, you know, getting through the reimbursement process to then be able to initiate therapy. So it's an ongoing process there.
You know, it's a competitive area and I think that speaks to the unmet medical need and we've been entering into this blindly and we entered it and it was a full recognition of what else is out there and how this approach might compete and we feel really good about that.
We know it's a competitive area and I think that speaks to the unmet medical need and we didn't enter into this blindly. We entered it with a full recognition of what else is out there and how this approach might compete and we feel really good about that. I apologize for leaving it there for the moment.
Okay, thank you. Please stand by for our next question. Our next question comes from Daegan Ha with CIFIL. Your line is now open. Great. Good morning. Thanks for taking my questions and congrats on the progress. One question on the BBS launch, just going back to the sequential announcement, I believe the first six weeks you have 50 prescriptions followed by 120 in the third quarter and then 200.13
Derek Christian Archila: Got it. That's good. If you have a question, Derek.
Yann Mazabraud: Yes, no, that's very helpful. And then just on Germany, I know you guys are ready for launch, and maybe you can kind of discuss what you're doing there. And then I think you said there are 1,500 BBS patients that are identified in Europe. I guess, how many of those are in Germany? John. That's sure.
in fourth quarter. So can you maybe walk us back to that initial six weeks, that 50 within six weeks seems to be fairly robust there? What happened there, and is there any chance that we could see another kind of picture like that emerge in 2023 at some point, or should we expect?
David P. Meeker: So I will not maybe give the exact number because first we don't know it exactly, but of course it's a significant portion of it. And as often in Europe, I would say that these patients are localized in centers of excellence, so many centers with a lot of patients in each. Thank you very much. Okay, I think, yeah, I mean, we're optimistic about Germany and a, And I think just to reinforce, Hunter's comments, you know, part of our goal in trying to give you a little more insight in terms of the breakdown between U.S. and Europe is, you know, as we learn and we try to help you understand how Europe evolves, as you do a tremendous amount of groundwork to get through the market access, get pricing established and the like.
kind of going back to Phil's point another 70 to 80 per quarter. And then question on this event, I realize a lot of details are under wraps at this point, but just looking at the board composition, it does seem fairly like it might be more ASO oriented. Am I on the right track? There is a more small molecule or even injectable biologic.
Any kind of insights that would be helpful. Thanks so much. Yeah, good. Jennifer, do you want to take the... Sure. You were asking about the number of scripts from the first couple of weeks. So I think that...
David P. Meeker: You have the advantage of better organized patient communities and centers of excellence, if you will. But there is this steady, gradual startup, so it's not a world where you tend to get a large bolus and you have a very big quarter. We expect this to build very steadily over time with Germany leading the way when we get approval for BPS here.
definitely because of that anticipated demand that patients were waiting to get osteotherapy. Also a reminder just in terms of we had patients already ready that were part of our global study that we were converting into commercial seedlast very important new
Operator: Please stand by for our next question. Our next question comes from Corinne Jenkins with Goldman Sachs. Your line is now open.
So that's part of the explanation in terms of the number of scripts that we received quite early on. But moving forward I think it's always a bit difficult to project but I will outline that we still have quite an opportunity just in terms of as we move forward. The script that we've received that we are still working through.
Corinne Jenkins: Yeah, good morning, everyone. You mentioned this earlier, but can you just expand on the degree of white space that remains among those 125 current prescribers for insulin based on the possibility that additional patients are under their care and might be appropriate for the drug?
Jennifer L. Chien: Yeah, so Jennifer Zillov, the 125 physicians with written prescriptions, how many do you think are holding other patients that they may be acting on or going to be acting on?
David P. Meeker: So of the subscribers, I would say approximately a quarter of them or so have written more than one script. Sorry, they're around 20% or so that have written more than one script. So we do already have physicians who have written more than one script. Within the area of rare diseases, I would say that, you know, a lot of physicians only have one patient. So it's not as normal that they would only have one patient at this point in time.
David P. Meeker: But there's still, once again, opportunities within other physicians who have yet to prescribe for very different reasons, just in terms of going through and, once again, identifying additional physicians to have patients as well. Okay, and then maybe on the GenVento acquisition. Should we expect that asset to be developed with a distinct mechanism of action, or are you looking to develop something more like a best in class strong against what are some of the known targets in that disease?
have in the past outline if we have very targeted mechanisms with just one a time in terms of how we're going about our efforts there. And I think, you know, all the questions and they're your question of course sums specifically, which we totally are sympathetic to and we have the same questions as we seek to understand that but I understand this.
Corinne Jenkins: Yeah, I think we'll, like I said in our press release and I commented, we'll provide an in-depth, greater in-depth presentation of where that program is and what we're going after. So we're not going to reveal the target today, but I will say, and if you will, The biology was incredibly compelling, and you know, why was this a good opportunity for us? And, you know, like all things, you start with, is there an unmet medical need, and is the biology and the approach to the problem, does it make sense, and is the progress that they've made sufficient to give you confidence that you could, you know, have a reasonable probability of success here.
I think what's been incredibly reassuring about this opportunity in BDS is that as we've now gone deeper into the launch in the fourth quarter, I think is a good stand-alone quarter in that sense. The demand is clearly there. What we hoped is one is, yes, you continue to work to find more patients, which we're doing successfully. Second, as you build the system, you get...
more centers, more individual physicians who are writing prescription and taking an interest, you begin to build an ecosystem with those patients who are seeking care and or think they might have BBS, start to find us. And so that process will continue. And again, there's nothing about the BBS opportunity today.
Corinne Jenkins: And so, does Invento detect all three of those boxes? We know it's a competitive area, and I think that speaks to the unmet medical need, and we didn't enter into this blindly, and we entered into it with a full recognition of what else is out there and how this approach might compete, and we feel really good about that. Apologize for leaving it there.
Operator: Okay, thank you. Please stand by for a moment.
And then David, what about the, this inventor? If there's any, oh sorry. Yeah, yeah. Oh, sorry. Yeah. Yeah. And again, as I said to Corinne, I apologize for not being more specific so we're not we're not going to reveal the modality that we're chasing. Just remind me again, I think the unmet need here, there's a tolerability issue with the current standard of care, there's some safety.
Operator: Please stand by for our next question. Our next question comes from Daegon Ha with Steeful. Your line is now open.
Dae Gon Ha: Great, good morning. Thanks for taking my questions and congrats on the progress. One question on the BBS launch, just going back to the sequential announcement, I believe, the first six weeks, you have 50 prescriptions followed by 120 in the third quarter and then 200 in the fourth quarter. So can you maybe walk us back to that initial six weeks? That 50 within six weeks seems to be fairly robust. bus there. What happened there?
issues related to the current standard of care, and then we think there's suboptimal efficacy. And so this solution, we would hope would address all three of those. But again, stay tuned on the exact modality of targets.
issues related to the current standard of care and then we think there's suboptimal efficacy. And so this solution we would hope would address all three of those. But again, stay tuned on the exact modality and target. Great, thanks so much.
Please stand by for our next question. Our next question comes from Whitney Ajim with Canacord. Your line is now open. Hey guys, good morning. Excuse me. Another kind of, I guess, type runway questions for you on scripts. Are any early color on compliance rate or refill rate, just as we think about that new prescription number you're giving versus kind of total prescription.
Jennifer L. Chien: And is there any chance that we could see another kind of picture like that emerge in 2023 at some point, or should we expect, kind of going back to Phil's point, another 70 to 80 per quarter? And then a question on Zinvento. I realize a lot of details are under wraps at this point, but just looking at the board composition, it does seem purely like it might be more ASO oriented. Am I on the right track there, or is it more small molecule or even injectable biologic? Any kind of insights or advice there would be helpful.
David P. Meeker: Thanks so much. Yep, got it. Jennifer, do you want to take the... Sure.
Jennifer L. Chien: Sure, so you were asking about the number of scripts in the first couple of weeks. So I think that's definitely because of some of that anticipated demand as patients were waiting to get osteotherapy. Also, a reminder just in terms of having patients already ready that were part of our local study that we were converting into commercial scripts. So that's part of the explanation in terms of the number of scripts that we received quite early on.
leads to a higher participants as well as the compliance rate. So when you think about our patient population, the hypervagia here is a key factor. It's something that just impacts them, like really day to day, hour to hour. And it's feeling a lift.
Jennifer L. Chien: But moving forward, I think, you know, it's always a bit difficult to project, but I will outline that we still have quite an opportunity just in terms of, as we move forward, the script that we've received, that we are still working through the reimbursement process, getting those patients onto therapy. It's an area of focus. You know, continuing to educate the positions that do have BDS patients just around the need to treat the hypofasia and the early onset with targeted therapy.
Now that, or relief of that, it would suddenly, to the weight loss, is something that they can feel in terms of benefit of being on death. And so we have, you know, seen a very high cost price rate, even with a direct debt goal we present it.
And once again, it's due to the benefits that they receive. From a discontinuation of persistence rate, it is early days, but I will say that we are quite happy just in terms of what we have seen. There was a lot of education on both the ACP as well as the paper.
Jennifer L. Chien: And, you know, the third pillar is definitely to find additional patients, which I have outlined in the past. We have very targeted mechanisms at this point in time in terms of how we're going about our efforts there.
David P. Meeker: And I think, you know, all the questions, and DeGan, your question, of course, specifically, which we totally are sympathetic to, and we have the same questions as we seek to understand, better understand this opportunity. All rare diseases, most diseases, including rare diseases, have, you know, some front loading as they go through development. There are patients who are tracking this, expecting that moment of approval, and looking to go on. So there's always a bit of that front loading.
and we're very pleased with that.
Awesome. Thanks. And then, one on HO. Can you remind us, are there any patients in an ongoing long-term extension study from the Phase II, or is there any additional longer-term follow-up in HO that we should be thinking about either being collected or being presented in 2023? Nicole sees a hideaway.
David P. Meeker: I think what's been incredibly reassuring about this opportunity in BBS is that as we've now gone deeper into the launch, and the fourth quarter, I think, is a good standalone quarter in that sense. The demand is clearly there. And what we hoped is, you know, one is, yes, you continue to work to find more patients, which we're doing, and we're doing successfully. Second, as you build the system, meaning you get more centers, more individual physicians who are writing prescriptions and taking an interest, you begin to build an ecosystem with those patients who are seeking care and or think they might have BBS, start to find us.
Yeah, so 14 patients entered the long-term extension and yes, you should be paying attention to that goal, be to update that experience. Some of this later in the year. Um OK, could we, further? She's fast it.
I've got to find the meeting in the specific abstract submission, but that would be our goals to link it to that. But that's a very importantness with all of these. The original 12 to 16 weeks is a very short period of time and with everybody including regulators are looking for durability. And so we're looking forward to being able to update further experience.
specific abstract submission, but that would be our goals to link it to that. But that's a very importantness with all of these. The original 12 to 16 weeks is a very short period of time, and with everybody including regulators are looking for its durability. And so we're looking forward to being able to update further experience. Thanks so much. Thank you.
Please stand by for our next question. Our next question comes from Michael Higgins with Leidenberg. Your line is now open. Thanks, guys, for taking the question. And congrats on the quarter, including the ongoing launch. A couple questions for Jennifer, if I could. I believe in you.
David P. Meeker: And so that process will continue. And again, there's nothing about the BBS opportunity to date that changes our view that this isn't a very meaningful opportunity in ways to track some of the other well-established, well-known examples of rare disease success stories.
David P. Meeker: So we'll keep you updated and try to give you as much insight as we can, but we are learning with you. And then, David, what about the, uh, there's an inventor? Oh, sorry. Yeah, yeah, oh, sorry, yeah.
David P. Meeker: Yeah, and again, as I said to Karen, my apologies will not be more specific. So we're not going to reveal the modality that we're taking, just reminding you again of the unmet need here. There's a tolerability issue with the current standard of care. There are some safety, you know, issues related to the current standard of care, and then we think there's some optimal efficacy. And so this solution, we would hope would address all three of those. But I Again, stay tuned on the exact modality. Great. Thanks so much.
are ongoing in terms of our efforts to continue the education process, not giving up in terms of really seeking positive reimbursement. And I would say that through our education efforts, we get more and more coverage decisions made for and temporary as we move forward into...
You know, from lots through this first year through in terms of approval. There are certain opportunities that we have that are perhaps more low hanging. For example, for Medicaid programs, they have an EPSDP program that's available for, you know, more pediatric and adolescents, which is an opportunity for us to follow up in terms of...
Operator: Please stand by for our next question. Our next question comes from Whitney. I'm Jim with Canacord. Your line is now open. Hey guys, good morning.
Whitney Glad Ijem: Hey guys, good morning. Excuse me.
Jennifer L. Chien: Another kind of, I guess, type of runway question for you on scripts. Do you have any early color on compliance rate or refill rate, just as we think about that new prescription number you're giving versus kind of total prescription headed into 2023? So I've worked in several different rare diseases in the past, and one thing that was, you know, interesting to observe, maybe not so interesting, but if and when patients actually feel a difference while being on the drugs, that tended to lead to higher persistence as well as higher compliance rates. So when you think about our patient population, hyperphasia here is a key factor. It's something that just impacts them, like really day to day, hour to hour.
and there's no way to work that until statutes change and other companies are trying to get that change. But everything else, there's never a definitive no. And we've organized it in a way where we recognize at some point it's not being that easy. You're true, but.
But there's never no, you just keep working this system in a surprising way. Some of those no way opportunities become yet. And it opens up and that patient gets coverage. I appreciate that. Is this something that is in the single digit rate? Is this something that's really infrequent or is it something that's maybe kind of a 25, 50% of programs?
Jennifer L. Chien: And feeling a list of that or release of that, which then leads to weight loss, is something that they can feel in terms of the benefit of being on the job. And so we have, you know, seen a very high compliance rate, even with a daily indexing, because, once again, it's due to the benefits that they receive. From this continuation of the persistence rate, it is early days, but I will say that we are quite happy just in terms of what we have seen.
scenario, which once you lift that, release that lever, you've got another avenue of patients. So just trying to characterize the degree of this impact thing. Yeah, I would think, you know, as we've looked at this and Jennifer's team, I mean right now, and this is again a dynamic scenario, I would put on the order of 20% of the states would have that relatively harder.
Jennifer L. Chien: You know, there was a lot of education on both the ACP as well as the patient side around expectations that hang, as well as ongoing engagements with our customers so that we could get them through the titration process and maintain them on drugs.
David P. Meeker: So I would say that the discontinuation rate is quite low, and we're very pleased with that. Okay, thanks. And then, excuse me, one on H.O. Can you remind us, are there any patients in an ongoing long-term extension study from phase two, or is there any additional longer-term follow-up in H-O that we should be thinking about? either being collected or being presented in 2023. Yeah.
the state is still working through its response, but we've had patients through. And then there's a smaller segment that we still haven't put a patient in front of that state. And so they remain that. But it is a relatively small percentage of the states today, which again, I think is, as a starting point, six months in, from my view, pretty amazing.
David P. Meeker: Yeah, so 14 patients entered the long-term extension, and yes, you should be paying attention to that. Our goal will be to update that experience and some of this later in the year. Again, we have identified the meeting in the specific abstract submission, but that would be our goal to link it to that. But, no, that's very important.
I appreciate that. One last one if I could. How many prescriptions are coming in outside of VBS? It can include on label as well as off. You've got some great data and HO obviously. I'm curious if there's any prescriptions there that you're aware of. No, so none that we're aware of. Again, we have the phase three trial.
Whitney Glad Ijem: It's with all of these, you know, the original, 12 to 16 weeks is a very short period of time, and what everybody, including regulators, is looking for is durability, and so we're looking forward to being able to update further on further experience. Excellent. Thanks so much.
up and running, actively screening is indicated, so there's an opportunity for patients to engage there, but we don't have any insight into patients who may be quote, quote, see not labeled for age or today. For the other, again, you know, I wanna apologize, it's just the policy left our world, and again, we believe there is.
Operator: Please stand by for our next question. Our next question comes from Michael Higgins with Laydenberg. Your line is now open.
Well, you know, there's tens of patients today, and that's the world, particularly in the US. We'll see how Europe continues to open up, slightly different dynamic as Jan described, but that in the tens is what you should expect for policy and left bars. Appreciate the feedback. Thanks guys and congrats again. Please stand by for our next question.
Michael John Higgins: Thanks, guys, for taking the questions and congratulations on the quarter, including the ongoing launch. A couple questions for Jennifer, if I could. I believe in your remarks you noted that there are some state Medicaid programs that have decided they will not cover in Sivry at this point. Is that something that can be revisited within the next year? Thanks.
Our next question comes from Joseph Stringer with Needham. Your line is now open. Your line is now open.
Jennifer L. Chien: Yes, so to your point, yes, I did outline that there are certain states that we have patients already on the path. You know, we are very ongoing in terms of our effort to continue the education process, not giving up, in terms of really seeking positive reimbursement. And I would say that through our education efforts, we get more and more coverage decisions made for different patients as we move forward into, you know, from launch through this first year through, in terms of approval.
Hi, thanks for taking our question. Just going back to persistence rates for patients that have started on commercial drug and have discontinued. What are some of the main reasons that you're hearing for that? Is there any particular reason that stands out?
for the discount, any particular reason. Yeah, at this point in time, like, you know, there's a variety of different reasons that are more like onesies, twosies, honestly, at this point of time. It could be hyperpigmentation. It could be based off of sort of, you know, the kind of, you know, the kind of, you know,
Jennifer L. Chien: There are certain opportunities that we have that are perhaps more low-hanging, for example, for Medicaid programs. They have an EPSD-T program that's available for, you know, more pediatric patients and adolescents, which is an opportunity for us to follow up in terms of getting reimbursement. But once again, the follow-ups and, you know, efforts just in terms of opening up access state-by-state are ongoing.
lots of follow-up opportunities. What I do find interesting is there are several folks that discontinued for personal reasons that are opportunities for potential reinitiation of therapy moving forward. So our teams remain in contact with the patients even after discontinuation in case there is an interest.
David P. Meeker: And Michael, that's really a critical point in the sense that, aside from something like Medicare where there's a statute, and, you know, there's sort of no way to work that until the statute's changed, and other companies are trying to get that change. But everything else, there's sort of never a definitive no. And we've organized it in a way where we recognize at some point, it's not immediate or near term. But there's never a note.
in terms of reinitiating and we heard this also from several physicians as well, that there may be opportunity in the future for reinitiation. Just to provide a little more context, so it's an important issue, which obviously we follow closely. So the current discount rate is in the mid single digit percentage range and as Jennifer highlighted, what's really, I think been highly reassuring is that the percentage of patients that are ever at large, are using this in the modern use measure which I think is ab—
Michael John Higgins: You just keep working this system, and in a surprising way, some of those, gosh, no way opportunities become, yeah, and it opens up, and that patient gives cover. I appreciate that. Is this something that is in the single digit rate? Is this something that's really infrequent, or is it something that's maybe kind of a 25, 50% of programs, an area where once you lift that, release that lever, you've got another avenue of patients? So just trying to characterize the degree of this impact thing.
are stopping because of known side effect profiles. We characterize on the order of a third of that, if you will, plus minus. I think that speaks to the job that several, like 95 percent of these patients consent in to rhythm and tune. We as a company and that team has the opportunity to engage individually.
Jennifer L. Chien: Yeah, I would think, you know, as we've looked at the St. Jennifer's team, right now, and this is, again, a dynamic scenario, I would put on the order of 20% of the states would have that relatively harder line, and those are the ones where, you know, some of those patients will move on to PAP as we continue to fight that battle. But the vast majority, 80% are either in what we call the green category, and patients are moving through with an unimpeded path.
overall tolerability and persistence in general here. And then she said, you've got a handful of patients who are discontinuing for personal reasons, which are in a sense unrelated to the drug and the problem that happens in any of the two areas.
Great, thanks for taking our questions. As a reminder to ask a question, please press store 11 on your telephone. Please stand by for our next question.
Our next question comes from Jeff Hung with Morgan Stanley . Your line is now open.
Jennifer L. Chien: or in a mixed category where, you know, the state is still working through its response, but we've had patients through. And then there's a smaller segment that we still haven't put a patient in front of that state. And so they remember that.
Hi, this is Michael Ria at Onford Jeffhong. Thank you for taking our questions. First, regarding the 22 percent of prescribers that weren't called on by territory managers, were they in any particular region of the country? And what is rhythm learning from these interactions and how could that be applied to bring in additional prescribers? Thanks....
David P. Meeker: But it is a relatively small percentage of the states today, which again, I think is, as a starting point six months in, pretty amazing. I appreciate that. One last one, if I could. How many prescriptions are coming in outside of VBS? It can include on-label as well as off. You've got some great data in H.O., obviously. I'm curious if there's any prescriptions there that you're aware of. No, so none that we're aware of.
Yeah, we're actually very happy, you know, seeing this percentage just in terms of patients that are coming through, not directly, through the efforts of our surgery manager. I think it speaks to a couple of different things in terms of our more broader-based efforts, our non-personal promotion efforts, that
David P. Meeker: Again, we have the phase three trial up and running, actively screening as indicated, so there's an opportunity for patients to engage there, but we don't have any insight into patients who may be, quote, seeking off-label treatment for H.O. today. For the other, again, I won't apologize. It's just the Palm C. Leferr world. Again, we believe there are, you know, tens of patients today, and that's a world, particularly in the U.S. We'll see how Europe continues to open up, a slightly different dynamic, as Yon described, but that in the tens is what you should expect for policy and the left bar. I appreciate the feedback. Thanks, guys, and congrats again. Please, Sam.
get to a broader set of both patients out there as well as physicians, which may be why there could be more of a skew in terms of this physician population doing more towards like primary care physicians. But you know these patients are in the hands of so many different physicians that they go through their journey. So we have to be both targeted in our field efforts but also broad base in terms of outreach through other supportive mechanisms. Things that would go into that category of course also relate to our presence at conferences.
Operator: Please stand by for our next question. Thank you. Our next question comes from Joseph Strings with Needham. Your line is now open.
Joseph Robert Stringer: Hi, thanks for taking our question. Just going back to persistence rates, for patients that have started on a commercial drug and have discontinued, what are some of the main reasons that you're hearing for that? Is there any particular reason that stands out? or the discount, any particular reason?
Jennifer L. Chien: Yeah, at this point in time, like, you know, there's a variety of different reasons that are more like one-s-to-sies at this point in time. It could be hyperpigmentation, it could be based off of sort of loss to flow-up opportunities.
our diagnoses patients are well known, is it more the logistics of getting sites up and running? And finally, what would you see as the biggest hurdle for this study? Thanks so much. Yep, it is the logistics. I think I talked about it on some of the earlier calls. The trial network or infrastructure globally, US for sure as well as
Jennifer L. Chien: What I do find interesting is there are several that discontinued for personal reasons that are opportunities for potential reinitiation of therapy living forward. So our teams remain in contact with the patients even after discontinuation in case there is an interest in terms of re-initiating. And we've heard this also from several physicians as well, that there may be opportunities in the future for reinitiation.
challenge coming out of COVID and so a number of these sites have personnel challenges, study nurses getting things through, you know, for pure logistics as you noted. So that is the issue. The patient demand is there. Now patients are, you know, every site that we talk to, we signed up to be part of this trial was enthusiastic and has a surprising number of patients relative to my experience at other trials to be serious. So that would be it. And then your question was anything that could make it go faster, it's shifting. So we get them set up, you know, we'll highlight to sites as we have already that we expect the enrollment to be competitive and that.
David P. Meeker: Just to provide a little more context, so the current discount rate is in the mid-single-digit percentage range, and as Jennifer highlighted, what's really, I think, been highly reassuring is that the percentage of patients that are stopping because of known side effects profiles is characterized on the order of, you know, a third of that, if you will, plus minus.
David P. Meeker: And so I think that speaks to the job that, um, several 95% of these patients consent to rhythm and tune. So we as a company and that team have the opportunity to engage individually. And there's a high level of touch there.
Joseph Robert Stringer: And that's incredibly valuable as people both get expectations set in a way, look, you're gonna experience nausea and potentially vomiting in the early phase, but it'll end. And you can walk patients through it, and that's working. So we feel really good about the overall intolerability and persistence in general here. And then, you know, she said you've got a handful of patients who are discontinuing for personal reasons, which are, in a sense, unrelated to the drug and a problem. That happens in any disease here. Great, thanks for taking our questions.
Again, we've remained incredibly encouraged by our initial experience on BBS. The R&D programs are up and running now and executing, so I feel good about that area. And I'm excited about a new opportunity, expanded opportunity to live in with Invento and look forward to updating on that. With that, we'll sign off. Thanks again.
This concludes today's conference call. Thank you for participating. You may now disconnect. The conference will begin shortly. To raise and lower your hand during Q&A, you can dial Star 11.
Operator: As a reminder to ask a question, please press Star 1-1 on your telephone. Please stand by for our next question. Our next question comes from Jeff Hung with Morgan Stanley. Your line is now open.
Michael Reid: Hi, this is Michael Riyad speaking on behalf of Jeff Hung. Thank you for taking our questions. First, regarding the 22% of prescribers that weren't called on by a territory manager, were they in any particular region of the country? And what is rhythm learning from these interactions, and how could that be applied to bring in additional prescribers?
Jennifer L. Chien: Yeah, we're actually very happy, you know, seeing this percentage just in terms of patients that are coming through, not directly through the efforts of our surgery manager. I think this speaks to a couple of different things in terms of our more broader-based efforts, our non-personal promotion efforts, that get to a broader set of those patients out there as well as physicians, which may be wide. There could be more of a skew in terms of this physician population going more towards, like, primary care physicians.
I.
Jennifer L. Chien: But, you know, these patients are in the hands of so many different physicians as they go through their journey, so we have to be both targeted in our field effort but also broad-based in terms of outreach through other supportive mechanisms. Things that would fall into that category, of course, also relate to who are present at conferences, our ongoing, you know, dialogue and relationship with the BBS Foundation, and such. But I would say that, you know, if there's a motivated physician who is willing to prescribe, this is a drug that can be prescribed and managed by, you know, a very different specialty background. So we continue our education efforts with each physician who has an interest and who has put in a prescription.
Michael Reid: Okay, thanks. And maybe a second follow-up.
David P. Meeker: For phase three in hyposlamic obesity, what factors would push enrollment closer to the 12-month mark, given patients are diagnosed and patients are well known? Is it more the logistics of getting sites up and running? And finally, what would you see as the biggest hurdle for this study? Thanks so much.
David P. Meeker: Yeah, it is the logistics. I think I could talk about it on some of the earlier calls. The trial network or infrastructure globally, the U.S. for sure, as well, is challenged coming out of COVID, and so a number of these sites have personnel challenges in terms of study nurses, getting things through, for pure logistics, as you noted. So that is the issue. The patient demand is there. Patients are, you know, every site that we talk to who's signed up to be part of this trial is enthusiastic and has a surprising number of patients relative to my experience in other trials in the DGD area. That would be it. And then your question was, was there anything that could make it go faster? It's sifting through.
Operator: As soon as we can get them set up, you know, we'll highlight to sites, as we have already, that we expect enrollment to be competitive, and that could be a useful dynamic because sites have a number of patients who may want to participate, and they'll be, hopefully, pushing together, limited only by maybe their study nurses' ability to process them also.
David P. Meeker: I show no for. I have no further questions at this time. I would now like to turn the conference back to David Meeker for closing remarks.
David P. Meeker: Great, well, thanks everyone for tuning in. As you know, you've been incredibly encouraged by our initial experience on BBS. The R&D programs are up and running now and executing, so that feels good about that area, and I'm excited about a new opportunity, an expanded opportunity to work with them on CINVento, and look forward to updating on that. So that will sign up.
Operator: This concludes today's conference call. Thank you for participating. You may now disconnect. The conference will begin shortly. To raise and lower your hand during TUNA, you can dial star 1-1. Thank you.
Operator: This concludes today's conference call. Thank you for participating. You may now disconnect. The conference will begin shortly. To raise and lower your hand during TUNA, you can dial star 1-1.
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Operator: Thank you. I'm going to be able to be.
Operator: Thank you. Thank you. Thank you. Thank you. Theeerner