Q4 2024 Scholar Rock Holding Corp Earnings Call
The opportunity to ask questions.
A question you May Press Star then one on your Touchtone phone to withdraw your question. Please press Star one again. Please note. This event is being recorded before we begin I'd like to point out that would be making various statements about scholar rock's expectations plans and prospects that constitute forward looking statements for the purposes of the safe Harbor provisions under the private Securities Litigation Reform Act of 90.
95, any forward looking statements represent our views only as of today and should not be relied upon as representing our views as of any future date I encourage you to go to the investors and media section of our website to find our most up to date FCC statements and filings a recording of today's event will also be available on our website should you want to rewatch at a later date.
Speaker Change: I will now turn the conference over to Jay Backstrom, President and CEO of scholar Rock Jae. Please go ahead.
Jay Backstrom: Well. Thank you operator, good morning, and welcome everyone and thank you for joining our fourth quarter 2024 business something we had an outstanding year in 2024, and we're off to a great start to 2020.
Forward looking statements for the purposes of the Safe Harbor provisions under the private Securities Litigation Reform Act of 1995 any forward looking statements represent our views only as of today it should not be relied upon as representing our views as of any future date I encourage you to go to the investors and media section of our web site to site, our most up to date SEC statements.
Jay Backstrom: For today's call I'll start by providing a review of the staff our results and our progress toward our regulatory milestones.
Speaker Change: <unk>, our chief commercial officer will share the terrific progress, we're making with our commercial preparation and our planning for 2025 launch because we're working with a sense of urgency to serve those living with SMA globally, starting with the U S. And then I'll follow with a review of our innovative <unk> platform.
Speaker Change: A recording of today's event will also be available on our website should you want to rewatch. It at a later date I will now turn the conference over to Jay Backstrom, President and CEO of scholar Rock Jae. Please go ahead.
Jay Backstrom: And our ambition to transform the current <unk> treatment paradigm for weight management.
Jay Backstrom: Well. Thank you operator, good morning, and welcome everyone and thank you for joining our fourth quarter 2020 for a business update.
Speaker Change: Following our prepared remarks, Tracy I'll be joined by Ted Myles, Chief operating Officer, and Chief Financial Officer, and Mark <unk>, Our Chief Scientific officer, the Q&A portion of today's call.
Jay Backstrom: And an outstanding year in 2024, and we're off to a great start to 2025.
Jay Backstrom: Moving to slide four.
Jay Backstrom: For today's call I'll start by providing a review of the SAP, our results and our progress toward our regulatory milestones Christine Sacco, our chief commercial officer will share the terrific progress, we're making with our commercial preparation and our planning for 2025 launch because we're working with a sense of urgency to serve those living with SMA globally, starting with the U S.
Jay Backstrom: With our success in 2020 for the stage is set but won't be a transformative year for scholar rock.
Jay Backstrom: And as I've said, we are working with a sense of urgency to bring the pilgrim after those living with SMA and we continue to hit our milestones on time or ahead of schedule.
Jay Backstrom: Starting with our regulatory applications for <unk>, we submitted the BLA in the U S. In January and we remain on track to submit the MAA in the EU in March we look forward to sharing the sapphire data at the muscular Dystrophy Association annual meeting in Dallas on March 19.
Jay Backstrom: And then I'll follow with a review of our innovative Myostatin platform.
Jay Backstrom: Our ambition to transform the current U L. P. One treatment paradigm for weight management.
Speaker Change: Following our prepared remarks, Tracy and I'll be joined by Ted Myles, Our Chief operating officer, and Chief Financial Officer.
Jay Backstrom: It will feature as an oral presentation. We will also be sharing our work with the murine version of the Kitimat in a non clinical model of DMD setting the stage for us to expand the development of a pedigree man into other neuromuscular indications.
Mark: Mark <unk>, our Chief Scientific officer, the Q&A portion of today's call.
Speaker Change: Moving to slide four.
Speaker Change: With our success in 2020 for the stage is set it won't be a transformative year for scholar rock.
And as I've said, we are working with a sense of urgency to bring <unk> integral map to those living with SMA and we continue to hit our milestones on time or ahead of schedule.
Jay Backstrom: We continue to make progress on our goal to expand treatment to even the youngest of those with SMA and we are on track to open the Opal study for those under two years of age in the third quarter.
Speaker Change: Starting with our regulatory applications for <unk> in SMA, we submitted the BLA in the U S. In January and we remain on track to submit the MAA in the EU March we look forward to sharing the sapphire data at the muscular Dystrophy Association annual meeting in Dallas on March 19.
Jay Backstrom: For our cardio metabolic program, we remain on track.
Jay Backstrom: To share the topline data from membrane in Q2 with the filing of the IND breast RK 43, nine are highly selective anti myostatin designed for cardio metabolic indications in the third quarter.
Speaker Change: Feature as an oral presentation, we will also be sharing our work with the European version of the Kitimat in a non clinical model of DMD setting the stage for us to expand the development of the pilgrim hat into other neuromuscular indications.
Jay Backstrom: Turning to slide five.
Speaker Change: Before I hand over to Tracy I want to review the positive topline results for staff on a registration study with the picker, Matt the only muscle targeted therapy with clinical success and a pivotal study in SMA, which has the potential to transform the standard of care.
Speaker Change: We also continue to make progress on our goal to expand treatment to even the youngest of those with SMA. We're on track to open the Opal study for those under two years of age in the third quarter.
Speaker Change: Ah Pinegar map the standard of care delivered gains of one eight point improvement compared to placebo plus standard of care.
Speaker Change: As measured by the gold standard SMA specific Hammersmith functional motor scale at week 52.
Speaker Change: For our cardio metabolic program, we remain on track.
Speaker Change: Sure the topline data from embraced in Q2 with the filing of the IND deep breaths RK for three nine are highly selective anti myostatin designed for cardio metabolic indications in the third quarter.
Speaker Change: <unk>, who are both clinically meaningful and statistically significant.
Speaker Change: Importantly, there was consistency across age groups two through 'twenty, one and a broad SMA population in.
Speaker Change: In addition, 30% achieved an additional three point or greater improvement in their Hammersmith scores when compared to placebo plus an SMN therapy. We're only 12, 5% achieved the same high bar.
Speaker Change: Turning to slide five.
Speaker Change: Before I hand over to Tracy I want to review the positive topline results for staff on a registration study with the pitaka, Matt the only muscle targeted therapy with clinical success pivotal study in SMA, which has the potential to transform the standard of care.
Speaker Change: Further as shown in the graph displaying motor function over the 52 week treatment period, those receiving a pittard remap achieved a gain and function while those receiving an estimate therapy alone lost function over this 52 week period.
Speaker Change: Ah Pinegar map the standard of care delivered gains of one eight point improvement compared to placebo plus standard of care as measured by the gold standard SMA specific Hammersmith functional motor scale at week 52 <unk>.
Speaker Change: With respect to safety the safety was consistent with the topaz data with over 95% rolling over and remaining in the long term follow up study, adding to our experienced in over 200 patients and we remain the only muscle targeted therapy that has over four years of clinical experience in SMA.
Speaker Change: Gains were both clinically meaningful and statistically significant.
Accordingly, there was consistency across age groups 2021 and abroad SMA population in.
Speaker Change: In addition, 30% achieved an additional three point or greater improvement in their Hammersmith scores when compared to placebo plus an SMA therapy. We're only 12, 5% achieved the same high bar.
Speaker Change: Together the data support an overall favorable benefit risk with the potential to shift the treatment paradigm and usher in a new standard of care to include a peterka man a muscle targeted therapy with an SMN directed therapy as part of the treatment regimen for ethylene.
Speaker Change: Further as shown in the graph displaying motor function over the 52 week treatment period, those receiving a <unk> achieved a gain in March while those receiving an estimate therapy alone lost function over this 52 week period.
Speaker Change: I will now turn the call over to Tracy, our Chief commercial officer to provide an update on our commercial preparations Tracy.
Speaker Change: With respect to safety the safety was consistent with the topaz data with over 95% rolling over and remaining in the long term follow up study, adding too are experiencing over 200 patients and we remain the only muscle targeted therapy that is <unk>.
Tracy: Thank you Jay moving to slide seven.
Tracy: Despite successes in treating the motor neuron over the past eight years progressive muscle weakness continues to be a critical unmet need in SMA and there are currently no approved muscle targeted therapy to treat muscle neuromuscular disease.
Speaker Change: As over four years of clinical experience.
Speaker Change: Yeah.
Speaker Change: Together the data support an overall favorable benefit risk with the potential to shift the treatment paradigm and usher in a new standard of care to include a peterka man a muscle targeted therapy with an SMN directed therapy as part of the treatment regimen for <unk>.
Tracy: Patients and caregivers have describe to us the debilitating impacts a progressive muscle weakness and how it significantly detract from their independence and their ability to perform basic daily activities like eating.
Tracy: That thing getting in and out of bed or their car.
Speaker Change: I will now turn the call over to Tracy, our Chief commercial officer to provide an update on our commercial preparations Tracy.
Tracy: Brushing teeth climbing stairs and using the bathroom.
Speaker Change: This is why 97% of patients surveyed by cure SMA identified improving muscle strength as an important means that they want to see from a new SME treatment.
Tracy: Thank you Jay moving to slide seven.
Speaker Change: Despite successes in treating the motor neuron over the past eight years progressive muscle weakness continues to be a critical unmet need in SMA and there are currently no approved muscle targeted therapy to treat this muscle neuromuscular disease pay.
Speaker Change: From our own market research, we know that more than 80% of treating neurologist agree that preserving muscle should start as early as possible in SMA. The.
Speaker Change: The SMA community is collectively calling for more to treat this relentless progression of muscle weakness and improve motor function in SMA.
Speaker Change: Patients and caregivers have describe to us the debilitating impact of progressive muscle weakness.
Speaker Change: And how it significantly detract from their independence and their ability to perform basic daily activities like eating dressing getting in and out of bed or their car.
Speaker Change: Next slide.
Speaker Change: Today, roughly two thirds of the 10000 people living with SMA in the U S and 35000 individuals globally have already received an SMN targeted therapy, yet we see from the data that Jay just presented that despite these effective therapies progressive muscle weakness still rubs these individuals' of their ability.
Speaker Change: <unk> teeth climbing stairs and using the bathroom.
Speaker Change: This is why 97% of patients surveyed by cure SMA identified improving muscle strength as an important need that they want to see from a new SME treatment.
Speaker Change: To function over time.
Speaker Change: This is like 74% of neurologists recognized that in the future a combination of modalities to target the motor neuron in the muscle will be necessary to treat SMA the.
Speaker Change: From our own market research, we know that more than 80% of treating neurologist agree that preserving muscle should start as early as possible in SMA.
Speaker Change: <unk> community is collectively calling for more to treat this relentless progression of muscle weakness and improve motor function in SMA.
Speaker Change: The future of SMA will be to directly treat both the muscle in the motor neurons to provide the best outcomes for patients.
Speaker Change: Our pedigree mab as a potential first approved muscle targeted therapy in SMA is leading the transformation of SME care.
Speaker Change: Next slide.
Speaker Change: Today, roughly two thirds of the 10000 people living with SMA in the U S and 35000 individuals globally have already received an SMN targeted therapy.
Speaker Change: Next slide.
Speaker Change: Scholar rock has been at the forefront of preparing the market for this potential new treatment paradigm in SMA.
Speaker Change: Yet we see from the data that Jay just presented that despite these effective therapy progressive muscle weakness still rubs. These individuals of their ability to function over time.
Speaker Change: Last year, we introduced the life takes muscle the first muscle focused SMA disease education campaign that amplifies, what we've been hearing from patients and caregivers for years about the devastating impact of progressive muscle progressive muscle weakness.
Speaker Change: This is like 74% of neurologists recognized that in the future a combination of modalities to target the motor neuron in the muscle will be necessary to treat SMA.
Speaker Change: Well it takes muscle has resonated with both the patient and HCP communities and lead to continued strong engagement with scholar rock.
Speaker Change: The future of SMA will be to directly treat both the muscle in the motor neuron to provide the best outcomes for patients.
Speaker Change: Additionally, our NFL team has also been meeting with leading cure SMA centers and engaging with top treating neurologists and care teams to educate on our phase III Sapphire topline data.
Speaker Change: <unk> as a potential first approved muscle targeted therapy in SMA is leading the transformation of SME Kerr next.
Speaker Change: Next slide.
Speaker Change: And Scott are continues to partner and learn from our patient advocacy partners, who have been so effective already in helping to bring new treatments to the SMA community.
Speaker Change: Scholar rock has been at the forefront of preparing the market for this potential new treatment paradigm in SMA.
Speaker Change: Last year, we introduced the life takes muscle the first muscle focused SMA disease education campaign that amplifies, what we've been hearing from patients and caregivers for years about the devastating impact of progressive progressive muscle weakness.
Speaker Change: Next slide.
We're doing all this with a team of experienced professionals with deep rare disease and launch experience, including prior SMA launch it and we're continuing to be a magnet to attract top commercial talent as we build out our team.
Speaker Change: It takes muscle has resonated with both the patient and HCP communities and lead to continued strong engagement with scholar rock.
Speaker Change: Next slide.
Speaker Change: 2025 is an important year for scholar rock and we are positioned for a successful launch will continue to build on our stakeholder engagement and education in this quarter have initiated outreach to top U S commercial and federal Payors ahead of our potential Q4 launch.
Speaker Change: Additionally, our NFL team has also been meeting with leading cure SMA centers and engaging with top treating neurologists and care teams to educate on our phase III Sapphire topline data.
Speaker Change: And Scott are continues to partner and learn from our patient advocacy partners, who have been so effective already in helping to bring new treatments to the SMA community.
Speaker Change: We will also be scaling our customer facing team of roughly 50 sales reimbursement and patient support personnel in late Q2, and early Q3 to be higher than on boarded ahead of our potential launch.
Speaker Change: Next slide.
Speaker Change: We're doing all this with a team of experienced professionals with deep rare disease launch experience, including prior SMA launches and we're continuing to be a magnet to attract top commercial talent as we build out our team.
Speaker Change: And finally scholar rock is building out our patient services offering and preparing to offer home infusion as an option at launch to provide excellent support and optionality to patients and traders alike.
Speaker Change: Next slide.
Speaker Change: 2025 is an important year for scholar rock and we are positioned for a successful launch will continue to build on our stakeholder engagement and education in this quarter have initiated outreach to top U S commercial and federal Payors ahead of our potential Q4 launch.
Speaker Change: We have been laying the groundwork for years and now we're putting the broader team and infrastructure in place for a successful U S launch to meet a critical need in the fight to continue to improve the lives of those living with SMA.
Jay Backstrom: I'll now turn the call back to Jay.
Speaker Change: We will also be scaling our customer facing team of roughly 50 sales reimbursement and patient support personnel in late Q2, and early Q3 to be higher than on boarded ahead of our potential launch.
Well, thank you Tracy and now turning to our cardio metabolic programs and moving to slide 13.
Jay Backstrom: It's impressive to see the impact of innovation from our industry and how the approved <unk> receptor agonists or transform the management of weight loss.
Speaker Change: And finally scholar rock is building out our patient services offering and preparing to offer home infusion as an option at launch to provide excellent support and optionality to patients and traders alike.
Jay Backstrom: Obesity is a top global public health issue and.
Jay Backstrom: And the potential public health impact of these highly effective weight loss therapies.
Jay Backstrom: Been incredible across a number of chronic conditions, including diabetes sleep apnea in cardiovascular disease.
Speaker Change: We have been laying the groundwork for years and now we're putting the broader team and infrastructure in place for successful U S launch to meet a critical need in the fight to continue to improve the lives of those living with SMA.
Jay Backstrom: With an estimated $40 million projected to receive treatment for opioid receptor items. The current market is anticipated to generate over 100 billion in sales.
Jay Backstrom: Moving to slide 14.
Jay Backstrom: I'll now turn the call back to Jay.
Jay Backstrom: With the extraordinary amount of weight loss seen with the current GOP. One receptor therapies. There is also a substantial amount of lean muscle that is also loss range from 12% to 40%.
Jay Backstrom: Well, thank you Tracy and now turning to our cardio metabolic programs and moving to slide 13.
Jay Backstrom: It's impressive to see the impact of innovation from our industry and how the approved <unk> receptor agonists or transform the management of wastewater.
Speaker Change: With the widespread use of these therapies. There is an increased awareness of the associated weakness and reduced strength that accompanies this loss of lean muscle ends at the end of the significant weight regained that occurs once stopping therapy with disproportionately more fat being regained in lean mass leading to a worst body composition and leading to angel.
Jay Backstrom: Obesity is a top global public health issue and.
Jay Backstrom: And the potential public health impact of these highly effective weight loss therapies.
Jay Backstrom: <unk> been incredible across a number of chronic conditions, including diabetes sleep apnea in cardiovascular.
<unk>.
Jay Backstrom: With an estimated $40 million projected to receive treatment GOP one receptor items. The current market is anticipated to generate over 100 billion sales.
Speaker Change: The on strength in mobility muscle as the main metabolic organ and plays a significant role in energy metabolism, increasing basal metabolic rate glucose uptake and improving insulin sensitivity.
Jay Backstrom: Moving to slide 14.
Jay Backstrom: With the extraordinary amount of weight loss seen with the current GOP. One receptor therapies. There is also a substantial amount of lean muscle that is also loss range from 12% to 40%.
Speaker Change: Given the critical role that muscle plays and overall, we believe our highly selective approach to blocking milestone when added to the GOP one receptor items can enhance.
Jay Backstrom: With the widespread use of these therapies. There is an increased awareness of the associated weakness and reduced strength that accompanies this loss of lean muscle lines and of the significant weight regained that occurs one stopping therapy with disproportionately more fat being regained that lean mass leading to a worst body composition and leading to an <unk>.
Speaker Change: Since their profile by reducing velocity muscle lines without introducing additional toxicity, leading to healthy and sustainable waste management.
Speaker Change: Moving to slide 15.
Speaker Change: To illustrate what can be expected from <unk>. This figures from the trees appetites for Mt. One study and illustrates the percent change in body weight over time.
Jay Backstrom: With me.
Gary: Gary shaded in Green represents the first two weeks of the study the time period corresponding to the efficacy assessment and embrace our randomized phase II proof of concept study with the reserve fund.
Jay Backstrom: Beyond strengthen mobility muscle as the main metabolic organ and plays a significant role in energy metabolism, increasing basal metabolic rate glucose uptake and improving insulin sensitivity.
Gary: As can be seen even by week 24, there is an impressive amount of weight loss of 14% to 60% of body weight. The continues to deepen over the course of 72 weeks.
Jay Backstrom: Given the critical role that muscle plays and overall, we believe our highly selective approach to blocking milestone when added to the GOP one receptor items can enhance their profile by reducing velocity muscle lines without introducing additional toxicity needs a healthy and sustainable weight management.
Gary: Approximately 25% of this weight losses lean that's an area that we believe we can address through our highly selective approach to blocking milestone the master regulator skeletal muscle by preserving lean mass and reducing the amount of lean muscle mass loss that can lead to healthier and sustainable weight loss and potentially change the treatment paradigm.
Jay Backstrom: Moving to slide 15.
Jay Backstrom: To illustrate what can be expected from <unk>. This figures from the <unk> appetite for Mt. One study and illustrates the percent change in body weight over time.
Gary: Weight loss management.
Jay Backstrom: Erie shaded in Green represents the first 20 weeks of the study the time period correspond to the efficacy assessment and embrace our randomized phase II proof of concept study with <unk> at that time.
Gary: Now moving to slide 16.
So, let's just preserving lean muscle mass mean with respect to clinical benefit and what amount is needed to have a meaningful impact.
Gary: What insights can be gained from our study of healthy young men, who were confined to strict bad risks for one week and lost about a kilogram of lean mass as assessed by nexis gains remarkably the loss of just one kilogram of lean mass resulted in significant decrease in leg strong exercise capacity and equally importantly in insulin sensitivity compared to base.
Jay Backstrom: As can be seen even by week 24, there is an impressive amount of weight loss of 14% to 60% of body weight. The continues to deepen over the course of 72 weeks.
Speaker Change: Approximately 25% of its weight losses Lima.
Speaker Change: Area that we believe we can address through our highly selective approach to blocking milestone the master regulator skeletal muscle by preserving lean mass and reducing the amount of lean muscle mass loss. It can lead to healthier and sustainable weight loss and potentially change the treatment paradigm for weight loss management.
Gary: One.
Gary: Considering that adults over 60 begin to lose 1% on lean mass per year with a 10% to 15% decrease in strength for decades, the additive effect of loss of lean mass associated with <unk> one receptor therapy in this age group and other subsets can be profile.
Speaker Change: Now moving to slide 16.
Speaker Change: So, let's just preserving lean muscle mass mean with respect to clinical benefit and what amount is needed to have a meaningful impact.
Gary: Now moving to slide 17.
Gary: With respect to embrace we had several key goals in mind, when we designed to embrace a randomized phase II proof of concept study comparing <unk> plus a pit or format such as appetite plus placebo.
Speaker Change: Insights can be gained from our study of healthy unmet they were confined to strict bed rest for one week and lost about a kilogram of lean mass as assessed by <unk> gains remarkably the loss of just one kilogram of lean mass resulted in a significant decrease in lifestyle exercise capacity and equally importantly, and insulin sensitivity compared to baseline.
Gary: For overweight adults first with respect to preserving lean muscle mass. We believe we can reduce the amount of loss as measured by debt to scans at week 24, with our highly selective approach to block my staff with.
Speaker Change: Considering that adults over 60 begin to lose 1% on lean mass per year with a 10% to 15% decrease in strength for decades.
Gary: We selected week 24, as the time points to assess since this was the steepest portion of the weight loss curve presented one recognizing that we'll need to assess the week 52 for us are capable of doing that program.
Speaker Change: Additive effect of loss of lean mass associated with GOP, one receptor therapy in this age group and other subsets can be profile.
Gary: As a proof of concept study, we're looking for trends in the magnitude of effect to help shape, our thinking regarding clinical meaningful improvement.
Speaker Change: Now moving to slide 17.
Speaker Change: With respect to embrace we had several key goals in mind, when we designed to embrace a randomized phase II proof of concept study comparing <unk> plus a picker, Matt such as hepatitis placebo. These are overweight adults first with respect to preserving lean muscle mass. We believe we can reduce the amount of loss as measured by <unk>.
Gary: <unk> learning from this study in young men, assuming a loss of lean mass between five four to five kilograms by reducing the amount of lean mass loss by 20% to 40%. We can preserve one to two kilograms of lean mass, which we believe will translate into clinical meaningful benefit since every kilogram of lean muscle mass mass.
<unk> scans at week 24, with our highly selective approach to blockbuster.
Gary: Second based on our selective approach one of our goals was to demonstrate that we can safely combined to us at the time and not introduce any.
Speaker Change: We selected week 24 at the time point to assess since this was the steepest portion of the weight loss curve zeppenfeld, recognizing that we will need to assess the week 52 for ISR Cape working on program.
Gary: Additive toxicity that can be associated with blocking other TGF beta ligand such as that.
Gary: Third with respect to weight loss at week 24, we are expecting to see comparable weight loss at this time.
Speaker Change: As a proof of concept study were looking for trends in the magnitude of effect to help shape, our thinking regarding clinical meaningful improvement.
Gary: Fourth based on our non clinical data. We believe we can blunt the thought regain associated with stopping tours episodes and a built in an additional <unk> scan performed eight weeks after stopping treatment to assess this important question.
Speaker Change: Extrapolating from the study in young men, assuming a loss of lean master from five four to five kilograms by reducing the amount of lean mass loss by 20% to 40%. We can preserve one to two kilograms of lean mass, which we believe will translate into clinical meaningful benefit since every kilogram of lean muscle mass mass.
Gary: These data will not be part of the topline results, we look forward to sharing next quarter.
Gary: This is a proof of concept study. We're also included exploratory endpoints such as hemoglobin <unk> C and functional measures, but we did not power or enrich the study with subsets of patients.
Speaker Change: Second based on our selective approach one of our goals was to demonstrate that we can safely combined tours at the time and not introduce any additive.
Speaker Change: Additive toxicities that can be associated with blocking other TGF beta ligand such as that.
Statistical significance or these explore Tony.
Gary: And then finally, an important key goal is for us to gain experience in the setting of obesity will have the opportunity for detailed review of all of the Embraer subject data to identify subgroups and to help inform the clinical development of SRP 439, or highly selective anti myostatin designed for cardio metabolic disorders, we've already shown our ability.
Speaker Change: Third with respect to weight loss a week 24, we are expecting to see comparable weight loss at this time.
Speaker Change: Fourth based on our non clinical data. We believe we can blunt. The fact regain associated with stopping tours episode and a built in an additional Dexter scan performed eight weeks after stopping treatment to assess this important question.
Gary: To deliver embrace ahead of schedule and this experience provides us with great momentum for SRP 439 program.
Speaker Change: These data will not be part of the topline results, we look forward to sharing next quarter.
Speaker Change: This is a proof of concept study. We're also included exploratory endpoints such as hemoglobin <unk> C and functional measures, but we did not power or enrich the study with subsets of patients.
Gary: Moving to slide 18, and with respect to SRP 4009, we're very excited with the data that's been generated to date in our non clinical program demonstrating we can preserve lean mass with further reduction Batman, we can improve the metabolic parameters such as blood glucose we've seen increase in lean mass gain once.
Speaker Change: Statistical significance or these explore Tony.
Speaker Change: And then finally, an important key goal is for us to gain experience in the setting of obesity. We will have the opportunity for detailed review of all of the embraced subject data to identify subgroups and to help inform the clinical development of Src or green on a highly selective anti myostatin designed for cardio metabolic disorders, we've already shown our ability.
Gary: The fat regain of fat mass after stopping the <unk> one receptor agonist therapy, and we've demonstrated greater potency and a direct comparison with Nancy <unk> animal.
Gary: Overall, the data suggests the best in class profile for SRP 4009, which has been featured at key scientific conferences in 2024, and we look forward to bringing <unk> to clinic later this year.
Speaker Change: To deliver embrace ahead of schedule and this experience provides us with great momentum for <unk>, 439%.
Speaker Change: Moving to slide 18, and with respect to SRP 4009, we're very excited with the data that's been generated to date in our non clinical program demonstrated we can preserve lean mass with further reduction Batman, we can improve the metabolic parameters such as blood glucose we've seen increase in lean mass gain one.
Gary: Moving to slide 19 in summary to address the important emerging problem with loss of lean mass associated weight loss weight loss therapies, we have taken a parallel path with our innovative industry, leading portfolio of highly selective anti myostatin therapies by conducting a proof of study proof of concept study with <unk> and <unk>.
Speaker Change: Fat regain of fat mass after stopping the <unk>, one receptor agonist therapy, and we've demonstrated greater potency and a direct comparison with Nancy <unk> animal.
Gary: <unk> and at the same time advancing <unk> hundred 90, <unk>, our highly selective novel anti Myostatin designed specifically for Marty cardio metabolic indications with the ambition to transform the currency <unk> one receptor agonist treatment there.
Speaker Change: Overall, the data suggests the best in class profile for SRP 439, which has been featured at key scientific conferences in 2024, and we look forward to bringing SRP 4900 clinic later this year.
Gary: This strategy has resulted in two important milestones in 2025, and we look forward to the readout of the topline data from embraced next quarter and the filing of the IND for US Okay $43 million in Q3.
Speaker Change: Moving to slide 19 in summer to address the important emerging problem with loss of lean mass associated weight loss weight loss therapies, we have taken a parallel path with our innovative industry, leading portfolio of highly selective anti myostatin therapies by conducting a proof of study proof of concept study with the telegraph and.
Gary: In closing and moving to slide 21.
Gary: 2025 will be a transformative year for scholar one we're off to a great start we have submitted the BLA for <unk> in the U S. In January we're on track to submit the MAA in the EU in March we were well on our way and our preparations to bring a pit agreement muscle targeted therapy.
Speaker Change: <unk> and at the same time advancing SRP 4900, <unk>, our highly selective novel anti Myostatin designed specifically for Marty cardio metabolic indications with the ambition to transform the currency <unk> one receptor agonist treatment there.
Gary: Central new treatment option for those living with SMA globally, starting in the U S. In Q4 with EU to fall in 2026, as we continue to work to expand our reach to the youngest of those with SMA and to other rare neuromuscular disorders.
Speaker Change: This strategy has resulted in two important milestones in 2025, and we look forward to the readout of the top line data from embrace next quarter and the filing of the IND for US Okay for three months in Q3.
Gary: We are on the threshold of establishing a neuromuscular franchise starting with SMA.
Speaker Change: In closing and moving to slide 21.
Gary: Look forward to reporting on our progress toward achieving our 2025 key milestones as we drive to commercialize and expand the development of a pit of reman and advance our cardio metabolic programs overall are very very exciting year for <unk>.
Speaker Change: 2025 will be a transformative year for scholar one we're off to a great start we've submitted the BLA for <unk> in the U S. In January we're on track to submit the MAA in the EU in March we were well on our way and our preparations to bring the <unk> muscle targeted therapy.
Gary: And operator that closes our prepared remarks, we'll now open up the call for questions.
Speaker Change: Thank you once again, ladies and gentlemen to ask a question or make a comment. Please press star one on your Touchtone phone to withdraw yourself from the queue. Please press star one again, we will pause for a moment, while we compile the Q&A roster.
Speaker Change: Central new treatment option for those living with SMA globally, starting in the U S. In Q4 with EU to follow in 2026, as we continue to work to expand our reach to the youngest of those with SMA and to other rare neuromuscular disorder. We are on the threshold of establishing a neuromuscular franchise starting with <unk>.
Allison <unk>: Our first question comes from Allison <unk> with Piper Sandler Your line is open.
Allison <unk>: Hi, good morning, guys and thanks for taking the questions.
Speaker Change: Maybe one on SMA, just with Sapphire data being presented next month at MDA can you just discuss your sense of what additional data points are going to be most meaningful to patients and docs. When you present that full data just maybe help frame that update for us and then one on obesity.
Speaker Change: That's it.
Speaker Change: We look forward to reporting on our progress toward achieving our 2025 key milestones as we drive the commercialized and expand the development of a pyramid and advance our cardio metabolic programs overall are very very exciting year for scholar.
Speaker Change: And operator that closes our prepared remarks, we'll now open up the call for questions.
Allison <unk>:
Allison <unk>: Just maybe help us understand what you need to see on the primary endpoint to be confident taken taking 4009 forward I think in the prepared remarks.
Speaker Change: Thank you once again, ladies and gentlemen to ask a question or make a comment. Please press star one on your Touchtone phone to withdraw yourself from the queue. Please press star one again, we will pause for a moment, while we compile the Q&A roster.
Allison <unk>: You discussed the 20% to 40% improvement in lean mass as being clinically meaningful just.
Allison <unk>: Did I hear that right and then you know what are you hoping to see an additional endpoints like everyone's seeing body composition.
Speaker Change: Our first question comes from Allison <unk> with Piper Sandler Your line is open.
Allison <unk>: Just curious to get your thoughts there. Thank you.
Allison: Hi, good morning, guys and thanks for taking the questions.
Allison <unk>: Yes, good Ela Hey, good morning. This is Jay so first starting with Sapphire, Yeah. We're really excited to have the opportunity for those data to be presented at a Congress and particularly the MBA conference where there is a lot of interest and a lot of investigators will have a chance to see the data beyond what we could share on the top line results.
Speaker Change: Maybe one on SMA, just with Sapphire data being presented next month at MDA can you just discuss your sense of what additional data points are going to be most meaningful to patients and docs. When you present that full data just maybe help frame that update for us and then one on obesity.
Allison <unk>: As we shared previously I think what's really important is the overall consistency and impacted the quality of the data. We've shared we've got effects across age groups and we're going to share additional endpoints and youll see that again I think there'll be interest in seeing the consistency and the impact we have across those additional endpoints. So I think that will.
Allison:
Allison: Just maybe help us understand what you need to see on the primary endpoint to be confident in taking 439 forward I think in the prepared remarks.
Allison: You discussed the 20% to 40% improvement lean mass as being clinically meaningful.
Allison: Did I hear that right and then what are you hoping to see an additional endpoints like ANC and body composition.
Allison <unk>: A really nice opportunity to really underscore that we really are on the threshold of bringing I think.
Allison: Just curious to get your thoughts there. Thank you.
Allison <unk>: Really nice new effective therapy to change standard of care in SMA.
Allison: Yes, good ally Hey, good morning. This is Jay so first starting with Sapphire, Yeah. We're really excited to have the opportunity for those data to be presented at a Congress and particularly the MBA conference where there is a lot of interest and a lot of investigators will have a chance to see the data.
Allison <unk>: And then with respect to embrace and 43 nine right I said, we have a very unique opportunity. We've got a really I think highly innovative platform of antibody therapies. We took full advantage of it did occur mapping in clinic study embrace.
Allison: And what we can share on the top line results.
Speaker Change: So we're looking I try to put some context around what is clinically meaningful with lean mass loss, but that's a question that comes to Wisconsin.
Allison: As shared previously I think what's really important is the overall consistency and impacted quality of the data. We've shared we've got fact across age groups and we're going to share additional endpoints and youll see that again I think there'll be interest in seeing the consistency and the impact we have.
Speaker Change: I do think Theres insights gained from the healthy volunteer study of young men, who were confined to bed rest of loss per kilogram.
That was a significant amount of strength loss, even in a young healthy right. So as we think about going forward that one kilogram that translates to about a 20% of them. We can double that thats two kilograms. So I think we're in that range of the signal seeking that'll give us insight.
Allison: Across those additional endpoint, so I think that'll be a really nice opportunity to really underscore that we really are on the threshold of bringing I think a really nice new effective therapy to change standard of care in SMA.
Speaker Change: That will allow us to continue to really think deeply about how we develop 439, but I want to make a caveat. We're studying this at week 24 on the steepest part of the slope of the curve is appetite and of course, we will do a 52 week study as we get into 43 nine. So there is a potential for that effect only mass to deepen over time. So we're looking at a snapshot it with <unk>.
Allison: And then with respect to embrace and 43 nine.
Allison: I said, we have a very unique opportunity. We've got a really I think highly innovative platform of anti milestone therapies. We took full advantage of it that are mapping in clinic study embrace.
Allison: So we're looking at trying to put some context around what is clinically meaningful with lean mass loss, but that's the question that comes to Wisconsin.
Speaker Change: For if we can show a nice effect and in that range of $20 to 40%, where we can think we have meaningful incremental benefit I think we have a really clear about those signals to move forward for $3 million, but we'll also be developing for three nine and we'll have to establish its own.
Allison: I do think Theres insights gained from the healthy volunteer study of young men, who were confined to bed rest of loss per kilogram.
Allison: That is a significant amount of strength loss, even in a young person right.
Allison: So as we think about going forward that one kilogram that translates to about a 20% of that we can double that thats two kilograms. So I think we're in that range of the signal seeking that'll give us insight.
Speaker Change: Dose et cetera, so lots to come with this total program, but very exciting time for us.
Speaker Change: Excellent. Thank you.
Speaker Change: One moment for our next question.
That will allow us to continue to really think deeply about how we develop 439.
Speaker Change: Our next question comes from Michael Yee with Jefferies. Your line is open.
Allison: But I want to make a caveat we're studying this at week 24 on the steepest part of the slope of the curve was appetite and of course, we'll do a 52 week study as we get into 43 nine. So there is a potential for that effect the only math to deepen over time. So we're looking at a snapshot at week 24, and we can show a nice effect and in that range of 20% to 40%.
Michael Yee: Hey, guys. Thanks for the question good morning.
Michael Yee: Just following up on thoughts around the obesity readout in the second quarter.
I appreciate that the expectation is that you should preserve needs muscle I was just wondering about how you guys are thinking about the biology or the effects of what would happen on the X more weight loss.
Allison: We think we have meaningful incremental benefit I think we haven't really cleared out those signals and report 439.
Michael Yee: There shouldn't be any material change, but I'm just wondering if there could actually be maybe more weight loss because of the metabolic effects.
Allison: We'll also be developing for three nine and we'll have to establish its own dose et cetera. So lots to come with this total program, but very exciting.
Michael Yee: <unk> and building muscle or that could actually be headline a little bit less weight loss, just because youre actually preserving the muscle. So just thinking about the biology, there certainly in the first 24 weeks.
Allison: Excellent. Thank you.
Speaker Change: One moment for our next question.
Speaker Change: Our next question comes from Michael Yee with Jefferies. Your line is open.
Michael Yee: Put that into context.
Michael Yee: Procurement muscle thank you.
Michael Yee: Hey, guys. Thanks for the question good morning.
Speaker Change: Yeah, Mike. Thanks for the question I'll try to frame that in a bit in the prepared remarks, so probably 24, given the magnitude of weight loss, it's already occurring with his appetite really don't expect at that time point to see we think the way. It also be comparable between the two arms recognizing that there is a potential with increasing muscle essentially.
Michael Yee: Following up on thoughts around the obesity readout in the second quarter.
Michael Yee: I appreciate that the expectation is that you should preserve needs muscle I was just wondering about how you guys are thinking about the biology or the effects of what would happen on the more weight loss.
Speaker Change: Wait, but the magnitude of the weight loss, which is appetite is probably going to make that a wash and so we think it will be comparable week 24.
Michael Yee: There shouldn't be any material change, but I'm just wondering if there could actually be maybe more weight loss because of the metabolic effects.
Speaker Change: To add to your point now that's a week 24.
Michael Yee: Myostatin and building muscle or there could actually be.
Speaker Change: If we look at effects over time, and the potential effect on basal metabolic rate and maintaining their absolutely has the potential to see some additional incremental weight loss over a period of time on treatment, but I want to set the expectations for week 24, we're expecting to be Paul.
Michael Yee: Headline a little bit less weight loss, just because youre actually preserving the muscle that youre just thinking about the biology there.
Michael Yee: Certainly in the first 24 weeks and put that into context.
Michael Yee: Procurement muscle thank you.
Michael Yee: Yeah, Mike. Thanks for the question I'll try to frame that in a bit in the prepared remarks, so probably 24, given the magnitude of weight loss is already occurring with this appetite really don't expect at that time point to see we think the way. It also be comparable between the two arms recognizing that theres, a potential with increasing muscle essentially.
Speaker Change: Got it thank you very much.
Speaker Change: One moment for our next question.
Speaker Change: Our next question comes from Trust Romero with Jpmorgan. Your line is open.
Trust Romero: Hi, good morning, JMP. Thanks, so much for taking our questions I look forward to seeing you guys at MDA.
Michael Yee: Wait, but the magnitude of the weight loss, which is appetite is probably going to make that a wash and so we think it'll be comparable week 24.
Speaker Change: So what is the right way to think about the exploration of additional neuromuscular indications, where a pedigree map could have potential here what framework can you give us with respect to those decisions in other words, how you will best allocate capital, while also ensuring proper investment and the launches for us.
Michael Yee: To your point now that's a week 24.
Michael Yee: We look at the effects over time and the potential effect on basal metabolic rate and maintaining their absolutely has the potential to see some additional incremental weight loss over a period of time on treatment, but I wanted to set the expectations for week 24, we're expecting 50 pump.
Speaker Change: And also the cadence and timelines with what you could or would start these clinical studies. Thanks, so much.
Michael Yee: Got it thank you very much.
Michael Yee: One moment for our next question.
Speaker Change: Yes. Thank you for the question.
Speaker Change: Important question, we're going through that work right now.
Speaker Change: Our next question comes from Tess Romero with Jpmorgan. Your line is open.
Speaker Change: As I indicated.
Speaker Change: P Morgan conference and with the success of a pit or have an SMA.
Tess Romero: Hi, good morning, JMP and thanks, so much for taking our questions I look forward to seeing you guys at MDA.
Speaker Change: I almost feel obligated for us to take a look at the adjacent neuromuscular indications to see if in fact, we can have an opportunity to impact and improve lives for those that have other diseases like BNP Fsh D Becker's and even AOS.
Speaker Change: So what is the right way to think about the exploration of additional neuro muscular indications, where <unk> could have potential here.
Speaker Change: So what we're showing at MDA as a bit of the work and thinking behind our approach to this.
Speaker Change: Framework can you go back with respect to those decisions in other words, how you will best allocate capital, while also ensuring proper investment and the launches for SMA and also the cadence and timelines with which you could.
Speaker Change: I am very keen on translational models to the extent that they can give us insight and I feel very fortunate with bonus teams to be able to do these models and so we're going to start showcasing how we're beginning to think about for example, bnb a little bit with them non clinical data, we're actively engaging experts across these indications to really be.
Speaker Change: Would start these clinical studies thanks, so much.
Speaker Change: Yes. Thank you for the question very important question, we're going through that work right now.
Speaker Change: As I indicated.
Speaker Change: Again to think about how we can take a look at both not only the opportunity in terms of the unmet need but the probability of technical success until we understand and enrich patient subset of patients that we can really show meaningful benefit we're doing all of that work and so you put all that together.
Speaker Change: J P Morgan conference and with the success of our <unk> in SMA.
Speaker Change: I mean, I almost feel obligated for us to take a look at the adjacent neuromuscular indications to see if in fact, we can have an opportunity to impact and improve lives for those that have other diseases like BNP Fsh D Becker's and even AOS.
Speaker Change: I will set the framework as we think about further investment in those indications, which as you can imagine is going to be.
Speaker Change: No.
Speaker Change: We're showing at MDA as a bit of the work and thinking behind our approach to this.
Speaker Change: Function of technical success unmet need potential opportunity et cetera. So we're doing all that work now over the course of frankly, we started that work even last year. So that work continues and as we get closer to that we'll certainly share housing thing with respect to our ability to do this in addition to.
Speaker Change: I am very keen on translational models to the extent that they can give us insight and I feel very fortunate with bonus teams to be able to do these models and so we're going to start showcasing how we're beginning to think about for example, DMV.
Speaker Change: Little bit than non clinical data, we're actively engaging experts across these indications to really begin to think about how we can take a look at both not only the opportunity in terms of the unmet need but the probability of technical success until we understand that enrich patient.
Speaker Change: Doing our launch we have a clinical team that really has demonstrated their ability to execute clinical trials sapphire and finish we have the ongoing study and the long term follow up but we're positioned to be able to take on an additional clinical study if not two but certainly won as we think about going forward.
Speaker Change: Set of patients that we can really show meaningful benefit we're doing all of that work and as we put all that together, yes that'll set the framework as we think about further investment in those indications, which as you can imagine is going to be.
Speaker Change: And again, what I tried to share it at JP Morgan was if you think about what we're trying to build here and the value we're trying to create at scholar rock.
Speaker Change: Function of technical success unmet need potential opportunity et cetera. So we're doing all that work now over the course of frankly, we started that work even last year. So that work continues and as we get closer to that we'll certainly share how the thing with respect to our ability to to do this in addition.
Speaker Change: Starts with SMA and as we've said, we think that there is a potential $2 billion plus of opportunity for us in SMA alone.
Speaker Change: During what we believe will be a paradigm shift in treatment and then if you start to build around that these additional neuromuscular indications.
Speaker Change: We're on the threshold assuming execution and success.
Speaker Change: Two doing our launch we have a clinical team that really has demonstrated their ability to execute clinical trials Sapphire next we have the ongoing study and the long term follow up but we're positioned to be able to take on an additional clinical study if not two but certainly won as we think about going forward.
Speaker Change: Build a multibillion dollar neuromuscular franchise and I think at the end of the day, if we do that properly, we'll definitely increase shareholder value, but importantly extend our reach to those in need.
Speaker Change: Thank you.
Speaker Change: One moment for our next question.
Speaker Change: And again, what I tried to share it at Jpmorgan was if you think about what we're trying to build here and the value we're trying to create at scholar rock.
Mark firm: Our next question comes from Mark firm with TD Cowen Your line is open.
Mark firm: Hi, This is Alex on for Mark. Thanks, So much for taking my question.
Speaker Change: Let's start with SMA and as we've said, we think that there is a potential of $2 billion plus opportunity for us in SMA alone.
Speaker Change: So the FDA recently issued a draft guidance on obesity clinical trials, which appear to reinforce the agency's focus on BMI and overall weight loss rather than shifting the focus to body composition changes and preservation of lean muscle mass.
Speaker Change: Considering what we believe will be a paradigm shift in treatment and then if you start to build around that these additional neuromuscular indications.
Speaker Change: What do you view as the potential implications here for your cardio metabolic program program, namely Port 39.
Speaker Change: We are on the threshold assuming execution of success.
Speaker Change: It's been a multibillion dollar neuromuscular franchise and I think at the end of the day, if we do that properly, we'll definitely increase shareholder value and importantly extend our reach to those in need.
Speaker Change: Yes. It's good question you know we were obviously following this with great intense and seeing and looking carefully at Fda's updated guidance.
Speaker Change: From my perspective kind of watching FDA over the years.
Speaker Change: Thank you.
Speaker Change: One moment for our next question.
Speaker Change: They tend to move slowly they tend not to go as fast as the field is trying to get them to go in terms of endpoints. So we were not surprised that they retain the along with.
Speaker Change: Yeah.
Mark: Our next question comes from Mark firm with TD Cowen Your line is open.
Mark: Hi, This is Alex on for Mark. Thanks, So much for taking my question.
Speaker Change: And the things that we took of interest though from that guidance, which I think further reinforces why I think we're actually on the right track here.
Speaker Change: So the FDA recently issued a draft guidance on obesity clinical trials, which appear to reinforce the agency's focus on BMI and overall weight loss rather than shifting the focus to body composition changes and preservation of lean muscle mass what do you view as the potential implications here for your cardio metabolic program program, namely 439.
Speaker Change: Is it now very clearly in that guidance. They are asking all sponsors will include within their clinical development very least a subset of their patients to understand the amount of lean mass loss on their trip.
Speaker Change: So it's recognizing that the loss of lean mass has the potential to not be a good thing. So that's assessed that at baseline and understand across programs. So I think that further reinforces the question around lean that.
Mark: Thanks.
Mark: Yes, it's good question.
Mark: We're obviously following this with great intense and seeing and looking carefully at Fda's updated guidance from.
Speaker Change: They clearly indicated in that guidance up if there is an interest and Bobby body composition come talk to us. So that to me is a bit foreshadowing where they may be tilting, but clearly that's not within the guidance now the body composition matters in the field is declaring that it's a really important event or endpoints. So I think that's something that we'll continue to.
Mark: From my perspective kind of watching FDA over the years.
Mark: They tend to move slowly they tend not to go as fast as the field is trying to get them to go in terms of endpoints. So we were not surprised that they retain BMO.
Mark: The things that we took of interest though from that guidance, which I think further reinforces why I think we're absolutely on the right track here is it now very clearly in that guidance. They are asking all sponsors will include within their clinical development.
Speaker Change: Follow with great attention, but also which I believe we will affect positively.
Speaker Change: We preserve lean mass. So we will have a nice impact on that but then they also said what is very clear is that if youre doing a combination program then you need to demonstrate some additional benefit from our drug for example, Exarchate 439, and what I was trying to showcase in todays discussion to bring further clarity to that but what I've said pretty consistently.
Mark: Or at least the subset of their patients to understand the amount of lean mass loss on their trip.
Mark: So it's recognizing that the loss of lean mass has the potential to not be a good thing. So that's assessed that at baseline and understand across programs. So I think that further reinforces the question around lean that.
Speaker Change: System across our entry into this or is it those endpoints that could be regulatory approval, one points or metabolic parameters such as further reduction in hemoglobin <unk> C. Clearly there is a potential for that given the role of muscle and there's clearly an opportunity to find a way to demonstrate that losing this.
Mark: They clearly indicated in that guidance.
Mark: There is an interest and Bobby body composition can talk to us. So that to me is a bit foreshadowing where they may be tilting, but clearly that's not within the guidance now the body composition matters in the field is declaring that it's really important that our endpoints. So I think that's something that we'll continue to follow with great attention, but also which I bill.
Speaker Change: Amount of lean mass really results in functional loss, that's significant and we have the potential within a subgroup of patients to show those functional measures and improvement, which ultimately I think will be sustainable and then there's other ways that we can look at how we can manage through mitigating weight regain maintenance approach was et cetera, with a lot of ideas a path to move this fall.
Mark: We will affect positively if in fact, we preserve lean mass. So we'll have a nice impact on that but then they also said what is very clear is that if youre doing a combination program then you need to demonstrate some additional benefit from our drug for example, <unk> or three nine and what I was trying to showcase in todays discussion.
Speaker Change: When we get into the clinic, but I think the guidance to come back to it are consistent but I think also we're pointing the way and I feel very good about fact that we're in this space.
Mark: To bring further clarity to that but what I've said pretty consistently across our entry into this is that those endpoints that could be regulatory approval endpoints are metabolic parameters such as further reduction in hemoglobin <unk> C clear.
Speaker Change: Great. Thank you.
Speaker Change: One moment for our next question.
Speaker Change: Our next question comes from Gary Nachman with Raymond James Your line is open.
Mark: Clearly there is a potential for that given the role of muscle and there is clearly an opportunity to find a way to demonstrate that losing this amount of lean mass really results in functional loss, that's significant and we have the potential within a subgroup of patients to show those functional measures and improvement, which ultimately I think will be sustainable.
Gary Nachman: Thanks, and good morning, so yeah background embrace if you hit the one to two kilograms of lean mass preservation with a pet agreement then how would you expect for three nine to perform based on that so how much better could it potentially be then a pedigree mab based on the preclinical data that you've seen.
Mark: And then there's other ways that we can look at how we can manage through mitigating weight regain maintenance approaches et cetera, we have a lot of ideas a path to move this forward when we get into the clinic.
Speaker Change: Since the space is getting a lot more competitive, but I'm trying to think from a commercial marketing perspective as well.
Mark: But I think the guidance to come back to it are consistent but I think also we're pointing the way and I feel very good about fact that we are in this space.
Gary Nachman: And then just with SMA.
Gary Nachman: Just a bit more on how the initial payer discussions are going and any update on how you're thinking about pricing as a combination drug.
Speaker Change: Great. Thank you.
Speaker Change: One moment for our next question.
Mark: <unk>.
Gary Nachman: How that's going to be received in the market. Thanks.
Mark: Our next question comes from Gary Nachman with Raymond James Your line is open.
Yes, Gary Thanks for the question I'll start with the 439 question and then I'll turn to Tracy.
Gary Nachman: Thanks, and good morning, so yeah background embrace if you hit the 1% to two kilograms of lean mass preservation with a pit agreement then how would you expect for three nine to perform based on that so how much better could it potentially be then a pedigree mab based on the preclinical data that you've seen.
Gary Nachman: To address the question on our interactions so far with payers.
Gary Nachman: It's interesting, it's like having two children and Youre going to say, which one is better right. I mean, I think what I would say to you Gary at 439, I really like the profile that were developed a really good I think the work that Moe and his team are showing us. This is performing beautifully it has greater affinity for the target in that.
Gary Nachman: Since the space is getting a lot more competitive so trying to think from a commercial marketing perspective as well.
Speaker Change: Could potentially help us certainly at least with the very much with the dosing such that we can then go in with a low dose sub Q formulation. So that is a clear clear advantage and we're looking forward to that.
Gary Nachman: And then just with SMA, maybe just a bit more.
Gary Nachman: On how the initial payer discussions are going and any update on how you're thinking about pricing as a combination drug.
Speaker Change: Now with respect to how much different than how much better. That's a really interesting question, Gary because what I was trying to say is it critical matters like signal seeking yes, we can show this.
Gary Nachman: Thats going to be received in the market. Thanks.
Speaker Change: Yes, Gary Thanks for the question I'll start with the <unk> hundred 39 question, and then I'll turn to Tracy.
Speaker Change: 439% that program and we will need to further explore with 439, how we optimize the dose of four three of them and how we begin to get some better insight into how it's impacted across these functional measures. So that's part of our thinking on the IMD opening sites. So more to come with 43 nine at the very least it's going to have.
Gary Nachman: To address the question on our interactions so far with payers.
Gary Nachman: It's interesting, it's like having two children and youre going to say, which one is better right.
Speaker Change: What I would say to you Gary on <unk> nine I really like the profile that were developed I really do I think the work that Moe and his team are showing us. This is performing beautifully it has greater affinity for the target and that could potentially help us certainly at least with the very much with the dosing such that we can then go in with a low dose.
Speaker Change: Similar effects I do think though it's designed to be low dose kind of sub Q presentation, which in this highly competitive space I think is something that we need to do.
Speaker Change: And so more to come but we're really moving rapidly on that toward IMT and then Tracey you want to make a comment on the payer interactions today.
Speaker Change: Q formulation, so that is a clear clear advantage and we're looking forward to that.
Speaker Change: Now with respect to how much different than how much better. That's a really interesting question, Gary because what I was trying to say is it <unk> like signal seeking yes, we can show this.
Tracey: Yes sure.
Payers have been very receptive to hearing from you know even if the new company and are very interested in learning more about our innovation as the FERC muscle targeted therapy in SMA.
Speaker Change: Or three 9% that program and we will need to further explore with 439, how we optimize the dose of $43 million and how we begin to get some better insight into how it impacts across these functional measures. So that's part of our thinking on the IMD openings items, so more to come with 43 nine at the very least it is going to have.
Tracey: They are familiar with SMA and recognize that there's still a continued need to treat this relentless disease and we know today that theyre already a third of lives covered up U S. Commercial payers already have policy covering what I would call combination treatment of an SMN targeted therapy post gene therapy. So that is a reflection of the open.
Speaker Change: Similar effects I do think though it's designed to be low dose kind of sub Q presentation, which in this highly competitive space I think there is something that we need to do.
Tracey: Next to address this recognition of unmet need.
Tracey: Ultimately, we expect U S and European payers alike to enable access reflective of the value of picker, Matt brings in SMA and our data and the overall profile of really strong we have a clear added benefit across all cohorts and high highly favorable safety profile. So it sets us up for really strong discussion.
Speaker Change: And so more to come but we're really moving rapidly on that toward IMT and then Tracey you want to make a comment on the payer interactions today.
Tracey: Yes sure.
Tracey: Payers have been very receptive to hearing from us even if the new company and are very interested in learning more about our innovation as the FERC muscle targeted therapy in SMA.
Speaker Change: Okay and just pricing.
Speaker Change: Any latest thoughts there just typical.
Tracey: They are familiar with SMA and recognize that there's still a continued need to treat this relentless disease and we know today that they are already a third of lives covered up U S. Commercial payers already have policy covering what I would call combination treatment of an SMN targeted therapy post gene therapy. So that is a reflection of the open.
Speaker Change: Along with the other SMN treatments.
Speaker Change: At this point you know, we're not in a position to share pricing, but ultimately we expect that access to be covered reflective of the value we bring them and we do have a sense of what the pricing is in the in the ethanol market Tonight.
Speaker Change: Okay, great. Thank you.
Tracey: To address this recognition of unmet need.
Speaker Change: One member for our next question.
Tracey: Ultimately, we expect U S and European payers alike to enable access reflective of the value of <unk> brain and SMA and our data and overall profile are really strong we have a clear added benefit across all cohorts and high highly favorable safety profile. So it sets us up for really strong discussion.
Speaker Change: Our next question comes from Chris defer a condo with true Securities. Your line is open.
Speaker Change: Hi, This is Alex on for Chris Thanks for taking our question.
Speaker Change: To talk about the.
Speaker Change: Future development path for.
Speaker Change: Okay and just pricing.
Speaker Change: The muscle preservation drug to be a little specific because we know that that overall.
Tracey: Any latest thoughts fair just typical.
Speaker Change: Along with the other SMN treatments.
Speaker Change: We definitely see the benefits of more muscle better bottom when it comes to the regulatory review and the specifics on the endpoint you mentioned a couple of different avenues that that you could explore with the HBA one seed.
Speaker Change: Yeah.
Speaker Change: At this point, we're not in a position to share pricing, but ultimately we expect that asset to be covered reflective of the value we bring.
Speaker Change: And we do have a sense of what the pricing is in the in the ethylene market Tonight.
Speaker Change: And mitigate weight regain but when it comes to the strength and points when we've seen a grip or stair climb or are these endpoints that are on the discussion table or are there other strength related functional outcomes that come to mind as potential options going forward for the program.
Speaker Change: Okay, great. Thank you.
Speaker Change: One moment for our next question.
Speaker Change: Our next question comes from Chris <unk> with true Securities. Your line is open.
Alex: Hi, This is Alex on for Chris Thanks for taking my question.
Speaker Change: Yeah really good question as you can imagine, we're giving us a lot of thought as we think about how to then really meaningfully moved 494 beyond just identifying the right dose and what to kind of add color to your to your point, but I think about once we establish the dose.
Speaker Change: So talk about the.
Speaker Change: And the future development path.
Speaker Change: The muscle preservation drug to be a little.
Speaker Change: Specific because we know that that overall.
Speaker Change: We definitely see the benefits of more muscle better, but when it comes to the regulatory review and the specifics on the endpoint you mentioned a couple of different avenues that that you could explore with the HBA one seed.
Speaker Change: Can envision that we would then have subgroups of patients in our proof of concept efforts to demonstrate the impact. We can have a for example, hemoglobin <unk> C and in that context, we would definitely enrich for a subset of patients where we think we can meaningfully show up there. So that that's a very clear regulatory path forward thats the metabolic.
Speaker Change: And the mitigate regain but when it comes to the strength and points, we've seen grip or stair climb are these endpoints that are on the discussion table or are there other strength related functional outcomes that come to mind as potential options going forward for the program. Thanks.
Speaker Change: Value the additional benefit of preserving that lean muscles. So that's one example.
Speaker Change: And the other example that you touched on which comes immediately to mind, but we've demonstrated functional improvement in SMA. So clearly functional measure of important improvement our interest.
Speaker Change: Yes really good question as you can imagine we are giving us a lot of thought as we think about how to then really meaningfully move for 394 beyond just identifying the right dose.
Speaker Change: We're not wed to grip strength and aircraft, we're giving a lot of thought around this I think there's a lot of insights that we're gaining from our work and our review and discussions and we'll have a really good opportunity. When we open up the <unk> with 43, nine and begin to meaningfully engage FDA and our thinking around the development.
Speaker Change: To kind of add color to your to your point, but I think about once we establish the dose.
Speaker Change: You can envision that we would then have subgroups of patients in our proof of concept efforts to demonstrate the impact. We can have on for example, hemoglobin <unk> C and in that context, we would definitely enrich for a subset of patients where we think we can meaningfully show up there. So that that's a very clear regulatory path forward thats the metabolic.
Speaker Change: Graham thinking around meaningful functional measures and endpoints and at the same time get some sense of how we impact those functional measures as we build the program from sad Mad into those early POC. So that we'd be in a really strong position to know exactly how to run in a registration program so that.
Speaker Change: Value the additional benefit of preserving that lean muscle. So that's one example.
Speaker Change: And the other example that you touched on which comes immediately to mind and we've demonstrated parks on improvement in SMA, So clearly functional measures and partner perimeter interest.
Speaker Change: That's our thinking right now I feel really good about it it's like where it looks like stair stepping right.
Speaker Change: I Love the fact that we've got embrace coming in the IND going into 14.
Speaker Change: We're not wed to grip strength and aircraft, we're giving a lot of thought around this I think there's a lot of insights that we're gaining from our work and our review and discussions and we'll have a really good opportunity. When we open up the R&D with 43 nine begin to meaningfully engage FDA and our thinking around the development.
Speaker Change: Really taken advantage of our platform as they are both coming that this momentum at 439 and now we're already beginning to see what the next couple of steps are so I'd tell you I can't wait to share all that with you.
Speaker Change: One step at a time, though we're driving to get the IMD open we're doing all of this nice work.
Speaker Change: More to come but I feel really good we've got great momentum running as the designs.
Speaker Change: Graham thinking around meaningful functional measures and endpoints and at the same time get some sense of how we impact those functional measures as we build the program from sad Mad into those early POC, so we'd be in a really strong position.
Speaker Change: Yeah, that's great. Thank you for the color.
Jay Backstrom: And I'm not showing any further questions at this time I'd like to turn the call back over to Jay for any further remarks.
Jay Backstrom: However, just to close this and thank you for your interest I mean, it really is an exciting time I tried to put energy into my voice when I do this prepared remarks I feel like they have more energy when we get into the Q&A period.
Exactly how to run in a registration program. So that's our thinking right now I feel really good about it it's like where it's like stair stepping right.
Speaker Change: I Love the fact that we've got embrace coming in the IND filling in for three months, we've really taken advantage of our platform as theyre, both coming that this momentum at 439 and now we're already beginning to see what the next couple of steps are so I'd tell you I can't wait to share all that with you.
Jay Backstrom: But honesty with this team is hustling. Thank you for your interest and we look forward to sharing the updates and progress over the course of the year and then we'll close the call.
Jay Backstrom: Ladies and gentlemen, this does conclude today's presentation. You may now disconnect and have a wonderful day.
Speaker Change: One step at a time, though we're driving to get the IMD opened we're doing all of this nice work more to come but I feel really good we've got great momentum running into the design.
Speaker Change: Yes, that's great. Thank you for the color.
Speaker Change: And I'm not showing any further questions at this time I'd like to turn the call back over to Jason for any further remarks.
Speaker Change: However, just to close this and thank you for your interest I mean, it really is an exciting time I tried to put energy into my voice when I do this prepared remarks, I feel like add more energy when we get into the Q&A period.
Speaker Change: But honesty witnessed team is hustling. Thank you for your interest and we look forward to sharing updates and progress over the course of the year and then we'll close the call.
Speaker Change: Thank you ladies and gentlemen, this does conclude today's presentation. You may now disconnect and have a wonderful day.
Speaker Change: Okay.
Speaker Change: [music].