Q2 2024 Scholar Rock Holding Corp Earnings Call

August 8, 2024

Operator: Good morning, and welcome to Scholar Rock's second quarter financial results and business update call. All participants will be in listen only mode. After the company's prepared remarks, call participants will have an opportunity to ask questions. To ask a question, you may press star, then one and one on your touch-tone phone. To withdraw your question, please press the star, then one and one again.

Good morning and welcome to Scholar Rock's second quarter financial results and business update call. All participants will be in listen-only mode.

Speaker Change: After the company's prepared remarks, call participants will have an opportunity to ask questions. To ask a question, you may press star, then 1 and 1 on your touchtone phone. To withdraw your question, please press star, then 1 and 1 again.

Operator: Please note, this event is being recorded. Before we begin, I'd like to point out that we will be making various statements about Scholar Rock's expectations, plans, and prospects that constitute forward-looking statements for the purpose of the Safe Harbor provisions under the Private Securities Litigation Reform Act of 1995. Such 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.

Please note, this event is being recorded.

Speaker Change: Before we begin, I'd like to point out that we will be marking various statements about Scholar Rock's expectations, plans, and prospects that constitute forward-looking statements for the purpose 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 i should not be relied upon as representing our views as of any year to date

Operator: I encourage you to go to the Investors and Media section of our website to find our most up-to-date SEC statements and filings. A recording of today's event will also be available on our website should you want to rewatch it at a later date. I would now like to turn the conference over to Jay Backstrom, President and CEO of Scholar Rock. Jay, please go ahead.

I encourage you to go to the Investors & Media section of our website to find our most up-to-date SEC statements and filings. A recording of today's event will also be available on our website should you want to re-watch at a later date.

I would now like to turn the conference over to Jay Backstrom, President and CEO of Scholar Rock. Jay, please go ahead.

Unknown Executive: Thank you, Sandra. Good morning, and welcome to our Scholar Rock second quarter 2024 business update. On behalf of our team, I'd like to thank you for joining our call, followed by Mo Qatanani, our Chief Scientific Officer, who will review the progress with our SRK 439 program in Ibiza. I'll close with a summary of upcoming milestones and then open the call to questions.

Jay Backstrom: Thank you, Sandra. Good morning, and welcome to our Scholar Rock second quarter 2024 business update. On behalf of our team, I'd like to thank you for joining our call. Turning to slide four, the focus of today's call is to highlight our exciting progress in 2024. After my introductory remarks, Jing Marantz, our Chief Medical Officer, will provide an update on our development programs, including a review of the 48-month data from TOPAS, our Pitica-MAB Phase II Proof of Concepts, followed by Mo Qatanani, our Chief Scientific Officer, who will review the progress with our SRK 439 program in Ibiza. I'll close with a summary of upcoming milestones and then open Moving to slide five.

Unknown Executive: We've made terrific progress over the first half of 2024, and we're on track to achieve all of our key milestones on time or ahead of schedule. The progress with our SMA program has allowed us to continue to advance toward commercialization. A goal that is coming closer to view for our lead product, Pitogramab, as we remain on track to report the top line results for SAFIRE, our phase three registration study in Q4.

Jay Backstrom: Thank you, Sandra. Good morning, and welcome to our Scholar Rock second quarter 2024 business update. On behalf of our team, I'd like to thank you for joining our call.

Jay Backstrom: Turning to slide four, the focus of today's call is to highlight our exciting progress in 2024.

Jing Marantz: After my introductory remarks, Jing Marantz, our Chief Medical Officer, will provide an update on our development programs, including a review of the 48-month data from TOPAS, our Pitica-MAB Phase II Proof of Concept study.

Followed by Mo Qatanani, our Chief Scientific Officer, who will review the progress with our SRK 439 program in obesity. I'll close with a summary of upcoming milestones, and then open the call up for questions.

Jay Backstrom: We've made terrific progress over the first half of 2024, and we're on track to achieve all of our key milestones on time or ahead of schedule. The progress with our SMA program has allowed us to continue to advance toward commercialization. A goal that is coming closer to view for our lead product, the Pitagor Man, as we remain on track to report the top line results for Sapphire, our phase three registration study in Q4.

Moving to slide five.

Jing Marantz: We've made terrific progress over the first half of 2024, and we're on track to achieve all of our key milestones on time or ahead of schedule.

Mo Qatanani: The progress with our SMA program has allowed us to continue to advance toward commercialization.

Speaker Change: A goal that is coming closer into view for our lead product, the Pitogramab, as we remain on track to report the top-line results for SAFIRE, our Phase III registration study in Q4.

Unknown Executive: Thanks to the focus and dedication of our study team and the incredible support from our investigators, their clinical study teams, and the families participating in SAFIRE, we are now only a few months away. At Scholar Rock, selectivity was foundational to our approach to designing a pyramid and is the hallmark of our differentiated platform, hitting the right target at the right time, and for our latent TGF-beta1 selective monoclonal antibody for fibrosis, now referred to as SRK373.

Jay Backstrom: Thanks to the focus and dedication of our study team and the incredible support from our investigators, their clinical study teams, and the families participating in SAFIRE, we are now only a few months away. At Scholar Rock, selectivity was foundational to our approach to designing a pyramid and is the hallmark of our differentiated platform.

Thanks to the focus and dedication of our study team and the incredible support from our investigators, their clinical study teams, and the families participating in SAFIRE, we are now only a few months away.

Speaker Change: At Scholar Rock, selectivity was foundational to our approach in designing a pyramid and is the hallmark of our differentiated platform.

Jay Backstrom: Our research team has been incredibly productive and has delivered and continues to deliver a portfolio of potential medicines that are highly differentiated and with best-in-class potential. We focused our industry-leading anti-myostatin programs in areas where we believe we can make substantial advances in care, creating new possibilities for those living with SMA and with obesity. High-value therapeutic areas that provide unique opportunities to fuel our growth. It is an exciting time at Scholar Rock.

Jing Marantz: our research team has been incredibly productive and is delivered and continues to deliver a portfoli of potential medicines that are highly differentiated and with best-in-class potential

Jing Marantz: We focused our industry-leading anti-myostatin programs in areas where we believe we can make substantial advances in care, creating new possibilities for those living with SMA and with obesity.

High value therapeutic areas that provide unique opportunities to fuel our growth. It is an exciting time at Scholar Rock.

Jay Backstrom: We are at a point in our trajectory where the next 12 to 24 months will be transformative. Turning to slide six, as a reminder, the scientific foundation for our company was based on deep structural insights that allowed us to harness the therapeutic potential of the TGF-beta superfamily growth factor by hitting the right target at the right time. Avoiding Unwanted Toxicities and Potentially Maximizing Epidemics. As shown on slide 7, we've applied this highly selective approach and produced a robust pipeline of innovative and differentiated products.

Jing Marantz: We are at a point in our trajectory where the next 12 to 24 months will be transformative.

Jing Marantz: Turning to slide 6, as a reminder, the scientific foundation for our company was based on deep structural insights that allow us to harness the therapeutic potential of the TGF-beta superfamily growth factors by hitting the right target at the right time.

Jing Marantz: Avoiding unwanted toxicities and potentially maximizing efficacy.

Jing Marantz: As shown on slide 7, we've applied this highly selective approach and produced a robust pipeline of innovative and differentiated products.

Jay Backstrom: Starting with our anti-myostatin programs, Scholar Rock was instrumental in bringing myostatin back into the forefront as a therapeutic target. With Pitogramab and SMA, we've re-established myostatin as a neuromuscular target, and our emerging data with SRK439 suggest the best-in-class potential to address the muscle loss associated with GLP-1 receptor agonist treatment, leading to sustainable, healthy weight management For our TGF-Beta-1 programs with SRK181 and immuno-oncology, we have pierced the immunosuppressive armor to overcome checkpoint inhibitor resistance, and for our latent TGF-1 selective monoclonal antibody for fibrosis, now referred to as SRK373, we applied our deep structural insights and antibody engineering expertise to solve a riddle that has not been solved before.

Speaker Change: starting with the antiizedestatin programs scholar rock was instrumental in bring milesestatt back into the forefront as a therapeutic target

Jing Marantz: With the Pitigramab and SMA, we've re-established myostatin as a neuromuscular target.

Jing Marantz: and our emerging data with SRK 439.

Jing Marantz: suggests the best-in-class potential to address the muscle loss.

Speaker Change: Associated with GLP-1 receptor agonist treatment leading to sustainable healthy weight management and obesity.

Jing Marantz: For our TGF-Beta 1 programs with SRK181 and immuno-oncology, we have pierced the immunosuppressive armor to overcome checkpoint inhibitor resistance.

Jing Marantz: And for our latent TGF-?1 selective monoclonal antibody for fibrosis, now referred to as SRK373.

Unknown Executive: We applied our deep structural insights and antibody engineering expertise to solve a riddle that has not been solved before. SRK373 is the first monoclonal antibody designed to uncouple the pro-inflammatory from the pro-fibrotic effects of TGF-beta1, with the potential to be best in class in indications such as IPF where TGF-beta1 and inflammation are key drivers for the disease. Moving to slide eight.

Jing Marantz: We applied our deep structural insights and antibody engineering expertise.

Jay Backstrom: SRK373 is the first monoclonal antibody designed to uncouple the pro-inflammatory from the pro-fibrotic effects of TGF-1, with the potential to be best in class in indications such as IPF or where TGF-1 and inflammation are key drivers for the disease. As further evidence of our capabilities, we have an elegant monoclonal antibody blocking RGMC, a validated target for unrestricted anemia, and we are excited to advance another neuromuscular program to development candidate from our internal research as we embark on our next wave of innovation. Moving to slide eight.

Jing Marantz: to solve a riddle that has not been done before.

Jing Marantz: SRK373 is the first monoclonal antibody designed to uncouple the pro-inflammatory from the pro-fibrotic effects of TGF-beta-1.

Jing Marantz: with the potential to be best-in-class in indications such as IPF or TGF-?1 and inflammation are key drivers for the disease.

Jing Marantz: As further evidence of our capabilities, we have an elegant monoclonal antibody blocking RGMC, a validated target for unrestricted anemia, and we are excited to advance another neuromuscular program to development candidate from our internal research as we embark on our next wave of innovation.

Jay Backstrom: We have been disciplined and focused in our efforts to advance the pipeline to key developmental milestones across all of the therapeutic areas. Starting with neuromuscular disorders, for our lead program of Pitigermab, the upcoming readout for SAFIRE is just around the corner, and we look forward to reporting out the top-line results in Q4. SAFIRE was designed to meet regulatory requirements for approval and to demonstrate both a statistically significant and clinically meaningful difference in the primary endpoint of mean change from baseline in the Hammersmith score at 12 months compared to placebo, with the ability to capture at least a two-point difference.

Jing Marantz: Moving to slide 8. We have been disciplined and focused in our efforts to advance the pipeline to key developmental milestones across all of the therapeutic areas.

Jing Marantz: Starting with neuromuscular disorders for our lead program of Pitigermab, the upcoming readout for SAFIRE is just around the corner and we look forward to reporting out the top line results in Q4.

Jing Marantz: SAFIRE was designed to meet regulatory requirements for approval and to demonstrate both a statistically significant and clinically meaningful difference.

Jing Marantz: and the primary endpoint of mean change from baseline in the Hammersmith score at 12 months compared to placebo with the ability to capture at least a two-point difference.

Jay Backstrom: SAFIRE was optimized for clinical success based on the TOPAS Phase II Proof of Concept study, and we're excited to share the TOPAS 48-month data on today's call. As you will hear from Jing in more detail, the updated Topaz data continue to impress, demonstrating sustained clinical benefit through 48 months. The sustained benefit over 48 months is particularly noteworthy when considering the long-term results of nusinersen-treated patients from the Cherry Shine study recently presented by Finkel and colleagues at Cure SMA, where the initial functional gains seen with nusinersen show a decline over time, highlighting the progressive nature of the disease and the need for additional treatment options, such as Pitigramab, a muscle-directed therapy.

Jing Marantz: SAFIRE was optimized for clinical success based on the TOPAS Phase II proof-of-concept study, and we're excited to share the TOPAS 48-month data on today's call.

Unknown Executive: As you will hear from Jing in more detail, the updated Topaz data continue to impress, demonstrating sustained clinical benefit through 48 months. In addition to the sustained functional improvement, the updated data continue to reinforce the safety and tolerability of epidigramab with over 90 percent remaining on treatment and no new safety issues. We formally announced our entry into the cardiometabolic area less than 10 months ago, and we've wasted no time in moving our programs forward.

Jing Marantz: As you will hear from Jing in more detail, the updated TOPAS data continue to impress, demonstrating sustained clinical benefit through 48 months.

Speaker Change: The sustained benefit over 48 months is particularly noteworthy when considering the long-term results of nusinersen-treated patients from the Cherry Shine study recently presented by Finkel and colleagues at CureSMA, where the initial functional gains seen with nusinersen show a decline over time.

Jing Marantz: Highlighting the progressive nature of the disease and the need for additional treatment options, such as epidigramab, a muscle-directed therapy.

Jay Backstrom: In addition to the sustained functional improvement, the updated data continue to reinforce the safety and tolerability of epidechromab with over 90% remaining on treatment and no new safety issues. Taken together, the 48-month data further reinforce our confidence in the SAFIRE study and the potential for pitagoramab to improve the lives of those living with SAFIRE. A successful SAFIRE study will allow Epidigomab to serve as the foundation for building a neuromuscular franchise, and we are planning to extend our efforts in SMA to children under two, as well as to expand into other neuromuscular indications.

Speaker Change: In addition to the sustained functional improvement, the updated data continued to reinforce the safety and tolerability of epidigramab with over 90% remaining on treatment and no new safety findings.

Speaker Change: taking together the 48-month data further reinforce our confidence in the SAFIRE study and the potential for epidechromab to improve the lives of those living with SMA.

Speaker Change: A successful SAFIRE study will allow Lipidogramab to serve as the foundation for building a neuromuscular franchise, and we are planning to extend our efforts in SMA to children under 2, as well as expanding into other neuromuscular indications.

Jay Backstrom: For our cardiometabolic programs, we believe our highly selective approach to blocking the pro and latent forms of myostatin can meaningfully contribute to healthy weight loss management. We formally announced our entry into the cardiometabolic area less than 10 months ago, and we've wasted no time in moving our programs forward. Starting with EMBRACE, our randomized phase two proof of concept study in obesity assessing Pitigrameb in combination with a GLP-1 agonist. It is ahead of schedule, and we are now positioned to complete enrollment in early Q4 and have updated our guidance for the top line results to Q2 2025.

Speaker Change: For our cardiometabolic programs, we believe our highly selective approach to blocking the pro and latent forms of myostatin can meaningfully contribute to healthy weight loss management.

Speaker Change: We formally announced our entry into the cardiometabolic area less than 10 months ago, and we've wasted no time in moving our programs forward.

Speaker Change: Starting with EMBRACE, our randomized phase 2 proof of concept study in obesity, assessing a pitigrameb in combination with a GLP-1 agonist. It is ahead of schedule, and we are now positioned to complete enrollment in early Q4 and have updated our guidance for the top-line results to Q2 2025.

Jay Backstrom: As you'll hear from Mo, the non-clinical data generated to date with SRK439, our novel anti-myostatin, continues to support a potential best-in-class approach for preserving muscle mass leading to healthy weight loss management. The data presented at ADA add to the body of evidence demonstrating an increase in lean mass and reduced fat mass regain with SRK439 following withdrawal of the GLP-1 receptor.

Unknown Executive: As you'll hear from Mo, the non-clinical data generated to date with SRK439, our novel anti-myostatin, continues to support a potential best-in-class approach for preserving muscle mass leading to healthy weight loss management. For our TGF-Beta 1 programs with SRK181 and immuno-oncology, we've demonstrated proof of concept and proof of mechanism in overcoming checkpoint inhibitor resistance. And we look forward to discussing the next steps with FDA at our end of Phase 1 meeting for SRK373, our selective latent TGF-beta monoclonal antibody for fibrosis.

Speaker Change: As you'll hear from Mo, the non-clinical data generated to date with SRK439, our novel anti-myostatin, continues to support a potential best-in-class approach for preserving muscle mass leading to healthy weight loss management.

Mo Qatanani: The data presented at ADA add to the body of evidence, demonstrating an increasingly mass and reduced fat mass regain with SRK439 following withdrawal of the GLP-1 receptor agonist.

Jay Backstrom: For our TGF-Beta 1 programs with SRK181 and immuno-oncology, we've demonstrated proof of concept and proof of mechanism for overcoming checkpoint inhibitor resistance, and we look forward to discussing the next steps with FDA at our end of Phase 1 meeting. For SRK373, our selective latent TGF-beta monoclonal antibody for fibrosis, we are excited about the best-in-class potential for indications such as IPF, where TGF-beta1 and inflammation are key drivers of disease, and we look forward to advancing the program to IND.

Mo Qatanani: For our TGF-Beta 1 programs with SRK181 and immunooncology, we've demonstrated proof-of-concept and proof-of-mechanism in overcoming checkpoint inhibitor resistance, and we look forward to discussing the next steps with FDA at our end-of-phase 1 meeting.

Mo Qatanani: For SRK373, our selective latent TGF-beta monoclonal antibody for fibrosis, we are excited about the best-in-class potential in indications such as IPF, where TGF-beta1 and inflammation are key drivers for disease, and we look forward to advancing the program to IND.

Unknown Executive: We are excited about the best-in-class potential in indications such as IPF, where TGF-beta 1 and inflammation are key drivers of disease. And we look forward to advancing the program to IND and are looking forward to our next major milestone, the top line results for Sapphire in Q4. A very exciting time at Scholar Rock.

Jay Backstrom: The strength of our platform affords us the opportunity to consider these high-value opportunities and to thoughtfully grow and advance our pipeline. It is exciting to see what has become possible given our insights into targeting the TGF beta superfamily of growth. Turning to slide nine.

Mo Qatanani: The strength of our platform affords us the opportunity to consider these high-value opportunities and to thoughtfully grow and advance our pipeline. It is exciting to see what has become possible given our insights into targeting the TGF beta superfamily of growth factors.

Jay Backstrom: As external validation of our innovation, our cutting-edge research is increasingly being recognized by the global scientific community. In the last two months alone, our data have been featured at the annual conferences of the American Society of Clinical Oncology and the American Diabetes Association. And most recently, our unique selective latent anti-TGF-beta-1 monoclonal antibody, SRK373, was featured in Science Signaling as further proof of our structural insights, leading to potential best-in-class therapy.

Mo Qatanani: Turning to slide 9, as external validation of our innovation, our cutting-edge research is increasingly being recognized by the global scientific community.

Mo Qatanani: In the last two months alone, our data have been featured at the annual conferences for the American Society of Clinical Oncology and the American Diabetes Association.

Speaker Change: and most recently our unique selective latent anti-TGF-beta-1 monoclonal antibody SRK373 was featured in Science Signaling as further proof of our structural insights leading to potential best-in-class therapies.

Jay Backstrom: As shown in slide 10, we have delivered on all of our key milestones to date and are looking forward to our next major milestone, the top line results for Sapphire and Q4. It's a very exciting time at Scholar Rock. And with that, I'm pleased to turn the call over to our chief medical officer, Jing Marantz, who will provide an update on our development programs, followed by our chief scientific officer, Mo Qatanani, who will walk us through an update from our research team. Jing?

Speaker Change: As shown in slide 10, we have delivered on all of our key milestones to date.

Speaker Change: And we're looking forward to our next major milestone, the top line results for Sapphire and Q4. A very exciting time at Scholar Rock.

Speaker Change: And with that, I'm pleased to turn the call over to our Chief Medical Officer Jing Marantz, who will provide an update on our development programs, followed by our Chief Scientific Officer Mo Qatanani, who will walk us through an update from our research team. Jing?

Jing Marantz: If we can turn to slide 12, Molly. We have three programs in the clinic. In June, as Jay mentioned, we have updated clinical data on our one-on-one program that was featured in an oral session at AFT. On today's call, I will focus on the progress of our SMA program, including an update on the 48-month data from Topaz and the EMBRACE study in obesity, starting on the left. We have a differentiated approach to selective muscle targeting based on deep insights into how skeletal muscle is regulated.

Speaker Change: entuses

Mo Qatanani: On today's call, I will focus on the progress of our SMA program, including an update on the 48-month data from Topaz and the EMBRACE study in obesity.

Unknown Executive: to start on the left. Leveraging the learnings from Topaz, our pivotal study is designed for clinical success. Turning to slide 13, before I share the updated data, it's helpful to take a look at the natural trajectory of patients treated with SMN-targeted therapy. As Shea mentioned, at the recent Cures May meeting in June, Dr. Finkel and colleagues presented the long-term outcomes data from the Cherish SHINE study, which enrolled SMA patients treated with Neusinerser.

Mo Qatanani: To start on the left.

Speaker Change: We have a differentiated approach of selective muscle targeting based on deep insights of how skeletal muscle is regulated.

Jing Marantz: Translating this into the clinic, we saw from the TOPAS trial substantial and durable benefit across broad SMA patients. Leveraging the learnings from Topaz, our pivotal study is designed for clinical success. Lastly, and importantly, with over 200 patient years of exposure, the safety profile to date has been favorable.

Mo Qatanani: Translating this into the clinic, we saw from the TOPAS trial substantial and durable benefit across broad SMA patients.

Speaker Change: Leveraging the learnings from TOPAS, our pivotal study is designed for clinical success.

Mo Qatanani: Lastly, and importantly, with over 200 patient years of exposure, the safety profile to date has been favorable. With over 90% of our patients with non-epidural transom A remaining on study, both of these observations support the potential for long-term use.

Jing Marantz: With over 90% of our patients with non-amplitude SMA remaining on study, both of these observations support the potential for long-term use. Turning to slide 13, before I share the updated data, it's helpful to take a look at the natural trajectory of patients treated with SMN-targeted therapy. As Shane mentioned, at the recent Cures May meeting in June, Dr. Finkel and colleagues presented the long-term outcomes data from the Charish Shine Study, which enrolled SMA patients treated with Neusinerse.

Mo Qatanani: Turning to slide 13, before I share the updated data, it's helpful to take a look at the natural trajectory of patients treated with SMN-targeted therapy.

Shea: As Shea mentioned, that recent Cures May meeting in June , Dr. Finkel and colleagues presented the long-term outcomes data from the Cherish Shine study, which enrolled SMA patients treated with nusinersen.

Jing Marantz: The orange lines represent the trajectory of patients initially randomized to this nurse. As clear from these graphs, motor function as measured by Hammersmith improved initially. After one to two years, Hammersmith started to plateau, and over time, it started to decline.

Speaker Change: The orange lines represent the trajectory of patients initially randomized to news nursing. As clear from these graphs, motor function as measured by Hammersmith improved initially. After one to two years,

Speaker Change: Hammersmith started to plateau and over time it started to decline.

Unknown Executive: The solid orange line on top represents the subgroup of patients who did not have any scoliosis surgery, whereas the dotted orange line represents those who underwent scoliosis surgery during the study, that's well into the interval where the Hemmerson score is expected to plateau or decline. The key point here is that despite treatment with a highly effective therapy, the natural trajectory of these patients is that of progressive decline after the initial impact.

Jing Marantz: The solid orange line on top represents the subgroup of patients who did not have any scoliosis surgery, whereas the dotted orange line represents those who underwent scoliosis surgery during the study. Psoriasis is an abnormal and progressive curvature of the spine that's part of the SMA disease pathology. The condition is commonly managed with surgery. However, scoliosis surgery is well known to be a confounding factor that impacts motor function assessment. Therefore, it's not at all surprising for you to see that the hemorrhage must decline faster for those patients who have scoliosis surgery.

Speaker Change: this solid orangejoining on top represents this subgroup of patients who did not have any sscoof surgery whereas adatted orange line representsatives who underwent coosis search during the study

Speaker Change: Scoliosis is an abnormal and progressive curvature of the spine that's part of the SMA disease pathology. The condition is commonly managed with surgery.

Speaker Change: Scoliosis surgery is well known to be a confounding factor that impacts the motor functioning assessments.

Mo Qatanani: Therefore, it's not at all surprising for you to see that the hemorrhage has declined faster for those patients with scoliosis surgery. For this reason, we'll focus on our discussion on data for those without scoliosis surgery.

Jing Marantz: For this reason, we'll focus on this in our discussion of data for those without scoliosis surgery. To put things in context, patients enrolled in our Topaz study had, on average, two years of prior mucinerosin treatment, that's well into the interval where the Hemmerson score is expected to plateau or decline. The blue-shaded area highlights the relative period of loose nursing exposure, similar to that of a Topaz patient

Speaker Change: To put things in context, patients enrolled in our Topaz study had, on average, two years of prior mucinerosin treatment. That's well into the interval where the Hemmersmith score is expected to plateau or decline.

Speaker Change: The blue shaded area highlights the relative period of looseners and exposure similar to that of TOPAS patients.

Jing Marantz: Focusing on this solid orange line within this period, over the course of four years for patients without scoliosis surgery, the Hema Smith score declined by greater than one point. The key point here is that despite treatment with a highly effective therapy, the natural trajectory of these patients is that of progressive decline after the initial impact. Returning to slide 14.

Speaker Change: Focusing on this solid orange line within this period, over the course of four years for patients without scoliosis surgery, the HEMIS score declined greater than one point.

Speaker Change: The key point here is that despite treatment with a highly effective therapy, the natural trajectory of these patients is that of progressive decline after the initial increase.

Jing Marantz: It is in this context that I'd like to provide a preview of the updated motor function data from the TOPAS trial at 48 months. Similar to how we previously shared our 24-month and 36-month data, these bar graphs represent the motor functioning outcomes measured by Hemmersmith for the pooled non-ambulatory SMA patients ages 2 to 21 on the left, and the 2-12 subset on the right. Hammersmith is a validated scale designed specifically for SMA that measures gross motor function. As mentioned before, scoliosurgery is a known confounding factor.

Unknown Executive: It is in this context I'd like to provide a preview of the updated motor function data from the TOPAS trial at 48 months and the 2-12 subset on the right. Hammersmith is a validated scale designed specifically for SMA that measures gross motor function. Turning to the next slide, a similar trend was observed for RUM, which focuses more on upper limb function. The improvement in RUM seen at six and 12 months continued to strengthen over time and was maintained over 48 months, both in the 2 to 21 group and in the 2 to 12 subset. Turn to slide 16. And it's just like 17.

Speaker Change: the turning to slide fourteen

Speaker Change: it is in this context i'd like to provide a preview of the updated motor function data from this hope z trial at forty eight months

Speaker Change: Similar to how we previously shared our 24-month and 36-month data, these bar graphs represent the motor functioning outcomes measured by Hemmersmith for the pooled non-ambulatory SMA patients ages 2 to 21 on the left.

Speaker Change: and the 2-12 subset on the right.

Speaker Change: Hammersmith is a validated scale designed specifically for SMA that measures the gross motor function.

Jing Marantz: Assessments for the surgery and after the surgery are censored in our analysis, but you can see from these graphs that Hammersmith continues to improve. The increase that we see at 6 and 12 months was maintained over the course of 48 months. Knowing that the motor function of these patients would otherwise decline at this point in their treatment journey, it is reassuring to see that the motor function benefit that we saw earlier was sustained over the course of 48 minutes.

Speaker Change: As mentioned before, scoliosurgery is a known confounding factor. Assessments for the surgery

Jing Marantz: Similar trend was observed for RUM, which focuses more on upper limb function. The improvement in RUM seen at 6 and 12 months continued to strengthen over time and was maintained over 48 months, both in the 2 to 21 group and in the 2 to 12 subset. For patients who are non-ambulatory, continued improvement in their upper lung function is particularly important, as it represents their ability to perform activities of daily living, such as their ability to lift a cup or push a button. Turn to slide 16.

Speaker Change: Similar trend was observed for run which focuses more on the upper limb function the improvement in brown seen at six and 12 months continued to strengthen over time and was maintained over 48 months both in the 2% to 21 group and in the two to 12 subset.

Speaker Change: For patients who are non ambulatory and continued improvement in their upper limb function is particularly important as it represents their ability to perform activities of daily living such as our ability to lift a cup or pushing that button.

Speaker Change: Turning to slide 16, so taken together the updated topaz data with sustained clinical benefit consistency of findings and favorable safety profile with low discontinuation rate reinforces our belief that a critical math has the potential to provide substantial benefit.

Jing Marantz: So taken together, the updated Topaz data would sustain a clinical benefit, consistency of findings, and favorable safety profile with a low discontinuation rate reinforces our belief that a pinnacle map has the potential to provide substantial benefit to patients with SMA by directly addressing the underlying muscle pathology. We plan to share additional detail at future medical meetings.

Speaker Change: Two patients with SMA by directly addressing the underlying muscle pathology.

Speaker Change: We plan to share additional detail at future medical meetings.

Speaker Change: Turning to slide 17.

Jing Marantz: Welcome to Learning is Topaz. Our pivotal SAFIRE study was designed for clinical success. Here you can see the study schematic to highlight just a few key points. The main advocacy population for SAFIRE reflects the population in Topaz that showed transformative potential.

Speaker Change: Those are the learnings with Topaz, our pivotal Sapphire study was designed for clinical success.

Speaker Change: Here you can see the study schematic to highlight just a few key points.

Unknown Executive: The main advocacy population for SAFIRE reflects the population in Topaz that showed transformative potential, to demonstrate both a statistically and clinically meaningful difference with the ability to capture at least a two-point difference on Hammersmith versus placebo. Importantly, we have been able to engage with both the FDA and EMA and align with them on key aspects of the study design.

Speaker Change: The main efficacy population for Sapphire reflects the population topaz that showed transformative potential.

Jing Marantz: The primary endpoint is Hemersmith at 12 months, the same as Topaz, and the 20 mg dose was chosen based on sustained target engagement and clinical benefits observed from Topaz. The twelve is designed to demonstrate both a statistically and clinically meaningful difference with the ability to capture at least two point difference on Hammersmith versus placebo.

Speaker Change: The primary endpoint is at 12 months the same as Topaz and then 28 dose was chosen based on sustained target engagement and clinical benefit observed from topaz.

Speaker Change: The trial is designed.

Speaker Change: To demonstrate both statistically and clinically meaningful difference with the ability to capture at least two point difference on Hammersmith versus placebo.

Jing Marantz: Importantly, we have been able to engage with both the FDA and the EMA and align with them on key aspects of the study design. This design balances the objective to optimize for clinical success with our effort to be broadly representative of the patient population we're trying to serve. Knowing the natural trajectory of the SMA patients instead of a progressive decline over time, despite the initial improvement seen with SMN therapy, we're encouraged to see that the clinical benefit from Topaz continues to hold.

Speaker Change: Importantly, we have been able to engage with both the FDA and EMA and align with them on key aspects of the study design.

Speaker Change: This design balances the objective to optimize for clinical success with our effort to be broadly representative of the patient population, we're trying to serve.

Speaker Change: Knowing the natural trajectory of SMA patients instead of a progressive decline over time. Despite the initial improvement seen with SMA therapy, we're encouraged to see that clinical benefit from Topaz continues to hold so taken together we are optimistic about our goal to bring this potential medicines to patients.

Jing Marantz: So taken together, we're optimistic about our goal to bring this potential medicine to patients. Now turning to our cardiometabolic clinical program on slide 18. Obesity is recognized as a significant OMAD need. The rapid adoption of semaglutide and shazapatide has brought about profound benefits for patients with obesity. A key issue that has arisen is the significant loss of lean muscle mass associated with its use. Aside from day-to-day physical function, muscle plays an important role in energy, metabolism, and glucose homeostasis, and therefore, maintaining appropriate levels of lean muscle is essential to healthy living.

Speaker Change: Now turning to our cardio metabolic clinical program on slide 18.

Speaker Change: Obesity is recognized as a significant unmet need the rapid adoption of smuggled tight and shows appetite has brought about about profound benefit to patients with obesity.

Speaker Change: The key issue that has arisen is the significant loss of lean muscle mass associated with its use.

Speaker Change: Aside from day to day physical function muscle plays an important role in energy metabolism in glucose homeostasis, and therefore, maintaining appropriate levels of lean muscle is essential to healthy living.

Jing Marantz: As a company with deep expertise in muscle, we're uniquely positioned to address this unmet need. To that end, I'm incredibly proud of our team that worked hard to enable us to initiate the EMBRACE study ahead of schedule. We're seeing great momentum in our enrollment, and now expect to report top line results in Q2 of next year.

Speaker Change: As a company with deep expertise in muscle, we're uniquely positioned to address this unmet need to that and I'm incredibly proud of our team that worked hard to enable us to initiate the embrace study ahead of schedule, we're seeing great momentum in our enrollment and now expect to report top line in Q2 of next year.

Jing Marantz: The primary objective of the study is to demonstrate the effect of a selective mild fat inhibitor to preserve lean muscle in a setting of obesity. We also want to confirm that the safety and tolerability profile in the obese population remains favorable, thus supportive of long-term use. And lastly, we're interested in understanding the potential effect across a number of exploratory endpoints, including the effect on metabolic profile and physical function. So to conclude, the study schematic is shown here. Overweight or obese patients are randomized one-to-one to either the combination of epidicomab plus a GLP agonist or the combination of placebo and a GLP agonist. Treatment duration for the combination is 24 weeks.

Speaker Change: The primary objective of this study is to demonstrate the effect of a selective models that inhibitor to preserve lean muscle in the setting of obesity.

Speaker Change: We also wanted to confirm that the safety and Tolerability profile in the obese population remains favorable that's supportive of the long term use and lastly, we're interested in understanding the potential effect across a number of exploratory endpoints, including the effect on metabolic profile and physical function.

Speaker Change: So to conclude the study schematic is shown here overweight or obese patients are randomized one to one to either the combination of a critical math plus GOP agonist or the combination of placebo and a <unk> agonist.

Speaker Change: Treatment duration for the combination of 24 weeks.

Jing Marantz: The primary endpoint is lean muscle mass change from baseline by DEXA scan at 24 weeks. Secondary endpoints include safety and tolerability, PKPD, and other weight loss parameters. Exploratory endpoints on metabolic profile and physical function are also included. The study includes an additional endpoint at 32 weeks so we can get a preliminary read of the durability of the effect. In other words, the potential effect to attenuate rebound weight gain. With this, I'm delighted to introduce Mo, our Chief Scientific Officer, to show you the exciting science behind our differentiated

Speaker Change: The primary endpoint is lean muscle mass change from baseline by <unk> scan at 24 weeks secondary endpoints include safety and Tolerability PK PD and other weight loss program.

Speaker Change: Anders.

Speaker Change: Exploratory end points on metabolic profile and physical function are also included.

Speaker Change: The study includes an additional assessment.

Speaker Change: At 32 weeks, so we can get a preliminary read of the durability of effect in other words, the potential effect to attenuate rebound weight gain.

Speaker Change: With this I'm delighted to introduce now.

Speaker Change: Our Chief Scientific Officer to show you the exciting science behind our differentiated approach.

Mo Qatanani: Thank you, Jing. And good morning, everyone. Next slide, please. I'm going to start with this slide that emphasizes the points made by Jay and Jing earlier.

Speaker Change: Thank you Jane and good morning, everyone next slide please.

Jane: I'm going to start with this slide emphasizes the points made by Jay and Jim earlier, we have a highly differentiated platform that is producing innovative and very selective candidates combined with our translational expertise focus and passion. We have translated these innovations to success in the clinic across many therapeutic areas to benefit our patients.

Mo Qatanani: We have a highly differentiated platform that is producing innovative and very selective candidates. Combined with our translational expertise, focus, and passion, we have translated these innovations into success in the clinic across many therapeutic areas to benefit our patients. First, we developed a particular map, our Selective Anti-Latent Myostatin for SMA, proved its efficacy in a translational mouse model, and took it to the clinic. And as you heard earlier, we have very promising data from our TOPAS trial in SMA patients, where we saw substantial and sustained improvement in motor function over 48 months with a superb safety profile. And we look forward to seeing our phase three SAFIRE trial data in Q4.

Mo Qatanani: Second, we developed SRK181, our selective anti-latent TGF-beta-1 antibody to overcome primary resistance to checkpoint inhibitors in patients with advanced solid tumors. We have shown its efficacy in multiple preclinical translational models, and took it to the clinic, where we showed promising efficacy across multiple tumor types in our Phase 1b DRAGON trial, as highlighted in our recent oral presentation at ASCII. Moving to SRK439, our selective anti-lipid myosin antibody that is designed for obesity, which showed its ability to preserve muscle mass and improve the metabolic profile during GLP-1-induced weight loss in multiple studies in translational obese mouse models.

Unknown Executive: Combined with our translational expertise, focus, and passion, we have translated these innovations into success in the clinic across many therapeutic areas to benefit our patients. Second, we developed SRK181, our selective anti-latent TGF-beta-1 antibody, to overcome primary resistance to checkpoint inhibitors in patients with advanced solid tumors. We have shown its efficacy in multiple preclinical translational models, and took it to the clinic, where we showed promising efficacy across multiple tumor types in our Phase 1b DRAGON trial, as highlighted in our recent oral presentation at AFSCME, which showed its ability to preserve muscle mass and improve the metabolic profile during GLP-1-induced weight loss in multiple studies in translational obese mouse models. We will be highlighting data that we recently shared in an oral presentation at the American Diabetes Association on this call, and we look forward to filing an IND in 2025 and advancing this therapy to the clinic.

Speaker Change: First we develop a particular amount of our selective until it in my statin for somebody who this efficacy and translational mouse model to get to the clinic and as you heard earlier, we have very promising data from our topaz child with SMA in SMA patients, where we saw a substantial and sustained improvement in motor function over 48 months with superb safety.

Speaker Change: Profile and we look forward to seeing our phase III Zafar trial data in Q4.

Speaker Change: We developed a socket.

Speaker Change: One our selective anti <unk> and TGF beta one antibody to overcome primary resistance to checkpoint inhibitors in patients with advanced solid tumors, we are showing its efficacy in multiple preclinical translational models to get to the clinic, where we showed promising where we showed promising efficacy across multiple tumor types in our phase <unk> Dragon trial.

Speaker Change: As was highlighted in our recent oral presentation at Astro.

Speaker Change: Moving to Africa for three long our selective anti <unk> antibody that is designed for obesity. We showed its ability to preserve muscle mass and improve the metabolic profile during <unk> induced weight loss and multiple studies in translational obese mouse models, we will be highlighting data that we recently shared in an oral presentation.

Mo Qatanani: We will be highlighting data that we recently shared in an oral presentation at the American Diabetes Association on this call, and we look forward to filing an IND in 2025 and advancing it to the clinic. Finally, we developed SRK373, our selective, highly differentiated anti-HLA and TGF-beta-1 antibody that has the added selectivity of inhibiting TGF-beta-1 only when it is presented in the matrix of tissues, but not Given this unique mechanism, a potential efficacy and safety advantage in fly product diseases.

Speaker Change: <unk> at the American Diabetes Association on this call and we look forward to filing in R&D in 2025 and advancing to the clinic.

Speaker Change: Finally, we developed <unk> hundred 73, our selective highly differentiated anti TGF beta one antibody that has the added selectivity of inhibiting TGF beta one only one presented and the matrix of tissues, but not immune cells. Given this unique mechanism of potential efficacy and safety advantage and fibrotic diseases, we showed.

Mo Qatanani: We showed efficacy of this molecule in multiple translational fibrotic disease models, including lung, renal, and liver fibrosis. This was recently highlighted in a publication featured on the cover of Science Signaling, and we look forward to filing an IMD in 2026 and testing this unique and differentiated mechanism in the clinic.

Speaker Change: Efficacy of this molecule in multiple translational fibrotic disease models, including lung renal and liver fibrosis. This.

Mo Qatanani: This was recently highlighted in a publication featured on the cover of Science Signaling, and we look forward to filing an IMD in 2026 and testing this unique and differentiated mechanism in the clinic. Focusing on SRK439 specifically, we have strong scientific validation and critical evidence that gives us confidence in its potential to drive healthier weight management during GLP-1 induced weight loss. We also showed preclinically that treatment with SRK439 leads to an increase in lean mass and attenuation of fat mass regain following GLP-1 withdrawal, leading to improved body composition. As you can see in the blue bar.

Speaker Change: This was recently highlighted in a publication featured on the cover of <unk> signaling and we look forward to filing an IND in 2026 and testing this unique and differentiated mechanism in the clinic.

Speaker Change: Slide 22.

Mo Qatanani: Focusing on SRK439, we have strong scientific validation and clinical evidence that gives us confidence in its potential to drive healthier weight management during GLP-1 induced weight loss. We have shown preclinically in a translational obesity mouse model that SRK439 leads to preservation of lean mass during GLT1 induced weight loss, solving one of the biggest challenges in this area. This was also accompanied by improvements in the metabolic profile, namely an additional 20% reduction in blood glucose levels on top of the reduction seen with GLP-1 treatment alone. That data was shared at a Keystone meeting earlier this year.

Speaker Change: Focusing on as I say it puts you in line, we have strong scientific validation and preclinical evidence that gives us confidence in its potential to drive healthier weight management <unk> induced weight loss, we have shown pre clinically and translational obesity mouse model that was okay for three nine leads to preservation of lean mass during <unk>.

Speaker Change: <unk> induced weight loss solving one of the biggest challenges in this area.

Speaker Change: This was also accompanied by improvements in metabolic profile, namely an additional 20% reduction in blood glucose levels on top of the reduction seen with <unk> treatment alone that data was shared at the Keystone meeting earlier this year.

Mo Qatanani: We also showed preclinically that treatment with SRK439 leads to an increase in lean mass and attenuation of fat mass regain following GLP-1 withdrawal, leading to improved body composition. This addresses another key challenge of GLP-1 receptor treatment, namely the durability of effects after treatment cessation. We will highlight some of that data today.

Speaker Change: We also show pre clinically that treatment with US Okay forty-nine leads to an increase in lean mass and that simulation of fat mass regain following DLP, one withdrawal leading to improved body composition.

Speaker Change: The address is another key challenge of DLP, one receptor attainment, namely the durability of effects after treatment cessation, we will highlight some of that data today.

Mo Qatanani: Finally, in a preclinical head-to-head study in the same diet-induced obesity model, we showed that SRK439 is superior to the non-selective anti-actin receptor antibody that is currently being tested in the clinic. As highlighted earlier, muscle is critical for overall health, and the ability of SRK439 to preserve muscle during weight loss highlights the potential it can play in driving healthier weight management and better outcomes in obese patient populations In addition to loss of lean mass during weight loss, another key challenge of incretin or GLP-1 induced weight loss is the durability of effect and the loss of benefits upon cessation of treatment.

Speaker Change: In a preclinical head to head study and the same dive in D. C. D. C model. We showed that it's okay for three nine is superior to the non selective anti activin receptor antibody that is currently being tested in the clinic.

Speaker Change: As highlighted earlier muscle is critical for oral health and the ability of US. Okay 439 to preserve muscle joined weight loss highlights of potentially can play in driving healthier weight management and better outcomes in obese patient population.

Speaker Change: Thanks, a lot.

Speaker Change: In addition to loss.

Speaker Change: Listen to lots of lean master and weight loss. Another key challenge over anchor tenant would you hope you Wanna induced weight loss is the durability of effect on the loss of benefits upon cessation of treatment.

Mo Qatanani: This slide highlights the ability of SRK439 to address this challenge in the translational obesity mass model. The graph on the upper left shows lean mass in different treatment groups during semiglutide-induced weight loss or upon semiglutide withdrawal, as you can see in the blue bar.

Speaker Change: This slide highlights the ability of our survey for three nine to address this challenge and translation of obesity mouse model.

Speaker Change: The graph on the upper left shows lean mass and different treatment groups during semi glucide induced weight loss or upon stomach we thought withdrawal.

Speaker Change: As you can see in the Blue bar.

Mo Qatanani: Semi-glutide treatment led to considerable lean mass loss during the treatment phase of 35 days, as expected. However, co-treatment with SRK439 led to the preservation of the lean mass during the semi-glutar treatment phase, as you can see in the green line. In addition, animals treated with SRK protein line had significantly higher lean mass after discontinuation of semaglutide if you compare the green line versus the blue line between days 35 and the end of the study. The lower graph shows the fat mass change during the study. Cessation of semiglutar treatment on day 35 led to a rapid rebound effect and fat mass regain, as expected.

Speaker Change: <unk> treatment led to considerable lean mass loss during the treatment phase of 35 days as expected.

Mo Qatanani: Co-treatment with SRK439 led to the preservation of lean mass during the semi-glutar treatment phase, as you can see in the green line. In addition, animals treated with SIPA protein line had significantly higher lead mass after discontinuation of semi-glutide if you compare the green line versus the blue line between days 35 and the end of the study. The lower graph shows the fat mass change during the study.

Speaker Change: Co treatment with as I say for three nine led to the preservation of the lean mass during the cycle looks like treatment phase as you can see in the Green line.

Speaker Change: In addition animals treated with RFA for three line has significantly higher lean mass after discontinuation of stomach Leuthard. If you compare the green line versus the Blue line.

Speaker Change: Between day 35 at the end of the study.

Speaker Change: <unk> graph shows the fat mass change during the study.

Speaker Change: Secession of <unk> treatment on day, 35 leads to rapid rebound effect and fat mass regain as expected.

Mo Qatanani: Co-treatment with SRK439 led to attenuation of the fat mass regain following semaglutide withdrawal, as you can see when comparing the blue line for semaglutide alone and the green line for SRK439 co-treatment. This slide shows the favorable body composition in the SIKF439 treated animals versus controls upon semaglutide withdrawal at the end of the study. In the graph on the left, animals treated with SRK-539 had higher proportions of lean mass after cessation of semaglutide treatment, as you can see in the green bar versus the blue bar.

Speaker Change: Treatment with US Okay, 439 led to attenuation of itself Atmos regain following <unk> withdrawal as you can see when comparing the full line or some of them along.

Speaker Change: Alone and the Green line, whereas I think for three nine per treatment.

Juan: Thanks Juan.

Juan: This slide shows the favorable body composition and designated <unk> hundred nine treated animals versus controls upon stomach we've talked with you all at the end of the study.

Mo Qatanani: In the graph on the left, animals treated with SRK439 had higher proportions of lean mass after cessation of somaglutide treatment, as you can see in the green bar versus the blue bar. This highlights the potential of SRK439 in addressing a key challenge in GLP-1-induced weight loss by supporting more durable weight management with a more favorable and healthier body composition. This highlights the competitive profile of SRK439 with superb efficacy in preserving muscle mass and enhancing loss of fat mass while avoiding the potential liabilities of non-selective approaches.

Speaker Change: The graph on the left animals treated with associated with your line has a higher proportion of lean mass after cessation of stomach flu type treatment as you can see in the green bar versus the Blue bar.

Mo Qatanani: In addition, if you look at the graph that measures fat mass, mice treated with SRK439 in the green bar had significantly lower regain in the fat mass percentage versus the IgG control in the blue bar. Hence, SRK439 treatment led to a more favorable overall body composition at the end of the withdrawal period. This highlights the potential of SRK-439 in addressing a key challenge in GLP-1-induced weight loss by supporting more durable weight management with a more favorable and healthier body composition.

Juan: In addition, if you look on the graph on the light that measures fat mass mice treated with US, Okay, 439, and the Green bar, how significantly lower regain in the fat mass percentage versus the ITG control in the Pilbara.

Juan: So I think for three nine treatment, but to a more favorable overall body composition at the end of their withdrawal period.

Juan: Highlights the potential of obstructive with Hunan and addressing a key challenge in the <unk> induced weight loss by supporting a more durable weight management with a more favorable and a healthier body composition.

Juan: Alright.

Mo Qatanani: This is data we recently shared during our investor event in May, where we highlighted the competitive profile of SRK 439 versus a non-selective MyStandard approach of another model. This is a head-to-head study in the translational diet-induced obesity mouse model, and the graph is showing the percent change in lean mass upon semidilatory treatment.

Speaker Change: This is data we recently shared during our Investor event in May where we highlighted the competitive profile of us okay for canine versus a non selective my sign approach of another molecule.

Speaker Change: This is a head to head study and the translation of Diamond <unk> Mouse model and the graph is showing the percent change in lean mass up on somebody will talk treatment.

Mo Qatanani: As expected, semaglutide led to a significant reduction in lean mass, as you can see in the blue bar on the left. Asake 439 treatment led to preservation of lean mass, dose-dependently, and with doses as low as 0.3 mg per kg, as you can see in the bars in green. Also, preservation was achieved at significantly lower doses than the anti-active interceptor antibody, where we see lean mass preservation only at the highest dose tested of 20 mix per kick, as you can see in the bars in grad.

Speaker Change: As expected <unk> led to significant reduction in lean mass as you can see in the Blue bar on the left.

Speaker Change: Three nine treatment led to preservation of the mess dose dependent Lee and with doses as low as <unk> three <unk> as you can see in the bars in green.

Speaker Change: Also preservation was achieved a significantly lower doses than dance, our activin receptor antibody, where we see lean mass visitation only at the highest dose tested of 'twenty mix per gig as you can see in the pause in growth.

Mo Qatanani: It is worth noting that we see equivalent lean mass preservation at the 1 mg per kick dose level of SRK-149 versus the 20 mg per kick dose for the anti-active interceptor antibody. However, treatment with SRK 439 was also associated with enhancement of fat mass loss. This highlights the competitive profile of SRK439 with superb efficacy in preserving muscle mass and enhancing loss of fat mass, while avoiding the potential liabilities of non-selective approaches. It also supports a best-in-class subcutaneous profile for SRK439.

Speaker Change: It is worth noting that we see equivalent lean mass preservation of the one <unk> dose level 439 versus the 20 Meg per kg dose for the anti activin receptor antibody.

Speaker Change: Treatment with US. Okay 439 also was associated with enhancement of fat mass loss.

Mo Qatanani: This also supports a best-in-class subcutaneous profile for SRK439. Finally, we are leveraging our expertise in MiSTAN and the ability to develop anti-MiSTAN antibodies with exquisite selectivity to test our hypothesis and inform our obesity program. We will use our learnings from the EMBRACE trial to inform and potentially accelerate the development of SRK439, which we expect to file for regulatory approval in 2025.

Speaker Change: Highlights the competitive profile of associated with your line with superb efficacy and preserving muscle mass and enhancing loss of fat mass while avoiding the potential liabilities of non selected approaches. This also supports our best in class subcutaneous profile of course are associated with your line.

Speaker Change: That's fine.

Speaker Change: Okay.

Mo Qatanani: Finally, we are leveraging our expertise in MiSTAN and the ability to develop anti-MiSTAN antibodies with exquisite selectivity to test our hypothesis and inform our obesity program. Since a particular MAP is already in the clinic, it allows us to test this hypothesis really quickly in a clinical setting through our M-BRACE proof-of-concept study. This will demonstrate that a selective anti-myostin has the ability to preserve lean mass and influence metabolic parameters in the context of obesity during GLP-1-induced weight loss.

Speaker Change: Finally, we are leveraging our expertise in milestone and the ability to develop and somebody is that antibodies with exquisite selectivity to test our hypothesis and inform our obesity program.

Speaker Change: So it's a particular amount was already in the clinic. It allows us to test this hypothesis really quickly in a clinical setting through our embrace proof of concept study.

Speaker Change: This will demonstrate that our selective antibodies then has the ability to preserve lean mass and influenced metabolic parameters in the context of obesity <unk> induced weight loss we.

Mo Qatanani: We announced on Investor Day back in May that we initiated the trial ahead of schedule and the trial is enrolling well, so we now anticipate top-line data in the second quarter of 2025. We will use our learnings from the EMBRACE trial to inform and potentially accelerate the development of SRK439, which we expect to file for R&D in 2025. Now I'll hand it back to Jay. Well, thank you, Mo.

Speaker Change: We announced we announced during our Investor day back in May that we initiated the trial ahead of schedule and the trial is enrolling well. So we now anticipate top line data in the second quarter of 2025, we.

Speaker Change: We will use our learnings from the embraced trial to inform and potentially accelerate the development of US Okay for three nine.

Speaker Change: Where we expect to file in R&D in 2025.

Speaker Change: Now I'll hand, it back to Jay.

Jay Backstrom: Well, thank you Mo.

Jay Backstrom: So, in closing, it is an exciting time for Scholar Rock. We have met or exceeded all of our goals to date, including conducting a prime pre-submission meeting with the EMA in preparation for our European submission for a pedigree map. Initiating EMBRACE, continuing to advance SRK 439 to IND, and we're looking forward to the top line readout for SAPPHIRE as our next important milestone as we continue to initiate key activities in preparation for commercialization. Overall, a great time for Scholar Rock. That concludes our formal presentation. Sandra will now open the call to questions.

Jay Backstrom: So in closing it is an exciting time for scholar rock, we have met or exceeded all of our goals to date, including conducting a prime pre submission meeting with EMA and preparation for our European submission for a pedigree mab initiating embrace continuing to advance <unk> hundred 90, <unk> D and we're looking forward to the top.

Operator: Thank you. As a reminder, to ask a question, please press star 11 on your telephone and wait for your name to be announced. To re-enter your question, please press star 1 and 1 again. We will now take the first question. On the line for Michael Yee from Jefferies, please go ahead.

Unknown Executive: Initiating EMBRACE, continuing to advance SRK 439 to IND, and we're looking forward to the top line readout for SAFIRE as our next important milestone as we continue to initiate key activities in preparation for commercialization. That concludes our formal presentation. Sandra will now open the call to questions.

Jay Backstrom: Offline readout for Sapphire as our next important milestone as we continue to initiate key activities and preparation for commercialization overall, a great time for scholar rock.

Jay Backstrom: That concludes our formal presentation Sandra will now open the call up for questions.

Speaker Change: Thank you.

Speaker Change: As a reminder to ask a question. Please press star one one on your telephone and wait for your name to be announced two weeks or your question. Please press star one on one again.

Speaker Change: We will now take the first question.

Operator: To re-enter your question, please press star 1 on 1 again. On the line from Michael Yee from Jefferies, please go ahead.

Speaker Change: From the line of Michael Yee from Jefferies. Please go ahead.

Michael Yee: Hello, good morning. Thank you guys for the update. We had two questions. First, obviously, you are reading out in SMA, the pivotal study, and some others are also reading out all around the same time. I guess I just wanted to understand your view on one of the competitors, Roche, because I think their antibody is similar. And so I just wanted to understand if you have seen or believe there are any differences in that study design or readout, how to think about that as it relates to your readout also coming around the same time.

Michael Yee: Hello. Good morning, Thank you guys for the update but we had two questions.

Michael Yee: First obviously you are reading out.

Michael Yee: In SMA the pivotal study and some others are also reading out all around the same time I guess I just wanted to understand.

Speaker Change: Your view on one of the competitors.

Speaker Change: Roche because I think they are antibody is similar.

Speaker Change: Just wanted to understand if you have seen or believe there are any differences in that study design or readout, how to think about that as it relates to your retail also coming around the same time.

Michael Yee: And on the obesity side, I wanted to understand, first, are you stratifying with terzapatide and SEMA? Because I noticed you're offering both, and those drugs do have different effects. And I wanted to know if you are stratifying, and do you expect that your drug will completely eliminate lean muscle loss, and that is your base case for both of those drugs in your readout? Thank you.

Speaker Change: And on the obesity side I wanted to understand first or you should try to fine with.

Speaker Change: With tours appetite in semi because I noticed your offering both drugs do have different effects.

Speaker Change: And I wanted to know if you start to find and do you expect that your drug will.

Speaker Change: Completely eliminate the lean muscle loss and that is your base case for both of those drugs and you read out. Thank you.

Jay Backstrom: Alright, so Michael, maybe I'll go ahead and tackle, this is Jay. I'll tackle the first question about the upcoming readouts. So clearly, we're excited to report out our top line in Q4.

Jay Backstrom: Alright, So Michael maybe I'll go ahead and tackle this is Jay I'll tackle the first question about the upcoming Readouts.

Michael Yee: So clearly we are excited to report our you know our topline in Q4.

Jay Backstrom: What we've seen as we follow others in the space, Roche in particular, they continue to suggest that they're gonna report out from their early phase of the study, so they're really establishing dose and effect as opposed to reporting out their top line phase three trial, which is ongoing. The most recent update that I'm aware of is that they're targeting somewhere in the 2026 or beyond phase.

Speaker Change: What we've seen as we follow our others in the space Roche in particular, they continue to suggest that they're going to report out from there.

Unknown Executive: early phase of the study. So they're really establishing dose and effect, as opposed to reporting out their top line phase three trial, which is ongoing. The most recent update that I'm aware of is that they're targeting somewhere in the 2026 or beyond phase.

Speaker Change: The early phase of the study or they are really establishing dose in effect.

Speaker Change: As opposed to reporting out their topline phase III trial, which is ongoing the most recent updates that I'm aware of is that theyre targeting somewhere in the 2026 or beyond it phase so.

Unknown Executive: So, you know, I think it'll be interesting to see their results, but clearly in a different place, and to remind them that they're studying only with RISDAPlan, where we're agnostic to both nusinersen and RISDAPlan. And then with respect to EMBRACE, you know, Jing can answer that question, but since I'm going to comment, no, we didn't stratify by semaglutide or terzapatide in this proof of concept study. We're really interested in just seeing the effect on both. We think we should have an effect on both. Similar to our SMA program, we think we should be agnostic to treatment.

Speaker Change: I think it will be interesting to see their results, but clearly in a different place and to remind them. They are studying only with risk to plan, where we are agnostic to both new centers and enrich the plan.

Speaker Change: And then with respect to embrace.

Jim: Jim can answer but.

Jim: I'm going to comment no we didnt stratify by some magnetite her tours appetite in this proof of concept study, we're really interested in just seeing the effect on both we think we should have an effect on both similar to our SMA program. We think we should we should be agnostic to treatment.

Jay Backstrom: Thank you very much. And we'll see. I think ultimately the amount of preservation for lean muscle will be interesting. I think what you saw from Mo is that the data presented at ADA were very impressive because it did show that we did actually maintain and preserve lean muscle mass upon cessation. And then, of course, we saw continued increase in lean muscle mass upon cessation.

Unknown Executive: And we'll see. I think ultimately the amount of preservation for lean muscle will be interesting. I think what you saw from Mo is that the data presented at ADA were very impressive because it did show that we did actually maintain and preserve lean muscle mass upon cessation. And then, of course, we saw continued increase in lean muscle mass upon cessation.

Speaker Change: And we will see I think ultimately the amount of preservation for lean muscle will be interesting I think what you saw from MAU is that the data presented at Ada were very impressive because it did show that we did actually maintain and preserve and then of course, we saw continued increase in lean muscle mass upon cessation I think those those results likely will be reproduced in clinic.

Jay Backstrom: I think those results likely will be reproduced in clinic. But again, we're running the proof of concept to see. So I'm looking forward to telling you the top line results. I'm glad we're going fast. The team is impressive, right?

Unknown Executive: I think those results likely will be reproduced in clinic, but again, we're running the proof of concept to see. So, I'm glad we're going fast. The team is impressive, right? We've accelerated the enrollments, and I'm looking forward to reporting our top line results for both.

Speaker Change: But again, we're running the proof of concept to see so looking forward to we're telling you the topline results, but I'm glad we're going fast the team is impressive right. We've accelerated the enrollment and looking forward to reporting our top line for both.

David Nierengarten: We've accelerated the enrollments and are looking forward to reporting our top line for both. Thank you. From the line of David Nierengarten from Bread for Securities, please go ahead.

Speaker Change: Thank you.

Operator: We will now take the next question. On the line from David Nierengarten from Bread for Securities, please go ahead.

David Nierengarten: We will now take the next question. On the line from David Nierengarten from Bread for Securities, please go ahead.

Speaker Change: We will now take the next question.

Speaker Change: From the line of David near and Garten from Wedbush Securities. Please go ahead.

Speaker Change: Hey, Thanks for taking the question that's on I put them are grabbing SMA.

Speaker Change: When you look at the longer term data or any effect on that.

Speaker Change: It could be attributed to the.

Speaker Change: The children aging or.

Speaker Change: Are you confident in the differential still.

Speaker Change: From the base from the base case on background therapy on the historical Clint.

Speaker Change: Clinical studies thanks.

Jay Backstrom: Yeah, well, maybe I'll start, maybe if Jing wants to add something about the historical data. You know, it's really interesting, right?

Ken: Yeah, well, maybe I'll start and maybe if Ken wants to add about the historical data. It's really interesting right I think the beauty, David as I say with the <unk> program is that given the safety and Tolerability that this can be chronic treatment for children with SMA and.

Jay Backstrom: I think the beauty, David, as I see it with the Epidogramab program, is that, given its safety and tolerability, this can be a chronic treatment for children with SMA. And I, you know, if we think about the physiology for maintaining and enhancing muscle growth and function, it actually would be optimal to see that continue through the growth and development of these children as they become young adults, and hopefully, maintain their activity of daily living and, in fact, if not, improve it further. So I think that it's likely a combination of several things.

Speaker Change: If we think about the physiology for maintaining and enhancing muscle growth and function. It actually would be optimal to see that continue through growth and development of these children as they get into young adults and hopefully maintain their activities of daily living and in fact, if not improve it further so I think that it's likely a combination I think the fact that.

Jay Backstrom: I think that the fact that we're continuing treatment is good. And again, what Jing said, it's very, very encouraging. We're very impressed as we continue to see the maintenance and sustained effect over time, particularly in light of the decline that you see with nusinersen. I don't know, Jing, if you wanted to add to that.

Speaker Change: We're continuing treatment as to the good.

Speaker Change: And again, what Jim said is very very encouraging I mean, we were very impressed as we continue to see the maintenance and sustained effect over time.

Jim: Particularly in light of the decline that you see with new centers and no change if you wanted to add to that yeah. So I think that you covered most of it Jay it sounds a couple of things to add one is that Mechanistically I think Jay pointed out this as well.

David Nierengarten: Yeah, I think that you covered most of it, Jay. So, just a couple of things to add.

Jing Marantz: Yeah, I think that you covered most of it, Jay. So, just a couple of things to add.

David Nierengarten: One is that mechanistically, I think Jay pointed out this as well, myostatin has there has been a large body of literature that really speaks to the effect of myostatin regulating muscle throughout life from early development all the way through adulthood. And so that has been well documented. An application of myostatin has had no documented negative effect.

Jing Marantz: One is that mechanistically, I think Jay pointed this out as well. Myelostatin has been a large body of literature that really speaks to the effect of myelostatin regulating muscle throughout life from early development all the way through adulthood. And so that has been well documented, and abrogation of myelostatin has had no documented negative effect.

Speaker Change: Modest, adding hasnt there hasnt been a large body of literature that really speaks to the fact that the non statin regulating muscle throughout life from early development all the way through adulthood, and so that has been well documented.

Speaker Change: And obligations of Myostatin has had no document at a negative.

David Nierengarten: And that's true in animals and in humans. So that's point number one. Point number two is that, you know, the question I think Jay addressed this, you know, there is probably a component of development. However, what's really important is that the patient population that I showed you and Dr. Finkel and colleagues presented are very similar patients. You know, if you look at our Topaz patients from the patient age, the sort of duration of prior therapy, and also the type of patients enrolled in baseline functional status, all of those things point out that these patients are very similar. So compared to what these patients are otherwise expected to do, we're very encouraged to see the continued benefit.

Jing Marantz: And that's true in animals and in humans. So that's point number one. Point number two is that, you know, the question Jay addressed is probably a component of development. However, what's really important is that the patient population that I showed you and Dr. Finkel and colleagues presented are very similar patients. You know, if you look at our telepaths patients from the patient age, the sort of duration of prior therapy, and also the type of patients enrolled in baseline functional status, all of those things point out that these patients are very similar. So compared to what these patients are otherwise expected to do, we're very encouraged to see the continued benefit.

Speaker Change: And that's true in animals and in human So that's point number one point number two is that a.

Speaker Change: The question I think Jay addresses the there is probably it.

Speaker Change: A component of the development. However, what's really important is that the patient population that I showed you and Dr. Finkel and colleagues presented or there is some of our patients.

Speaker Change: You know if you look at our the topaz patient from the patient age the sort of the duration of prior therapy and also types of patients enrolled in baseline functional status all of those things to point out that these patients are very similar ourselves.

Speaker Change: Compared to what these patients are otherwise expect it to do we're very encouraged to see the continued benefit Holt.

Speaker Change: Thanks.

Speaker Change: Yeah.

Speaker Change: Thank you we will now take the next question.

Etzer Darout: Thank you. We will now take the next question. On the line from Etzer Darout from VMO Capital Markets, please go ahead.

Operator: From the line of Etzer Darout from VMO Capital Markets, Please go ahead.

Speaker Change: From the line of it Sir.

Diverged: Diverged from BMO capital markets. Please go ahead.

Etzer Darout: Great, thanks for taking the question. Just a couple here. As we approach the top-line SAFIRE data, I just wondered if you had any updated insights on sort of potential access or pair dynamics for the use of the pedigree map to standard of care, or will you need, you know, data in hand, I guess, for more productive conversations? And then, as you advance SRK 373 for fibrosis and look sort of across your TGF beta portfolio as it grows, you know, how are Yeah, very good. So, let me try it.

Speaker Change: Great. Thanks for taking our question just a couple here as we approach the topline data just wondered if you had any updated insights on sort of potential.

Speaker Change: Sensor payer dynamics for the use of pilgrim added to standard of care or would you need data in hand, I guess from a productive conversations and then as you advance sort of <unk> hundred 73, fibrosis and look sort of across your TGF beta portfolio as it grows.

Speaker Change: How are you sort of thinking about <unk>.

Speaker Change: To kind of develop these assets relative to kind of focus on anti myostatin. Thanks.

Jay Backstrom: Yeah, very good. So let me start with the top line and payer interaction. We've had preliminary payer interactions that we shared in previous calls, and, of course, we continue to do that. You know, I do think that there is precedent set with the current therapy. So I do think that gives us some insight into the value of functional gains in these children and the ability to add to and enhance that. Of course, we'll continue with more payer interactions as we have the top line data. And, as you point out, of course, that gives us a more rich and robust discussion.

Etzer Darout: Yeah, very good. So, let me start with the top line and payer interaction. We've had preliminary payer interactions that we shared on previous calls. And, of course, we continue to do that.

Speaker Change: Yes, very good so let me start with the topline and payer interaction we've had preliminary payer interactions that we've shared in previous calls and of course, we continue to do that.

Unknown Executive: You know, I do think that there is precedent set with the current therapy. So I do think that gives us some insight into the value of functional gains in these children and the ability to add to and enhance that. Of course, we'll continue with more payer interactions as we have the top line data. And, as you point out, of course, that gives us a more rich and robust discussion. But I do feel, from what I've seen so far, very pleased with the preliminary interactions and the recognition that these children need additional care. And I think that is further reinforced by the updated data that we've seen from Cherish and Shine. It's really interesting.

Speaker Change: I do think that there is the prior precedent set with the current therapies. So I do think that gives us some insight into the value of functional gains in these children and the ability to add and enhance that of course, we will continue with more payer interactions as we have the topline data and as you point out of course that gives us a more rich and robust discussion, but I do feel from what I have.

Jay Backstrom: But I do feel, from what I've seen so far, very pleased with the preliminary interactions and the recognition that these children need additional care. And I think that is further reinforced by the updated data that we've seen from Cherish and Shine. It's really interesting.

Speaker Change: <unk> seen so far very pleased with the preliminary interactions and the recognition that these children need additional care and I think that is further reinforced by the updated data that we've seen from cherish and shine, it's really interesting I, we've talked a bit about what to expect from the natural history. We've been looking for sources to give us information around it.

Jay Backstrom: We've talked a bit about what to expect from natural history, and we've been looking for sources to give us information on it. You know, we've said repeatedly that we expected it to plateau, the Newson-Erson effect. But we did believe everything we've heard and talked to from the community and from physicians, that there is an inherent progressive nature to this disease. And in fact, the long-term data show that. So that's the kind of evidence behind what we've been believing.

Unknown Executive: We've talked a bit about what to expect from natural history, and we've been looking for sources to give us information on it. You know, we've said repeatedly that we expected it to plateau, the Newson-Erson effect. But we did believe everything we've heard and talked to from the community and from physicians, that there is an inherent progressive nature to this disease. And in fact, the long-term data show that. So that's the kind of evidence behind what we've been believing. And if you put that together with the data that we're sharing with Topaz, which we're able to maintain and sustain, I think that will translate well into the payer interaction.

Speaker Change: We've said repeatedly that we expected it to plateau, the new centers in effect, but.

Speaker Change: But we did believe everything we've heard and talked to from the community physicians. There is an inherent progressive nature to this disease and in fact, the long term data show that so that's the kind of the evidence behind what we've been believing and if you put that together with the data that we're sharing with topaz, where we're able to maintain and sustain.

Jay Backstrom: And if you put that together with the data that we're sharing with Topaz, which we're able to maintain and sustain, I think that will translate well into the payer interaction. And then, with respect to the pipeline and where to go next, you know, I spent some time on this call talking about the pipeline. You know, I've been here now going on two years.

Speaker Change: I think that will translate well into the payer interaction.

Speaker Change: And then with respect to the pipeline and where to go next.

Venmo: I spent some time on this call talking about the pipeline you know I've been here now going on two years I Love the pipeline I Love Venmo and team have done and it's really finding the opportunity to really further advance I think our strategic decisions to go into the anti myostatin spaces will prove to be very good as we see the upcoming SMA data.

Jay Backstrom: I love the pipeline. I love what Mo and his team have done, and it's really finding the opportunity to really further advance. I think our strategic decisions to go into the anti-myostatin spaces will prove to be very good as we see the upcoming SMA data and the obesity data. I feel very good about that. So the TGF Beta 1 data is extraordinarily interesting to me, and I think, you know, when we started to highlight programs that I've touched on but really not spoken a lot about, I think we're coming into a phase of our growth as a company where we will have more and more opportunity to further invest behind the pipeline, which I believe really holds enormous promise and great value.

Venmo: And the obesity data feel very good about that.

Venmo: The TGF beta one data extraordinarily interesting to me and I think when we started to highlight programs that I've touched on but really not spoke a lot about I think we're coming into a phase of our growth as a company that we will have more and more opportunity to further invest behind the pipeline what I believe really holds enormous promise and great value.

Venmo: So more to come as we go forward for the year, but again to be clear to everyone listening first and foremost very focused company very deliberately focusing on myostatin and I'm really pleased with the team and their dedication to get us to the close to the readout for Sapphire, She really very exciting and it's been a very good time for us.

Jay Backstrom: So more to come as we go forward for the year. But again, to be clear to everyone listening, first and foremost, a very focused company, very deliberately focusing on myostatin, and I'm really pleased with the team and their dedication to get us close to the readout for SAFIRE. It's really very exciting. It's a very good time for us. Thanks.

Venmo: Thank you.

Tess Romero: We will now take the next question. On the line from Tess Romero from JP Morgan, please go ahead.

Speaker Change: We'll now take the next question.

Operator: From the line of Tess Romero from JP Morgan, please go ahead.

Speaker Change: From the line of test from Merrill from JP Morgan. Please go ahead.

Tess Romero: Good morning, Jay and team. Thanks so much for taking our questions. So the first question from us is on the longer-term data that you presented this morning. Can you tell us a little bit more about the distribution of the input on Hammersmith?

Speaker Change: Good morning, J&J. Thank so much for taking our question. So the first question from Martin is on the longer term data that you presented this morning can you tell us a little bit more about the distribution.

Speaker Change: And on the Hammersmith.

Jay Backstrom: And what might be driving that meet up from 36 to 48 months, particularly in the two to 12 age group? Just curious, like how wide that range of observations been and has this increased or decreased with time? And then the second question we had was just if you could let us know what percent of patients have seen at least a three point improvement for the age two to 21 group.

Speaker Change: And what might be driving that need up from 36 to 48 months, particularly in the 2% to 12 each group just curious like how wide.

Tessa Romero: has that range of observations been and has this increased or decreased with time? And then the second question we had was just if you could let us know what percent of patients have seen at least a three point improvement for the age two to 21 group. I think it was about 39% as of 36 months. And then, if I can just ask about timing for SAFIRE, is there any clarification you can give us on time between the last patient out, which I think would be in September, and a possible top line result? Can you give us any kind of idea of, like, what needs to be done in that timeframe? Thanks so much.

Speaker Change: Has that range of observation ban and has this increased or decreased with time.

Speaker Change: And then the second question you had was.

Speaker Change: If you could let us know what percent of patients have seen at least a three point of improvement for the each Q2 'twenty. One group I think it was about three 9% at the 36 months.

Jay Backstrom: I think it was about 39% as of 36 months. And then, if I can just ask about timing for SAFIRE, is there any clarification you can give us on time between the last patient out, which I think would be in September, and a possible top line result? Can you give us any kind of an idea of what needs to be done in that time frame? Thanks so much.

Speaker Change: And then.

Speaker Change: If I can just ask on timing for Sapphire is there any clarification you can give us on time between last patient out, which I think would be in Canberra and a possible top line results can you give us any kind of like what needs to be done in that timeframe. Thanks. So much.

Jay Backstrom: Yeah, Tessa, Jay, maybe I'll tackle those. You have really good questions about the granularity of the updated 48-month data. And as Jing mentioned on the call, we have plans to really advance that and get that at a medical meeting where we can go with much more granularity about the detail, the distribution, the percent that achieved a three-point change. Just recall, you know, when we were asked about 48-month data at the beginning of the year, we were planning. We know this is an important data set, and we were planning to do it, just not now.

Unknown Executive: Yeah, Tessa, Jay, maybe I'll tackle those. You have some really good questions about the granularity of the updated 48-month data, and as Jing mentioned on the call, we have plans to really advance that and get that at a medical meeting where we can go with much more granularity about the detail, the distribution, the percent that achieved a three-point change. Just recall, you know, when we were asked about 48-month data at the beginning of the year, we were planning. We know this is an important data set. We were planning to do it, just not now.

Speaker Change: Yes, 10, associate Jay maybe I'll tackle those.

Speaker Change: You have really good questions about the granularity around the updated 48 months data and as Jim mentioned on the call. We have plans to really advance that and get that at a medical meeting where we can go with much more granularity about the details of distribution the percent that it achieved a three point change just recall when.

Speaker Change: We were asked about 48 month data at the beginning of the year. We were planning. We know this is important data set we were planning to do it just not now.

Jay Backstrom: We were able to do it now, frankly, because the team has just been so incredibly driving toward getting us in good shape for SAFIRE. I didn't want to distract them from the SAFIRE data. That's critical to us. The 48-month data is really important, but on a priority list, SAFIRE took priority. They're delivering beautifully, Tess, so that allowed us to update the 48-month data. So, as Jing said, this is a bit of a snapshot, so more to come. We'll give you more detail as we get this in front of a medical meeting.

Unknown Executive: We were able to do it now, frankly, because the team has just been so incredibly driving toward getting us in good shape for SAFIRE. I didn't want to distract them from the SAFIRE data. That's critical to us. The 48-month data is really important, but on a priority list, SAFIRE took priority. They're delivering beautifully, Tess, so that allowed us to update the 48-month data. So, as Jing said, this is a bit of a snapshot.

Speaker Change: We were able to do it now frankly, because the team has just been so incredibly driving toward getting us in good shape for Sapphire I didn't want to distract them from the Sapphire data that's critical to US. The 48 month data is really important but on our priority list sapphire to a priority there.

Jay Backstrom: And then that goes to your second part of the question, not to distract this team from where they're going and how to get there. You know, the classic is, you know, we've got to clean and lock the database and be sure that the data meets all the quality checks that we have to for registration. So, there are some established timeframes in there.

Speaker Change: Theyre delivering beautifully tests, so that allowed us to update the 48 month data. So as Jim said this is a bit of a snapshot so more to come we'll give you more detail as we get this in front of a medical meeting and then that goes to your second part of the question.

Unknown Executive: Some more to come. We'll give you more detail as we get this in front of a medical meeting, and then that goes to your second part of the question, not to distract this team from where they're going and how to get there. You know, the classic is, you know, we've got to clean and lock the database and be sure that the data meets all the quality checks that we have to for registration, so there are some established time frames in there, so I'm not going to give any more granularity on the timing in Q4.

Speaker Change: Not to distract and his team from where they're going and how to get there. The classic is we've got to clean and lock the database and be sure that the data meets all the quality checks that we have to for registration. So theres. Some established timeframes in there so I'm not going to give any more granularity on the timing in Q4.

Jay Backstrom: So, I'm not going to give any more granularity on the timing in Q4, just to say this team is driving to get us there as quickly as possible with high quality to be able to allow us to really stand behind the integrity of the data. They've done a fabulous job to date. And I hope you get energy from me on this call, right? These teams are really driving. We are driving. We are focused. We're delivering. So, we'll get it as soon as we can, Tess, as I said in my remarks.

Unknown Executive: Just to say this team is driving to get us there as quickly as possible with high quality to be able to allow us to really stand behind the integrity of the data. They've done a fabulous job to date, and I hope you get the energy from me on this call, right? These teams are really driving. We are driving too. We are focused. We're delivering, so we'll get it as soon as we can, Tess. They will come soon, as I said in my remarks.

Speaker Change: To say this team is driving to get us there as quickly as possible with high quality to be able to allow us to really stand behind the integrity of the data they've done a fabulous job to date and I Hope you get the energy for me on this call right. These teams are really driving we are driving we're focused we're delivering so we will get it as soon as we can.

Speaker Change: <unk> tests.

Speaker Change: Coming soon as I said in my remarks.

Unknown Executive: Okay, thanks so much for taking our question.

Tess Romero: Okay, thanks so much for taking our question.

Speaker Change: Okay. Thanks, so much for taking our question.

Speaker Change: Thank you.

Operator: We will now take the next question from the line of Gary Nachman from Raymond James. Please go ahead.

Gary Nachman: We will now take the next question from the line of Gary Nachman from Raymond James. Please go ahead.

Speaker Change: We'll now take the next question from the line of Gary Nachman from Raymond James. Please go ahead.

Gary Nachman: Thanks. Good morning.

Gary Nachman: Thanks, Good morning, so the Sapphire phase III study is only at the 12 months, but if positive do you think the label could potentially include some of this longer term data from Topaz, that's pretty compelling and really important for these SMA patients.

Speaker Change: That could also help the case with the payers.

Speaker Change: And then secondly, just on obesity.

Speaker Change: If you have data front embraced in the second quarter of next year. How soon will be will you be able to file the IND for <unk> three nine.

Speaker Change: Assuming it soon out there, but what would the gating factor there.

Gary Nachman: So the SAFIRE Phase 3 study will only be after 12 months. But if positive, do you think the label could potentially include some of this longer-term data from Topaz that's pretty compelling and really important for these SMA patients? That could also help the case with the payers? And then secondly, just on obesity, if you have data from EMBRACE in the second quarter of next year, how soon will you be able to file the IND for 439? I'm assuming it's soon after, but you know, what would the gating factor there be? Thank you. Yeah,

Unknown Executive: So the SAFIRE Phase 3 study is only after 12 months. But if positive, do you think the label could potentially include some of this longer-term data from Topaz that's pretty compelling and really important for these SMA patients? That could also help the case with the payers?

Speaker Change: Thank you.

Speaker Change: Yeah. Good question. So let me start Gary with the first one about.

Unknown Executive: Yeah, good question. So maybe start, Gary, with the first one about... The long-term data from Topaz, you know, clearly we find these data of interest. And like you, I think they're meaningful from a variety of perspectives.

Speaker Change: The long term data from Topaz.

Speaker Change: Clearly we find these data of interest and like you I think there are meaningful for a variety of perspectives.

Speaker Change: From the regulatory perspective, you should think about it the safety and Tolerability is essential and that will clearly contribute to our safety profile and expect to see that for the FDA and EMA looking for that data to help them with that benefit risk assessment, and we will do everything we can to optimize the opportunity for that to be in the.

Speaker Change: For the regulatory review to support the application, where we were removed to the payer piece I think as you know in those interactions publication data. The additional data that we have that entire dataset will be open and available to them to review.

Speaker Change: And to add to your comment because I do think it's important when we think about the benefit for patients that is sustained over time my past experience in the payer interactions and Thats a meaningful data point at patients continue to benefit so we'll definitely maximize that and those interactions.

Speaker Change: And then from the SDK for three nine program again. These are in parallel so Simone his team, we're really driving towards the IMD, we're doing the IND, enabling tox work. So that is kind of maybe the gate to it do we get that done, but it's on track and on schedule and as we shared at the beginning of our discussion on our journey into the Ob.

Speaker Change: <unk> space, we're targeting sometime midyear next year, so there'll be pretty concurrent although with the speed with which the embrace team has enrolled its likely we will report those data out in advance it will certainly support the target and our strategy, which will be helpful. And we will we'll include that in the indie interactions.

Unknown Executive: All right, great. Thank you.

Speaker Change: Alright, great. Thank you.

Speaker Change: Thank you.

Speaker Change: We will now take the next question.

Speaker Change: From the line of Sri creep up there.

Speaker Change: <unk> from <unk> Securities. Please go ahead.

Speaker Change: Hey, guys. Thank you so much for taking my question.

Speaker Change: I know you just started in drilling.

Obesity: But obesity said EBITDA it.

Speaker Change: It looks like Youre seeing better enrollment than expected.

Speaker Change: I was wondering if you can provide a little bit more color if possible on what sort of patients.

Speaker Change: It seems to be the target for this.

Speaker Change: And also are you targeting a certain ratio between.

Speaker Change: Overweight and obese patients does it matter and given the just following up on an earlier question. The Tis deputised in semi blue tie they have slightly different profiles. So.

Speaker Change: Is there anything you took into account in terms of file powering assumptions.

Speaker Change: About the distribution between tours appetite than some of your tight thank you.

Jay Backstrom: Yeah, good question. So maybe start, Gary, with the first one about...

Jay Backstrom: Yeah. Good question. So Chris this is Jay maybe I'll start with our with the trial design and then I'll have Jim add onto it and talk about sort of the patient population that's being included in the study.

Jim: Again. This is proof of concept studies. So we really wanted to be able to kind of see an effect on that preservation of lean muscle mass I think to your point <unk> and <unk>. Both have the effect I think the speed with which you see that decline difference between the two and so there may be some difference in terms of when you can detect our ability to preserve.

Jim: That but I think seeing the effect on either of those groups would be helpful. So we considered it but we didn't really as the earlier question came from.

Speaker Change: On the call we didn't stratified by that for the study, but we believe there will be able to demonstrate the effect that we expect to see and then Jim about the population that we've included in the embrace study yeah. So creep up.

Unknown Executive: Yeah, so Kripa, we did not strive for a particular ratio for the overweight versus the obese population. You know, just importantly, the objective for the study was really to have a quick proof of concept, as I mentioned, really just to kind of assess the ability to preserve lean muscle in the context of a GOP agonist. And as to your second question about the ratio between, you know, the difference between semaglutide and terzapotam, our view is that we do not think there's a fundamental difference between those two. If you look at the degree of weight reduction, I think terzapotam probably has a greater degree of weight reduction. But the overall safety profile is quite similar between the two.

Jim: It did not strive for a particular ratio for the overweight versus the obese population.

Jay Backstrom: The long-term data from Topaz, you know, clearly we find these data of interest. And, like you, I think they're meaningful from a variety of perspectives. From the regulatory perspective, you think of it, safety and tolerability are essential, and that'll clearly contribute to our safety profile. And we expect to see that, you know, for the FDA and EMA, looking for that data to help them with that benefit-risk assessment. And we will do everything we can to optimize the opportunity for that to be in the regulatory review to support the application.

Jay Backstrom: Where we move to the payer piece, you know, I think, as you know, in those interactions, publication data, the additional data that we have, that entire data set will be open and available for them to review. And to add to your comment, because I do think it's important, we think about the benefit for patients that is sustained over time. My past experience with the payer interactions, that's a meaningful data point that patients continue to benefit from, so we'll definitely maximize that in those interactions. And then from the SRK 439 program, again, these are in parallel.

Jim: Just importantly, the objective for this study is really to have a quick proof of concept as I mentioned really just to kind of assess the ability to preserve lean muscle in the context of a GOP agonist and as to your second question about the ratio between.

Jay Backstrom: So Mo and his team are really driving toward the IND. We're doing the IND-enabling TOCS work, so that is kind of maybe the gate to it, to get that done, but it's on track and on schedule. And as we shared at the beginning of our discussion and our journey into the obesity space, we're targeting sometime mid-year next year, so they'll be pretty concurrent, although with the speed with which the EMBRACE team has enrolled, it's likely we'll report those data out in advance. It will certainly support the target in our strategy, which will be helpful, and we'll include that in the IND interaction.

Speaker Change: The different between some advertising, which as I've said, our view is too.

Speaker Change: We do not think there is a fundamental difference between those two if you look at the degree of a weight reduction I think there's appetite probably has a greater degree of weight reduction, but the overall safety profile are quite similar between the two and that the proportion of the lean muscle loss in a context of DLP, one are very similar or intended to their.

Unknown Executive: And the proportion of the lean muscle loss in the context of GOP1 is very similar between the two. Their ability to kind of reduce cardiovascular risk in both studies, both studies have shown that. So, in our view, it's basically thinking about the pathway of GOP agonism to, you know, lose weight, but then lose muscle along the way. And how do we counter that so we can preserve lean muscle? That's really the primary objective, and the trial is set up to do that. And so, therefore, that's our focus.

Speaker Change: I hate to kind of reduce cardiovascular risk and both studies. Both studies have shown that so so in our view, it's basically it's more thing thinking about the pathway of those GOP agonism too.

Speaker Change: Lose weight, but then lose muscle along that and how do we counter that said, we can preserve lean muscle that's really the primary objective in the trial is set up to do that and so therefore, that's our focus.

Gary Nachman: All right, great. Thank you.

Unknown Executive: Okay, great. And then there's just one more follow-up question on that.

Speaker Change: Okay, Great and then just one more follow up question on that so this is a proof of concept study primary endpoint is changed from baseline in Lima by Texas, Ken by the time, you're ready to do a pivotal trial do you expect any update or change in FDA guidance in terms of how to develop.

Unknown Executive: So this is a proof-of-concept study. Your primary endpoint is change from baseline and lean mass by DEXA scan. By the time you're ready to do a pivotal trial, do you expect any update or change in FDA guidance in terms of how to develop muscle preservation drugs, or do you think you have all you need at this point in time?

Speaker Change: And preservation drugs or do you think you have all you need at this point of time.

Speaker Change: Yes, Chris This is Jay I think the answer is going to be it's going to be an evolving field and I think FDA will begin to take into consideration.

Speaker Change: The strategies to really have healthy weight loss management, although as you know I think regulatory change tends to be delayed so whether we get greater insight as we go forward remains to be seen having said that I feel very good about the information we've received to date from the FDA I think we need to demonstrate clinical benefit in addition, and I think as we.

Mo: You see from Mo and what really gets me excited as we are walking through what Moe and his team are doing on the non clinical data and just ask you to take a look at that it's starting to shift foreshadow, where we could take this medicine right. We have an effect on glucose metabolism, that's a clear measure of clinical benefit.

Speaker Change: Data at the Ada show that we preserve the lean muscle in fact, we maintain a lean muscle and in fact increased the lean muscle mass upon withdrawal of <unk> and we mitigate the weight rebound that fat rebound, so youre seeing opportunities, where what we've been saying is sustainable.

Speaker Change: And I think we can find strategies there on the maintenance side or in combination to really position I think those trying to lose weight to not lose it at the expense of muscle, which plays such a critical role in metabolism.

Speaker Change: Alright, thank you so much.

Srikripa Devarakonda: Thank you. We will now take the next question. From the line of Srikripa Devarakonda from tourist security, please go ahead.

Speaker Change: Thank you we will now take the last question.

Srikripa Devarakonda: Hey guys, Thank you so much for taking my question.

Speaker Change: From the line of Mark from from TD Cowen. Please go ahead.

Srikripa Devarakonda: I know you just started enrolling for the obesity study with Epidemiomab, and it looks like you're seeing better enrollment than expected. I was wondering if you could provide a little bit more color, if possible, on what sort of patients seem to be the target for this. And also, are you targeting a certain ratio between, you know, overweight and obese patients? Does it matter? And just following up on an earlier question, terzapotide and semaglutide have slightly different profiles. So is there anything you took into account in terms of trial powering assumptions about the distribution between terzapotide and semaglutide?

Speaker Change: Hey, Thanks for taking my questions.

Speaker Change: <unk> already been answered, but maybe to follow up on Mike's question right at the beginning.

Srikripa Devarakonda: Thank you.

Unknown Executive: These kind of differences between the molecules in the in the trial designs in SMA.

Speaker Change: Do you guys view that those differences are.

Speaker Change: So significant that they are very likely to lead to.

Speaker Change: Completely different outcomes for trials in terms of just outright sales.

Speaker Change: Failing to reach statistical significance or succeeding in other cases.

Speaker Change: Or do you think that these are likely to be just more subtle okay.

Speaker Change: Aspects of the overall kind of profile that youre able to market to that each company might be able to market to in terms of how big that efficacy signal really is and obviously the safety profile and then I'll have a follow up question after that.

Jay Backstrom: Yeah, a good question. So Kripa, this is Jay.

Unknown Executive: Yeah, Okay, sorry, Marc this is Jay.

Unknown Executive: Yeah, so talking about the differences in the profiles of the programs, because I got I got a side distraction as you were answering the question. I want to make sure I understood it correctly in terms of what's expected to be seen from each of the different profiles.

Speaker Change: Yes, so talking about the differences in the profiles of the programs because I got it yes.

Unknown Executive: I got aside distraction as you were answering the question I wanted to make sure I got it correctly.

Speaker Change: In terms of what's expected to be seen from each of the different profiles.

Jimmy Carter: Yes, Jimmy Carter.

Speaker Change: Is it significant enough that there's going to be very important to success failure or is it or do you view, it's more subtle as to just how impressive the data that's going to be.

Speaker Change: Yes, it's really interesting I'm going to start first and foremost again I made a comment about where we are.

Speaker Change: Treating children and young adults and we have plans to move even into earlier ages under two right. So if you think about that.

Speaker Change: Is everything we've said about our strategy safety really trumps you've got to be able to have a safe therapy, you've got to be able to administer it it's got to be able to be administered without regard for growth and development and we've been able to demonstrate that across so safety is really paramount.

Speaker Change: I think that there is.

Speaker Change: Differences in terms of each of the strategies, but I like our strategy on the safety side. So let me start there I think with respect to kind of want to see from the efficacy side again.

Jay Backstrom: Maybe I'll start with the trial design, and then I'll have Jing add on to it and talk about sort of the patient population that's being included in the study. Again, this is a proof-of-concept study, so we really want to kind of see an effect on that preservation of lean muscle mass. I think, to your points, trizepatide and semaglutide both have that effect.

Jay Backstrom: I think the speed with which you see that decline differs between the two, and so there may be some difference in terms of when you can detect our ability to preserve that, but I think seeing the effect on either of those groups would be helpful. So, we considered it, but we didn't really, as the earlier question came from, on the call, we didn't stratify by that for the study, but we believe that we'll be able to demonstrate the effect that we expect to see. And then, Jing, about the population that we've included in the EMBRACE study? Yes.

Speaker Change: Again, I think we selected the Hammersmith scale for a reason it was what's used for new centers.

Speaker Change: There are other motor scales, but quite honestly from the field I believe this is the gold standard and we're really looking forward to reporting out our data against that gold standard measures. So I think that's important.

Speaker Change: The Tolerability, which is linked back to safety, but the tolerability will be critical as I think about it from a payer interaction in our ability to commercialize.

Speaker Change: We have seen very little if any drop from our topaz data going forward that really is impressive I recall from our previous setting that I was in and the CEO at the time would make a comment that he doesn't know what the median duration of treatment is because patients are still on so if you just think about the implications.

Speaker Change: <unk> to that I think we are really doing well I'm not sure that's true across the other programs we will see.

Speaker Change: But I like where we're going in and the final point is I do like that we're agnostic to treatment I think that is really important. This is an established market with several players we have an opportunity as youll see going forward to really show. This in the background of gene therapy, not just SMN up regulating therapy I.

Speaker Change: Think that is a really good place to play because we're neutral in terms of the choice and I think that maximizes our opportunity to go forward. So so all of those things together I feel really good about where we are and frankly looked like you looking forward to being able to tell you the topline results.

Jing Marantz: Yeah, so Kripa, we did not strive for a particular ratio for the overweight versus the obese population. You know, just importantly, the objective for the study was really to have a quick proof of concept, as I mentioned, really just to kind of assess the ability to preserve muscle in the context of a GOP agonist. And as to your second question about the ratio between, you know, the difference between semaglutide and terzapotide, our view is that we do not think there's a fundamental difference between those two. If you look at the degree of weight reduction, I think terzapotide probably has a greater degree of weight reduction, but the overall safety profile is quite similar between the two.

Speaker Change: Okay. That's helpful and then just.

Jing Marantz: And the proportion of the lean muscle loss in the context of GOP1 is very similar between the two, their ability to kind of reduce cardiovascular risk, and both studies have shown that. So in our view, it's basically, it's more thinking about the pathway of those GOP agonism to, you know, lose weight, but then lose muscle along that. And how do we counter that so we can preserve lean muscle? That's really the primary objective, and the trial is set up to do that, and so, therefore, that's our focus.

Srikripa Devarakonda: Okay, great. And then there's just one more follow-up question on that. So you're doing this is a proof-of-concept study; your primary endpoint is changed from baseline to lean mass by DEXA scan. By the time you're ready to do a pivotal trial, do you expect any update or change in FDA guidance in terms of how to develop, you know, muscle preservation drugs, or do you think you have all you need at this point in time?

Srikripa Devarakonda: Sikandar Devilere Sivabaraman Layada Layada Sutile Layada Sutile Layada Isabel Vela Velar Velar??

Jay Backstrom: Srikripa, this is Jay. I think the answer is going to be, it's going to be an evolving field, and I think FDA will begin to take into consideration the strategies to really have healthy weight loss management. Although, as you know, I think regulatory change tends to be delayed. So whether we get greater insight as we go forward remains to be seen.

Speaker Change: Well open the trial will be positive.

Speaker Change: Just curious what else you may need to gather to be ready to file that BLA is it really just the data in writing it up or are there other things on the CMC side that still need to kind of come in house.

Speaker Change: Yes, as you know with most applications. This is a work in progress the beauty of it is is that we've been preparing the BLA over the last 12 to 18 months to be honest right Theres sections that you can complete and do the non clinical sections that work is done. Those reports are written they are being included the CMC team is doing there CMC work in <unk>.

Srikripa Devarakonda: Having said that, I feel very good about the information we've received to date from the FDA. I think we need to demonstrate clinical benefit in addition. And I think, as you see from Mo, and what really gets me excited is we're walking through what Mo and his team are doing with the non-clinical data. I just ask you to take a look at that.

Jay Backstrom: It's starting to foreshadow where we could take this medicine, right? It has an effect on glucose metabolism. That's a clear measure of clinical benefit. The data at the ADA show that we preserve lean muscle. In fact, we maintain lean muscle and, in fact, increase lean muscle mass upon withdrawal of semaglutide. And we mitigate the weight rebound, or fat rebound. So you're seeing opportunities where what we've been saying is sustainable.

Jay Backstrom: And I think we can find strategies there on the maintenance side or in combination to really position those trying to lose weight to not lose it at the expense of muscle, which plays such a critical role in metabolism.

Marc Frahm: Thank you. We will now take the last question. On the line from Marc Frahm from TD Cohen, please go ahead.

Marc Frahm: Thanks for taking my questions. A lot have already been answered, but maybe to follow up on Mike's question right at the beginning, just on these kinds of differences between the molecules and the trial designs in SMA. Do you guys view that those differences are so significant that they're very likely to lead to, you know, completely different outcomes for trials in terms of, you know, just outright failing to reach statistical significance or succeeding in other cases?

Marc Frahm: Or do you think that these are likely to be just more subtle? Yeah, okay. Aspects of the overall kind of profile that you're able to market to, that each company might be able to market to in terms of, you know, how big that efficacy signal really is, and obviously the safety profile. And then I'll have a follow-up question after that.

Jay Backstrom: Yeah, okay. Sorry, Marc. This is Jay. Yeah, so talking about the differences in the profiles of the programs, because I got a side distraction as you were answering the question. I want to make sure I understood it correctly in terms of what's expected to be seen from each of the different profiles.

Marc Frahm: Yeah, is it significant enough that you think that is going to be very important to success or failure? Or is it? Or do you view it's more subtle as to, you know, just how impressive the data is?

Jay Backstrom: Yeah, it's really interesting. I mean, they start first and foremost. Again, I made a comment about us treating children and young adults, and we have plans to move even into earlier ages under two, right? So if you think about that... As we've said about our strategy, safety really trumps. You've got to be able to have safe therapy. You've got to be able to administer it.

Jay Backstrom: It's got to be able to be administered without regard for growth and development, and we've been able to demonstrate that across. So safety is really paramount. You know, I think that there are, you know, differences in terms of each of the strategies. But I like our strategy on the safety side.

Jay Backstrom: So let's start there. I think with respect to kind of what to see from the efficacy side, you know, again, I think we've selected the Hammersmith scale for a reason. It was what was used for nusinersen.

Jay Backstrom: There are other motor scales, but quite honestly, from the field, I believe this is the gold standard. And we're really looking forward to reporting out our data against this gold standard measure. So I think that's important. I think tolerability, which is linked back to safety, but tolerability will be critical as I think about it from a payer interaction and our ability to commercialize. We have seen very little, if any, drop from our Topaz data going forward. That is really impressive.

Jay Backstrom: I recall from a previous setting that I was in, and the CEO at the time would make a comment that he doesn't know what the median duration of treatment is because patients are still on it. So if you just think about the implication of that, I think we're really doing well. I'm not sure that's true across the other programs.

Jay Backstrom: We'll see. But I like where we're going. And the final point is I do like that we're agnostic to treatment. I think that is really important. You know, this is an established market with several players. We have an opportunity, as you'll see going forward, to really show this in the background of gene therapy, not just SMN upregulating therapy. I think that it is a really good place to play because we're neutral in terms of the choice.

Speaker Change: Runs and getting all that stuff. So that's running beautifully and then the clinical team is really working to populate the modules.

Speaker Change: There are some things that we will incorporate the topaz data as was raised earlier by Gary definitely we're going to include that in our application, but that data as well as evolving we have enough to put in there. So all of that is coming together beautifully.

Jay Backstrom: And I think that maximizes our opportunity to go forward. So, all of those things together, I feel really good about where we are. And, frankly, like you, I am looking forward to being able to tell you the top line.

Marc Frahm: Okay, that's helpful. And then, obviously, we're hoping that the trial will be positive.

Speaker Change: We're pleased and very fortunate to have a really outstanding head of regulatory come in and he's just done a fabulous job of getting us ready for submission. So Jane and team are flying most team is hustling and the rest of us are trying to keep up with that mark.

Marc Frahm: Can you just remind us what else you may need to gather to be ready to file that DLA? Is it really just the data and writing it up? Or are there other things on the CMC side that still need to kind of come in house? Yeah.

Jay Backstrom: Yeah, as you know, with most applications, this is a work in progress. The beauty of it is that we've been preparing the BLA over the last 12 to 18 months, to be honest.

Jay Backstrom: There are sections that you can complete and do. The non-clinical sections, that work is done, those reports are written, they're being included. The CMC team is doing their CMC work and PPQ runs and getting all that stuff, so that's running beautifully.

Jay Backstrom: And then the clinical team is really working to populate the modules. You know, there are some things that we will incorporate. The Topaz data, as was raised earlier by Gary, definitely, we're going to include that in our application. But that data, while it's evolving, we have enough to put in there. So all of that is coming together beautifully. We were pleased and very fortunate to have a really outstanding head of regulatory come in, and he's just done a fabulous job of getting us ready for submission. So Jing and her team are flying, Mo's team is hustling, and the rest of us are trying to keep up with them.

Marc Frahm: Okay, all right. Thank you.

Speaker Change: Okay alright, thank you.

Speaker Change: Thank you.

Operator: There are no further questions at this time.

Speaker Change: There are no further questions at this time.

Jay Backstrom: Okay, well listen, thank you all. We're going to close the call. Thanks for your interest, and I appreciate you joining us today.

Unknown Executive: Okay, well listen, thank you all. We're going to close the call. Thanks for your interest, and I appreciate you joining us today.

Speaker Change: Okay, well listen thank you all were going to close the call. Thanks for your interest and I appreciate you joining us today.

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

Speaker Change: This concludes today's program.

Speaker Change: In school. Thank you for participating you may now disconnect.

Unknown Executive: Okay.

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Unknown Executive: Okay.

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Unknown Executive: Yes.

Unknown Executive: Okay.

Unknown Executive: [music].

Unknown Executive: Okay.

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Unknown Executive: Okay.

Speaker Change: Uh huh.

Unknown Executive: Okay.

Unknown Executive: [music].

Unknown Executive: Yeah.

Unknown Executive: Okay.

Unknown Executive: Yeah.

Jay Backstrom: So, you know, I think it'll be interesting to see their results, but clearly, in a different place, and to remind them, they're studying only with the RISD plan, where we're agnostic to vote in this nurse and at RISD. And then with respect to Embrace, you know, Jenkins' answer, but since I'm going to comment, no, we didn't stratify by some a We're really interested in just seeing the effect on both. We think we should have an effect on both similar to our SMA program. We think we should be agnostic about treatment.

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