Good morning, and welcome to Scholar Rock's call on the top-line results from the pivotal phase III SAPPHIRE trial of apitegromab in SMA. During today's call, you will hear from Jay Backstrom, President and CEO of Scholar Rock, and Jing Marantz, Chief Medical Officer. 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 one one on your touchtone phone. To withdraw your question, please press star one one again. Please note this event is being recorded. Before we begin, I'd like to point out that the company will be making various statements about Scholar Rock's expectations, plans and prospects that constitute forward-looking statements for the purposes of the safe harbor provisions under the Private Securities Litigation Reform Act of 1995 .
Any forward-looking statements represent the company's views only as of today and should not be relied upon as representing its views as of any future date. You are encouraged to visit the Investors and Media section of Scholar Rock's website to find the most up-to-date SEC statements and filings. A recording of today's events will be available on the company's 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.
Well, thank you, Michelle. Good morning, and welcome, everyone. I'm thrilled to be with you this morning to discuss the positive top-line results for our pivotal phase III SAPPHIRE study of apitegromab, our highly selective anti-myostatin in spinal muscular atrophy. Before I review the results, I want to take a moment to remind everyone why we're here today. We've spent years at Scholar Rock listening to the SMA community, including people like Liza, who made it clear that they want more. More, meaning gaining muscle strength and function so that they can maintain their independence for basic daily activities that we may take for granted. Activities such as feeding yourself, rolling over in bed, or operating a motorized wheelchair, activities that could be achieved with a one- to two-point improvement on the Hammersmith Functional Scale.
When we asked Liza about what she was seeking, her message was clear: muscle is everything. SMA is a progressive disease, and despite ongoing chronic standard of care therapy, individuals like Liza will lose function over time. This was recently illustrated at the June Cure SMA conference, where those receiving chronic treatment with nusinersen were observed to lose one point per year on the Hammersmith Functional Motor Scale after four to five years of treatment. Scholar Rock is an innovator and designed apitegromab to selectively block the activation of myostatin, a negative regulator of muscle. We designed and conducted SAPPHIRE, a randomized controlled study with apitegromab plus standard of care, either nusinersen or risdiplam, comparing it to placebo plus standard of care, to see if we could create new treatment possibilities for those like Liza living with SMA. Now, turning to our exciting results.
As we announced earlier today, our pivotal phase III SAPPHIRE study met the primary endpoint with a 1.8-point improvement for apitegromab plus standard of care, compared to placebo plus standard of care, as measured by the gold standard SMA-specific Hammersmith Functional Motor Scale at week 52. This clinically meaningful benefit was statistically significant with a p-value of 0.0192. Patients receiving apitegromab demonstrated early an increasing motor function improvement versus placebo, as measured by the Hammersmith scale, with the apitegromab patients gaining function, while those receiving placebo lost function despite being on standard of care treatment. Importantly, apitegromab demonstrated remarkable consistency of effect across doses and age groups 2 through 21 in a broad SMA population.
Further, apitegromab showed transformative clinical activity, with 30% of patients who were already receiving standard of care achieving a three-point or greater improvement in their Hammersmith scores. With respect to safety and tolerability, SAPPHIRE confirmed apitegromab's favorable safety profile, which was consistent with the established safety profile that we've seen in over four years of treatment in SMA patients based on our phase II TOPAZ study, and is expected as based on our highly selective approach to blocking myostatin. This is a clear win for SAPPHIRE, and we believe these data collectively show that apitegromab has the potential to become part of a new standard of care in SMA. I would like to thank the patients, their families and caregivers, and the investigators and study staff who participated in SAPPHIRE and helped us get to this point.
I also want to thank the entire Scholar Rock team, who worked tirelessly to ensure the trial was conducted with the highest quality standards. Collectively, we strive to keep patients at the center of everything we do. Now, let me turn the call over to Jing Marantz, our Chief Medical Officer, to review the top-line SAPPHIRE study results in more detail. Jing?
Thank you, Jay, and welcome to the call. I'm really excited to be here with you today. Let's start with an overview of the study design. SAPPHIRE is a placebo-controlled phase III study designed to meet regulatory requirements for registration. We have worked closely with both the FDA and EMA, and their input have been reflected in our study design and the statistical analysis plan. The trial enrolled a total of 188 patients and evaluated two populations: the two to 12 main efficacy population and the 13- 21 age exploratory population.
... All patients were on chronic background standard of care, nusinersen or risdiplam. SMA patients were randomized two to one to apitegromab and placebo. Based on input from the FDA, we included two doses, 10 mg per kg and 20 mg per kg, in the two to 12 main population, reflecting insights from TOPAZ that 10 and 20 are pharmacologically similar, allowing us to preserve the two to one randomization. The primary endpoint for both populations is Hammersmith at 52 weeks. Secondary endpoint included RULM, WHO scale, safety, and PK/PD. Patients who completed this study had the opportunity to enroll into the long-term extension study called ONYX. Next slide. Turning to our pre-specified statistical analysis plan. The primary objective of the study is to determine whether apitegromab is superior to placebo in the two to 12 main efficacy population.
The outcome measure is Hammersmith, the gold standard for assessing motor function, specifically validated for SMA. Given the expectation that 10 and 20 mg dose are pharmacologically the same, we have pre-specified two analyses as the primary confirmatory test, the 10 and 20 combined dose of apitegromab versus placebo, and the 20 mg dose versus placebo. For the trial to meet statistical requirements, both comparisons are analyzed concurrently. Statistical significance is achieved if either analysis crosses the more rigorous boundary of zero point zero two five. As Jay mentioned earlier, the study met primary endpoint based on the combined dose analysis, which crossed the more rigorous boundary of zero point zero two five, highlighted here in green boxes. We've also pre-specified an analysis compared to 10 mg dose versus placebo. Next slide. Now, turning to results from SAPPHIRE.
A total of 188 patients were randomized for the two to 12 age group, shown on the left. 156 patients entered the study, 99% completed the study, a reflection of the quality of the trial conduct. Similarly, for the 13- 21 age population shown on the right, 32 patients enrolled in the study, 97% completed treatment. Overall, 98% of patients continued on to the ongoing long-term extension study. This high rate of patient retention is similar to what we saw in the four-year experience from TOPAZ. Next slide. The study enrolled a population that is broadly representative of the SMA population today. The baseline demographics and disease characteristics were all well-balanced across treatment arms. The blue box in the middle highlights the stratification factors, the type of standard of care therapy, and the age at which these therapies were initiated.
What's particularly notable is how long the study participants were already treated with the standard of care. Patients had about five years on nusinersen and about three years on risdiplam when they entered the study, and therefore, were on the more advanced phase of their treatment journey. Next slide. To put the SAPPHIRE patient population into context, it's helpful to understand the natural trajectory of patients on a chronic standard of care therapy. Here's the recent data showing long-term motor function by Hammersmith on nusinersen-treated patients from the CHERISH/ SHINE study. The orange line here on top represents the trajectory of patients randomized to nusinersen. You can see here motor function improved for the first two years, but for the next two years, we see a plateau.
After about four years, you see a progressive loss of motor function over time, losing about one point per year despite being on a standard of care therapy. The gray shaded box towards the right represents the time period similar to SAPPHIRE patients in terms of duration of nusinersen therapy. So the SAPPHIRE patients were clearly on a declining phase of their treatment journey. Next slide. Returning to results from SAPPHIRE. As we shared earlier, the study met the primary endpoint, achieving statistical significance. As shown on the top row, the combined dose analysis showed a 1.8-point improvement in Hammersmith compared to placebo, on top of standard of care, with a p-value of 0.0192, crossing the more stringent statistical boundary of 0.025.
All the dose analysis favored apitegromab and showed an improvement in Hammersmith compared to placebo, including the pre-specified analysis of 10 mg dose versus placebo, showing a 2.2-point improvement with a nominal p-value of 0.0121. Next slide. The strength of the results is well-illustrated here by a forest plot of all the pre-specified analysis. There's remarkable consistency across analysis, all showing improvement favoring apitegromab, with point estimates on the right of the plot. Starting at the top, you can see the combined dose analysis, followed by the 20 mg dose and then the 10 mg dose. All the point estimates fall within the confidence interval of the primary analysis. Data on pharmacodynamics, or PD, were superimposable for 10 and 20 mg dose.
This means that myostatin target is saturated at 10 mg dose, confirming that the two doses are indeed effectively identical. In addition to the consistency across doses, apitegromab also demonstrated remarkable consistency across age groups. Note the mean difference for Hammersmith versus placebo is 1.8 for the combined dose analysis of the two to 12 age group shown on top. It is also 1.8 for the 13- 21 older age group in the fourth row, as well as the entire study population, aged two to 21 at the very bottom. This consistency speaks to the strength and robustness of our results. These findings are in keeping with the underlying biology of myostatin and the mechanism of how apitegromab works. Next slide. Now, to take a look at the, how apitegromab affects motor function over time, we'll show you the Hammersmith change by visit.
These line graphs beautifully articulate the treatment effect of apitegromab over the course of the entire treatment period. The blue line represents apitegromab-treated patients, and the gray line represents placebo control. As you can see, Hammersmith improved in patients on apitegromab as early as eight weeks. That is the first post-baseline assessment. By contrast, Hammersmith decreased in those on placebo, with a change from baseline of negative 1.2 points. So our placebo arm performed similarly to the long-term natural history of nusinersen-treated patients, which lost about 1 point per year after four years of treatment. There is clear and early separation between apitegromab and placebo. The difference widens towards the end of the treatment period, underscoring the effect of apitegromab on the disease course from losing function despite being on a standard of care, to gaining function by adding apitegromab. Next slide.
To further underscore the functional improvement, we see approximately 30% of patients on apitegromab achieving a three-point gain versus 12.5% for those on placebo. This transformative level of improvement is extraordinary on top of chronic standard of care. Again, the strength and consistency of these results demonstrate the ability of apitegromab to alter the course of disease from losing function to gaining function, with profound impact on patients' lives. Next slide. As Jay mentioned, apitegromab was designed to selectively block myostatin, avoid toxicities associated with blocking other TGF-beta growth factors. The safety profile from SAPPHIRE is exactly as we expected. It was consistent with the established safety profile seen in our phase II trial, now with over four years of treatment experience in SMA. Importantly, we see no discontinuation or study withdrawal due to adverse events.
The type and frequency of the adverse events are consistent with the underlying disease, the background standard of care therapy, or common childhood events. This is a great example of how industry-leading science translates into the clinic. To summarize, the trial has demonstrated clear and clinically meaningful improvement in motor function, with consistency across the full age range, two to 21. Apitegromab showed a 1.8-point improvement in Hammersmith versus placebo on top of chronic standard of care, with a p-value of 0.0192. Patients on apitegromab are gaining function, while those on placebo are losing function over time, despite being on a standard of care. The safety profile is favorable and supported with over 4 years of treatment experience from our TOPAZ phase II trial.
Taken together, the totality of the evidence in efficacy, combined with a well-tolerated safety profile, gives us strong conviction that apitegromab has the potential to alter the course of disease from losing function to gaining function. That's redefining the standard of care in SMA. With that, I conclude the data section and turn it over to Jay for conclusion.
Thank you, Jing. Next slide. We are fulfilling our mission to create new possibilities for people living with serious diseases, starting with SMA. These results are a validation of our industry-leading scientific platform and of our selective anti-myostatin programs, and will serve as the catalyst for us to become a fully integrated commercial-stage biotech company. Clearly, a very exciting time at Scholar Rock. We are innovating a new era in the treatment of spinal muscular atrophy. Our selective approach to blocking the pro and latent forms of myostatin was designed to deliver a favorable safety profile, and SAPPHIRE now confirms the efficacy as well. Our understanding of the biology and our world-class antibody engineering has allowed us to succeed where others have failed. Apitegromab is the first and only muscle-targeted therapy to show clinically meaningful and statistically significant functional improvement in SMA.
In addition, apitegromab is the first and only anti-myostatin therapy to demonstrate a functional improvement in a pivotal phase III study in any indication. As I mentioned at the start of the call, we are thrilled with these results and what it means for the SMA community, patients, their families, caregivers, and physicians. The SAPPHIRE study shows the transformative potential that apitegromab can have on SMA disease progression. From a regulatory perspective, SAPPHIRE was designed to be our registration study and was a well-conducted, randomized, placebo-controlled study. SAPPHIRE met the primary endpoint with a 1.8-point improvement, as measured by the Hammersmith Functional Motor Scale at week 52. This clinically meaningful benefit, shown on the background of chronic treatment with standard of care, was statistically significant, with a p-value of 0.192.
Patients receiving apitegromab demonstrated early and increasing motor function improvement, while those receiving placebo, as Jing pointed out, lost function despite being on standard of care. Importantly, apitegromab demonstrated remarkable consistency of effect across doses and age groups, two to 21 in a broad SMA population. In addition, apitegromab showed transformative efficacy, with 30% of patients who were already receiving standard of care, achieving a three-point or greater improvement in their Hammersmith scores. And finally, SAPPHIRE confirmed apitegromab's favorable safety profile, which is consistent with what we've seen over four years of treatment in SMA patients based on our phase II TOPAZ data, and as expected, given our highly selective approach to blocking myostatin. Taken together, we believe the benefit risk for apitegromab is very favorable.
Overall, this is a clear win, and we believe apitegromab has the potential to alter the course of SMA and change the standard of care for patients living with SMA. We at Scholar Rock are working urgently to bring apitegromab to the SMA community as soon as possible. For next steps, our regulatory applications are well underway, and we expect to submit to both FDA and EMA in the first quarter of 2025. We plan to take full advantage of the expedited regulatory review pathways and will request priority review and an accelerated assessment with FDA and EMA, respectively. We are also eligible for a priority review voucher, assuming regulatory approval. Continuing our positive momentum, we look forward to the results of the EMBRACE study in obesity in Q2 2025, and to initiating OPAL, our SMA study in children under two.
We believe with the safety profile of apitegromab, treating as early as possible has the potential to provide the best long-term outcomes for children. Finally, with the top-line results in hand, we plan to move forward with the preparations for our first commercial launch in the U.S. in Q4 2025, with Europe to follow. So that concludes our formal remarks, and we'll now open up the call to questions. Michelle?
Thank you. As a reminder, to ask a question, please press star one, one. If your question has been answered and you'd like to remove yourself from the queue, please press star one, one again. Our first question comes from David Nierengarten with Wedbush Securities. Your line is open.
Hi, thanks for taking the question, and congrats on the data. Just a couple questions from us. On the maybe you could put into context the improvement above and beyond the you know background therapy for these patients. Getting a couple questions on the magnitude of benefit here. And then on the under two study, just a quick question: Would you be looking at a different dose there, or would you continue to think about the 10 and 20 mg dose? Thanks.
Yeah, so good questions, David. Let me start with the under two. You know, the expectation on the under two is to help guide clinicians with dosing. We have weight-based dosing, so we'll take full advantage of the PK/PD, you know, treatment effect, exposure response from SAPPHIRE and use that to inform the milligram per kilogram dosing on the under two. And again, I think that's a really important population for us to get to, to give these children the greatest chance of really having the best outcomes. With respect to the benefit and effect, I think it's absolutely clear. I mean, we have gain in function where those on the background are losing function. That loss of functions we saw in this trial was exactly what we would expect from the long-term nusinersen data, which is sobering.
I mean, the SMN therapies are amazing innovation, but it's clearly not enough. So I think our week 52 endpoint, we met it with great rigor. I think with the 30% improvement, functional improvement, with everything we've seen, with the consistency, David, I think this is a really, really, really strong benefit risk.
Thank you.
Thank you. Our next question comes from Michael Yee with Jefferies. Your line is open.
Hey, guys, thanks. Good morning, and congrats on great data. We had two questions. The first was around the dose response and your thoughts around 10 mg and 20 mg, and 10 mg outperforming a little bit. I just wanted to think about the totality of all the consistency of the data and how you think about, I guess what you said, PD data also that would help support why you think that both of them are basically the same. And then also, maybe just thinking forward, what, if any, read-through do you have here on obesity? Were there any muscle endpoints or other factors that would lead you to believe that there's probably gonna be a positive effect in obesity as well? Thank you.
Michael, good question. So let me start maybe with the last one, and then I'll go back up to the SAPPHIRE data. So you know, clearly, we've shown functional improvement in this study. We had clear evidence of that, I believe, in the TOPAZ, so functional endpoints met. You know, from all of our work, and you saw what we did with the SRK-439 data, there's no question, it's on biology. We block myostatin, we're gonna increase muscle. So I felt good about EMBRACE going before these data. I feel equally good, if not more bullish about them as we lead in, but, you know, more to come. We'll see those data, and as you know, we're really working rapidly to complete these studies and have that in Q2.
Now, with respect to the, to the SAPPHIRE and dose, I think Jing articulated it really well. You know, going into the trial, we never expected dose response with 10 and 20. We expected 10 to be the same as 20. That, that was the plan, and it, it was really interesting because FDA advised us to include the 10 mg dose, and it turned out that was really good advice. Because what we've demonstrated is that the PD effects are identical, which... So the combined dose analysis is apitegromab versus placebo, in this trial, 10 equal 20, so they're identical.... And I, you know, it really gives us really, really strong data set to go forward. As you know, the, in today's world of drug development, we're looking for the dose, the lowest dose that gives you the best efficacy and safety.
I think we have a really strong argument here with our data to recommend the ten, but I think the dose, no expected dose response, but a clear win, clear win and consistency across the study.
Thank you.
Thank you. Our next question comes from Allison Bratzel with Piper Sandler. Your line is open.
Hey, good morning, guys. Huge congrats on this data. Maybe just two questions from me. First, just, you know, based on the TOPAZ experience, would you expect a deepening of response? You know, just looking at slide 15, it sort of looks like you're already seeing a deepening of response over the course of 52 weeks of treatment. Just curious how you would expect that to evolve over time. And then just secondly, you know, building on some prior comments, could you help us just understand your assumptions on labeling? You know, with the consistency of data across age groups, it would seem to support a broad label encompassing patients over age two. And then also, would you anticipate the need to run additional trials in ambulatory patients, for them to be included in a label? Thank you.
Yeah. So Ali, thank you for the questions. First, I think with respect to the effect that we saw at week 52, you know, the beauty of this trial is we met the primary endpoint at week 52, which is outstanding. The TOPAZ data, if any extrapolation, suggest that we hold that effect over time, and we'll continue to follow these patients in ONYX. But I think at week 52, unambiguous, I think it's really terrific. With respect to the age group, you know, going into this study, and I've been very front-footed on that, the 13- 21 year-old group I described as a predefined subgroup, I've put that in quotes, is a group that we really wanted to see.
If the effect size in that group was consistent with the broader population, I felt like we had a really good opportunity to move that forward into labeling. I, when you take a look at that point estimate, one point eight, which is identical to the combined dose, very, very clear and compelling for me. FDA views the SMA as one disease. I think these data are strong. We certainly would lean in on getting the full breadth of age, because I believe these data were very supportive of that. And to further amplify that, you know, we've been very fortunate to have a very strong partnership with the Cure SMA community. And in my discussion with the leadership at Cure SMA, this teenage, this young adult, older adult group, they're crying out for additional help and additional benefit.
I think this study shows that we have a potential solution here. Very clear effect on the 13-21 , and we'll certainly move forward with the plan to seek the broad age group in our regulatory interactions.
Thank you. Our next question comes from Tessa Romero with JP Morgan. Your line is open.
Hi, good morning, Jay and team. Congratulations on the data here. So a couple of questions from us. If the doses were pharmacologically similar here, and the patient populations enrolled in the dose arms were similar, why do you think the treatment arms didn't perform nearly the same? Could that just be within the noise of the endpoint? And, you know, relatedly, double-clicking on slide 15, what do you attribute the improvement in Hammersmith in the placebo arm from 8-week to 24 weeks? And then, final question from us is, can you frame what types of analyses we should prepare for in the first quarter of 2025 as a follow-up to these results? Thanks so much.
Yeah, so good questions, Tessa. Good morning, and thanks for joining the call. Regarding the dose and the way the 20 and 10 performed, your point about sample size is the answer. I mean, we have 10 and 20 are identical. You take a look across the consistency of effect. So I think it's a function, just the small number is not of any difference. And in fact, 10 equal 20, and the point estimate is 1.8 on these combined doses, so very, very, very solid response. With respect to the time course and the placebo response, you know, there's. If you look at other studies, their placebo effect is, has a little bit of increase at the beginning points.
I think the important thing to really look at in that data are where patients started, where they ended up at week 52, and the validity of these results relative to what we saw in nusinersen. Just put this in context, this is sobering. Even in the conduct of a 12-month study, patients randomized to placebo on the best available therapy lost a point over a period of 12 months. That's the disease, and we've brought apitegromab into this setting, showing we can gain function, gain function, while the natural course on the best available therapy has lost the function. And this is an amazing result. And then you look at the 30% improvement on top of standard of care, you look at the consistency of effect. This was a clear win, Tess, very clear win.
What do we have-
Oh, and additional data? Yes, sorry. Yeah, yeah, sorry. We have, we're looking forward, Tess, to being able to really present these data at an upcoming medical meeting, and it's a rich data set. We'll have a lot of opportunity to share more detail behind it. These are top-line results released today, and hence we're focusing on top line. Looking forward to more data.
Thank you. Our next question comes from Gary Nachman with Raymond James. Your line is open.
Hi, good morning, everyone. This is Tejas on for Gary from Raymond James. Congrats on the data, really great to see. And we have two questions. So kind of talking about maybe that subgroup analysis a little bit, is there any group of patients you can at least qualitatively speak to that was more likely to get that plus, 3+ point Hammersmith improvement, or was it fairly distributed? And then our other question is, with patients on TOPAZ, your phase II rolling into the open-label at the 20 mg per kg level, do you think there's any question with the FDA maybe wanting a little bit more long-term data at the 10 mg level before you wanted to submit for that? Thank you.
Yeah, so good. First question regarding subgroups. More to come on that. We'll be reporting out more detailed data on subgroup analysis, along with some of the other data at an upcoming medical meeting, so more to come on that. Regarding the need for further follow-up exposure on 10 mg, you know, just think about the exposure is really driven by the amount of drug given. The 20 mg certainly is gonna be comparable to 10, so I don't believe we need any additional data to follow. I think we have a very robust data set here to give FDA and the European agency regulators sufficient information to understand the safety. And to further underscore that, we have four years of treatment on TOPAZ, four years. I mean, it's just, it's so clean.
You know, I think about safety, it starts with the target. Myostatin is one of the cleanest targets I've worked on in my career. Target starts with how we target it. It's highly selective, our selectivity matters. We're only hitting myostatin, and then you add to our four-year experience. Now we're in a very good place with long-term follow-up on safety.
Appreciate it. Thanks for the color.
Thank you. Our next question comes from Kripa Devarakonda with Truist Securities. Your line is open.
Hey, guys, congrats again on the data, and thank you for taking my question. A couple from us. Now, you know, you've talked about how earlier the treatment start, the better. And while the patients have been on background therapy for a few years before the start of apitegromab, you know, about five to six years on nusinersen and about three years or so on Evrysdi, I was wondering if you can talk about your strategy when you discuss these results with the FDA. Like, what is the minimum amount of time they need to be on the drug before they can get apitegromab? And the second one, you know, given that majority of your patients were treated with nusinersen, and, you know, for practical reasons, that was the case, but still less than or around 20% were on risdiplam.
What is your confidence in a broad label? Thank you.
Yeah, so good questions. First of all, I think the time to initiate apitegromab relative to risdiplam or nusinersen, frankly, we've controlled for that in the conduct of the study just so we can make sure that there's like even and it's balanced. But frankly, there's no reason not to start this as early as possible. I think the goal in practice would be give the drugs, just go, move it, get it up front. But again, from the trial design, you want people to be on stable background dosing, so hence we have that timeframe. I again think earlier is the better. I think Jing really said something really powerful. You know, we have an effect across age groups. We saw that in the 13- 21.
The biology would suggest that we should be able to have an effect, but from the trajectory of SMA, I think giving these children a boost as early as possible, I think would really be helpful. Hence, I think the reason for the under two study and the reason to move forward. With respect to our experience with risdiplam, and I think we have adequate experience here, because we had randomized to it. We saw risdiplam in the two to 12, and we also have risdiplam patients represented in the 13- 21 year age grade. So I think we have sufficient experience on both, and I would expect we would get a label that would be agnostic to the treatment.
Okay, great. Can I ask a follow-up question? Just, I don't... If I missed it, I apologize, but do you have plans in ambulatory patients?
Oh, that was a question earlier.
Yeah, sorry.
We have a full life cycle plan for apitegromab.
Okay.
You know, in New York, I made a comment that, you know, I think this is really kind of us to establish ourselves in a neuromuscular franchise. I think with these data, gives us the chance to go out and become a commercial company. So what an inflection point for the company. When I look at apitegromab, there's plenty of opportunity for us to expand around apitegromab, both within SMA and in other neuromuscular areas. So we've got a lot of vision for where we think we can take this highly effective therapy, which is extraordinarily safe. That ambulatory group, you know, we have other discussions to talk about other age groups and other subgroups within SMA that we're going to experience.
So more to come on our development plans, but the one thing that we are absolutely on track to do is to get that under two study initiated. Again, earlier, better, and I really can't wait for our team to get that study up and running.
Great. Thank you so much, and congrats again.
Thank you. Our next question comes from Marc Frahm with TD Cowen. Your line is open.
Hi, congrats on this morning's data. Also, maybe following up on last question, just this idea of supporting the broad label and kind of consistency of the set. Can you speak to the efficacy kind of by SMA subtype? Just any trend there in terms of Type Twos versus Type Threes? And then, can you just remind us kind of the scale of commercial organization that you now need to build, given the outcome here today?
... Yeah, so we haven't really gone through the subgroup analysis by type. You know, I think the typing is really becoming a little bit more historic reference. It's really more functional status now, where clinicians are using the guide to treat. But more to come on subgroup analysis as we go forward and we present these data at subsequent medical meetings. And then I have Ted Myles on the call with me here, and I'll turn to Ted for a discussion around our commercial build-out.
Sure, thanks. Thanks for the question, Mark. You know, nothing changes other than, plans are now being activated. We've been planning for this for a long time. It's been a careful, thoughtful build, sort of the scaffolding, so that we'd be ready to get ready. And now, as we sit here, hopefully inside of a year of commercial launch, it's time to really, you know, get ready. And so I think Tracey guided during our May 22nd Analyst Day in New York, that this was a, a build of, call it, about 50 patient-facing professionals. That includes reps and MSLs. So fairly achievable, you know, very, very manageable, build, and that would be the U.S. and probably about the same or a little smaller in Europe.
The plans are ready, everything's set to go, and we're excited to get this drug to patients.
Okay, thank you.
Thank you. Our next question comes from Andres Maldonado with H.C. Wainwright. Your line is open.
Hi, guys. Thanks for taking my questions and congrats on the data. On the horizon of the open study start, just a quick question there. Could you remind us, for this age group, what are some of the differences in the disease etiology for these patients? I mean, the challenges that may arise with the quantification of any endpoint in this population. Thank you very much.
Andres, could you repeat the question? It's a little hard to hear you.
Are you asking about the biological differences among the patients?
Yeah, so, I could repeat it really quick. So could you remind us for this patient age group, for the OPAL study, you know, based upon the age, what are some of the difficulties in the quantification of the endpoints in this population?
Okay, good deal. So the question's around the OPAL under two study. So there's two things. There's two real, two real things that we need to achieve with that. First is to make sure that we can study a dose to guide, you know, the pediatricians who are caring for these children to know how to use and guide the dose. And, you know, as I mentioned earlier, a lot of that is done by PK/PD modeling that we do from the SAPPHIRE study. And so we'll certainly have PK/PD endpoints included in that study. That's really FDA's expectations. They're really looking more for that verification of dose, and we can do that in a study. There are other endpoints that can be used. Maybe I'll ask Jing to make a comment on a few that are used to measure in these early children.
Yeah, so, there are a number of very well-validated endpoints. We've actually aligned with both Europe and the FDA about the endpoint that is specifically designed for the under two age group, and we look forward to update you as we start the study.
Yes, and so as we have on other studies, once we get this up, posted on clinicaltrials.gov, we'll have an opportunity to kind of go through the design, the endpoints, et cetera, but you know, we've, you know, we've been working on getting this study up over the last year, anticipating success with Sapphire, so looking forward to getting that started. Thanks for the question.
Thank you. Our next question comes from Etzer Darout with BMO Capital Markets. Your line is open.
Great, thanks for taking the question, and congrats on the data today. So any meaningful differences in how the EMA would interpret these data versus the FDA? I guess I'm trying to, you know, get a sense on how regulators look at SMA, maybe similarly or differently, and maybe same with sort of SMA, sort of treating physicians or community, the SMA community. And I have a follow-up. Thanks.
Yeah, so I think from both FDA and EMA, they see this as a single disease, and as you know, there's a lot of collaboration back and forth with FDA and EMA. They have constant ongoing discussions and reviews. We've socialized both with FDA and EMA, so we really have good insight. They're very aligned in their view. They were aligned on the protocol. They were aligned on the endpoints. So I think we're really in a good position. You know, and I mentioned earlier on a quarterly earnings call, we had a pre-submission meeting with EMA. They're actually welcoming us, they're encouraging us to come.
I mean, we're looking forward to getting these applications in, which is why you heard me say, we're gonna take advantage of all the expedited review pathways available to us in both the U.S. and Europe to try to get this through the regulatory process as quickly as we can.
Great. Thank you. And, you know, we noted also, I guess, the consistency of the data across doses and age groups, but just wanted to know, even though I guess it's early, you know, any differences in activity based on sort of the background therapy that patients had, whether it be nusinersen or risdiplam?
Yeah, no, I mean, we're gonna, we're gonna go through all of the subgroup data in a subsequent medical meeting, and we'll really give you great insight into that. Again, going into the study, we expected risdiplam and nusinersen to be the same. They're both affecting SMN protein, and so there really should be no reason that there would be differences. And we'll go through that and demonstrate that in a subsequent medical meeting.
Great. Congrats again.
Thank you. This concludes the question and answer session. You may now disconnect. Everyone, have a great day.