Scholar Rock Holding Corporation (SRRK) Earnings Call Transcript & Summary

Good day, and welcome to the Scholar Rock Conference Call. [Operator Instructions]. As a reminder, this call is being recorded. I would now like to turn the call over to [ Rashmi Nofsinger ], Vice President of Investor Relations and Corporate Affairs. You may begin.

Good morning, and thank you for joining us on today's call to review the 24-month extension period results from our TOPAZ Phase II clinical trial of patients with Type 2 and Type 3 spinal muscular atrophy, or SMA. The webcast slides for this call can be accessed on the Events and Presentations section of the Investor Relations page on the Scholar Rock website. I wanted to note that we'll be making various statements about Scholar Rock's future 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. Actual results may differ materially from those indicated by any forward-looking statements as a result of various important factors, more fully discussed in the section entitled Risk Factors in our quarterly report on Form 10-Q for the quarter ended March 31, 2022, as well as other important factors in Scholar Rock's future filings with the Securities and Exchange Commission. Any forward-looking statements represent our views only as of today and should not be relied upon as representing our views as of any future date. We disclaim any obligation to update any forward-looking statements unless required by law. Next, let's review the agenda for today's call as outlined on Slide 3. Nagesh Mahanthappa, our Founding President and CEO, will provide opening remarks. Yung Chyung, our Chief Medical Officer, will review the new data from the TOPAZ trial extension period and provide a brief overview of the ongoing Phase III SAPPHIRE trial. Nagesh will be joined by Ted Myles, our Chief Operating Officer and Chief Financial Officer, to provide a business update, and then we will take questions at the end of the call. Thank you, and I will now turn the call over to Nagesh.

Thank you, [ Rashmi ]. If we could turn to Slide 4. I would like to just remind everybody the focus of Scholar Rock [Technical Difficulty] development of novel monoclonal antibody therapeutics. Our unique platform is directs cutting-edge antibody discovery technologies towards protein growth factors, making use of cutting-edge structural biology insights. More particularly, we are focused on members of the TGFß superfamily. And what distinguishes our approach is the fact that we actually target protein growth factors in their precursor or pro forms rather than mature growth factor. We believe this offers a novel pharmacological profile across multiple members of the TGFß superfamily as exemplified by our clinical-stage programs. If we could turn to Slide 5. As a quick a reminder as to the disease on which we are focused in our current Phase III program and the Phase II program that we'll be discussing today, this spinal muscular atrophy, or SMA. SMA is a rare neuromuscular disease that causes from a genetic origin death of motor neurons. Subsequent to the death of the motor neurons lead to lack of control of skeletal muscle and atrophy of those muscles. There are now 3 approved therapies for the treatment of spinal muscular atrophy, all of which are intended to increase the survival of motor neurons. However, significant deficits remain, and we believe a muscle-targeted therapy has the potential to make a very significant impact on these patients. In point of fact, apitegromab has already demonstrated great promise in Phase II TOPAZ study when we reported the 12-month data, and today, we're excited to talk about the future of this program. Now if we can turn to Slide 6. I think many of you are aware that spinal muscular atrophy presents as a spectrum of severity with Type 1 being the most severe through Type 2 and Type 3. The focus of Scholar Rock at present is on Type 2 and Type 3 SMA, which from a prevalence perspective, represent a vast majority, approximately 2/3 of all SMA patients living today. In the U.S. and Europe, this constitutes approximately 30,000 to 35,000 patients. Now, beyond the demographics, let me turn to the nature of the unmet need on Slide 7. The Hammersmith Functional Motor Score Expanded is a validated assessment of motor function in patients with SMA. A maximum score on the HFMSE is 66. This is an evaluation of 33 listing tasks, scored 0, 1 or 2. The data we're showing here on this slide is representative data from the Phase III study of Type 2 and Type 3 SMA patients' mature style, a trial of Spinraza. These patients, on average, without treatment, show a score in the high 20s. Now with treatment, you see improvements on the order of 4 to 5 points, which is very significant for the patients, but I think you'll see that there's still a long way to go to reach that score of 66. So much opportunity for a muscle-targeted therapy. Now if we turn to Slide 8, again, just to talk about the efficacy of drugs that are SMA [indiscernible], such as nusinersen, Spinraza or risdiplam [indiscernible]. You can see that these drugs do, in fact, make a significant impact for patients over the initial dosing period, but in both cases, you see that patients start to plateau. So it is here that we believe that there is opportunity to further increase the levels of muscle strength and muscle function in patients with SMA. And the data that we'll look at today for the 24-month readout from the continuation of the TOPAZ study underscore our belief in the potential of this drug and why this we're so excited to be in the middle of our Phase III pivotal SAPPHIRE study as well. So with that, let me turn it to our Chief Medical Officer, Dr. Yung Chyung.

Thank you, Nagesh. I want to take a moment to thank the Scholar Rock team for all their hard work and contributions. We are also very impressed by and appreciative of the outstanding effort and contributions from our clinical trial investigators, physical therapists, study coordinators, study site staff and our CRO colleagues. Most importantly, thank you to the patients and their families for their dedication to the trial, despite the challenges of the ongoing COVID-19 pandemic. Let's now direct our attention to the TOPAZ trial, starting with Slide 9. In a moment, we will walk through the 24-month analysis and data, and later today, at the Annual Cure SMA Research and Clinical Care Meeting, the detailed 24-month TOPAZ results will be presented as a podium presentation by Dr. Thomas Crawford of Johns Hopkins Medicine and the Lead Principal Investigator of the TOPAZ trial. As an initial overview of the study results, we observed sizable and sustained motor function gains in the nonambulatory Type 2 and Type 3 SMA population, treated with apitegromab in use with background nusinersen as measured by the primary efficacy measure of HFMSE. There was also evidence for continued improvement in the Revised Upper Limb Module, a key secondary outcome measure, as well as continued observation of a dose response. In the ambulatory Type 3 population, there was generally stability observed in the Revised Hammersmith Scale measure on motor function or a subgroup of patients receiving apitegromab in use with background nusinersen. And there were no identified serious safety risks, based upon the 24-month analysis. We are pleased with the results of this 24-month TOPAZ readout as they further reinforce our enthusiasm about the therapeutic potential of apitegromab. Now let's move to Slide 10 to briefly review the TOPAZ trial design. This Phase II proof-of-concept trial consists of 3 parallel cohorts, each evaluating a distinct subpopulation of patients with Type 2 and Type 3 SMA. All patients were treated with apitegromab in this trial, and the primary treatment period was 12 months. Two of the cohorts enrolled nonambulatory patients, who are already receiving background nusinersen therapy. One cohort evaluated patients who had previously initiated nusinersen treatment before 5 years of age, and another cohort evaluated patients who had previously initiated nusinersen treatment at the age of 5 or older. Within Cohort 3, patients were randomized to receive either a high dose or a low dose of apitegromab. This study also evaluated ambulatory Type 3 SMA through a separate cohort, patients in this cohort which were treated with either apitegromab as a monotherapy or in use of background nusinersen. Going to Slide 11. This slide shows the baseline characteristics of the TOPAZ patient population. As a reminder, patients receiving background nusinersen in this trial were well into the chronic maintenance phase of SMA treatment at baseline, receiving on average approximately 5 new enrollment, which corresponds to roughly 2 years of nusinersen. So as outlined on Slide 12. Following the 12-month primary treatment period, patients were offered the option of participating in an extension period to continue receiving apitegromab treatment for another 12 months. All 57 patients, who completed the primary treatment period, opted to enroll in the extension, and 55 of these 57 patients completed the second year of treatment. Patients originally assigned to the high dose of apitegromab stayed on this high dose. Patients originally assigned to the low dose were all switched to the high dose during year 2. The precise timing of the switch vary from patient to patient as each individual had a different duration of study participation prior to the dose switch being done across the group. As an additional note, there were a small number of individuals in the TOPAZ extension period who underwent scoliosis surgery as part of routine standard of care for their underlying SMA disease. In addition to the main analysis approach, we also conducted a supplemental analysis that took into consideration the potential after effect of scoliosis surgery. Finally, as of the beginning of this month, 54 patients continue to participate in the TOPAZ extension. As a refresher on the primary efficacy measure in TOPAZ of HFMSE, let's advance to Slide 13. The HFMSE is a validated endpoint used in SMA trials, including serving as a primary efficacy endpoint for nusinersen in the Phase III CHERISH trial. It encompasses 33 distinct measures of an individual's ability to perform [ various tasks ], including raising a hand to head in a [ sitting ] position, rolling to one side, standing for 3 seconds while supported by one hand or ascending or descending 4 steps. Each task is scored at 0, 1 or 2 points, in which 0 means you cannot perform the task, 2 means you can, and 1 means that it can be done either partially or with adaptation. These tasks are important and relevant to individuals living with SMA, which is why we believe a 1-point gain has the potential to make a meaningful difference for individuals with SMA, let alone a 3-point or even greater increase. Let's now go to the HFMSE data on Slide 14. There were sizable and sustained gains in the HFMSE observed after 2 years of apitegromab treatment in patients from the nonambulatory TOPAZ cohorts receiving background nusinersen therapy. The results shown here were based upon an Observed Case Analysis approach, using the data available for a given time point. This analysis population includes patients treated with the low dose as well as patients treated with high dose and does not exclude any patients who missed apitegromab doses due to COVID-19 site access restrictions. The graph on the left-hand side pulls together with full population of Cohort 2 and Cohort 3 patients. After 12 months of apitegromab treatment, there was a mean HFMSE increase from baseline of 3.6 points. And after 24 months of apitegromab treatment, there was a mean HFMSE increase from baseline of 4.0 points. The graph on the right-hand side looks at the exploratory subset of Cohort 2 and Cohort 3 patients, who are in the age range of 2 to 12 years old. Here, after 12 months of apitegromab treatment, there was a mean HFMSE increase from baseline of 4.6 points. And after 24 months of apitegromab treatment, there was a mean HFMSE increase from baseline of 4.6 points. Together, we believe that these 24-month HFMSE results from the ongoing TOPAZ extension highlights the therapeutic potential of apitegromab in patients with nonambulatory Type 2 and Type 3 SMA receiving SMN therapy. And we look forward to investigating that potential further through randomized, double-blind, placebo-controlled Phase III SAPPHIRE trial. As a reminder, there were a small number of individuals who underwent scoliosis surgery during the TOPAZ extension period as part of routine standard of care for their underlying disease. So it can be informative to have a supplemental look at the HFMSE data, which takes into consideration the impact of such surgery. Slide 15 provides further background on this topic. Scoliosis is a common complication of SMA, leading to surgery in many individuals. In this natural history case series of 17 patients with Type 2 or Type 3 SMA, who underwent scoliosis surgery, most patients had subsequent decline in their HFMSE of at least 3 points. In fact, among the 14 individuals with such a loss, the mean HFMSE change was a 12-point decrease after undergoing scoliosis surgery. With this as background context, please turn to Slide 16. If we exclude data following scoliosis surgery in the TOPAZ extension period then the mean HFMSE change from baseline after 24 months of treatment was a 4.4 point increase in the full [ pool of ] nonambulatory population. And for this analysis for the age 2 to 12 subgroup within the pool of nonambulatory cohorts, the mean HFMSE change from baseline after 24 months of treatment was a 5.2 point increase. Advancing to Slide 17. Let's look at the effect of different doses of apitegromab upon efficacy. We continue to observe a dose response, based upon the mean HFMSE change from baseline through the second year of apitegromab treatment. This graph displays Cohort 3 data by dose level and use the Observed Case Analysis approach with exclusion of data following scoliosis surgery in the TOPAZ extension. Here, the high dose of 20 milligrams per kilogram numerically outperformed the low dose of 2 milligrams per kilogram in terms of mean HFMSE change from baseline across every time point in the 2-year treatment period. And as patients in the low-dose arm switched to the high-dose treatment at various time points in the second year, there were signs suggesting that this group may have had further increases in their HFMSE. Turning to Slide 18. The PK and target engagement data provide further color in interpreting the dose response. On the left graph, you can see that the 20 milligram per kilogram dose offered high levels of drug exposure relative to the 2 milligram per kilogram dose. And as one would expect, the dose switch to the high dose in the originally low dose-treated patients led to increases further in the serum drug concentration. The right graph shows the effect of the 2 and 20 milligram per kilogram apitegromab doses upon levels of serum latent [ myostatin ], which we use as a marker of target engagement. Both the 2 and 20 milligram per kilogram doses led to high levels of target engagement as reflected by the greater than 100-fold increases from baseline in the systemically circulating concentrations of latent myostatin after treatment. The 20 milligram per kilogram dose, however, led to higher mean increases from baseline of latent myostatin relative to that 2 milligram per kilogram dose. And as patients treated with the low dose switch to the high dose, there were further increases. Based on these results, the pattern of dose response seen with the target engagement marker appears consistent with the pattern of dose response observed with the HFMSE results. Let's now turn our attention to the results of the secondary outcome measure of Revised Upper Limb Module for SMA and TOPAZ. As background, on Slide 19, the Revised Upper Limb Module, or RULM in short, evaluates motor task performance in the upper limb. This measure evaluates a patient's ability to perform 19 different activities such as bringing a cup to one's mouth, picking up a coin, opening a zip lock bag or drawing a line on a paper, and the maximum achievable score is 37 points. The RULM is validated for SMA and has been used previously by other drug development programs in SMA as an important secondary endpoint. Slide 20 shows the RULM results in TOPAZ, based on the Observed Case Analysis approach. The graph on the left-hand side pools together the full population of Cohort 2 and Cohort 3 patients. After 12 months of apitegromab treatment, there was a mean RULM increase from baseline of 1.3 points, and after 24 months of apitegromab treatment, there was a mean RULM increase from baseline of 1.9 points. The graph on the right-hand side left at the exploratory subset of pooled Cohort 2 and Cohort 3 patients, were in the age range of 2 to 12 years old. Here, after 12 months of apitegromab treatment, there was a mean RULM increase from baseline of 1.2 points. After 24 months of apitegromab treatment, there was a mean RULM increase from baseline of 1.8 points. Slide 21 provides further insights into these results by taking into consideration the impact of scoliosis surgery. If we exclude RULM data following scoliosis surgery in the TOPAZ extension period, then the main RULM change from baseline after 24 months of treatment was a 2.3 point increase in the full pooled nonambulatory population. And for this analysis for the age 2 to 12 subgroup within the pool of nonambulatory cohorts, the mean RULM change from baseline after 24 months of treatment was a 2.2 point increase. These RULM results support the potential of apitegromab in impacting upper limb function, which is of particular importance for individuals with SMA or nonambulatory. Let's now look at HFMSE and RULM together in considering the motor function effects of apitegromab by turning to Slide 22. Represented here are scatter plots, in which each individual patient's data are represented by a dot. As the 24-month data on the right-hand side illustrates, there was a correlation between observed changes in HFMSE and that in the RULM. Notably, the majority of patients experience improvements from baseline in not just one but both of the HFMSE and RULM measures after 24 months of treatment. The HFMSE and RULM are two independent but logically related measures of motor function. And the results here provide further support for the therapeutic potential of apitegromab. Let's now direct our attention to Cohort 1, evaluating ambulatory Type 3 SMA as summarized on Slide 23. In the subgroup of patients treated with apitegromab while receiving nusinersen, motor function as measured by the RHS was generally stable, with a mean change from baseline of minus 0.7 points after 24 months. In a subgroup of patients treated with apitegromab as monotherapy, the mean RHS change from baseline was minus 2.8 points after 24 months. Of note, there is a subset of individuals across the full ambulatory Type 3 SMA cohort, who had improvements in RHS after 24 months of treatment as approximately 40% of individuals had at least a 1-point increase from baseline and approximately 20% of individuals had at least a 3-point increase from baseline. We find the results from this Cohort 1 analysis to be encouraging and support further exploration of the therapeutic potential of apitegromab in ambulatory Type 3 SMA. Now let's move to Slide 24 to review the safety results from this 24-month TOPAZ analysis, which did not identify any serious safety risks for apitegromab treatment. The incidence and severity of adverse events were consistent with the underlying patient population and background therapy with the 5 most [ recently ] recorded treatment-emergent adverse events, or TEAEs, being headache, pyrexia, upper respiratory tract infection, cough and nasopharyngitis. No deaths or serious unexpected adverse reactions were reported. Adverse events continue to be reported as mostly mild to moderate in severity as observed in the 12-month analysis. Together, the safety results further support the continued evaluation of apitegromab through our clinical trial program. The next slide, Slide 25, summarizes key highlights from this 24-month TOPAZ data readout in the nonambulatory Type 2 and Type 3 SMA population treated with apitegromab [ when used ] in background nusinersen, sizable and sustained gains in the HFMSE were observed, together with continued increases over time in the RULM. Further evidence of a dose response was observed for apitegromab through the 2-year treatment period. In the ambulatory Type 3 population, there was generally stability in the RHS observed for the subgroup of patients treated with apitegromab in use with background nusinersen, as well as subsets of individuals who experience RHS increases after 2 years of therapy. Collectively, the results from this 24-month TOPAZ readout further strengthened our enthusiasm about the potential for apitegromab to offer motor function improvement for patients with SMA. We are excited to be continuing the development and investigation of apitegromab through the ongoing SAPPHIRE trial, the design of which is outlined on Slide 26. SAPPHIRE is a randomized, double-blind, placebo-controlled Phase III clinical trial that will evaluate the efficacy and safety of apitegromab. The main efficacy population will be patients aged 2 to 12 years old with a nonambulatory Type 2 and Type 3 SMA. Patients will be randomized 1:1:1 to receive for 12 months apitegromab 20 milligram per kilogram, apitegromab 10 milligram per kilogram or placebo by IV infusion every 4 weeks added on top of background SMN therapy. Patients receiving background nusinersen as well as patients receiving background risdiplam will both be eligible for enrollment. Slide 27 provides further details on the trial design. For example, at baseline, all patients will be required to be in the chronic maintenance phase of SMN therapy. Randomization will be stratified by both which particular background SMN therapy a patient is on, as well as the age at which that therapy had been initiated. The primary efficacy endpoint will be mean HFMSE change from baseline at 12 months. The trial provides the opportunity for an interim analysis when at least 50% of patients in the main efficacy population have completed 12 months of treatment. Separately, from the main efficacy population, an exploratory population will be evaluated, and there will also be an open-label extension study for patients who complete the 12-month primary treatment period. To close, there continues to be very high unmet medical need for individuals living with SMA, and the apitegromab development program, including this ongoing SAPPHIRE trial, is aimed at testing whether or not apitegromab can meaningfully address this important need. We look forward to providing updates in the future on our SMA program. As we turn to Slide 28, I'll now hand it back over to Nagesh. Nagesh?

Thank you so much, Yung. So as you can see, tremendous energy and excitement around the TOPAZ 24 months data, which underscores our enthusiasm for the ongoing Phase III SAPPHIRE study. So looking at our overarching pipeline, again, we will be [ continuing ] TOPAZ. Bulk of the patients in Phase II in the 24-month study have over for a third year of treatment, and as we've reiterated, SAPPHIRE is ongoing and enrolling. In addition, we are very excited about our anti-TGFß1 inhibitor of activation, SRK-181, this molecule is currently in Phase I testing, proof-of-concept in patients with solid tumors, the DRAGON study. And as a reminder, this study will start to report out data, initially biomarker data, subsequently, hopefully, clinical response data, over the course of the latter half of this year. And then finally, we have, in fact, gained an exciting core research group, who are prosecuting very intriguing and interesting next-generation programs. We believe that we have the opportunity here to build a sustainable pipeline for the long term. In closing for me, I would just like to, first of all, thank Yung so much for 6 years of service, as he leaves us at the end of June. He has been ingenious, creative and an amazing leader. Yung, thank you so much. I'd also like to again thank the patients. I'd like to thank their families. I'd like to thank the clinical sites and all the clinical support staff for all they have done to support us as we advance these programs. And with that, let me turn it over to Ted to wrap up and read out on very exciting financial news and overall corporate updates. Thank you very much.

Thanks, Nagesh. So turning to our final Slide 29. We are very pleased today to announce the completion of a financing, raising $205 million that will fully fund the Phase III SAPPHIRE trial, in addition to the clinical advancement of our immuno-oncology program, SRK-181, through Part B of the Phase I DRAGON trial. We are thrilled to have such experienced, dedicated, long-term-oriented investors supporting the company through this next stage of development. Importantly, this extends our cash runway into 2025. In May, we announced our plans to reduce operating expenses and prioritize these 2 programs while focusing our discovery work to advance only select preclinical programs that best exemplifies the value of our platform. We are very pleased to be in such a strong financial position as we continue to forge ahead with the streamlined focus on programs that will be key near- and long-term value drivers for our company and our patients. That concludes our formal remarks. We can now turn to Q&A. Operator?

[Operator Instructions] Our first question comes from Tessa Romero with JPMorgan.

Congrats on the update here. So our question is really around in the nonambulatory patients. Were there any notable differences in the baseline characteristics of the patients that impacted the response kinetics that you've observed here, based -- whether it's baseline HFMSE score or a [ term ] that the patients started SMN [ RX ] or any other factors? And then I have one follow-up.

Sure, I can take that. So I think that the main one that we observed was in relation to the age at which your background SMN therapy, nusinersen in this case, had been initiated. We call relative [ alerts ] in patients who had been -- had a background of therapy started earlier in life, which makes sense mechanistically, right, because you intervene earlier, you have potential to -- there's more motor neurons to have a base on which we potentially could build [indiscernible]. We did look at some various other factors such as, for example, prior duration of nusinersen therapy before enrolling in TOPAZ as reflected by the number of maintenance dosing nusinersen. And we did not see any particular correlation between the prior duration of nusinersen therapy with the HFMSE increases that were observed in the study. So I think we looked at various factors. Nothing obvious now. There was an exploratory analysis that we've done after 12 months or -- ambulatory population, actually in nonambulatory, where the presence of significant [ contractor ] scoliosis could have an impact on your Hammersmith Scale gains or losses over the course of the study.

Okay. That's helpful. And then one kind of clarifying question for you. I know in kind of the 12-month update in the past, you've sort of provided a portion of patients that have achieved 1 point, 3 points, 5 points. Just wondering, was that kind of also stable from the 12 to 24 month time point, if you happen to have looked at that analysis as well?

Yes. So the more details of these results, including those type of numbers, will be available at the Cure SMA podium presentation by Dr. Crawford later today. But as an overall overview, the large mean increases that were observed through the 24-month analysis did not seem to be driven by a few outliers. And on the contrary, there was a broad-based set of improvements across many patients just like how we saw in the 12-month analysis.

Our next question comes from Do Kim with Piper Sandler.

Congrats on the strong data update. Question for Yung. When you look at the patients -- nonambulatory patients who started on 20 mg per kg, it looks like there -- I mean, sorry, HFMSE score remained stable during year 2. Do you think that the benefit from apitegromab has peaked? Are patients reaching the maximum score, which seem like they should be? Or is there a damage from the disease that is potentially nonreversible?

Yes. So I think we kind of think about as we look at the effects over time for the high dose versus low dose, it appears that a lot of the gains, which we believe are sizable and have the potential to be quite meaningful for patients, happens in year 1. And we are thrilled to see that they're sustained and durable through year 2. Now, whether or not there is an opportunity over further treatment for further gains, TBD, right? We don't know. We've only done this through 2 years, and we see most of the increases are -- the increases happen in year 1 and sustaining this year. Now in the low dose side, we did see that [ nusinersen ] further increases, but that makes sense as there's potential for further gains. If you have a fully saturated targeting, you cross over to a high dose. Interestingly, when we look at a secondary outcome measure of the Revised Upper Limb Module, there it seems to be a somewhat different [ kinetic ], where there is improvement or increase through year 1, whether you're in the high dose or low dose, and it seems to have this further increases in year 2. So raising the question that for the Revised Upper Limb Module, there has to be potential for further increases over time. I mean through this [ 2-year ] time period, there seems to be increases -- continuing increases through year 2. So as we continue to get more data, a little more insight, test hypothesis through the ongoing SAPPHIRE trial as well as year 3 of the TOPAZ extension period, we'll have more insights that will inform this question.

Great. And a question on the patients that went under scoliosis surgery. Maybe you could help us understand what drives that decision for patients to get the surgery? And if you were to take those patients out of the 12-month data, how would the remaining patients compare from 12 months to 24 months?

So going to your second part, I don't seem to recall the scoliosis surgeries during the first 12 months of treatment, but in case the analysis excluding post scoliosis [indiscernible] was rolling for year 2 as outlined on the slide. But just taking a step back and thinking about your broader question about what goes into the scoliosis surgery. So there are varying degrees of severity of scoliosis as well as the progression of scoliosis. So those are key variables in informed decision as well as the impact of scoliosis on the patients activity, right? It's not a trivial decision to undergo major surgery, but for some patients, it's the investigator or the clinician and the patient and family that decided it makes sense because scoliosis can be quite impactful and has to be addressed. And so those are the factors that go into it. But as you pointed out, it's a complex decision and not a trivial one.

Our next question comes from Marc Frahm with Cowen & Company.

This is [indiscernible] for Marc. Just -- my first one would be a follow-up to that scoliosis question. For -- in the TOPAZ trial, should we expect that population of age 2 to 12 to be patients that are likely to undergo scoliosis? And is that -- for this surgery? I mean if that's the case, are you doing anything to account for that?

Yes. So our approach is just like we did for TOPAZ that primary 12-month treatment period, in SAPPHIRE, we are guiding the sites or instructing the sites to not enroll patients who are anticipated to undergo scoliosis surgery or any other major surgery over the next 12 months because as you're alluding to, I imagine, there's confounding potentially, right, from having scoliosis surgery or major surgery during the 12-month period. So step one is making sure to our best of our ability and the sites' ability to exclude patients who may be more likely to have scoliosis surgery over the 12 months. And as we pointed out -- and even just in TOPAZ, it was only a very small number of patients who underwent scoliosis surgery. And so that was -- it speaks to just how well the sites [ fit ] in investigating this. Step 2, and this is more of a TBD thing because there's ongoing discussions with regulators like the [ dose response ] analysis approach, but there are potential ways to go out on the back end as an [ internal ] current event. But it's a little premature to talk about those details just yet because we are still having active ongoing discussions with regulators, but this [ still is the analysis ].

Got it. That's helpful. And [ pilot ] trial also, do you have any enrollment updates? And do you have any idea when you would reach the interim analysis?

So in terms of the enrollment, I mean things are moving along. Sites are getting up and running. They're starting to bring in patients for screening, dosing, et cetera, et cetera. So we're pleased with the progress to date. In terms of specific guidance on enrollment at this time, I think it's premature to start thinking about when exactly the timing of enrollment -- how the dynamics they happen? I mean just -- there's always the intrinsic uncertainty with COVID-19. Hopefully, we'll see that it won't be like in the past years, but it's something we have to be open and understand and acknowledge. And so we're pleased with the momentum to date, but it's too early to try to predict the timing of when we'll hit certain correction [indiscernible] patients.

Yes, we are confident, and we're really thrilled by the financing we completed and announced today and really confident that the financing gets us through SAPPHIRE data and -- with room to spare. So that was one of the core objectives of not only the refocusing and restructuring that we took on last month but also this financing.

Yes. Got it. Congratulations on the data again.

[Operator Instructions] Next question comes from Gary Nachman with BMO Capital Markets.

This is Dennis on for Gary. Congrats on the positive results. Just a couple of quick ones. Could you just remind us about any differences or similarities between the inclusion and exclusion criteria between the Phase II and the Phase III? And then finally, could you talk about why the decision was made to look at the 10-milligram dose for the Phase III instead of the 2-milligram dose again?

Yes. So one of the key advantages of our TOPAZ trial, in terms of the way it was designed, was, it was a learning trial as much as a proof-of-concept trial, right? And so we apply learnings and insights from TOPAZ and form and optimize the potential for success in the SAPPHIRE trial. So things would include -- that was the reason why we focused our inclusion, exclusion criteria, study population on the Type 2 nonambulatory Type 3 population. We're looking at age 2 to 12. We want to ensure the patients were in the chronic maintenance phase and a variety of other measures to really take our learnings from TOPAZ to -- and apply them to SAPPHIRE. In terms of -- and also, of course, we're using the same primary efficacy measure of HFMSE and going with a 12-month time point. In terms of the -- your question about the 10 milligram per kilogram rationale, so our prior hypothesis continues to be that 20 milligram per kilogram, we believe, is the potential dose, based upon how it performed in our dose response analysis in the TOPAZ trial. With that said, we're do acknowledge that it is possible and plausible that a dose between 2 and 20 milligram per kilogram might offer comparable benefit as the 20 milligram per kilogram dose. And so you test that hypothesis and potential, we are including a 10 milligram per kilogram [ bar ]. Now, to avoid the challenge of multiplicity introduced by that and avoid any having to allocate alpha spend across these different dose arms, the approach is more of a [ hierarchal ] statistical analysis approach, where step 1 hypothesis is looking at 20 milligram per kilogram versus placebo. And only that win is where we then look at the 10 milligram per kilogram [ bar ]. And so if we win at 20, we look at 10, it's comparable to 20. That would be really fighting as upside, right, because then you don't have to -- one, it increases the drug supply de facto, right? But second, it would allow patients to have not necessarily receive such a higher dose. And quite some interesting down the road potential life cycle management opportunities about less dosing, et cetera, et cetera.

This concludes the question-and-answer session and our conference call. You may now disconnect. Everyone, have a great day.