Scholar Rock Holding Corp Q2 FY2020 Earnings Call

Ladies and gentlemen, thank you for standing by, and welcome to the Scholar Rock Management Intro and Second Quarter 2020 Financial Results and Business Progress Conference Call. At this time, all participants are in a listen-only mode. After the speaker presentation, there will be a question-and-answer session. Please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker today, to Catherine Hu, Vice President, Investor Relations and Corporate Communications. Thank you. Please go ahead.

Good morning, and thank you for joining us on today's call to provide an update on second quarter 2020 financial results, as well as an introduction to our newly appointed President and CEO, Tony Kingsley, and CFO and Head of Business Operations, Ted Myles. Yung Chyung, our Chief Medical Officer, will also be joining Tony and Ted on today's call. 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. Before I turn it over to Tony, I wanted to note that during today's call, we will 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, Scholar Rock's actual results may differ materially from those indicated by any forward-looking statements as a result of various important factors, as fully discussed in the section entitled Risk Factors in our quarterly report on Form 10-Q, 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. Thank you and I will now turn the call over to Tony.

Thank you, Catherine, and thank you, everyone, for joining us this morning. Scholar Rock is at an inflection point. The company's science is beginning to prove its potential clinical utility, our programs are moving quickly toward multiple data readouts, and the company has new leadership to take it to the next phase. Let me tell you a little about myself and why I have joined Scholar Rock at this time. As described on Slide 3, I was most recently President and CEO of Taris Bio, a development stage oncology company that was acquired by Janssen Pharmaceuticals at the end of 2019. Before Taris, I served as President and COO of the Medicines Company, and prior to that, I headed commercial operations at Biogen. I bring extensive experience in later-stage drug development and commercialization, both of which are rapidly becoming critical to Scholar Rock's success. And I have provided both strategic and operational leadership to life sciences companies in times of great transition and growth. That is the profile that the Scholar Rock Board was seeking to replace our founding CEO, Nagesh. This was a very planned and purposeful transition, and it signals confidence in the future. The fact that I was able to bring on Ted Myles as our CFO and Head of Business Operations almost immediately should also signal to you that this transition is about building for success. Ted has served on our Board for nearly two years and knows the company well. You will hear from Ted shortly. Now let me describe what drew me to Scholar Rock: powerful science, great programs, and talented people. I've been impressed with the level of execution, collaboration, and commitment to take on tough targets as we work towards the goal of changing medical practice and helping patients suffering from cancer and neuromuscular disease. My conviction on the scientific platform and programs has only increased as I have fully immersed into the culture of the company. Now going to Slide 4 in our presentation. My top three takeaways are: first, the scientific platform has produced multiple programs with significant therapeutic potential. Our two most advanced programs, SRK-015 and SRK-181, are advancing quickly, and both address markets that are well-developed and growing very rapidly. There are multiple programs at multiple milestones, and that offers near and long-term value inflection points as well as significant strategic optionality. I can clearly see Scholar Rock's growth potential. The science is highly differentiated. The clinical programs are well-designed. And as you will see on Slide 5, we are moving quickly toward multiple milestones over the next 12 months that will elucidate each program's potential to help patients with serious diseases. I believe this slide captures the breadth and depth of our pipeline and demonstrates the power and productivity of our scientific platform and our talented scientists. It also illustrates the key factors that drove my decision to join Scholar Rock. To start with SRK-015 in spinal muscular atrophy, or SMA, we will be reporting interim results from the ongoing TOPAZ Phase II trial in the fourth quarter, followed by 12-month data in the first half of 2021. Our goal here is to establish SRK-015 as the first muscle-directed therapy for patients affected by SMA. Next, we're making rapid progress in building momentum on the DRAGON Phase I trial for SRK-181, a potential therapeutic backbone to cancer immunotherapy. We are advancing to Part A2 of the study this quarter to evaluate SRK-11 in combination with checkpoint inhibitors, and we'll provide an update on dose escalation in the next quarter. We believe we have the power to unlock the key to improve the efficacy of checkpoint inhibitors. We are the first and only company to specifically target the TGFß1 isoform, which we believe has the potential to improve efficacy while minimizing the risk of adverse events. We believe that SRK-181 has immense potential to increase response rates to checkpoint inhibitors and change medical care for cancer patients across multiple solid tumor types. In addition to these two clinical assets, there are many potential opportunities for us to extend our science, whether it's additional indications, additional tumor types or treatment settings, or additional growth factors. Furthermore, we have an important partnership with Gilead around fibrosis, which continues to progress well. This collaboration is another proof point on the attractiveness of our platform and our approach.

Thanks, Tony. I want to extend another warm welcome to you and Ted. Thanks to everyone for joining us on this call today. I'm very excited to provide an update on the great progress we are making across all of our development programs. First, I want to say how proud I am of the team's dedication and commitment to advancing our clinical programs and how appreciative we are of the high level of engagement from our clinical trial investigators and study sites despite the challenges of the ongoing COVID-19 pandemic. We continue to make great strides towards important readouts for both the SRK-015 and SRK-181 program. Starting with our most advanced product candidate, SRK-015, which is a fully human monoclonal antibody and a highly specific inhibitor of the activation of pro and latent myostatin. Our goal is to establish SRK-015 as the potential first muscle-directed therapy to promote a clinically meaningful increase in motor function for patients with SMA. As outlined on Slide 7, we view the SMA treatment landscape as being classified into two distinct but complementary therapeutic strategies: SMN upregulator therapies and muscle-directed therapies. Over the past few years, there have been advances in the development of SMN upregulator therapies, also known as SMN corrective therapies, which are aimed at addressing the SMN deficiency in order to prevent further motor neuron deterioration. While the advent of such therapies represents important progress, the primary benefit of such an approach appears to be to stabilize one's disease course. Even with early intervention, individuals continue to have motor function impairment as complete correction of the disease manifestations is unlikely. Therefore, we believe that a second category of therapies, namely muscle-directed therapy, is needed to aim at driving absolute improvements in motor function. This need for therapeutic advances to go beyond SMN upregulators is highlighted by data from the Phase III CHERISH trial of nusinersen in later onset SMA, as shown on the right-hand side of the slide. Patients treated with nusinersen for 15 months experienced a mean improvement from their baseline of 3.9 points on the expanded Hammersmith Functional Motor Scale, or HFMSE, as shown in green. While this result is certainly viewed as clinically meaningful, there is still significant room for improvement in motor function. Taking a deeper look at the CHERISH trial on Slide 8, it is evident that the improvements in Hammersmith scores predominantly occurred in patients who were treated at a very young age. In contrast, patients who were aged five and older at the time of nusinersen initiation appear to primarily experience stabilization, with less than 15% able to achieve at least a 3-point improvement, even with 15 months of nusinersen treatment. A 3-point improvement in the Hammersmith score is widely considered to be clinically meaningful and a very favorable patient outcome as compared to the usual course of disease. A similar phenomenon of motor function stabilization was observed in the SUNFISH trial of risdiplam in patients with Type 2 or non-ambulatory Type 3 SMA between the ages of 2 and 25, as shown on the right-hand side of the slide. The primary endpoint in this trial used a different motor function scale, the MFM32 score, over 12 months of treatment. While this primary endpoint was met, most patients over the age of five did not obtain a 3-point improvement. This motor function stabilization phenomenon was also observed across all patients in the SUNFISH trial in the HFMSE secondary endpoint, which showed a mean 0.58 point improvement over placebo, which was not statistically significant. To reiterate, SMN upregulators represent an important advance in the treatment of SMA as these agents prevent further motor neuron deterioration and stabilize the disease course. Now the stage is set for the next era of SMA drug development that seeks to drive motor function improvements. Towards this vision, we believe SRK-015 has the potential to be the first muscle-directed therapy in SMA and potentially become the backbone of treatment for any SMN upregulator. With that as a backdrop, let's now turn our attention to SRK-015 and the ongoing TOPAZ Phase II trial. We have made substantial progress on the path towards investigating the therapeutic potential of SRK-015, as outlined on Slide 9. We have formulated a strong translational rationale for investigating myostatin blockade in SMA. We have demonstrated a therapeutic effect preclinically in the SMN Delta 7 Mouse model. We have completed a Phase I trial in adult healthy volunteers that showed initial safety; a pharmacokinetic profile that supports the every-4-week dosing regimen we are evaluating in the TOPAZ trial; and importantly, pharmacodynamics data that confirm robust engagement of the target of SRK-015, the latent form of myostatin. Preliminary therapeutic data from the TOPAZ trial demonstrated this target engagement in patients with SMA as well. We are far along on the development path for SRK-015 and look forward to the interim efficacy and safety analysis expected in the fourth quarter. Turning to Slide 10 to review the TOPAZ trial design. This Phase II study consists of three parallel cohorts, each evaluating a distinct subpopulation of patients with Type 2 and Type 3 SMA. At the beginning of this year, we completed enrollment of a total of 58 patients in the U.S. and Europe. More specifically, Cohort 1 enrolled 23 patients with ambulatory Type 3 SMA between the ages of 5 and 21. These patients are either treated with SRK-015 as a monotherapy or in conjunction with an approved SMN upregulator. Cohort 2 enrolled 15 patients with Type 2 or non-ambulatory Type 3 SMA, also between the ages of 5 and 21, and all patients are treated with SRK-015 in conjunction with an approved SMN upregulator. Cohort 3 enrolled 20 patients with Type 2 SMA, aged 2 and older, who had initiated treatment with an approved SMN upregulator before the age of 5. All patients of the study received IV SRK-015 dosed every 4 weeks for 12 months. The primary efficacy endpoint planned to be evaluated in the TOPAZ study are the expanded Hammersmith Functional Motor Scale, or HFMSE, for non-ambulatory SMA, and the Revised Hammersmith Scale, or RHS, for ambulatory SMA. The HFMSE is a validated outcome measure specifically designed for SMA, is often used in clinical practice and clinical research, and served as the primary efficacy endpoint previously used in the Phase III CHERISH trial of nusinersen. The RHS is very similar to the HFMSE, with some modifications to tailor the assessments to patients who are ambulatory. Let's now walk through our expectations for the 6-month interim analysis, which we expect to receive and disclose in the fourth quarter of this year. We are planning for a robust readout looking across efficacy and safety endpoints. Starting with Cohort 1 on Slide 11. We will be looking at the mean change from baseline in the Revised Hammersmith Scale to evaluate if SRK-015 treatment can indeed lead to absolute improvements in motor function over baseline rather than merely just stabilization. We will also evaluate the proportion of individual patients to achieve at least a 3-point improvement in RHS over baseline. To reiterate, a 3-point improvement in a given patient would be unexpected in most patients and is also widely considered to be clinically meaningful. In addition to RHS, we will also be looking at timed motor tests, such as the 6-minute walk test, and 10-meter walk and run, and timed rise from floor. While our base assumption is that SMN correction through an SMN upregulator will be necessary to complement the effect of SRK-015 in this patient population, it would be interesting to see if SRK-015 monotherapy may have any impact. For Cohort 2, we will be looking at the mean change from baseline in HFMSE, and we'll also evaluate the proportion of individual patients retaining at least a 3-point improvement in HFMSE over baseline. We will be evaluating additional outcomes, including Revised Upper Limb Module, or RULM in short, and the World Health Organization motor development milestones. Cohort 3 enrolled a younger patient population to investigate the potential benefit of SRK-015 in patients who were initiated on nusinersen before the age of 5. We're also conducting dose exploration in this cohort by seeing if a lower dose may still offer meaningful efficacy. We will be looking to see if treatment can lead to a substantial improvement in HFMSE. Additionally, patients will have to be evaluated on the RULM and WHO motor developmental milestones. While we are enthusiastic about SRK-015's potential in all three cohorts, we should note that each of the three cohorts evaluates a different SMA subpopulation, which there is a sizable number of patients and there is high unmet medical need. The demonstration of proof-of-concept for any one of these three cohorts would, therefore, be an important result to us and would also encourage us to broaden the subsequent investigation of SRK-015 to a broader population of patients, whether via wider age range or in combination with any approved SMN upregulator. In addition, a successful proof-of-concept result in Cohort 3 would encourage us to further evaluate SRK-015's therapeutic potential in the early intervention setting, such as patients with Type 1 SMA or presymptomatic individuals. Furthermore, we believe that a positive efficacy outcome across any of the three cohorts would validate the motor function building hypothesis of SRK-015 and support the investigation of SRK-015's therapeutic potential in other neuromuscular disorders for which fast-twitch fiber deficits play a key role. Before turning to SRK-181, I just want to remind everyone that while all patients receive active treatment with SRK-015 in the TOPAZ trial, we are firewalled from the efficacy data. We are eager to see the interim results and look forward to sharing the data with you in the fourth quarter. As a final note, as of August 1, of the eight patients who have completed the entire 12-month treatment, all eight have elected to enroll in the voluntary 12-month extension study. Now let's discuss SRK-181, our highly selective inhibitor of TGFß1, which we believe has the potential to increase response to checkpoint inhibitor therapies and may be the backbone of a new era of cancer immunotherapy.

Thank you, Yung. Like Tony, I'll start by describing why I made the decision to join Scholar Rock. This is a dynamic time for Scholar Rock. The company is growing and advancing quickly, and we are just months away from some important clinical data readouts, which, if positive, could lead us to potentially initiating a registrational trial as early as next year, subject to feedback from regulatory authorities. I'm excited to apply my expertise as a senior financial and operational executive at late-stage clinical and commercial stage biopharmaceutical companies to Scholar Rock as we advance our important clinical programs. Ultimately, the goal is to commercialize our therapies so that we can help the broadest set of patients in need. I look forward to partnering with Tony, Yung, and the rest of the executive team to begin the long-range strategic planning necessary to execute our ambitious plans. Furthermore, I had the honor of serving on Scholar Rock's Board of Directors for nearly two years before joining as CFO and Head of Business Operations last month. This gave me a clear view into the many accomplishments of the company and is also why I have a high degree of confidence in the scientific platform, the clinical programs, and the team's ability to execute. Now let's turn to Slide 21 to highlight second quarter GAAP financial results. Revenue in the quarter was approximately $4 million and was exclusively related to the Gilead collaboration. R&D expense was approximately $17 million in the second quarter compared to $14 million in the prior year quarter. The year-over-year increase can be attributed to the ongoing TOPAZ SRK-015 trial, a payment to Specifica for the delivery and acceptance of a customized antibody display library, as well as higher personnel-related costs. G&A expense was approximately $6 million compared to just about $5 million for the year-ago quarter. This year-over-year increase was primarily the result of personnel-related costs and professional services. Net loss for the quarter was about $19 million, for a net loss of $0.65 per share. This compares to a net loss of $12.5 million, or $0.48 per share, for the quarter a year ago. To summarize, our spending for the second quarter and the first half of 2020 was aligned with our plan and is focused on advancing our clinical development programs, investing in our research and discovery platform with ambitions to generate many more clinical stage products in the future, and investing in G&A capabilities that can support our expanding R&D infrastructure. As of June 30, 2020, we had cash and cash equivalents and marketable securities of approximately $141 million versus $157 million at the end of 2019. Our current operational plan points to a runway that extends into the fourth quarter of 2021. To wrap up my comments, we believe that we have a productive scientific platform, and we'll continue to invest our drug discovery efforts to feed the pipeline. We have two ongoing clinical trials. SRK-015 is on the cusp of important value-creating milestones. SRK-181 is moving quickly towards clinical data, and we believe it has immense potential to change the treatment landscape for cancer patients. On top of these clinical programs, we have a lot of optionality in terms of next indications. Simply, there is a lot going on and many great programs for us to invest in. Now I'll turn it back to Tony for some closing remarks.

Thank you, Ted. To close, I want to say how impressed I am with the progress the company has made, especially against the backdrop of this ongoing pandemic. Coming back to Slide 22, the next six quarters are filled with a number of important R&D milestones that will continue to elucidate the potential of our programs and our scientific platform. We are very much looking forward to providing updates from both SRK-015 and SRK-181 in the fourth quarter. Based on our achievements with our scientific platform, I'm confident that we can take on some of the toughest targets in medicine so that more patients benefit. I want to thank my colleagues for their hard work and dedication to the many patients who are awaiting our therapies. I also want to thank our shareholders for their support and time this morning. I think we can now turn to Q&A, operator.

Thank you, sir. I show our first question comes from the line of Michael Yee from Jefferies. Please go ahead.

Hi good morning, thanks guys and congrats, Tony, on the new role. Looking forward to this. Maybe two questions for Yung. On 015, you might think that Cohort 3 would be the group you could see the greatest effect given the most youngest patients. But in that group, you also see a lot of improvement with Spinraza in the CHERISH study. So maybe you could just delineate how you think about a 3-point improvement in Cohort 3 versus Cohort 1 and 2? In other words, how do you delineate your expectations between those groups? And then on 181 and TGFß, are you expecting you could actually see responses even at low doses and dose escalation in data that we're going to see later this year? Thank you so much.

Hi, Mike. Yes. Regarding your first question about understanding efficacy across the different cohorts, for Cohorts 1 and 2, patients aged five and older started on nusinersen typically have an expectation of disease stabilization rather than significant improvements in motor function. We're interested in observing a mean change from baseline that shows genuine improvement in motor function instead of no change at all. A key analysis will focus on how many patients achieve at least a 3-point improvement from their baseline, based on data from the Phase III nusinersen trials as well as from risdiplam. Notably, it's uncommon for individual patients to show significant improvement—less than 15% was seen in the CHERISH trial. Therefore, it would be promising if a significant number of patients in SRK-015 can achieve a 3-point or greater improvement from baseline, which aligns with expected outcomes. For Cohort 3, patients who start on nusinersen before age five can show some improvement beyond stabilization of motor function. We aim to observe substantial enhancements in motor function, exceeding what is typically seen with nusinersen, both in magnitude and over time, as data indicates a gradual improvement with the drug. Additionally, a crucial part of the Cohort 3 analysis includes exploring different doses. We want to see if the low-dose group exhibits efficacy alongside the high-dose group, which could inform future dosing strategies. We're also assessing other outcome measures such as the revised upper limb module and the WHO motor milestone. It’s essential to note that achieving efficacy on the WHO motor milestone is challenging; even in the nusinersen CHERISH study, significant improvements were not observed, with about only 20% making one milestone gain. Therefore, there are various methods to evaluate therapeutic effects from SRK-015 in Cohort 3 on top of nusinersen. As for your question about efficacy in relation to dose escalation for SRK-181 and checkpoint inhibitors, we believe that Part B is where we will thoroughly assess the efficacy potential of combining these treatments. We are investigating several tumor types with considerable patient numbers, particularly those who have experienced primary resistance to checkpoint inhibitors. If we begin to see efficacy with the combination, even among relatively few patients, it would be significant considering their prior resistance histories. In Part A, we will also investigate potential efficacy, viewing it as a potential positive surprise if it does occur. The study population in Part A2 includes patients who did not respond to prior checkpoint inhibitors, allowing us to see the effects of the combination treatment. Overall, our primary expectation for efficacy signals is in Part B, but we will continue to monitor and evaluate outcomes during dose escalation in oncology.

Our next question comes from Do Kim from BMO Capital.

This is Jameson on for Do. Two on 181 from us. First one for Yung. Could you elaborate a little bit more on expectations for us on that data that will be presented by year-end? The amount of patients, type of biomarkers, and how we should interpret that as a potential read-through for the full readout in 2021? And then the second question for Tony maybe. Given that the 181 study is targeting a wide variety of tumor types, significantly large opportunity in that checkpoint-resistant market, could you tell us your thoughts on the commercial strategy and how you see the program being developed going forward?

Yes. So for the first question on the update on dose escalation. In the fourth quarter, we're anticipating any update on progress in dose escalation. In other words, how far along we've gotten in the dose escalation process. We'll make sure that there are no major safety signals that would limit dosing. One thing I should point out is we do anticipate, given the progress we've observed to date, that we will be starting the combo dose escalation, Part A2, this quarter. Part A1 and A2, as a reminder, are staggered. We anticipate providing updates on where we stand at dose escalation in the fourth quarter, heading towards a goal of initiating Part B in the first quarter of next year with expectations of seeing clinical response and safety data in 2021.

Thanks, James. This is Tony. On commercial strategy, let's be clear, task one is the DRAGON trial and what's ahead of us. We need to prove the case here. Having said that, our thinking is that this drug, if it performs as we think it could, could be a backbone therapy. There's reasonable potential to use it across multiple checkpoint inhibitors. We'll obviously be exploring its use across multiple tumor types. There are exciting possibilities. You could start in primary resistance. Is there a chance to expand the checkpoint, etc.? This could lead to a substantial development plan with associated significant commercial possibilities. But job one is to get DRAGON done and start to establish some efficacy. We're thinking about this development in a very broad way.

So we'll start with the kind of big picture question about SRK-181. So you have the dose escalation and the dose expansion cohorts. So kind of the big question to Tony is, how far do you go with 181 on your own versus kind of looking for a collaboration or a partner to kind of more broadly test this drug for TGFß inhibition in a broader array of I-O combination studies?

Yes. Thank you for the question. Oncology is a big space. There is potential for this to be a significant drug with multiple development avenues. We would certainly be open to partnering in this development area as it makes sense, especially given the size and commitment of the oncology field. The question is timing; we want to engage in discussions from a position of strength. I believe that we have the necessary resources to push forward and add value until we can generate proof of concept data.

And then a more micro question on 181. So is the decision to go into Part A2 this quarter based on safety data you've seen from the initiation of Dose Escalation? Is it based upon safety and PK data? Have you reached a PK level where you think you're starting to see drug exposures that will be impactful when combined with PD1? Can you detail how you think about the dose escalation for Part A2 given what you might have seen so far in Part A1 from DRAGON?

Yes. Taking a step back, our approach to dose selection was informed by where we believe, based on modeling and the preclinical data, the potential therapeutic effect range would be. We aim to have drug coverage above that to provide an additional buffer. As we progressed through part A1, we have made sure there are no dose toxicity challenges that would prevent escalation. The primary decision-making process remains safety-driven. As we progress, we will evaluate additional parameters such as PK and biomarker data. The key focus is to push the dose to as high as we can go until proven otherwise and ensure we are well within the therapeutic range we hypothesized could yield the effects we hope to observe.

In the healthy volunteer study, did healthy volunteers see muscle growth on myostatin inhibition therapy? Given the genetics of myostatin, did you see any change in muscle mass in those healthy volunteers?

The healthy volunteers? Our focus both for the Phase I trial and Phase II is on motor function, particularly fast-twitch fiber function. That wasn't a focus of ours. The key here is, as opposed to rodents, humans have a much more mixed balance proportion of fast-twitch and slow-twitch fibers. Given that myostatin has a preferential effect in fast-twitch fibers, you can imagine that individuals might not see a significant change. While there are studies focused on that aspect, our focus is really on the fast-twitch fiber function. This is why we think it really makes sense to evaluate SRK-015, to see if we can drive fast-twitch fiber function improvements that we will measure directly through the Hammersmith scale and other clinically meaningful outcomes to see if our hypothesis holds true.

Given the preclinical data you have, combining the SMA mouse models with an SMN modulator, do you think six months will be enough time from myostatin inhibition to improve motor function? Do you think you'll see greater improvements at 12 months versus six months? How are you thinking about the kinetics of myostatin inhibition improving motor function?

Yes. This is a 12-month study, but it's plausible and conceivable that we may see therapeutic effects at six months. Given preclinical data, we observe effects in a shorter course of time with treatment. We want to explore the potential for SRK-015 to show benefits at that six-month time point. So that's why we're conducting interim analyses to assess if we observe effects at that point. Of course, we are committed to the full 12-month study as well.

On the patients who have completed the 12-month treatment period for 015, could you tell us how many were monotherapy patients, or in that would be Cohort 1 and monotherapy?

Yes. We haven't broken out just in terms of where those patients are. But at a high level, there have been eight patients who have completed the 12-month treatment period, and all eight have opted in to continue forward. It's early in the rollover opportunities for extension, but we are encouraged to date, as we continue to see strong patient engagement as well as clinical trial investigator and site engagement across the whole study.

Congratulations on the new roles across the team. Focusing back on the DRAGON update, will the update focus on enrollment status, or can we expect data on PD markers and those types of analyses as well?

Yes. Regarding the fourth quarter update, we will primarily focus on the status of our enrollment and how far we've advanced in both Part A1 and Part A2. We will ensure there are no major safety signals being reported. While we will be looking at PK and exploring various biomarkers, efficacy data will primarily be available in 2021. Again, we will also focus on ensuring Part B is designed to interrogate efficacy while Part A offers some opportunity for early signals. In terms of the TOPAZ update before the end of the year, one of the therapeutics you listed was having a substantial portion of patients achieve a 3-point increase on the various scales. Can you provide more granularity on what you define as 'substantial'? Are we talking about 10%, 20% of patients, or more like 50% or greater achieving that level? Yes. There are two aspects to consider for both Cohorts 1 and 2: mean change from baseline and the proportion of patients achieving a 3-point improvement from baseline. Historically, data shows it was uncommon for individuals to reach that number in the context of treatments like nusinersen. Our goal is to see if we can have a mean change that indicates absolute improvement and if a substantial proportion, which would ideally be well above 15%, achieves that 3-point increase, which would be exciting given the expected course of disease.

I show no further questions in the queue at this time. I would like to turn the call over to Mr. Tony Kingsley, President and CEO, for closing comments.

Good. Thanks all for joining. Exciting science. We're moving fast. We've got a lot of data potentially coming out in the next quarters. So we're going to get back to work and pursue our destiny. Thank you guys for joining this morning. Look forward to following up with you.

Thank you, sir. Ladies and gentlemen, this concludes today's conference call. Thank you for participating. You may now disconnect.