Solid Biosciences Inc. (SLDB) Earnings Call Transcript & Summary

Ladies and gentlemen, thank you for standing by, and welcome to the Solid Biosciences IGNITE DMD data review call. [Operator Instructions] Now it is my pleasure to introduce to you our speaker today, Mr. Tim Palmer, Corporate Communications Manager. Sir, the floor is yours.

Good afternoon. Thank you, operator. Before we get started, I would like to remind everyone that during today's conference call, we may make forward-looking statements, including statements about the company's financial results, financial guidance, future business strategies and operations, and product development and regulatory progress, including statements about the ongoing IGNITE DMD clinical trial. Actual results could differ materially from those discussed in these forward-looking statements due to a number of important factors, including uncertainty inherent in the clinical development and regulatory process, the extent and duration of the impact of the COVID-19 pandemic, and other risks described in the Risk Factors section of our most recently filed annual report on Form 10-K and other periodic reports filed with the SEC. We undertake no obligation to update any forward-looking statements after the date of this call. With me on today's call are Ilan Ganot, Co-Founder, President and Chief Executive Officer of Solid Biosciences; Dr. Joel Schneider, our Chief Operating Officer; Dr. Cathryn Clary, our acting Chief Medical Officer; and Dr. Carl Morris, our Chief Scientific Officer. We are also honored to have with us Dr. Barry Byrne, Associate Chair of Pediatrics and Director of the Powell Gene Therapy Center at the University of Florida and Principal Investigator of the IGNITE DMD clinical study. On Thursday afternoon, Dr. Byrne will present data from the ongoing IGNITE DMD Phase I/II clinical study at the Muscular Dystrophy Association Virtual Clinical and Scientific Conference. Before I turn the call over, I want to acknowledge that our full year finances have been reported and can be found in our Form 10-K for the year. For opening remarks, I'd like to turn the call over to Ilan Ganot. Ilan?

Thank you, Tim, and thanks to all of you for joining us this afternoon. During today's call, we will review safety, efficacy and patient-reported outcomes from the first 6 patients dosed in IGNITE DMD and details of the recent safe dosing of patient setup. Cathryn will review the trial design, safety, biomarker and functional data. Dr. Byrne will review patient clinical outcome measures and his overall assessment of the patients. John will then review our previously reported clinical protocol amendments and second-generation manufacturing improvements. We achieved several critical objectives in 2020 and entered 2021 with significant momentum towards goal this year and beyond. We are pleased to report today that we have safely reinitiated dosing under our amended protocol with SGT-001 produced using our improved manufacturing process, and Joel will provide additional information on these patients later in the call. We also established a partnership with Ultragenyx under which our proprietary and differentiated microdystrophin construct will be delivered using Ultragenyx' AAV8 vector platform. This partnership adds a new program to our pipeline and provides a better shot of growth for patients with our nNOS restoring microdystrophin. In January, we laid out our priorities and anticipated milestones for 2021 and agreed that, with today's announcement, we have already achieved 2 of them, resuming dosing and presenting 12-month efficacy and safety data for patients 1 through 6. We remain on track for additional IGNITE DMD data presentations in the second half of 2021 and are making progress towards our other corporate goals. It's an honor to have Dr. Byrne joining us today and in person for this call. Barry has been our partner for many years and an important leader in the field of gene therapies for neurodegenerative diseases for even longer. I'll now turn the call over to Cathryn, who will begin the data review. Cathryn?

Thank you, Ilan. As can be seen on the left, when we originally designed IGNITE DMD, it was designed as a randomized, controlled, ascending dose trial and subsequently modified to an open-label [ still ] randomized design. To date, 3 patients were enrolled in the low dose, 3 at the high dose, and a total of 3 patients were analyzed as part of an untreated control cohort. Let me now draw your attention to the right side of the slide. The study population and entry criteria are at the top, and the endpoints are summarized on the bottom. The primary endpoints of the trial were safety and changes in microdystrophin protein levels in muscle biopsies as assessed by western blot for efficacy. Baseline demographic information for the first 6 patients dosed in IGNITE DMD are summarized here. As I noted before, there are 3 patients in the low-dose cohort and 3 in the higher-dose cohort. Note that patient 1 in the control group and patient 1 in the low-dose group were not assessed with NSAA or 6-minute walk test because they were not ambulatory at the time they entered the study. Before we do a deeper dive into the various assessments, I'd like to share with you a table that offers a very encouraging view of the totality of data we'll be presenting today, data that suggest SGT-001 may offer meaningful benefit for patients with Duchenne and at the higher dose, they offer more benefit than the lower dose. While these are small numbers of patients in each cohort, the results across a range of important outcomes in Duchenne suggest separation for the known natural history of the disease as well as from the study's control cohort. The multiple functional endpoints, the patient-reported outcomes that are being evaluated in IGNITE DMD reflect the many aspects of patients' physical functioning and ability to partake in typical daily activities that are impacted by Duchenne. We believe that by examining the totality of these endpoints as displayed here will help clinicians, patients and parents understand the potential benefit that SGT-001 may have on the trajectory of the disease. Now let's move to the safety, biomarker and clinical outcomes data. This is a snapshot of the endpoints evaluated in the interim analysis we'll be sharing today. To the best of our knowledge, IGNITE DMD is the first gene therapy trial in Duchenne to present results from the 6-minute walk test, pulmonary function testing and patient-reported outcomes in addition to NSAA. Taken together, these endpoints provide a broad understanding of the potential benefit that SGT-001 could provide to patients, their families and clinicians. The most common drug-related clinical adverse reactions for the first 6 patients dosed with SGT-001 were nausea, fever and vomiting early on after the infusion. These adverse reactions are common in gene therapy. The most common drug-related laboratory abnormalities previously reported are also summarized on this slide. Also, as previously reported, 3 of these 6 patients developed in total 4 SAEs, all of which have fully resolved. No new drug-related safety findings have been identified with follow-up post infusion in our 6 patients of 17 to 37 months. As we previously shared, 90-day biopsies from the 3 patients in the high-dose group showed widespread distribution of microdystrophin-positive muscle fibers, ranging from 10% to 70% positive fibers. On the right, you see representative histology evaluations from the fifth patient dosed, demonstrating co-localization of our microdystrophin with nNOS and beta-sarcoglycan at 90 days post dosing. As mentioned by western blot, the average level of microdystrophin protein expression in these 3 patients at 90 days averaged about 10% of normal dystrophin levels, with a range of about 5% to 17% abnormal. We also saw meaningful decreases in creatine kinase, a marker of muscle damage, in patients in the high-dose group. While this biomarker value can be variable, the average sustained CK decline of approximately 50% in patients at the high-dose cohort seen after 1 year may suggest improved integrity of muscle fibers and a potential protective effect of SGT-001. As I move on to the functional outcomes data, I want to note that for each functional assessment, we'll provide some context about the natural history of this disease seen on that parameter. First, we'll discuss the North Star Ambulatory Assessment. The figure on the right shows changes in NSAA over time among a group of 395 patients with Duchenne, with the gray lines reflecting individual patient trajectories and the black line showing the mean for this natural history cohort. As seen here, these boys usually have about a 1 to 2 point per year improvement in NSAA between the ages of 4 to about 7 years of age and then a 3 to 4 point [ a ] year decline thereafter. With that in mind, let's look at the NSAA scores at 1 year and at last visit at IGNITE DMD. The 3 high-dose patients are shown in blue. And in comparison with the control group trajectory shown in black, all show benefit at 1 year, with 2 of the 3 showing improvement from baseline at this time point. Both ambulatory patients in the control cohort had absolute decline from baseline to 1 year. Results for the 2 ambulatory patients in the low-dose cohort are shown in purple. And while there were mixed results at 1 year, at their last visit, which was at 24 months, both patients have done better than the natural history trajectory and had absolute improvements in NSAA compared with their best baseline scores. This 2-year observation is an intriguing finding, which may suggest improvement post the predefined 1-year endpoint typically being used in trials of gene therapy, something we look forward to examining in our entire cohorts over time. This slide shows the baseline, 1 year and last visit NSAA scores for these same 7 patients. One thing I'd like to highlight is that baseline scores were generally higher than expected based on natural history. These higher baseline scores may make it more difficult to see an improvement at the 1-year time point. Additionally, while both patients in the control cohort declined for baseline, the trend in both the low- and high-dose cohorts is towards improvement, either an absolute change from baseline or in comparison with control and natural history. We continue to monitor all patients in the study and are encouraged by and interested to see if the NSAA scores further improve over longer periods of time as we're seeing with the 2 low-dose patients at year 2. Next, we'll discuss the 6-minute walk test. The 6-minute walk test measures the distance in meters that the patient's able to cover in 6 minutes. It's been well described as an outcome measure in Duchenne and is part of an assessment of sustained muscle activity. As shown here in figures from 2 different evaluations of natural history data, there is a decline in 6-minute walk distance of about 35 to 50 meters per year, beginning around age 7. These data provide context in which to consider the 6-minute walk test results seen to date in IGNITE DMD. Here again, we show a nice DMD 6-minute walk test data overlaid on a large natural history data set but also highlights the mean natural history trajectory. Patients in both the low- and high-dose cohorts had absolute improvements in 6-minute walk distance from baseline to 1 year with the mean changes above the generally accepted, minimally clinically important difference of 30 meters. As shown in the figure on the right, the 2 low-dose patients had further increases at 24 months. Here, you see the individual 6-minute walk test distances for each of the patients at both 1 year and at their last visit. As mentioned, the results show the mean change for each dose cohort was greater than a clinically meaningful 30-meter distance versus not seeing any observed changes in the control patients. Individually, both low-dose patients and 2 younger high-dose patients showed meaningful changes at the last time point assessed. The positive changes seen in the 6-minute walk test and SGT-001-treated patients are promising, and we're looking forward to generating additional data for this endpoint as we dose more patients in IGNITE DMD. Another novel endpoint we're evaluating is IGNITE DMD and pulmonary function. In patients with Duchenne, deterioration in the strength of diaphragmatic abdominal auxiliary muscles leads to decrease in ability to cough and restrictive pulmonary disease. Neither the NSAA or 6-minute walk test provides any direct insight into pulmonary function. Based on discussions with our external advisers and members of the Duchenne community, we believe that demonstrating benefit and pulmonary functions will be meaningful to patients that could be an important endpoint in future clinical trials. This graph shows the natural history trajectory for forced vital capacity [ in those ] spirometry-based pulmonary function test, useful in detecting change in pulmonary function in Duchenne. As highlighted in the natural history, boys with Duchenne exhibited steady decline from age 6 onward when values are normalized for age, gender, race and height, a value that's called the percent predicted score. The left panel is the graph I just showed you on the previous slide, and the graph on the right overlays the high-dose, low-dose and control cohort patients from IGNITE DMD over the natural history trajectory for patients with Duchenne. As you can see, all the treated patients outperformed the natural history with respect to percent predicted FVC. And all patients in the high-dose cohort and 2 of 3 patients in the low-dose cohort also had absolute increase in FVC from baseline to 1 year. In contrast, all 3 patients in the control cohort had absolute declines in this measure of pulmonary function. This slide shows absolute change from baseline for percent predicted FVC. We believe that the result of the PFT to be meaningful to patients. We'll continue to collect pulmonary function test data as we dose additional patients in order to better understand what information this endpoint may provide with respect to patient function and benefit. In summary, we're really encouraged by these data and the benefit we're seeing in functional motor outcome. Now I'll turn the call over to Dr. Barry Byrne, who will review the patient-reported outcomes data. Barry?

Thank you, Cathryn. I'm really pleased to be part of today's discussion, and I'm looking forward to further discussion of the IGNITE DMD data during my MDA presentation on Thursday. In the 3 years that we've been following the subjects enrolled in IGNITE DMD, we've had the opportunity to work closely with the children and families participating in the study. The study is complex, and I'm pleased to say that both the active and delayed cohort patients are fully engaged and committed to this study, which is a huge undertaking for each participant. There have been a total of over 200 study visits over the 3-year period since the study was initiated. We've evaluated the children by time function tests and imaging biomarkers, yet there are many aspects of their daily functioning, which are not captured in time function tests but more properly reflected in activities of daily living and quality of life measures. Today, I'll be sharing the results from 2 different patient-reported outcome measures that are being evaluated in IGNITE DMD, as shown here, patients with Duchenne have a steady decline in motor function compared with healthy children of a similar age. As measured by transfer and basic mobility domain and the sports physical functioning domain of the PODCI or Pediatric Outcomes Data Collection Instrument. As reported previously, there is a good correlation between PODCI global and transfer mobility scores versus changes in the 6-minute walk distance. These observed improvements are reflected in the improvements measured in the patients by the 6-minute walk test. And overall, the PODCI results provide additional encouraging outcome to the functional measures described by Cathryn. Here, we see the results for the 4 motor function domains of the PODCI for the patients in IGNITE DMD. Consistent with what would be expected based on natural history data I just showed you, the 2 patients in the control cohort had decline in scores for all 4 domains. In contrast, patients in the high-dose cohort had significant improvements in all 4 domains, and the patients in the low-dose group improved on the majority of domains as well. These improvements reflect the benefits observed in these patients with respect to the North Star Ambulatory Assessment and 6-minute walk test. This chart shows the symptoms and impacts assessed using the results based on semi-structured interviews conducted by Modus Outcomes Research. Here, we see the color-coded scoring results for IGNITE DMD; and as you can see on the left side, for the low-dose and high-dose cohort, there were no reported declines in any domain or any of the patients who received SGT-001 at either dose. And all of them, other than patient 2, had improvements in at least 5 domains noted below the charts. Interestingly, all 3 patients in the high-dose group and 1 patient in the low-dose group had improvements in the symptom of fatigue, which is, again, supportive of the potential effect of the nNOS binding domain that is part of the microdystrophin construct in SGT-001. These results are consistent with improvement in motor function domains in the treated patients and agree well to the PODCI results I mentioned before. In contrast, both patients in the untreated group had declines in at least 2 domains, and only 1 domain improved between both patients. We regularly interact with the families and children in the study, and their participation in the study has been transformative in many ways. So I'd like to share a few notable anecdotes from the studies that are not easily captured at time function tests. First, boys with Duchenne rarely run. It's been very rewarding to hear from the families where new found ability to run and other skills have led to the ability to participate in team sports or ride a bike. These moments are an important part of childhood, and I'm very grateful to share these moments of the families participating in the study. Now I'll turn the call over to Joel for a review of the previously reported IGNITE DMD clinical protocol updates and Solid's second-generation manufacturing improvements. Joel?

Thanks, Barry. We're so glad to repeat part of today's data review, and we're looking forward to your presentation at MDA. As we reported on October 2020, when the FDA lifted the clinical hold on IGNITE DMD, we made several amendments to the IGNITE DMD clinical protocol to enhance patient safety based on our understanding of the causality of the SAEs experienced. Another important amendment to the IGNITE DMD protocol was the use of SGT-001 produced using our second-generation manufacturing process. Our new second-generation process results in a significant improvement in the percentage of full capsids, resulting in 90% full capsids in the final drug product. This improvement is an important aspect of our clinical strategy because it allows us to reduce the total viral load needed to deliver a dose of 2E14 vector genomes per kilogram by 47%. This reduction in viral load is expected to improve the dosing safety of SGT-001. As we announced in today's press release, we have resumed dosing in IGNITE DMD, and patient 7 who was dosed earlier this year has met our predefined criteria for establishing the effectiveness of our clinical risk mitigation strategy. This patient has experienced no serious adverse events, has not demonstrated any complement-mediated adverse events and has had substantial reduction in laboratory measures of complement activation compared with patients dosed under the prior protocol. We are very encouraged by these results. We are optimistic that the next patient dose will also meet these criteria. We are actively screening and enrolling additional patients in IGNITE DMD, and we look forward to sharing additional data from the first 6 patients and additional patients dosed under the amended protocol with you in the second half of 2021. I'll now turn the call back to Ilan for closing remarks. Ilan?

Thanks, Joel, Cathryn and Barry. We're pleased to see promising evidence of benefit in 6-minute walk test and North Star Ambulatory Assessment total score following administration of SGT-001, along with improvements in pulmonary function tests as well as clinically meaningful improvements in patient-reported outcomes that assess motor function and fatigue. Taken together, the totality of the data potentially supports the role of our microdystrophin, providing differentiated benefits to patients. For us at Solid, these data are the combination of 7-plus years of learnings, preclinical studies and advancements made in the clinic, and in manufacturing and process development. While our journey has not been easy nor straightforward, I'm proud of the progress made to date and excited for the future of our company and of SGT-001. Before we end today's call, I'd like to revisit the slides that Dr. Clary presented. As she noted, the totality of this data is encouraging, and we believe that they collectively provide preliminary evidence that SGT-001 can provide benefit with respect to multiple endpoints that we believe to be meaningful to patients. We are glad to have safely resumed dosing IGNITE DMD under our amended protocol and with SGT-001 produced with our second-generation manufacturing process. On behalf of everyone at Solid, I would like to thank the FDA for the collaborative and supportive dialogue as we work to address and ultimately lift the clinical hold last year. Additionally, I would like to thank the team at UCLA led by [ Dr. Carrie ] for safety dosing patient 7 as well as the patient and his family and all patients enrolled today in IGNITE DMD. We recognize that the decision to enroll in the clinical trial is not taken likely, and I'm grateful for all patients who choose to participate for taking this journey with us as we strive to improve outcomes for patients living with Duchenne. I would also like to thank Dr. Byrne for joining us today. If any of you would like to hear Dr. Byrne's talk at MDA on Thursday or participate in our sponsored lunch symposium at the conference, which is also taking place on Thursday, you can do so by registering to attend the MDA conference. A link to MDA registration information is included in the press release issued prior to this call. We look forward to sharing additional IGNITE DMD data with you in the second half of the year and to providing additional updates on our progress towards our other 2021 milestone in the months ahead. Thank you all for dialing in, and we're now happy take...

[Operator Instructions] Your first question comes from the line of Joe Schwartz of SVB Leerink.

Congrats on all the progress. My first question is on efficacy, and I was wondering if you could just give us your thoughts on what seems like an apparent disconnect between the NSAA and other endpoints that were collected, particularly in the high-dose group? And how do you feel about the ability to be able to produce a statistically significant separation on NSAA? Based on this data from other sponsors, it seems like that may be a challenging endpoint, but you might also be contemplating endpoints other than NSAA in future studies.

Yes. Thank you very much for the question. As you saw, what we've focused on in this presentation on what we think is relevant is to actually look at the totality of the data because different functional endpoints measure different aspects of functioning. In terms of the NSAA, we were heartened by the fact that the NSAA trajectories of our patients who had relatively high scores at baseline, so there may have been a bit of a ceiling effect, nevertheless, were better than the trajectory seen in natural history as well as the control group in our trial. In terms of future trials, clearly, we are thinking about -- we're just starting to think about a registration trial, but we're thinking about not necessarily one particular endpoint that's a composite or an innovative endpoint. We haven't made any decisions, but I'm not sure that an NSAA would be the primary endpoint of such trial.

That's helpful. And then looking forward, what do you hope to see in the additional patients who are being dosed with the product from the new manufacturing process in terms of microdystrophin expression? When you report that in the second half, how many patients of data might we expect when that's ready for its release?

Yes. Thanks for the question. So as we said in the presentation, we were heartened by the fact that patient 7 was safely dosed by our a prior criteria, utilizing the new manufacturing process and risk mitigation protocol. Certainly for upcoming patients, we also want to see safe dosing, and we'll be evaluating our efficacy with microdystrophin expression at 90 days, and we'll be evaluating that. We're currently actively screening for additional patients in the trial.

Next question comes from the line of Gena Wang from Barclays.

So my first question is regarding patient #7. Just want to confirm the new updated amended protocol that also include the [ profi ] Soliris; or C1 inhibitors. Just want to make sure that patient received the [ profi ] Soliris? That's the first question. And the second question is regarding the data and maybe one question for Dr. -- so the PODCI, in your view, is that more subjective or less subjective compared to North Star? And then the second question is regarding the CK level. We did see the low dose has a higher increase versus the placebo, while the high dose had lower. So any thoughts there? And then another endpoint, actually, FDA consider also very important is the time to rise, and we did not see that data here. Wondering if you will be testing that. And for the endpoint, if you are saying you are not using North Star, what kind of other endpoint you'll be thinking about?

All right. Let me take them from the top. So first of all, for patient 7, he was dosed under our new amended protocol, which does include pretreatment with both eculizumab and a C1 esterase inhibitor. Going forward, all patients will be dosed with that -- with our new process as well as that amended protocol as we -- and then we'll be evaluating safety as we go forward. Creatine kinase, I believe you asked about that. That is, as you said, it's a variable measure. Older patients may have declines just because they don't have enough functioning muscle to really throw off creatin kinase. What we found encouraging about the data that we showed you today was pretty consistent declines in the high-dose group with a lot of variability than we saw in either the low-dose group or the control group. Patient reported outcomes, you're asking about the sensitivity about patient reported outcomes and some of the functional measures. Certainly, there's a bit of subjectivity in the North Star, 6-minute walk because they're effort based to a certain extent. What's interesting in talking to experts around patient reported outcomes, first of all, it's a unique and different domain than a functional test, which is done in the clinic and evaluated by the valuer. These are the patients' and their parents' own assessment of how they're doing, functioning. And they're a year post dosing, so probably a bit less likely to have a major subjective effect a year after dosing when they really are seeing true functional improvements such as the ability to ride a bike or some of the aspects that Dr. Byrne has mentioned. So that was, I think, 3 of the questions.

Then, Gena, I think your last question was about our pivotal study. We're not in a position today to answer which endpoints. This whole study was designed to go across ages, across different groups and stages of the disease and really flesh out what can and cannot be measured reliably in the clinic. And we like the dose response. We like the significant number of outcomes that we're able to monitor here. And this is exactly the kind of conversations we will have now. Maybe Carl wants to add something.

Yes. I think you mentioned -- Gena, you mentioned the time to rise specifically and as part of the North Star, was assessed. Given the age range of patients, so we started the study as a dose escalation, exploratory Phase I/Phase II. So we added a significant number of endpoints to assess. We are looking at those, but some are very age specific, and we'll sort of -- we're evaluating those. And that allows for us to get PODCI for -- as an overall evaluation. We have North Star for some of the younger patients, 6-minute walk and even the pulmonary functions for the older patients where there are expected changes to occur. So I think, again, we're coming back to that totality discussion, where we pull everything together to really to get a -- evaluate the range of Duchenne patients and age ranges of Duchenne patients to help guide us towards that next step in that registration study.

Next question comes from the line of from Gbola Amusa from Chardan.

Wanted to hone in on patient 7 and the good safety outcome there, and I know it's an n of 1. But to what extent do you feel that the safety you've seen so far is driven by earlier and more aggressive use of complement inhibitors versus maybe also having a better product with half the total capsid load. And I'm asking that because if the 2 compartment model is relevant here, maybe we might see something interesting on safety as a consequence. And then I have a follow-up.

Yes. I know it's a really interesting question, and clearly, we did 2 things at once. We improved our product and we put in a risk mitigation protocol, and we're going to be very carefully assessing patient by patient, as we move forward, what we want to do strategically if the patients remain safely dosed. We do think that there's a bit of an advantage in having this risk mitigation protocol because if we continue to show the same results we showed with patient 7, we hope that it will enable us to dose patients that are a higher weight than the 18 kilograms, which we committed to for our first 2 patients because, remember, Solid's mission when it first started was really we wanted to dose -- we wanted to be able to treat patients of all ages with Duchenne, which would mean higher weight patients. So it may be that we decided this is an effective protocol. We'll keep it in the protocol.

Right. And sometimes we've seen in the aging space that optimizing immune regimens can enhance efficacy as well. Is that part of your goal? Or is it really focused on safety here?

Yes. I mean we really focused in on safety. The patients are getting the same dose that the first 6 patients got and the same amount of vector genomes per kilogram, the 2E14. So we're not expecting there to be higher efficacy. If that didn't happen, we'd be very pleased.

Got it. And then one last question if I may. I think some recent research shows that 0.5% dystrophin in terms of percentage of normal can lead to functional benefits for patients, and we've seen your data being much higher than that. But -- and I know this is unfair because it's about your competitors. But what is the reason that they give for not showing more functional data? I'm not on those calls. I'm just curious if you've heard anything.

So this is Carl. So I will talk about our data. I think, first off, we're getting comparable percent positive microdystrophin-positive fibers in our biopsies. And that seems to be somewhat consistent with variability amongst the 3 different studies. The connotation we have load, it isn't really -- we don't consider that to be a factor as we move towards the evaluation -- full evaluation of function -- functional data. Again, we selected this as a dose escalation and exploratory study. We have a wide range of endpoints and some of which we showed today. And that's sort of what we've hoped to go forward with. And it'll allow us to better understand the disease and [ all issues ] going forward.

And last thing I would just add is that the second-generation manufacturing process and the average 47% decrease in total viral load, given the correlation we've seen between safety and the total viral load and the dialogue we had with FDA, including comparability of the new process to the old, that's here to stay. And we think that's a pretty neat quality of the drug. So hopefully, that would open the door to significant options in the future.

[Operator Instructions] Your next question comes from the line of Tyler Van Buren from Piper Sandler.

Just I guess 3, hopefully, quick ones. The first one is just a quick point of clarification. For patient 7, the mild adverse events that were experienced, maybe I missed it, but I don't recall you mentioning those. So if you could just clarify that. And then with respect to efficacy, if you look at patient 5 and 6, they've got a higher proportion of microdystrophin-positive fibers. And when you stare at the table, they appear to be doing better than patient 4. Did you see kind of the same thing occur with patients 1, 2 and 3? Or in other words, do you believe there to be a correlation with efficacy with the number of microdystrophin-positive fibers when you're looking at the totality of the data? And then the last one is just on the forced vital capacity pulmonary endpoint looks like a pretty interesting objective endpoint. So I know you can't speak towards what the registrational trial primary endpoint will be. But do you think it's possible that, that could be the endpoint or somehow used as a primary?

Yes, great question. So on patient 7, patient 7 has mild to moderate transient and manageable AEs. None related to complement. So as we mentioned, they were not complement-related AEs. They're typical ones we would see. In terms -- I'm going to answer the question about forced vital capacity and then turn it over to Carl to talk about correlation. We do find forced vital capacity to be a very interesting endpoint. It's clearly relevant to what's happening with patients with Duchenne. We -- it's very early to say whether we would think about that as a primary efficacy endpoint in the trial. As we've said before, we're just beginning to think about efficacy endpoints. But we certainly are intrigued by the data, and we'll continue to follow that. Carl, did you want to answer the question about correlation?

Sure. Yes. I think we only have 3 patients, the high dose and then 2 to 3 patients with the low dose depending on the outcome. So very different -- difficult to tie together correlations between expression and function, and you can see that there's some variability so -- in North Star or 6-minute walk when you look at those patients. So it's very early days. We need to collect more data to really evaluate any potential correlations between there. And it's really unclear now how low there is in terms of expression to get a threshold benefit. There are reports out there at very low levels of [ expression ], providing meaningful change in patients with Duchenne [ and Becker ]. So I think it's very early days. We'll collect more data and continue to look for correlation between expression and function.

Our next question comes from the line of Salveen Richter from Goldman Sachs.

So when we look at the forward path for these patients as well as you kind of assessing the changes that have been made to resume dosing but then formulate these new endpoints, how much data and over what duration do you think you need in order to kind of assess how to move forward here?

Yes. Thanks, Salveen. Appreciate the question. We have made a number of changes to the clinical strategy, include, obviously, the pretreatment that we highlighted with complement inhibitors and alongside the second-generation process, which does have a significant impact on total viral load. I think moving forward, we really have to dose a few patients, really understand both the safety and efficacy profile. It's a new process. We took a while in demonstrating the comparability of it to move forward. And so I think, over the next period of patients, we'll really see what the data looks like. Not promising a specific number in having substantial changes but really want to understand the totality of data to drive the best clinical development profile we can. I think 1 last highlight is that IGNITE DMD allows us to enroll 16 to 32 patients. So we have some room there. Not necessarily tying ourselves to any specific number, but we are going to dose a few patients. We've highlighted that, later this year, we'll share more data on how all that's looking and really what that'll translate to as our path forward for the clinical strategy.

And I'm sorry if I missed this, but can you help us understand the rationale for the changes with the steroid regimen?

Yes. So we were -- as we were thinking about our new protocol last year and looking at what others in the field were doing, we decided that we wanted to give patients every opportunity in that first month to have a dampened immune response. The -- Pfizer increased their steroid dose in the first month, and we've looked into it with articles, et cetera. We also did have 1 patient, patient 4, who had [ hepatic toxicity ] 30 days probably because he stopped taking his steroids for a few days. But that's why we increased it for a month, and then it'll go back down to the 1 milligram per kg in the second month.

Our next question comes from the line of Maneka Mirchandaney from Evercore.

Just based on what you're seeing here as well as in the field broadly, can you talk about your latest thoughts on the optimal age range for microdystrophin gene therapy approach on -- and how you're thinking about incorporating that into your development path forward. Doesn't seem like there's a clear correlation between age and benefit here, but just curious how you're thinking about that going forward.

Yes. So again, we have -- this is a very small group of patients at different ages. So we are certainly thinking about it but have come to no conclusions at this point about where we would go with the larger study. I mean we're watching what's going on in the field. We're looking at our own data, and we certainly will come to a conclusion about that at some point, but we have not yet.

And then just to add on what Cathryn highlighted, we designed the study to potentially dose all comers to really explore a variety of endpoints. What you're seeing today is a byproduct of the assessments. It's a small number of patients, but certainly, we're highlighting today promising outcomes across both low-dose and high-dose patients. And so as we move forward, we're going to continue to assess the data. It may come down to that -- the primary endpoints suitable for a 4- to 5-year-old patient are actually very different for an 8 to 9 year old or a 10 to 11 year old. And certainly our vision and ambition has been to treat all patients that desperately need it. So that's sort of our vision. That was the ambition and design of the original study. And you're seeing the byproduct and outcome of that today in the form of totality of data representing a broad spectrum of promising results.

[Operator Instructions] Our next question comes from the line of Martin Auster from Crédit Suisse.

This is Matt Terwelp on for Marty. Please, correct me if I'm wrong, but I recall you were planning on taking 1-year biopsies as well? And if so, how did the data compare to earlier biopsies in terms of microdystrophin expression and percent positive fibers over time?

Yes. Thanks. That's a great and a natural question. So we -- unfortunately, because of the COVID pandemic, there were 2 1-year biopsies in our 3 high-dose patients that were delayed. We are currently in the process of getting those, and that will be done fairly soon. We want to analyze all 3 of the samples together. We think that makes more sense, and we are planning to disclose those later on probably in the first half of the year.

Our next question comes from the line of Anupam Rama from JPMorgan.

Maybe a quick clarification question. With the seventh patient now dosed, can you remind us what the -- how much follow-up the patient -- the FDA wants from patient 7 before you can dose, say, patient 8 and 9? At what point do you think there could be an inflection in sort of the enrollment curve? I think, Joel, you said 16 to 32 patients is what you could do.

Yes. Thanks. It's a great question. So when we redid our protocol and FDA approval for it, what we committed to was that after each of the first 2 patients dosed, we would collect 30 days' worth of clinical and laboratory data, go to our DSMB, get their recommendation about dosing the next patient. So after patient 7, we'll consult with the DSMB. After patient 8, we'll consult with the DSMB. So there'll probably be about a 45-day, at least, delay between each of those 2 patients. After that -- and by the way, we do not have to go back to FDA. This is really with the DSMB. Once we've gotten through the first 2 patients, if they're both dosed safely, our hope is that we will then be able to increase the cadence of dosing a bit, and you've heard that we can go up to 16 to 32 patients. We haven't committed to how many patients we'll dose this year, but we're hoping that we can increase the frequency and get the number of patients -- the amount of patient data we need in order to help us with our decision-making.

Anupam, I'll just add that, once implemented, the new process is basically getting used up now. We're going to make more material, dose more patients. And [ this can be -- already realizes ] the next one. So that's already passed and we are screening as we speak. And there's one more of those, and then we are good to go.

There are no further questions at this time. Speakers, please continue.

Thank you. We appreciate you taking the time to listen to our update this afternoon. As we highlighted for you today, we're excited to share an update on resumption of dosing in IGNITE DMD using our second-generation manufacturing process, which really has a meaningful impact on the total viral load given to patients. We're also very excited to share a totality of data that really represents a broad spectrum of dose-related response and promising efficacy through the first-time presentation of a number of meaningful endpoints not previously shown in DM gene therapies. We appreciate your time and look forward to providing continued updates over the year as we continue to advance our IGNITE DMD trial and the promising microdystrophin and SGT-001. Thank you for your time.

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