Good morning and welcome to the Solid Biosciences conference call. At this time, all participants are on a listen-only mode. Following management's prepared remarks, there will be a question-and-answer session. Please be advised that this call is being recorded at the company's request, and a replay will be available on the company's website. I would now like to turn the conference over to Nicole Anderson, Solid's Director of Investor Relations and Corporate Communications. Thank you, Nicole. Please go ahead.
Thank you, Operator, and thank you all for participating in today's call. This morning, we announced positive initial data from the first participant's dose in our Phase 1/2 INSPIRE DUCHENNE clinical trial. The press release outlining this news is available on our website at solidbio.com. Before we begin, I would like to remind all listeners that this call will contain forward-looking statements based on the company's beliefs and assumptions and on information currently available to management. These statements include, but are not limited to, statements regarding Solid's future expectations, plans, and prospects, its ambitions related to SGT-003, its clinical trials, business strategies, use of capital, results of operations, and financial position. These forward-looking statements involve risks, uncertainties, and other factors that may cause actual results, performance, or achievements to differ materially from those indicated by these forward-looking statements.
These risks, uncertainties, and other factors include, but are not limited to, risks associated with the company's ability to advance its SGT-003 clinical program on the timelines expected or at all, obtain and maintain necessary approvals and designations from the FDA and other regulatory authorities, replicate in clinical trials positive results found in its preclinical studies, and replicate preliminary or interim data from early-stage clinical trials in the final data of such trials. For more information on risks and uncertainties and other important factors, any of which could cause the company's actual results to differ from those contained in the forward-looking statements, please see the risk factors section, as well as discussions of potential risks, uncertainties, and other important factors in the company's most recent filings with the Securities and Exchange Commission. Joining us on today's call will be Bo Cumbo, President and Chief Executive Officer,
Dr. Gabriel Brooks, Chief Medical Officer, Kevin Tan, Chief Financial Officer, and Dr. Craig McDonald, Professor and Chair of the UC Davis Health Department of Physical Medicine and Rehabilitation and an investigator in the INSPIRE DUCHENNE study. With that, I would like to turn the call over to our CEO, Bo Cumbo. Bo?
Thank you, Nicole, and thank you all for joining us this morning for this initial update from the INSPIRE DUCHENNE clinical trial of our Duchenne gene therapy candidate, SGT-003. We are thrilled to share what we believe are compelling and comprehensive early signs of the potential benefit of our therapeutic candidate, SGT-003. While early and limited to our first three patients for expression and muscle integrity, we believe these initial data demonstrate the potential for a best-in-class medicine that may truly deliver on the promise of a next-generation gene therapy. Since the beginning of this journey to bring a next-generation gene therapy to young boys who need it, we've always believed that Duchenne is a disease driven by the loss of muscle integrity and concordant muscle dysfunction.
From the time these boys are born, the disease relentlessly targets muscle fibers, deteriorating overall muscle health, and ultimately leading to a loss of ambulation, cardiac and pulmonary failure, and inevitably death. At Solid, we are armed with extensive experience developing therapies for this terrible disease. Personally, I've always believed in microdystrophin as the right approach for these young boys, and our team is committed to building and bringing forward a true next-generation gene therapy to treat Duchenne. I am hopeful with these results we are showing today that we can quickly speak with the FDA, who we plan to reach out to in mid-2025, to discuss the potential for an accelerated approval pathway to move this therapy into the treatment landscape for children who could benefit from this next-generation gene therapy. We will continue to dose patients in the meantime to build a robust database for this discussion.
SGT-003 represents a next-generation potential best-in-class transgene that was designed to robustly transduce and protect muscle health. This all begins with our microdystrophin transgene, the only therapy we are aware of in the clinic to contain the R16, R17, and nNOS -binding domain. Binding nNOS to the appropriate location in the muscle, the sarcolemma, is essential to protect the muscle from stress, to prevent fibrosis, and to promote repair. The ability to recruit nNOS to the dystrophin protein complex and appropriately localize to the muscle sarcolemma is unique to only our transgene. Our proprietary next-generation capsid AAV-SLB101 was designed with peptide insertions to specifically target multiple integrin receptors that are upregulated in dystrophic or fibrotic tissue. AAV-SLB101 was also designed to decrease liver targeting.
We saw highly compelling transduction and expression data in our preclinical animal models using this capsid that we hoped to see translate into the clinic, and we're extremely pleased by the robust quality and initial data we were able to share today, which also serves as a first-in-human evaluation of this capsid. I just mentioned the nNOS -binding domain as a key differentiating characteristic of our microdystrophin transgene. We can now say that our microdystrophin gene therapy has demonstrated proper nNOS localization and activity in Duchenne patients. This is measured by an enzymatic activity assay, so we can see that 42% of muscle fibers showed nNOS expression and activity at the sarcolemma at Day 90 in the first three participants in our INSPIRE DUCHENNE study. There is a body of literature to support the value and importance of NOS.
It plays an important role in muscle health, adaptation, and performance and restoration of properly localized activity is critical in order to protect cardiac and skeletal muscle. We believe that SGT-003 is the only next-generation gene therapy candidate in development with the potential to bring this aspect of muscle protection to children suffering from Duchenne. Today, we're going to talk about the first three participants in the INSPIRE DUCHENNE clinical study. As of the data cutoff of February 11th, we had dosed six participants. Of the first three study participants that we will be presenting data on, two of the boys were five years of age, and the third was seven years old at the time of dosing. Importantly, as indicated at the bottom of the slide, dosing was well tolerated in all participants as of the data cutoff date. There have been no AEs or SAEs observed.
No observations of TMA or aHUS. We did see transient cases of apparent thrombocytopenia that had no clinical consequence and resolved without intervention over a few days. Dr. Brooks will comprehensively cover all the safety information later in this presentation. Before going through each of the data points, let's first linger on the totality of the data. We believe we've compiled one of the most comprehensive sets of early data for a Duchenne gene therapy to understand the potential impact on muscle integrity and preservation. This includes not only a multitude of biomarkers, many of which speak directly to not just protein expression, but the actual integrity of the muscle, but also looking at these same biomarkers using multiple assays.
While these data are early data on a limited number of patients, in looking at the data through these multiple perspectives, we were struck by the consistency of the findings, and we believe it all supports a next step in the possible treatment of this disease. Understanding that Duchenne is a disease of muscle wasting and lack of muscle integrity, upon embarking on this study, we committed to comprehensively measure muscle health, integrity, and cardiac function, and we will delve deeply into each critical measure of muscle and cardiac health. I can confidently say that while early, I believe the data we are sharing today represents one of the most robust and comprehensive data packages in the microdystrophin Duchenne gene therapy field.
As we will discuss, when we analyze these data, we were expecting a waterfall cascading first from microdystrophin expression levels to percent dystrophin-positive fibers to key pieces of the dystrophin protein complex to biomarkers of muscle integrity and resilience. That's exactly what we observed in the first three participants dosed. By the end of the presentation, from the initial formation of microdystrophin protein to the formation of the dystrophin -sarcoglycan complex with nNOS activation, and ultimately to signals of muscle integrity by looking at both acute and chronic signals of muscle damage, as well as the reduction in embryonic myosin heavy chain protein suggesting muscle maturation. Our hope is that you walk away with the understanding that microdystrophin we are producing is suggesting evidence of having a beneficial effect on muscle integrity, which we believe has the potential to lead to clinical benefit over time. Let's start with microdystrophin.
Our mean microdystrophin expression level by Western blot is 110%, which to our knowledge is the highest mean expression data that has been shared to date of any Duchenne gene therapy. While exciting, we have always known the limitations of Western blots and the challenges of assay-to-assay variability between studies. To that end, we made the decision to measure our microdystrophin expression by three different approaches, and we are gratified to see the consistency between our Western blot, mass spec, and immunofluorescent measures. Importantly, we will always see a step down from the Western blot or mass spec analysis to dystrophin-positive fibers at only 12 weeks of time in the intermediate biopsy. Our measurement of dystrophin-positive fibers showed an average of almost 80% of the muscle fibers expressed are microdystrophin, which we believe is an incredible result at just 90 days post-dose.
We believe that the skeletal muscle should continue to accumulate microdystrophin within the fibers over the time, even though we are near saturation at 12 weeks post-dose. SGT-003 has shown highly differentiated potential class-leading microdystrophin expression. These data, in particular, we are very excited about. We saw incredibly robust vector transduction and increased binding capacity, again, with our next-generation capsid SLB101 that on average is five times greater than that seen in the FDA-approved Duchenne gene therapy at a 25% lower dose. I want to take a moment to note that this is our only dose level. The INSPIRE DUCHENNE study is not a dose escalation trial.
Based on the extensive preclinical data we generated, we were confident in the dose, which showed enhanced skeletal muscle and cardiac muscle tropism with decreased liver targeting, and we are pleased to see that these results bore out in our first three human participants. These are strong initial results, not just for 003, but for the SLB101 capsid as well, setting the stage for it to potentially be used in many more clinical settings and disease states. We have already transitioned SGT-601, our candidate for TNNT2 dilated cardiomyopathy, to this capsid. We are excited for many opportunities these data may open. There is a lot we can do with SLB101 with this dataset in mind. Now, I want to pause on this slide for a moment, as it's critical to understanding why we are so excited about our data.
We've shown exciting positive fiber expression levels at almost 80% mean microdystrophin expression. But from there, you have to put the entire dystrophin-associated protein complex together. For the first time, we demonstrated that from a positive fiber count standpoint, 70% of fibers showed restoration of the beta-sarcoglycan, a key stabilizing component of the entire protein complex. And as I've mentioned, we could also see for the first time 42% of fibers showed nNOS expression and activity, followed by a host of muscle integrity biomarkers that give us confidence that SGT-003 provides evidence of benefit to these brave trial participants. In case there are questions surrounding the specificity and precision of our assays, the top row on each table shows the absolute expression level of dystrophin-positive fibers of microdystrophin, beta-sarcoglycan, and nNOS activity, respectively.
The middle row lists baseline values that are very close to zero, which speak directly to the precision and specificity of our assays. Given mean baseline levels across three measurements remaining consistently less than 1.5%, which are in line to what you would normally see in DMD with revertant fiber count, our assays are highly specific, which means that expression values are not biased upwards or abnormally high baseline measures. Finally, the bottom row shows fold change from baseline, which we believe is class-leading. But we added this in to ensure clarity on the top row of impressive figures in DMD. We were pleasantly surprised by the robustness of these data at the early time point. Again, we believe this is evidence that SGT-003 has the potential to be best in class and a disease-modifying treatment for DMD. Moving on to our biomarker evaluation.
Some markers listed here track acute muscle damage. Others are more indicative of chronic muscle breakdown, and we also have biomarkers for muscle maturation. People with Duchenne typically have very high baseline levels of each of the markers highlighted in orange. Therefore, reduction in these markers is a powerful signal of muscle preservation, of preservation of muscle integrity, and increased muscle resilience. Historically, AST and ALT have been considered liver enzymes and have been used in safety monitoring for liver injury, but in Duchenne, where muscle fibers are constantly being ravaged and destroyed, elevated ALT and AST are well-known markers of acute skeletal injury. LDH is another marker that is released into the blood upon acute tissue damage. CK is a marker of acute muscle damage and is one that has typically been measured in Duchenne patients by our peers.
It is well understood that CK levels can be highly variable. So we also decided to take a look at titin, which is another marker that is released into serum and urine upon muscle damage when the muscle is decomposing, which is less variable to CK and ties nicely to the acute versus chronic phase of muscle integrity. Recent literature published in Nature has identified titin as a sensitive biomarker of disease progression in Duchenne. eMHC, or embryonic myosin heavy chain, is a critical marker that I want to highlight as an indicator of muscle preservation, which we believe may become central to the Duchenne gene therapy thesis. Are muscle fibers being protected by the new microdystrophin being produced enough to reach maturation? And finally, cardiac troponin I, which is an interesting cardiac marker we are evaluating in certain patients who may have early signals of Duchenne-related cardiomyopathy.
With this, I will turn the call over to Dr. Brooks to dig into these biomarker findings. Dr. Brooks?
Thanks, Bo. As Bo previewed on earlier slides, we're extremely pleased to see such consistent and comprehensive effects across the range of biomarkers we've evaluated. Shown here is a consistent mean reduction in AST, ALT, CK, and LDH, which are markers of muscle injury and stress. These results suggest that SGT-003 may have contributed to improvements in muscle integrity and resilience. We have been so robust in our interrogation of the biomarkers of muscle health and muscle injury because we recognize that these markers are variable, and therefore, we wanted to make sure that we were able to see the whole picture of muscle health of all of the participants.
It is then even more remarkable that not only are these declines compelling and consistent, all of the biomarkers showed improvement in muscle health in unison. Muscle fibers in Duchenne are fragile, and when they deteriorate, muscle satellite cells are activated to attempt to replace the damaged fibers. During this attempted regeneration process, newly formed fibers express myosin heavy chain, or eMHC. It is abnormal to detect more than trivial eMHC after birth. However, in Duchenne, eMHC is detectable as satellite cells are differentiating into myofibers in the muscle's attempt to repair itself. Since these new muscle fibers are dystrophic and since the supply of satellite cells is finite, meaning exhaustible, this process is futile. As the process fails, we see organ failure, whether that's skeletal muscle with a loss of ambulation, diaphragmatic muscle leading to respiratory failure, or cardiac muscle leading to cardiomyopathy.
We believe that eMHC is a critical biomarker for disease progression and an objective measure of treatment response. When we look at the story behind SGT-003, this slide really tells the entire premise of the biologic effect of muscle preservation. On the left, we have 90-day mean positive fibers for microdystrophin of 78% that lead to substantial recruitment of beta-sarcoglycan as well as nNOS, measured by an activity assay in 42% of the fibers on average. The biologic consequence of this evidence of increased muscle stability can be seen in the significant decrease in serum titin. Titin is released when muscle is degraded, not just injured like CK. Therefore, it is encouraging that we see a 42% mean reduction in titin, heralding what appears to be a protective effect of SGT-003 in these brave boys.
Shown on the right is a histologic stain for eMHC at baseline and at day 90 biopsy. The top image represents the baseline muscle biopsy from one of the brave boys who participated in this study. Each of the bright green staining cells in this gastrocnemius muscle biopsy represents one of his stem cells undergoing differentiation into muscle fiber. Each one of these fibers represents a reduction in his stem cell reserve in the continuation of the dystrophic regeneration process. Therefore, we are incredibly encouraged to see that after only three months of dosing with SGT-003, there's a nearly 60% reduction in eMHC. As you can see in the bottom image, there are virtually no green cells indicating a dramatic reduction in eMHC consistent with the preservation of his muscle.
We believe that the reduction seen here in titin and eMHC are strong indications that SGT-003 may have the potential to lead to muscle preservation and an interruption of the cycle of muscle degeneration and dystrophic replacement. All of these markers of integrity lead us to believe that SGT-003 is already providing benefit to these brave boys and has the potential to lead to clinical benefit over time. Back to you, Bo.
Thanks, Gabe. Now, we will also spend some time talking a bit about early signals of potential treatment-related benefit in a participant with underlying signals of cardiomyopathy, which is the leading cause of death in Duchenne and must be addressed.
About 60% of individuals with Duchenne will have evidence of early signals of cardiomyopathy by the age of 10, whether it's higher levels of troponin early in life or lower than normal ejection fraction as a boy matures into their teens. Literature indicates that early troponin elevation can be predictive of severe cardiac disease and neuromuscular diseases, including Duchenne, and that early detection and reduction of this marker may provide benefit by lowering the risk of severe cardiomyopathy. We knew from our preclinical studies that this novel capsid AAV-SLB101 not only resulted in enhanced skeletal muscle transduction and binding capacity compared to first-generation capsids, but in human cardiomyocytes, we were seeing a 21-fold increase compared to AAV9. We also knew that in non-human primates, AAV-SLB101 transduced the diaphragm 5 to 10 times greater than AAV9 or first-gen capsids.
Internally, we hypothesized this program could be beneficial for children suffering from DMD since cardiac and pulmonary failure is ultimately the cause of mortality in these children. So we have actively enrolled children who have some early signals of cardiac abnormality to see if SGT-003 can be beneficial to them. In addition, now that we have initial data in hand, we are considering if this program can help boys both earlier and later in their disease progression. I will now turn it back over to Dr. Brooks to discuss cardiac findings as well as safety.
It was mentioned earlier that AAV-SLB101 capsid demonstrated strong skeletal and cardiac muscle tropism in animal studies. As shown in the graph on the left, AAV-SLB101 outperformed AAV9 by nearly 21-fold in human cardiomyocytes in non-clinical studies. So we know that SGT-003 potently transduces myocardium.
What we're seeing on the right may be an early signal of the benefit of this transduction. On the right-hand side, we are showing left ventricular ejection fraction data out to day 180 for participants one and two. Note that participant one had an abnormally low ejection fraction for his age. We were extremely gratified to see that with this early data, the mean baseline cardiac function of these two participants increased 8% from baseline to normal levels at day 180. We hope to see these trends continue. We only had 90 days follow-up on participant number three as the data caught up. Based on the other two participants, we would hope to see that his day 180 numbers double off as well.
Ejection fraction is something that we will continue to monitor in the study participants moving forward and may be an indicator of positive cardiac remodeling treatment effect with SGT-003. Participant number three also had elevated cardiac troponin I levels at baseline, which we have closely monitored for safety and potential signals of therapeutic benefit. We were very pleased to see that this participant's troponin decreased by approximately 36% at day 90, which we believe is an exciting early finding. This finding again suggests that SGT-003 is getting directly to the heart and may have a positive impact on dystrophin-associated cardiomyopathy. Participant number one and two had normal levels of troponin at baseline and throughout follow-up. Of note, we have now dosed two boys that have elevated troponin at baseline.
We are only reporting data for the first participant with elevated troponin at baseline because the second child with elevated troponin at baseline has not yet reached day 90 follow-up. Now transitioning to a comprehensive summary of our initial safety and tolerability findings. Though we have focused primarily on the first three participants, for which we have at least 90 days of data, the data presented on this slide are a summary from the six boys treated with SGT-003 through the data cutoff. The key take home here is that SGT-003 has been well tolerated with adverse events consistent with those observed commonly in AAV gene therapy. It is important to emphasize that SGT-003 is administered in the setting of a prophylactic corticosteroid regimen alone. No intensive immunomodulation agents such as eculizumab or sirolimus were used either before or after dosing.
All AEs that occurred happened within the initial days after dosing and resolved within a matter of days or a week or two at the most. There were no serious adverse events or SAEs observed. The most common AEs were nausea and vomiting, which were commonly seen in gene therapy. We did see apparent transient thrombocytopenia in three patients that was generally mild. One participant had CTCAE Grade 3 thrombocytopenia. Each thrombocytopenic event was characterized by platelet counts going down in around day six and then rebounding after a couple of days back to baseline without intervention. We looked carefully for any signs of TMA, which is characterized by thrombocyte activation, reduction in platelet counts, hemolysis, and renal injury. We did not see any signs of this, and no indications of renal injury were seen. We also looked for any signs of platelet activation leading to hemolysis.
Hemoglobin levels remained stable throughout follow-up, and blood smears were carefully monitored for signs of red blood cell breakdown called schistocytes, which were not observed. Each event resolved without intervention, with no recommendation for our DSMB to use any additional steroids or any intensive immunomodulation. There was one additional CTCAE Grade 3, which is an infusion-related hypersensitivity reaction and was mild. Participant number six had a mild transient troponin elevation at baseline, which increased during the first few days after dosing and returned to baseline without intervention. I am pleased to share that not only did this level return to baseline without intervention, but they declined below elevated baseline levels. We have called out elevated troponin as an adverse event of special interest because of our commitment to investigating the heart health of our participants throughout this trial.
As such, we closely interrogated this episode and found no evidence of myocarditis, EKG changes, or echocardiographic changes. Very importantly, we saw no AEs of hepatic transaminitis or increases in GGT. As mentioned earlier, we have had the ability to present analysis of AST and ALT as muscle injury markers instead of liver health. This is possible because we do not see any signs of hepatic injury with this drug as of the data cutoff. This is novel for AAV gene therapy and may provide additional differentiation from first-generation AAV gene therapies if these trends continue over time in additional patients. As a physician, I am truly gratified to see these initial safety and tolerability findings paired with a robust and impressive initial clinical experience of SGT-003.
These data create a highly compelling value proposition that SGT-003 may have the potential to improve muscle integrity and preserve cardiac and skeletal muscle fibers. On that note, I would like to invite Dr. Craig McDonald, Professor and Chair of the UC Davis Health Department of Physical Medicine and Rehabilitation and an investigator in the INSPIRE DUCHENNE study, to discuss his interpretations of the initial findings. Dr. McDonald.
Thank you, Dr. Brooks. These initial data from the INSPIRE DUCHENNE study of SGT-003 trial are extremely encouraging to me. The robust microdystrophin expression consistently seen using multiple complementary and standardized methodologies, improvements in markers of muscle integrity and health, and the favorable safety profile observed to date in this cohort of participants is really very promising.
First of all, I think we are really seeing high levels of transduction down to the nucleus level in terms of vector copies per nucleus, ranging from 7 to 28 copies per nucleus. That's really clearly resulting in high positive fiber count of microdystrophin with nice distribution and high percentage of dystrophin-positive fibers and high levels of microdystrophin expression level by Western blot and mass spec and a dystrophin protein complex that is consistent really with stabilization of the sarcolemmal membrane and less need for ongoing muscle fiber regeneration. I also find the biomarker data shared today by Solid Biosciences to be really very exciting. There's evidence of reduced CK leak and improvements across a number of biomarkers, improving muscle fiber health and integrity with reduced risk of contraction-induced injury.
This early evidence of really the muscle fibers becoming shored up and becoming more stable should lead to long-term clinical benefit. So I think in the landscape of genetic therapies for Duchenne, individual microdystrophin constructs likely have unique efficacy and very unique safety profiles. I am really very encouraged by the results reported today. I look forward to seeing further data and longer-term functional data that will further inform our understanding of the role of the nNOS-binding domain, which is really unique to SGT-003 and really what role that may play in improving clinical outcomes of our patients. However, what I'm most excited about is what we are both the preclinical data and these initial clinical data, a potential benefit in what ultimately causes mortality in these children, namely cardiomyopathy.
These early signals are incredibly encouraging to me because I think about all the children with Duchenne, not only younger kids, but the older patients with more advanced disease progression with very severe cardiomyopathy who could potentially benefit from a drug that could impact cardiac outcomes. These findings need to be investigated further because this could represent a critically large unmet need in the Duchenne treatment field, particularly in patients with more advanced cardiac disease. And I'm happy to take any questions from the audience in a few minutes, and I'll turn things back over to Dr. Brooks. Thank you.
Thank you, Dr. McDonald. We were incredibly thrilled about the data that we have shared today, which we believe is highly robust first-in-human experience of SGT-003 and our second-generation AAV-SLB101 capsid.
I want to spend a moment to discuss our clinical strategy and potential opportunities that we see for therapeutic improvement. I'll linger here on our clinical study design. All of us at Solid have been in the Duchenne field for many years, and in that time, we've learned many lessons from previous and ongoing clinical studies of microdystrophin gene therapies. We have taken those learnings, and in partnership with leading Duchenne experts, we have defined what we believe is a potential best-in-class clinical study for a potential best-in-class therapy, and now that the muscle integrity biomarkers demonstrate improvement from baseline, we feel confident that with the correct study design, we can help achieve our ultimate goal of clinical benefit for these boys.
Whereas previous studies selected younger, healthier participants and used the NSAA to evaluate functional endpoints 12 months after dosing, we have decided to select a broader range of children and have refined the inclusion-exclusion criteria, such as optimizing the time-to-rise cutoff, and are dedicated to evaluating specific functional measurements, such as stride velocity, out to a later time point, 18 months after dosing. These changes have created a clinical study design that we believe gives us the best opportunity to accurately evaluate the therapeutic effect of SGT-003, and with that, I will now turn it back over to Bo to finish up the presentation.
Thank you, Gabe. As mentioned, we will continue to dose patients over the coming weeks and months, and we expect we will have dosed more than 10 total patients in the trial by early Q2 2025.
In fact, we dosed patient number seven on February 17 and plan to enroll approximately 20 total patients in the trial by Q4 2025. Additionally, we are continuing to expand clinical trial sites on a global level and are pleased to share that we now ha ve CTAs approved by the U.K. and Italy and that we've already dosed our first international patient as well. In the middle of this year, we plan to request a meeting with the FDA to discuss a potential accelerated approval pathway for SGT-003 after accruing 90-day data from additional participants. I also want to linger briefly on the potential commercial opportunity for SGT-003. With the exciting results we've shared today and the aggressive clinical trial and regulatory strategy we have designed, subject to discussions with the FDA, we believe we have the potential to rapidly come to market with SGT-003.
I'm incredibly excited about early data generated in our labs indicating potential to redose with our capsid after initial treatment with AAVrh74, the capsid used in the FDA-approved Duchenne gene therapy. This again speaks to potential differentiation aspects of AAV-SLB101 and may allow us to open up the total addressable market. On the left-hand side, you will see we started with mice to evaluate cross-reactivity between rh74 and AAV-SLB101 neutralizing antibody titers. We were surprised to see extremely low titer cross-reactivity, and then we asked the same question in non-human primates and again replicated the findings of low titer cross-reactivity. Finally, we received serum samples from three different individuals with Duchenne who were treated with the FDA-approved Duchenne gene therapy, ranging from six months to five years after initial dosing.
In those serum samples, we again saw low neutralizing antibody titers to AAV-SLB101 at levels low enough to suggest that potential redosing with AAV-SLB101 may be possible with the use of an additional agent like IdeS or FcRn and/or plasmapheresis. These data, while early, are a very exciting indication that maybe the Duchenne market could open back up, and based on these preliminary data, we believe that AAV-SLB101 may allow for potential redosing based on antibody levels post-initial treatment with the FDA-approved Duchenne gene therapy. We are now in the process of gathering additional samples from Duchenne patients treated with the FDA-approved Duchenne gene therapy and will plan to analyze those samples.
While these findings are early, they give us a lot of hope that we may be able to open up the market, leave no patient behind, and provide a meaningful treatment for the Duchenne community as a whole. We believe the initial findings discussed today provide both an entirely unique data set and also a reinvented perspective on what a next-generation gene therapy may offer for individuals living with Duchenne. We hope, ultimately, that these initial data from SGT-003 offers new hope to the entire Duchenne community, and we remain committed to delivering on the promise of next-generation gene therapies. I would also like to thank our new and existing investors who have both stood by us through this journey and helped breathe new life into Solid's mission to bring forward meaningful treatments for devastating genetic neuromuscular and cardiac diseases.
We are humbled by the overwhelming showing of support represented by the $200 million equity offering we announced this morning, consisting of a deep roster of leading healthcare investors. We would not be here without your support, and we look forward to executing on behalf of all our shareholders and patient communities in the years to come. And with that, I'll turn it over to the operator to open up for questions and answers.
Thank you. The floor is now open for questions. If you would like to ask a question, please press star one on your telephone keypad at this time. A confirmation tone will indicate your line is in the question queue. You may press star two if you would like to remove your question from the queue. For participants using speaker equipment, it may be necessary to pick up the handset before pressing the star keys.
We do ask that you please limit yourself to one question. Again, that is star one to register a question at this time. Today's first question is coming from Maury Raycroft of Jefferies. Please go ahead.
Hi, good morning. Much congrats on the robust data update. I'm wondering, for your meeting with FDA coming up in the middle of 2025, can you provide more specifics on the plan there? How many total patients of data do you need to have for the meeting? And do you need to have functional data such as time-to-rise velocity or SV95C? And then will you disclose the new data cut to the public before or after the FDA meeting?
Yeah, thank you, Maury. I'll start with the question, and I'll turn it over to Dr. Brooks immediately after. What we're going to do, this data is really, really exciting.
It's early, but we're very pleased. We are going to try to gather 90 days' worth of data for 10 to 12 patients and then meet with the FDA over the summer and talk to them about an accelerated approval pathway. At that time, we do feel that we'll have a much more robust database based on what we've shown today. It's what another seven or seven to nine patients worth of data and 90 days to share with them. And we'll be sharing everything with them, all the biomarkers, the acute phase, the chronic phase, the muscle maturation phase, as well as the cardiac biomarkers that we're sharing. And we'll talk to them about a future pathway. And to your answer to your question, we will share the data. Yeah, what we'll do is we'll meet with them. We'll wait for their feedback.
And then after that conversation, after we have their feedback, we'll share with you the data of the 10 patients or 12 patients, depending on what we have, and we'll go from there. And Dr. Brooks, I'll turn it over to Gabe. Gabe, why don't you talk about the upcoming dosing and how many patients you have and the timing?
Absolutely. And thank you, Maury. So as Bo's indicating, we are rapidly enrolling right now, and we will have 10 to 12 participants with follow-up data by Q3 to go to the FDA with biopsy data as well as early biomarker data and functional data. There, we intend and we believe that we will have a very productive discussion with the agency around an accelerated approval pathway, given multiple markers here that can show differentiation as well as reasonable likely benefit.
And those include the very impressive microdystrophin expression, the effect on biomarkers, including embryonic myosin heavy chain. We are seeing some early signs of potential cardiac benefit. And then, Maury, what should not be overlooked is that this vector, that this capsid, that this therapy does not seem to have the liability of liver toxicity, which currently can be an issue with high-dose AAV gene therapy. So there are four areas of differentiation that we believe the agency will be excited to partner with us on to try to accelerate getting this meaningful drug into the hands and to the armamentarium of treating clinicians. And one last thing, as we are having a discussion with the agency, we in parallel are working on our confirmatory phase three trial in the rest of the world.
So this discussion with the agency will be in the context of an ongoing and recruiting Phase 3 clinical trial, which we know by the guidance gives them a great deal of comfort in terms of moving forward with accelerated approval. I'll now turn it over to Bo again. Thank you. Next question, please.
T hank you. The next question is coming from Joseph Schwartz of Leerink Partners. Please go ahead.
Hi, Jenny on for Joe. I was just wondering if you can talk a bit more about how you're selecting patients for the INSPIRE DUCHENNE trial and why you think this is going to be key for differentiation. Also, given the high level of expression and biomarker movement we are already seeing at 90 days, is there a potential to see clinical changes before 12-18 months? And is that something you've incorporated into your study design?
Will we be able to see any of that data, or will it stay blinded for registration? Thank you.
Yeah. Yeah, thank you very much. I'll take the last question, and then I'll turn it over to Gabe for the first part. The last part of the question is about clinical endpoints in early days. This is why we're focusing on muscle integrity. One of the questions, one of the things we want to give confidence to everybody is this is a disease of muscle integrity and dysfunction. And so really, to give confidence that we were ultimately going to hit a P value with a clinical endpoint, then you'd have to feel coming out of this that muscle integrity is shaping up and the muscle is shoring up. And that's what we're trying to show today. We know, though, early days, 90 days is very early.
You can even look at muscle fiber, like positive muscle fibers. Typically, at the 12-week or what's called an intermediate biopsy, they're lower than what they will be at 52 weeks, so the muscle hasn't even had time to shore up yet from the drug that you're just adding, and we've learned this over time. This is a biochemical phenomenon that we need to understand. You dose with the microdystrophin, the muscle really needs to shore up over the first couple of months, and then you'll get, hopefully, that long-term clinical benefit, especially if you can show the muscle biomarkers like I'm showing, so that's a long-winded way of saying we believe it's too early. We are collecting it. We'll share it with the FDA. We'll share it with you at the 52-week or 18-month end time point, but I'll turn it over to Gabe for a quick answer.
Yeah, and I'll attempt to be brief because I know our time is short. I think that, look, we have to acknowledge our really pioneering colleagues here in the field with Sarepta and Pfizer with the EMBARK and CIFFREO studies. And though those trials were negative, we've learned a lot, and we've been able to partner with folks such as Dr. McDonald to really interrogate how we can better construct trials to look for clinical benefit in Duchenne. And from that, we've learned that we need to not just focus on age as an instrumental variable of disease, but also very specifically on specific inclusion/exclusion criteria. Our time today is too short, but we have enacted those refinements and, in addition to looking at more sensitive endpoints as well as making sure that we allow enough time for the biologic effect of this drug to take hold.
I'll now turn it back over to Bo.
Thank you. Next question, please.
Thank you. The next question is coming from Biren Amin of Piper Sandler. Please go ahead.
Yeah. Hi, guys. Thanks for taking my questions and congrats on the data. Maybe it's a three-part question. First, I guess, on the patient that experienced grade 3 thrombocytopenia, anything you can glean from patient baseline as it relates to this patient versus the other five patients? Second question, when can we expect maybe the next data update? I think PPMD is coming up in June. Should we expect additional follow-up there on all six patients, including biopsy data on the most recent three? And then I guess the third question is for Dr. McDonald. With these data, how would you compare these data and SGT-003's profile to ELEVIDYS or to REGENXBIO's DMD gene therapy program? Thanks.
Great. Thanks, Biren.
I'm going to take the MDA question, and I'm going to turn it over to Dr. Brooks for the thrombocytopenia question, and then Dr. McDonald to his question. So the data update for the MDA, we are going to be presenting data at the MDA conference. I don't know if we'll have additional data because the conference is actually coming up in about a month or so. And so it's highly unlikely you're going to get anything new because I doubt we're going to have it internally. So that's the only reason. So we're giving you as much data as we actually have, and the conference is right around the corner. So I'm going to say probably not on MDA conference, but maybe down the road. I'll turn it over to Dr. Brooks for thrombocytopenia and then also Dr. McDonald for his question as well.
Thank you, Bo.
With regard to participant number three, there wasn't anything extraordinary. He was maybe a little bit lighter, on the lighter side, but otherwise, nothing remarkable about his inclusion/exclusion criteria. And just to reiterate that the thrombocytopenia resolved with just expected monitoring, meaning there was no other action taken and there was no clinical consequence. So this is early days, and we're continuing to watch these patients. I'll turn it over to Dr. McDonald.
Yeah. So I think your question pertained to a comparison with the profile of SGT-003 with other gene therapies such as ELEVIDYS and the REGENXBIO therapy. I think certainly we have much more long-term clinical data with ELEVIDYS. And I think as clinicians, we're feeling very comfortable with how the patients are benefiting from that therapy.
I think what excites me in terms of the differentiation here with SGT-003, I think, first of all, I think preclinically, we're seeing some detargeting of the liver. And I think, in fact, the first few patients that have been treated now have not shown evidence of acute liver injury. And while early, I think that's exciting to me as a clinician. And then also, I think looking at the preclinical data and the potential for expression in the myocardium, I think that potentially here we could see some positive effects on the cardiomyopathy, which is really quite exciting to me as a clinician, particularly in the older patients with Duchenne dystrophy, the older non-ambulatory patients who may have more severe cardiomyopathy, but also higher body weight.
And if we can give them a lower dose, reduce the risk of liver injury, and perhaps get some benefit in cardiac function as well as upper limb function, I think that would be huge for patients we treat that are further along in the disease progression. Now back to Bo.
Thank you, Dr. McDonald. Next question, please.
Thank you. The next question is coming from Anupam Rama of J.P. Morgan. Please go ahead.
Hey, guys. Thanks so much for taking the question and congrats on the data. I had a quick clinical trial question. In your kind of clinical trial slide, you talked about some of the changes that you're making relative to what others have studied.
But I was still struck by the age range that you're studying, four to less than 12, because I think some of the competitors have had some issues in terms of in that lower cohort, four to six group, showing a benefit because those patients are still in the gain-of-function phase. How do we think about that? And along those lines, for Dr. McDonald, what would be your advice to the company in terms of controlling heterogeneity in the clinical trial overall, but in particular for that younger cohort of patients where it's been more difficult to show functional benefit? Thanks so much.
Yeah. Thank you, Anupam. I'll take the first part. I'm going to turn it over to Gabe and Dr. McDonald to answer.
But the first part, listen, we believe that the reason we're studying four to less than 12 is because we believe from a clinical endpoint, it's very challenging for a four, five, and six-year-old to tease apart benefits. Typically, four and five, these are while they're not normal children, they're actually developing relatively quick, and you see them hitting milestones at a pretty rapid pace. And so you can even have a kid that's on placebo and actually see them produce pretty significant numbers in development milestones. So we chose to enroll a broader age group, four to less than 12. However, from a clinical endpoint, we're just looking at seven, eight, nine, 10, and 11 years of age of that specified group to look at clinical endpoints because that's going to really be a more homogeneous population where they're starting to either plateau or decline.
The other thing we got rid of is a blunt instrument of composite score of NSAA. We think that it needs to be more sensitive, and then last thing is I talked about it earlier. Someone asked a question about clinical improvements at day 90. We fundamentally believe that you need a couple of quarters for the muscle to actually shore up, and that's why we're showing you integrity. And so if you think about a typical 52-week trial and your muscles in the first quarter or two are just then showing signs of integrity due to the drug, your trial's like halfway over. And so it's very hard to show a P value. So we've changed all this up to make sure that we're thinking very strategically. We know now we're making a benefit in these children from a muscle integrity standpoint.
Now it's about choosing the right kids to enter the trial from a homogeneous population, choosing the right endpoint, and choosing the right length of time. That's what we've done. I'll turn it over to Gabe and Dr. McDonald.
Yeah. Absolutely. Thank you, Anupam. Just to give maybe a little bit of color very briefly on what Bo's mentioned, indeed, you're absolutely right that the younger boys are a lot of times gaining functional capacity at the same time as the disease is impacting them, which makes treatment effect very difficult for any therapy. We are focused, and we've been partnered with key leaders in the field like Dr. McDonald on trying to determine what actually is the best functional characteristics to have a more homogeneous patient population and that sometimes age is part of it, but it's only one part of it.
And then the other piece is, as Bo indicates, length of time is important, and then having the right key functional endpoint, like time to rise. We are still looking at NSAA as a more comprehensive measure, but it has been demoted in terms of its rank as an endpoint. Dr. McDonald?
Yeah. Thanks. I think there's really been a lot of thought from the academic neuromuscular specialists with regard to the right endpoints, the right trial design, and importantly, the most appropriate inclusion criteria for a clinical trial. And I participated in a European advisory board as well as a recent U.S. advisory board. And I think there's been some really great input in terms of the inclusion criteria with regard to age and time to rise, the most appropriate clinical endpoints.
We do know that testing those younger patients, you need a longer trial design to really show clinical benefit, and I think Solid Biosciences is really thinking about a confirmatory trial that would likely be 18 months in duration, and again, that's not to say that we shouldn't be focused on the younger patient population because I think treating patients younger may well lead to higher peak obtained function followed by stabilization or a slower rate of decline subsequently, so we're excited also about the possibility of treating young patients. It's going to take a longer period of time to show a long-term clinical benefit, but I think with using some of the objective technologies such as the 95th centile stride velocity, which is obtained with a wearable device, and longer-term follow-up, I think we're likely to see some real benefit in the young treated patients as well.
And back to Bo.
Next question, please.
Thank you. The next question is coming from Charles Duncan of Cantor Fitzgerald. Please go ahead.
Hey. Good morning, Bo and Gabe. Congrats on great data. And thanks for taking the question. I had a question along the lines of the cardiac benefit that is emerging, which seems pretty interesting to me. I guess I'm wondering if you mentioned that you actively enrolled some patients with cardiac signals. Was that based on the troponin levels or ejection fraction? Do you anticipate being able to use those biomarkers going forward? And within the 20 patients by year-end, would you like to enrich for a certain number of patients that have those biomarkers? And then if I could ask the KOL, Dr. McDonald, what he thinks about the left ventricular ejection fraction changes at 180 days if that 8% is meaningful to him. Thanks.
Thanks, Charles, and thanks for your support. I'm going to turn this over to Gabe and Dr. McDonald.
Thanks so much, Charles, so we recognize that as we are dosing these boys, that all boys with Duchenne have cardiomyopathy, whether it's subclinical or we're starting to see signs, and so by definition, our trial is treating boys with some form of cardiomyopathy. Specific to your question, I think it's when it's overt, when you're starting to see the effects, and we knew that just in our initial study design, which only went up to age seven, that we would be recruiting and enrolling boys that had some impacts. We didn't actively look for them to your question. However, because we are really quite vigilant, of course, in terms of safety and potential efficacy, we have been sampling very densely troponin and imaging the patients with echocardiography.
We did pick this up that there were some boys that did have elevated troponin at baseline, and that's to be expected. As we enroll boys that are older and more advanced in their disease, we are expecting to see more of overt clinical manifestations of cardiomyopathies, borderline low ejection fractions, for example. Finally, before handing it over to Dr. McDonald, how does this early data and promising data compel us to alter our study design? I think we have been using echocardiographic imaging because we are so dedicated to safety. As this potential benefit may be seen, I think it means that we're going to incorporate cardiac MRI more early in our trial into the older boys so that we can more closely track changes to the ejection fraction. We, of course, will continue to follow their troponin levels. Dr. McDonald?
Yeah. I think absolutely in the older patients in the more advanced stage of the disease, I think the cardiac MRI will be critical in terms of evaluating cardiac efficacy. I think in general, the left ventricular ejection fraction from cardiac echo can certainly be somewhat variable on the order of 5% from episode to episode in terms of when patients are evaluated. I think looking at this data, when you have patients that are below a normal ejection fraction in the below 55%, such as participant 1, who actually had an improvement by over 10% on their left ventricular ejection fraction, that's very encouraging to me in terms of that one patient. But again, we have to remember this is, again, small numbers.
I think it's an encouraging initial sign, but we'll need to have a much more robust database, probably in a patient population that's enriched for some degree of cardiomyopathy, perhaps left ventricular ejection fractions on the order of 45%-50% or some parameter like that. And obviously, we'll have to engage the pediatric cardiologists that are really experts in the management of Duchenne-related cardiomyopathy in the trial design as well as the interpretation of the data. And back to Bo.
Thank you. Next question, operator.
Thank you. The next question is coming from Sami Corwin of William Blair. Please go ahead.
Hi there. Good morning, and thank you for taking my questions. I have another one on the cardiac benefit. How are you thinking about capturing the potential functional cardiac benefits in a pivotal or confirmatory trial, and how might that support a stronger and more differentiated label?
Then we've seen with other products a decrease in the % positive fibers in older patients compared to younger patients. So I guess, what are your expectations for this tropism and expression in 8- to 11-year-olds given the robust expression you've seen in the first three patients? Thank you.
Yeah. Yeah. Thanks, Sami. I'm going to take the second question. I'm going to turn the cardiac question over to Gabe in a second. On the positive fibers, what I'm so impressed with on the positive fibers, so I'm going to try to answer your question the best I can because we do know that as you age and unfortunately, these children do lose muscle over time, so they have less muscle. But I'm just struck by how consistent we are seeing our positive muscle fibers.
You always have at the intermediate biopsy a step down from just the raw protein of Western blot or mass spec, and then you get to a positive fiber count. But what's encouraging is positive fibers tend to go up. I'm close to saying that we're close to saturation right now or very close to saturation at roughly 80% in these three boys. And if it goes up over time, that's very encouraging. And so if you're getting the same type of transduction, like when you look at the vector genome copies per nucleus, I mean, it's really quite robust. It actually tells me two things. One, I've got a great Duchenne drug. Number two, I probably have the best skeletal muscle and cardiac capsid that's ever been dosed in patients. And so going back, though, I think that it's going to be encouraging.
We probably have the best shot of anybody based off this capsid transduction to have robust positive fibers in the older boys. But I'll turn it over to Gabe for the cardiac discussion.
Yeah. Thank you, Sami. It's a stupid question for sure. I think that, as you know, the gene therapy landscape is very dynamic. We have really great colleagues in this space that have had discussions with the FDA around cardiomyopathy endpoints that it will be meaningful for demonstrative of change. And I think when we look at that structure and function by imaging is a critical piece as well as circulating biomarkers such as troponin. So if we think of - we look at Rocket with Danon or Lexeo with their Fabry program - sorry, their Friedreich's ataxia program, excuse me.
I think that having a key aspect of being able to alter the disease course with an improvement in ejection fraction or even just a stabilization of ejection fraction with an improvement in troponin would certainly be compelling to the agency. And we're looking forward to developing that data set. Dr. McDonald, anything that you'd have to add?
No. I think, again, I think that development of a more robust data set in the older population with actual impaired cardiac function is going to be really important. But I think the agency, my guess, will be really quite open to consideration of cardiac MRI data in addition to skeletal muscle data. And back to you, Bo.
Yeah. Thank you. Next question, please.
Thank you. The next question is coming from Arthur He of H.C. Wainwright. Please go ahead.
Hey. Good morning, Bo and Gabe. Congrats.
So for me, I just want to follow up on the cardiac function discussion. So could you tell us what kind of biomarker potentially could be recognized by the FDA for an accelerated approval in terms of the cardiac function benefit? And also for Dr. McDonald, besides the microdystrophin expression level, what other data, including biomarker or functional data, you'd like to see to be solidified the accelerated approval pathway for SGT-003? Thank you.
Yeah. Thank you, Arthur. I'll turn the questions over to Gabe and Dr. McDonald, please.
Great. Thank you, Bo. And thank you, Arthur. So we feel very, very confident that we can partner with the agency around looking for signs of improvement in the cardiomyopathy through imaging of structure and function based on their agreements with other companies looking at gene therapy with cardiomyopathy.
So if we look at Danon with Rocket and then the PREDICT with Alexion, as well as, frankly, the very promising discussions that Capricor has had with the agency as well around improvements in left ventricular ejection fraction and improvements in troponin in boys with DMD, we feel that we can have a very productive discussion with a drug that shows an improvement in structure and function such as left ventricular ejection fraction and a decrease in troponin in the totality of the overall safety package and efficacy package. So we feel quite confident there. And then Dr. McDonald?
Yeah. And I think my experience has been with the Capricor cell-based therapy.
I think their recent BLA submission has been largely based on the cardiac data set where long-term, this is, again, long-term data following patients out to three years showing stabilization of cardiac function in terms of cardiac MRI, left ventricular ejection fraction, as well as some of the left ventricular volumes and so forth. It had been really quite encouraging and really unprecedented in terms of the degree of stabilization. I think that's really what got the agency, I think, open to at least that BLA submission. I think we're coming out of time in the last few years with these other therapies and other diseases where I think the agency has become much more open to consideration of cardiac MRI data in terms of a biomarker for approvals. We'll see how this obviously plays out.
I think obviously other biomarkers that I think at least the neurology division of the FDA recently, I think, has indicated some openness to has been skeletal muscle MRI, I think, would also be a really important biomarker to explore in some of the upcoming trials as well. I think probably more so than some of the blood-based biomarkers. But I think when you have the totality of data around the biomarkers that we see here, I think that's also quite reassuring.
Thank you. Next question.
T hank you. The next question is coming from Gena Wang of Barclays. Please go ahead.
Thank you for taking my questions. Also, thank you for such a comprehensive and thorough analysis of the data, very good data. So maybe I would just follow up on the biomarker data just discussed in the past few questions.
We know that we saw the data from five to seven years old. Those are relatively younger patients. I know we do wanted to enroll patients up to 12 years old. What are your thoughts based on the other data, the older patient population? What could be the biomarker look like? Would that look a little bit worse than what we see now in the younger patient population? And also regarding the biomarker for muscle integrity, I think you have about seven, eight different measurements. Just wondering, I know these are the mean numbers. How consistent across the three patients? I know it's only three patients, but I think these are the data that do not have a standard deviation. If you can share that.
And quickly on the exclusion criteria for this study, I know in the past you did mention you were very cautious on the patient enrollment to make sure the safety that will meet the standard. You can show pretty good safety. So maybe if you can share a little bit more of the thoughts going forward, are you willing to lose a little bit the inclusion criteria to include certain patient population with certain mutations?
Yeah. Thanks, Gena. We'll try to get to everything there. There's a lot to unpack in that question. I'll take the beginning part, and then I'm going to turn it over to Gabe for a much more robust. Your first part of the question was about younger boys versus older boys, and do you expect to see changes?
Realistically, all of these kids, whether you're young or whether you're old, they're going to have muscle impact. And it can be skeletal muscle. It can be diaphragm. It can be cardiac muscle, intercostal muscles. But a lot of the biomarkers will roughly be the same as long as they have muscle left to transduce, albeit as you get older, you'll have less muscle to transduce, especially skeletal muscle, unfortunately. But you should be able to see muscle integrity biomarkers shore up in some way, shape, or form. It might not be as robust because you have less muscle, so your baselines might be lower than they are in four and five. But that's why we're committed to continuing to look at biomarkers. We also, as we look at biomarkers, and I've said this a couple of times, we think about it in three phases.
You think about the acute injury phase, the chronic phase, which is where titin and troponin come in. So the acute will be the ALT, AST, lactate dehydrogenase, CK. And obviously, if you have less muscle, you're going to have a lower baseline. Chronic phase will be more titin when muscle is decomposing, as well as troponin I. And then the latter phase that Dr. Brooks is talking about, the embryonic myosin heavy chain, where really you're just depleting your satellite cells while they're trying to keep up. And that shows muscle maturation. So we're going to look at all of them. Do we expect changes? Of course we do because, unfortunately, kids as they get older, they have less muscle, which means you got to protect their heart. And so I'll turn it over to Gabe for the rest of the question.
Thank you, Bo.
So very briefly, Gena, so we're using really our inclusion-exclusion criteria and functional characteristics there to develop a more homogeneous patient population as opposed to just thinking about age. So that may help. But I think getting to the last part of your question around the genotypes, I think this is a very important one. We are committed to really engaging all patients with Duchenne muscular dystrophy in the study of this. And we understand that the exclusions around specific genotypes make that less possible. So we are working with experts in trying to make sure that we can treat as many boys with Duchenne as possible and are looking forward to doing that.
In terms of the standard deviation of the biomarkers, we will be thrilled to share more detailed data at an upcoming neuromuscular congress where we can go into all of those details, including more detailed imaging of the slides, which are very robust. I will share that in all of the boys that we've presented thus far, all of the biomarkers are coming down within a fairly tight range. But we'll be able to share all of the details at a more fulsome presentation at an upcoming congress. Back to Bo.
Thank you. Yeah. Thank you very much. I'll bring next question, please.
Thank you. The next question is coming from Joon Lee of Truist Securities. Please go ahead.
Hey. Congrats on the impressive data, and thanks for taking our questions. Your biomarkers look very impressive.
So just curious about your preference for month 18 assessment versus month 12 by some of your peers. Thank you.
I apologize, Joon. I had a hard time hearing you. What was that question?
Yeah. Just curious why you prefer to assess for efficacy at month 18 versus month 12 by some of your peers.
Yes. Okay. That's an easy question. Look, we fundamentally believe in muscle integrity. Once you understand that you're shoring up the muscle, it leads to a clinical benefit. But you can also look at any of the companies that have published data in the past. Dystrophin-positive fibers at the intermediate biopsy, they tend to go up over time. That means that your body hasn't even adjusted to the drug you've dosed. And so you need to get to a place where your muscle fibers are stable and they've absorbed all the new microdystrophin.
If you think about a 52-week trial, let's say it takes six months because we really don't know. We know that muscle fiber positivity rate goes up over time. We're looking at only a 12-week time at basically 80% positive fibers. So if it takes six months for you to become stable in your expression of fibers and you have a 52-week trial, your trial is halfway over. And now you're fighting time on top of a blunt instrument of NSAA on top of a four, five, six-year-old that's increasing development milestones makes it almost impossible to really tease out differences. So that's why we went 18 months. We now know our drug is having some activity in the body shoring up muscle. Now it's about clinical trial design, the strategic nature of it, and the time.
I appreciate it.
We got to run and operate our next question.
Thank you. The next question is coming from Laura Chico of Wedbush Securities. Please go ahead.
Hi. Thank you very much for taking the question. This is Dylan on for Laura Chico. We're just wondering, so what are your expectations on the timing for regulatory feedback? And beyond that, will you also engage with ex-US regulators this summer?
Yeah. And I'll take this and then because we're running short on time, we are going to meet with the FDA over the summer. So we're going to dose, as I've stated before, we'll dose 10 to 12 patients. We would like to have 10 to 12 patients at 90 days' worth of data as we go into the FDA to have those discussions. I mentioned on the call that and in the slide deck, we should have 10 to 12 patients dosed by mid-April if everything stays forward.
So you can roughly figure out when we'll start requesting a meeting over the summer. We'll share information when we'll have to. Once we come out of that FDA meeting and get meeting minutes, the meeting request, I think it takes like 60 days, and then it's like a 30-day follow-up. So you can sort of think through strategically about the timing of that conversation. It should be over the summer to Q3 and then feedback after.
Yes. We'll be talking to you as well.
Thank you. Next question, please.
Thank you. The next question is coming from Silvan Türkcan of JMP Securities. Please go ahead.
Hi, Bo. Congratulations on the data, and thanks for taking my question. This is Josh on for Silvan. Is there any context that we need to analyze these data in relation to the non-dystrophin-related biomarkers for this age group?
So similarly to the functional endpoints in the four to seven age group where they may increase, is there any potential for the non-dystrophin biomarkers to improve? And is there any maybe natural history data for some of these biomarkers that you've looked at to sort of confirm? Thanks.
Yeah. I'll turn this one over to Gabe in a second. I think we're doing. I would say we're doing something unique. We're doing something holistically that no one else has done. And we feel obligated to take a look at everything from biomarkers to cardiac to clinical endpoints, etc. But I'll turn it over to Gabe. I don't believe there's a lot of data out there because we're doing something that's pretty unique. But Gabe, care.
Yeah. Absolutely. And Bo, absolutely.
We are being very robust and fulsome in our interrogation of the muscle health through these multiple different biomarkers, which can look orthogonally, look at different perspectives. In terms of prediction, they're variable in terms of the data that's available. But the aggregate is, I think, really, really robust as we're seeing drops across everything. Endomyocard—I'm sorry, embryonic myosin heavy chain is novel. So there's not so much natural history there. But as something that is reasonably likely to predict benefit, it's hard to think of anything stronger than being able to sample the muscle and show that you have interrupted the dystrophic regenerative process that's ultimately futile. And that's really what embryonic myosin heavy chain is showing. So we're very eager to discuss that with the agency.
Yep. Thank you very much. Operator, I think we need to end the call.
Understood.
Ladies and gentlemen, this brings us to the end of today's teleconference. We thank you for your participation and your interest in Solid Biosciences. You may disconnect your lines at this time or log off the webcast and enjoy the rest of your day.