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spk04: Pardon me, this is the operator. Today's conference is scheduled to begin shortly. Please continue to stand by and thank you for your patience. Thank you. Thank you. Ladies and gentlemen, thank you for standing by, and welcome to the Solid Biosciences Strategic Business Update and Financial Results Conference call. At this time, all participants are in a listen-only mode. Please be advised that today's conference may be recorded. After the presentation, there will be a question-and-answer session. To ask a question, please press star 1 on your telephone to get in the queue. I would now like to hand the conference over to Caitlin Lowy, Vice President of Communications and Investor Relations at Solid Biosciences. Ms. Lowy, you may begin.
spk06: Good morning. 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 company's Ignite DMV clinical trial. Actual results could differ material 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 Ganote, Co-Founder, President, and Chief Executive Officer of Solid Biosciences, Dr. Joel Schneider, our Chief Operating Officer, Dr. Carl Morris, our Chief Scientific Officer, and Dr. Roxana Donisa Dragic, Senior Vice President and Head of Clinical Development. During today's call, we will share details of the strategic update the company announced this morning. We'll begin with opening remarks from Ilan. followed by Joel who will share details of an intended change we'll be making to the manufacturing approach for SGT001. Carl will then review new preclinical data related to SGT003. Finally, Elan will provide an overview of the organizational strategy that aligns behind these two programs before opening the call to questions. Before I turn the call over to Elan, I want to acknowledge that our first quarter financial results have been reported and can also be found on our form 10Q, which was filed with the SEC this morning. For opening remarks, I'd like to turn the call over to CELD's CEO, Ilan Ganot. Ilan?
spk10: Thank you, Caitlin, and thanks to all of you for joining us this morning. CELD's ongoing focus on Duchenne has produced two potential therapies for this devastating disease. and to explore the potential benefits of SUT003's novel capsid to deliver our differentiated microdystrophin. This is all supported by a cash position of approximately $180 million at the end of the first quarter of 2022. The Board and SOLID's leadership team remain committed to the progress of both programs, and I'll now summarize our path forward. First, following a thorough assessment currently available alternatives for the manufacturing of STT001, we identified a process that we believe will produce high-quality drug products while narrowing the organization's focus to a single production platform and streamlining our operating structure to a more efficient model. Joel will discuss our revised strategy to advance STT001 into late-stage clinical development with transient transfection-based manufacturing. We believe this transition has minimal impact to our timeline for further development through to the potential BLA filing and improves our potential to make a difference for those living with Duchenne. Second, our next-generation capsules used in STT-Z gene therapy as well as for the broader gene therapy field for muscle disorders. We will continue to advance towards an IND submission in early 2023 and further de-risk this program and the novel Capsid. We expect the clinical proof of concept for HT003 in 2023 will provide further support of our next generation Capsid platform. As a result of the focused approach on these programs and SOLID's CASH runway through Q2 2024, the company will be able to progress through important telephone milestones for both gene therapy programs. I will now hand it over to Joel to go through our SGT001 update in more detail. Thanks, Salon.
spk02: In March, we released an interim analysis of functional and durability data from the first three patients dosed in the high-dose cohort two years after treatment with SGT001 as part of the IGNITE DMV Phase 1-2 study. Across all measures, including motor function, pulmonary function, and patient-reported outcome measures, patients are showing consistent, durable improvements after dosing compared to expected declines in untreated patients. We also shared that patients recently dosed in the high dose cohort demonstrated micro dystrophin expression and localization at 90 days within the range of earlier patients in the high dose cohort at the same period of time. And finally, all IGNITE DMV patients continue to do well with no long-term safety events. These data are important as they continue to support the potential that solids NMOS-containing microdistrophin is providing durable benefits to patients and warrants further clinical development. We are now focusing on finalizing late-stage clinical and regulatory strategies supported by a commercial-scale manufacturing process. As part of our platform development efforts, we undertook a comprehensive analysis comparing transient and HSV-based manufacturing process across a number of factors. We collected multiple data sets from different scales of manufacturing to help us compare the processes and to assess how they would scale for production. Overall, our analysis concluded that by developing SGT001 and SGT003 using transient production platforms, we believe we can achieve a high-quality and highly potent product demonstrating high levels of microdistributing expression in both our in vitro and in vivo expression assets. We can improve our consistency in product supply yields and have access to a broader supply chain, which is reflective of the adoption of this more commonly utilized manufacturing platform. The turnkey commercially scaled solution will allow us to ease our sole reliance on internal development and manufacturing operations. Organizationally, transitioning SGT001 to a transient-based process will bring SOLID under a single manufacturing methodology, allowing us to streamline our operations. Now, I will walk through the next 12 months for SGT001 as we look to resume dosing in the first half of 2023. Importantly, activities to transition to the new manufacturing process have already begun. with products expected to be available in early 2023, aligning well with our regulatory and clinical activities to support dosing patients. The transition to the new manufacturing process was a natural opportunity for us to pause and consider how to proceed with clinical development. As part of our strategy, we have decided to conclude enrollment in IGNITE DMV, and moving forward, Patients will be dosed using material from the new process, and we have already begun conversations with the FDA to determine the design of a future clinical study. In addition, we will be initiating a natural history study that will support future clinical activities, both for SGT001 and SGT003, helping us establish the risk-benefit of our programs. There are a number of milestones over the next 12 months that we aim to communicate, such as updates on our discussions with the FDA and additional data coming out of Ignite DMD, including one-year biopsies and functional analyses of all patients' dose in the program, as well as three-year follow-up on functional data from patients four to six. Now, I will turn the call over to Carl. Carl? Thanks, Joel, and good morning, everyone. I'm pleased to be able to share new data coming out of our Melville Capsid Library Development Program. Let me briefly review our HTT003 program. This program utilizes a novel, rationally designed capsid that has demonstrated improved muscle tritism compared to AV9 and packages solids, differentiated, and non-spiny domain-containing microdystrophins. This microdystrophin is the same that is used in SGT001. And as Joel shared earlier, it has been shown to deliver durable and promising benefits to patients in the IGNITE D&D study. Over the last couple of years, we have shared a variety of data on SGT003, and it's summarized on this slide. After observing promising data in mouse and human Duchenne muscle cells, as shown on the left, we compared by distribution and micro dystrophin expression in dystrophic mice of the novel capsules versus AAV9. Improved muscle turpism was observed with the novel capsules that also resulted in apparent significant reduction in circulating creatine kinase levels versus AAV9 as shown in the center of the slide. Additionally, we ran an in vivo study in wild type mice to determine if we would see similar changes in the level of expression as seen in the MDX mice. For this study, we used a reporter CMV luciferase construct. As you can see on the right-hand side of this page, we did observe increased expression in the wild-type mice as well. And when analyzed, we found more targeted expression to the muscles with lower biodistribution expression in the liver when compared to AB9. After the promising results seen in human cells and the mouse studies, we wanted to further test the translatability of the increased muscle tropism in non-human primates, as well as have an exploratory look at safety in larger animals. So, earlier this year, we initiated a study using CMV luciferase-reported transgene and dosed eight cinnamologous monkeys. Four of them, two male and two female, were dosed with the reported construct using AV9, while the other four were those with novel capsules being used in SGT003. Our goal for the novel capsules program has been to see at least a two-fold improvement compared to AV9 in biodistribution to skeletal and cardiac muscle. What we're highlighting here today is an increase in biodistribution greater than the goal of two-fold improvement to both skeletal and cardiac tissue. We also see a promising two-fold reduction in biodistribution to the liver. On the next slide, we similarly observed an increase in luciferase expression as measured using an activity assay in both skeletal muscle and cardiac muscle, with greater than ten-fold improvements seen in both tissues. And consistent with the biodistribution results, we see decreased expression in the liver with the novel capsules. So overall, these results suggest we may be able to reduce the dose while maintaining expression when compared to AAV9. As we look to next steps for the program, we will continue R&D efforts on both the novel capsid and SGT003 program for Duchenne, using learning and the promising clinical data from the SGT001 program. For SGT003, we are working closely with our manufacturing partner, to have product ready to support patient dosing. We are looking to engage with the FDA later this year regarding an IND submission we plan for early 2023. We are very optimistic about the potential that SGT003 holds for patients. The preclinical data continues to suggest that we may be able to improve expression at a lower dose, therefore reducing viral loads. We will continue to develop this next-generation capsid to the sham patients with the SGT-003 program, as well as potentially engage with companies developing gene therapies in other muscle-related disorders. With that, I will hand it back to Alon.
spk10: Thank you, Carl, and thanks, Joel. We have a lot of work ahead of us, but we have focused our operations to support these two programs, which utilize a single manufacturing approach. That has allowed us to streamline our organization's structure and reduce our headcount by approximately 35%, which enables us to extend our runway into Q2 of 2024 and achieve important clinical milestones. And over the next 12 months, we will be sharing further data from long-term patient follow-ups and updates on our regulatory interactions for both SGT001 and SGT003, and potential updates on SGT001 CMC and clinical plans as well as SGT003 IMD filing, clinical trial, and dosing plans. I also want to mention that as you may have seen in this morning's press release, Joel will be leaving SOLID. He has accepted an opportunity to become a CEO of an early stage privately held gene therapy company. Joel will be staying on through the end of May. Before we open for questions, I want to take a moment to say thank you. First, I want to say thank you to all of Solid's employees for their tireless efforts to bring our treatments to patients. To those who were unfortunately impacted by the strategic reorganization we announced today, I hope you know that your work has made a meaningful contribution to improving the lives of patients living with Duchenne, and for that, I'm deeply grateful. I also want to thank Joe for his eight years of service and commitment to SOLID. Joel's been instrumental in building the company, the teams, and the treatments that are being developed at SOLID. I now speak on behalf of everyone at SOLID when I thank Joel for his leadership, partnership, and friendship, and wish him success with his new chapter. Finally, I would like to extend a special thank you to the patients, families, and physicians involved in IgniteDMD, thanks to whom we are now in a position to move to the next phases Thank you all again for dialing in. We'll take some questions now.
spk04: Thank you. And again, ladies and gentlemen, to ask a question, simply press star 1 on your telephone. That is star 1. We'll take our first question from Jenna Wang of Barclays.
spk01: Thank you for taking my questions, Joe. Congrats on your next journey, and we will certainly miss you. So I have two sets of questions. Maybe the first one is regarding the SGT003. So you did show luciferous reporter gene data. Did you test the microdystrophin transgene in the new capsid? And based on the current data, what would be your initial thoughts regarding the phase one dose range? Like, will you be able to go down to the E12 range? My second question, second set of question is regarding the SGT001. So now with the new transient transfection-based outsourced manufacturing process, so do you need to do additional GNC or comparability study before you move forward to a pivotal study?
spk10: Great questions, Gina. Thank you. I'll have Carl take on the 003 and Joel respond to the 001.
spk12: Yeah, thanks, Gina. It would be great to get down to E12, but I don't think that's possible. You know, we are looking at doing a, we still need to do a dose selection study. And so we hope to get, drop the dose and so maybe get down by at least two-fold. And that is what the goal of the program was always, was to get a two-fold difference versus AV9. And so it appears that we've done that both in mice and monkeys. The second part of your question was around the luciferase versus microdystrophin. We didn't dose non-human primates with microdystrophin, We dosed them with the luciferase, but we did do mice and compared the luciferase and the microdystrophin. And so luciferase has a little bit higher signal, but the microdystrophin in the mice was about threefold, while the luciferase in mice was tenfold. So we think we're sort of in the right ballpark for the microdystrophin as well. Going into wild-type animals that already have dystrophin, it's a bit problematic trying to administer a microdystrophin and evaluate levels. But this is good. We did it in wild-type mice as well with SipRace, and it showed quite promising results there as well. So as a platform, we think this is sort of a really good first step for us.
spk10: I would just add, you know, we had a bunch of internal discussions bars that we needed to cross to get excited about 003. And we crossed them, and we are excited, and we're taking it to the clinic. And, you know, we think there's a lot more potential here outside of Duchenne, too. And hopefully, you know, very soon we'll see it in patients and see how good it really is. John, do you want to cover 001? Sure.
spk11: Thanks, Gina, for the question. You know, on comparability, of course, it's solid. We have a lot of experience in demonstrating comparability between different manufacturing methods. In fact, we just recently accomplished that when we transitioned to our second-generation-based HSV manufacturing approach. We've already begun to engage with regulators about the path towards dosing a patient to the new process and believe that the comparability will need to be demonstrated, but that that can be accomplished through analytical methods and perhaps some in vivo dosing to demonstrate comparability overall. But obviously a lot of experience internally with how to demonstrate that comparability and feel comfortable confident that we can have a seamless transition between manufacturing methodologies.
spk10: Maybe I'll just add to this, too, that in the process of switching, you know, we did a lot of analytical work, and so we are pretty confident that the new materials will, you know, qualify at least as good, if not better.
spk04: Thank you very much.
spk10: Thank you, Gina.
spk04: Then your next question comes from Joseph Schwartz with SVB Securities.
spk07: Thanks very much, and I'd like to also add my best wishes to Joel and his next endeavors. It sounds like you are satisfied that you understand how to best administer SGT-001 in a safe and effective manner now that you've wrapped up Ignite. So I was wondering if you could summarize what the key features of the risk mitigation protocol are for ensuring that patients who receive SGT001 can tolerate it optimally?
spk10: Hey, Joe. Thank you for the question. Obviously, we completed enrollment. We don't wrap up the study because we continue to monitor patients, you know, out to five years at least from dosing, and we've dosed nine and have a number of other patients in the study. But I'll have Roxana jump in a little bit on risk-benefit and how we feel about moving forward in those things.
spk03: Thank you, Ilan. Yes. Very good question. Thank you. We feel very confident in the risk-benefit profile of SGT001 based on the nine of those subjects to date. Our two-year results show that the patients are experiencing a sustained benefit across all the functional outcomes in terms of motor function, pulmonary function, and patient-reported outcomes. In terms of the risk mitigation strategy, we feel very confident that this is the right way forward. We are thinking about finalizing that risk mitigation strategy for the new material, so not maybe everything is going to stay in place as it is right now, but as you know with previous updates, we've shared that we've optimized our eculizumab regimen, and we've definitely optimized our follow-up of the patient previous to infusion and after the infusion in the first couple of weeks through very close monitoring. So we're, of course, assessing that once again to make sure that everything is still applicable for the new material.
spk07: Okay, thanks. And then what are the next steps for SGT001 then? When do you expect to get back in the clinic and what types of patients will you be focusing on enrolling in the next study for SGT001? And if you scheduled an end of Phase II meeting with the FDA yet, are you thinking about undertaking a Phase III at this juncture? Can you help us understand your strategy there?
spk10: Sure, Joe. I'll take this. It's a quick one. We've already started engaging with the regulators around the switch. We intend to have material ready to those patients with STT001 early in 2023, and all the aspects of the clinical trial design, as well as the number of patients, the age inclusion, are being finalized. Okay, well, stay tuned.
spk07: Thanks for taking my questions.
spk04: Thank you. Your next question comes from Maury Raycroft with Jefferies.
spk08: Hi, good morning, and thanks for taking my questions. For the new process, besides the scaling and the streamlined process and transient transfection, are there any other fundamental changes we should be aware of?
spk11: Thanks, Maury. I'll take this one. You know, one key aspect for this solution that we've identified for late-stage development of 001 is that it's already at what we would consider a Phase III appropriate and commercial scale. We've done extensive work internally on scaling the agency process, and as we performed our comprehensive analysis between our internal process and external options, we did seek a process that was already sufficiently optimized for late-stage clinical entry and ultimately commercialization. And so we're excited to be able to access that. A couple other key aspects of this is that, of course, transient production is a very widely adopted manufacturing platform, and we think that this will enable us to have broader access to a much wider net of supply chain efforts or supply chain networks. It will also allow us to, we think, overall improve our manufacturability of clinical supply. And so really fundamentally, it's a streamlining of our manufacturing unified behind a single platform for both gene therapy programs.
spk08: Got it. That's helpful. And then I'm just wondering if you can clarify what you mean by a new outsource process. I guess are there going to be new manufacturing collaborations on the horizon, and how much of a contribution does Forge Biologics have in the new process?
spk11: We're really excited about the work that Forge is doing for us on SGT-003, but simply for diversification purposes as well as the opportunity to work with a commercially scaled process, we are building a new relationship with a new vendor for the production of SGT-001 at those scales. On the aspect of... Sorry, actually I'm blanking on the first part of the question.
spk08: Just a I mean, you basically answered it, just if there's anything additional. Yeah.
spk11: Yeah, the differentiator there for us is that the HSE process is something that we've worked on extensively internally for the last six or seven years. We are excited to be leveraging external expertise and capabilities to rapidly integrate their expertise into our own around transient production. And so it's really a notion of, you know, recognizing the incredible work that our internal teams have done to scale and optimize the HST process, but recognizing that, you know, we can now relieve some of those bandwidth constraints by working with external parties, leveraging their proprietary manufacturing platforms, and really focus on bringing our therapy to patients.
spk08: Got it. That makes sense. Okay. Thanks for taking my questions. Thanks, Maureen.
spk04: Thank you. And as a reminder, to get in the queue, simply press star 1 on your telephone. Your next question is from Allison Bradsell with Piper Sandler.
spk05: Hi. Good morning. Thank you for hosting the call and for taking the questions. So first, just a couple of clarifications for me on Ignite DMV. And apologies if you've covered these. I just want to make sure I'm clear. I guess how many total patients did end up being dosed in Ignite DMV, I think, We know nine were dosed as of November, so just confirming that that's the total number of patients dosed. And then could you also clarify the cadence for data updates from those patients? I think the prior guidance was to disclose 12-month functional data from patients 7 to 9 by year end 22. So just want to make sure we should still be looking for that. And then just lastly for me, a clarification just on the cash runway data. I think the guidance is that you'll have a runway through Q2 24 through important clinical milestones. Could you just kind of outline the important clinical milestones we should be expecting between now and Q2 24? And just what does that new cash runway guidance assume for the start of pivotal work? Thanks.
spk10: Let me try to wrap it all up in a quick answer. With these nine patients, we were always going to adopt couple more and with this switch, we decided to stop enrollment, evaluate the data and move to transfection starting early next year. We obviously continue to monitor all the patients that have been dosed, and yes, we will continue to provide additional clinical and biomarker data as it comes in during this year and probably in the future. We are very excited about the durability of the data that we're seeing. We have biopsies out for years that are stable or actually increasing, and we have functional outcomes especially looking at some of the physical measurements, respiratory measurements. There's some pretty interesting observations there that we continue to monitor and evaluate and measure and report. The runway will get us, you know, for the next two years and a lot of clinical milestones on both programs.
spk04: Thank you.
spk10: Thank you.
spk04: Our next question comes from Anupam Rama with JP Morgan. Please go ahead.
spk09: Hey, guys. Thanks so much for taking the question. I have, like, maybe just a broader strategic question in terms of you're starting dosing for 001 in 2023, and, you know, theoretically your IND goes in for 003 early next year, and maybe you start dosing patients soon, too. Like, why not just prioritize one? and maybe extend the cash way a little bit longer?
spk10: Good question, Anupam. You wouldn't be surprised if it came up internally, too. We're not in the business of shooting down things that work. We think 001's got great data that supports continued development. I can tell you, as somebody with some firsthand experience of this disease, I would love to see that touch more patients, if possible. If 003, once active in patients, does show the same effect that we've seen in mice, that we've seen in monkeys now, certainly the expression levels and the biodistribution levels of the vector, then that's a great finding. It's a really exciting moment for not just solids, but I think science and muscle diseases. And at that point, we can make different decisions than we do today. Right now we are confident that both these programs deserve a day in the summer.
spk09: Got it. Thanks for taking my question.
spk04: Thank you. And with that, we conclude our Q&A session and today's call. All parties may now disconnect. Thank you and have a great day.
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