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Solid Biosciences Inc. (SLDB) Q1 2021 Earnings Call Transcript | The Motley Fool

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Solid Biosciences Inc. (NASDAQ:SLDB)
Q1 2021 Earnings Call
May 14, 2021, 8:30 a.m. ET

Contents:

  • Prepared Remarks
  • Questions and Answers
  • Call Participants

Prepared Remarks:

Operator

Ladies and gentlemen, thank you for standing by, and welcome to the Solid Biosciences update call. [Operator instructions] Please be advised that today’s conference is being recorded. I would now like to hand the conference over to your speaker today, Mr. Tim Palmer, corporate communications manager at Solid Biosciences.

Sir, you may begin.

Tim PalmerCorporate Communications Manager

Good morning. Thank you, operator. Before we get started, I would like to remind everyone that during this conference call, we may make forward-looking statements, including statements about the company’s financial results, financial guidance, future business strategies and operations and product development and regulatory progress, including statements about the ongoing IGNITE DMD clinical trial. Actual results could differ materially from those discussed in these forward-looking statements due to a number of important factors, including uncertainty inherent in the clinical development and regulatory process, the extent and duration of the impact of the COVID-19 pandemic and other risks described in the Risk Factors section of our most recently filed annual report on Form 10-K and other periodic reports filed with the SEC.

We undertake no obligation to update any forward-looking statements after the date of this call. With me on today’s call are Ilan Ganot, co-founder, president, and chief executive officer of Solid Biosciences; Dr. Joel Schneider, our chief operating officer; Dr. Cathryn Clary, our acting chief medical officer; and Dr.

Carl Morris, our chief scientific officer. For opening remarks, I’d like to turn the call over to Ilan Ganot. Ilan?

Ilan GanotCo-Founder, President, and Chief Executive Officer

Thank you, Tim. Good morning, and thank you all for joining us today. The focus on today’s call is to provide an update on our current corporate activities as we continue to progress along our 2021 corporate goals and what our progress means for patients with Duchenne muscular dystrophy. First, we’ll provide an update on dosing in IGNITE DMD.

Two patients were dosed this quarter in IGNITE DMD using SGT-001 produced with our improved manufacturing process and under an amended clinical protocol. As previously reported, patient seven has been dosed safely and continues to do well. Today, we are reporting on an additional patient dosed. Patient eight experienced a serious adverse event, or SAE, but has since been discharged.

And as of the patient’s 30-day follow-up visit, lab values have either returned to normal or continue to trend toward normal. In a moment, Dr. Cathryn Clary will review this SAE and the steps we are taking to evaluate its cause. Following Cathryn’s review of the patient dosing, Dr.

Carl Morris will present on encouraging long-term biopsy data collected from the first three patients dosed at the 2×10^14 [ph] vector genomes per kilogram dose. Carl will also be presenting this data later today at the American Society of Gene & Cell Therapy Annual Meeting. The data provides evidence of sustained microdystrophin expression for 12 to 24 months post dosing and are potentially supportive of the recently reported positive trends in clinical biomarker and functional data from the IGNITE DMD study. To our knowledge, IGNITE DMD is the first Duchenne gene therapy trial to show durable microdystrophin expression out to 24 months.

In conjunction with our growing clinical experience, we believe that the totality of the clinical data will establish a risk-benefit profile for SGT-001 that will be meaningful to patients with Duchenne. Today, as Dr. Joel Schneider, Solid’s chief operating officer, will share, we are also providing an update on our preclinical pipeline, which includes the nomination of SGT-003 program as our next development candidate and an update on our ongoing collaboration with Ultragenyx. SGT-003 will combine a novel capsid and our proprietary microdystrophin construct to enable a next-generation gene therapy for Duchenne with enhanced delivery to muscle cells.

Data from our novel capsid program have also been presented at ASGCT. I’m pleased with our progress on all these fronts as we continue to generate additional evidence to support the long-term potential of SGT-001 while expanding our pipeline of differentiated gene therapies. I’ll now turn the call over to Cathryn, who will briefly review our clinical updates and the steps we are taking as we progress the SGT-001 program.

Cathryn ClaryActing Chief Medical Officer

Thank you, Ilan. As we reported in March, we’ve resumed enrollment in IGNITE DMD and have subsequently dosed two patients under our amended clinical protocol. As a reminder, we’re working closely with our Data Safety Monitoring Board, or DSMB, to carefully review all the data generated with a built-in waiting period of 45 days minimum between each dosing. We also previously reported that patient seven dosed at the 2E14 vector genome per kilogram was dosed uneventfully and continues to do well.

As we do with all patients, we are continuing to monitor this patient, and we’ll be collecting additional data throughout the year. Today, we’re sharing that patient eight experienced an inflammatory response, which was classified as a serious adverse event and considered by the investigator to be drug related. This event is described in our investigators brochure and is not considered unexpected. As of the patient’s 30-day follow-up visit, laboratory values had either returned to normal or continue to trend toward normal.

We’ve shared the data related to this SAE with the FDA and also the IGNITE DSMB and are working closely, both internally as well as with external experts, to further our understanding of the outcome of this dosing and how it may impact our clinical strategy moving forward. While we already had a minimum built-in waiting period of 45 days between dosing patients eight and nine, the complexity of this event requires us to carefully analyze all the data before continuing to dose additional patients in IGNITE DMD. This will allow us to determine what, if any, changes we might make to the clinical protocol to further enhance patient safety, which is always our top priority. I’ll now turn the call over to Carl, who will review the long-term biopsy data from patients four through six, which we believe supports the potential of SGT-001 to provide benefit to patients with Duchenne.

Carl?

Carl MorrisChief Scientific Officer

Thank you, Cathryn. Today, I’m excited to share our analysis of the long-term biopsy data from patients four to six, which provide compelling evidence that a single dose of SGT-001 at the 2E14 vector genomes per kilogram dose leads to sustained expression of our proprietary microdystrophin construct containing the neuronal Nitric Oxide Synthase, or nNOS, binding domain for up to 24 months post dosing. The muscle biopsies were collected from patients four to six and taken at 24, 18 and 12 months, respectively, post dosing of SGT-001. For each patient, the baseline and the last time point biopsies were taken from the right quadriceps, while the day 90 sample was acquired from the last quadriceps muscle.

Over the next few slides, I will share with you immunofluorescence and western blot data from the long-term biopsies that demonstrate microdystrophin expression remains comparable to the levels observed in the day 90 biopsies for all three patients at this high dose. I will then walk you through results highlighting microdystrophin protein function through the co-localization of a dystrophin-associated protein, beta-sarcoglycan, as well as nNOS. Finally, we’ll look at some morphological analyses of the muscle biopsies that demonstrate overall only minimal muscle deterioration since the day 90 time point with mild active dystrophic pathology observed in the long-term biopsies. Collectively, these data are potentially supportive of the positive trends in the clinical biomarker and functional data, which we shared in March.

Slide 7 shows immunofluorescent results from patients four through six at baseline, day 90 and at their last time point. As we previously shared, the 90-day biopsies showed microdystrophin-positive fibers in all three patients that weren’t seen in the baseline samples. The longer-term data that we are reporting today show that proportion of microdystrophin-positive fibers is maintained for up to 24 months. Specifically, patient four has 10% to 30% positive fibers at 24 months.

Patient five is seen to have 85% positive fibers at 18 months, while patient six shows 50% to 60% positive muscle fibers at 12 months post dosing. On Slide 8, we show western blot data collected for patients four and five in the top panels and then patient six in the bottom panel. As shown in the table on the right-hand side, patient four’s microdystrophin level remains below the level of quantitation of 5% of normal dystrophin but is still detectable out to 24 months. Patient five’s microdystrophin level is seen to be 69.8% of normal at 18 months, compared to 17.5% at day 90.

For Patient six, an average level of 20.3% of normal was found at 12 months post dosing, compared to 8% at day 90. Slide 9 summarizes the microdystrophin expression as assessed by western blot and IF up to three 2E14 vector genome per kilogram patients for up to two years post dose. The figure on the upper left shows the western blot I mentioned on the last slide. Interestingly, you can see there is an apparent increase in microdystrophin expression for both patients five and six that both had quantifiable levels at three months.

While Patient four’s microdystrophin expression remains clearly detectable but below the level of quantitation of 5%. On the right-hand side, we’ve shown the immunofluorescent results from our validated automated analysis. The results show a measurement of stable, persistent microdystrophin-positive muscle fibers out to the 24-month timepoint to remain comparable to the levels seen in the day 90 samples. Switching to additional functional analysis of the biopsies, we observed restoration of dystrophin-associated proteins to the muscle cell membrane and show co-localization in microdystrophin-positive muscle fibers.

The column on the left shows microdystrophin in red. Middle column shows beta-sarcoglycan in green, while the right column shows these two images merged with co-localized proteins appearing yellow. As you can see, these two proteins co-localize in a membrane — cell membrane, which demonstrates the capacity of our microdystrophin to recruit dystrophin-associated proteins to the muscle sarcolemma. On Slide 11, we show a similar analysis but looking at nNOS activity and localization to the muscle membrane.

Again, microdystrophin is shown in red on the left, while the right panel shows nNOS activity using an enzymatic stain as indicated by dark purple staining at the muscle cell membrane. These results demonstrate both nNOS activity and its localization to the muscle membrane aligning with the expression of our microdystrophin protein. The continued nNOS activity observed in these long-term biopsies provides additional evidence of the durable functionality of our microdystrophin construct. The next slide shows histological staining of the muscle biopsies from each patient at baseline, 90 days and at 12 to 24 months.

Although these muscle biopsies show variable degrees of dystrophic pathology, it is encouraging to see limited disease progression between baseline out to the long-term time point. And out to two years, only mild active dystrophic changes in muscle pathology were observed, supporting the role of microdystrophin and slowing progression of muscle loss. So overall, these new results from the long-term biopsies are encouraging as they demonstrate persistent and potentially increased microdystrophin expression between 90 days and out to 12 to 24 months. The minimal progression of muscle deterioration since the baseline provides potential support for the recently reported positive trends in the clinical biomarker and functional data from the IGNITE DMD, as summarized on the previously reported efficacy heat map.

As Ilan noted at the start of the call, I’ll be presenting these data at 1:45 p.m. today at the ASGCT Conference. My full presentation will be posted to the Solid Biosciences website once my talk is complete. Now I’ll turn it over to Joel for an update on the preclinical pipeline.

Joel SchneiderChief Operating Officer

Thanks, Carl. The growing body of evidence supporting the potential for SGT-001 to provide benefit to patients with Duchenne is very encouraging, and we look forward to generating more data for this program as we dose additional patients in IGNITE DMD. While advancing SGT-001 remains our priority, we continue to explore new and innovative ways to improve outcomes for patients with Duchenne and to potentially address the needs of patients with other musculoskeletal disorders. Toward that end, we have been actively evaluating a library of novel, rationally designed AAV9-based capsids.

Today, we are announcing our next-generation Duchenne microdystrophin gene transfer program called SGT-003. This program is an internally developed preclinical asset that leverages our broad expertise in gene therapy and muscle biology. Data presented at the ASGCT meeting by Dr. Jennifer Green demonstrate that we have successfully developed a library of novel capsids with increased muscle tropism that corresponds with decreases in liver biodistribution and drive improved efficiency compared with AAV9 in various in vitro and in vivo models.

SGT-003 is a preclinical candidate that combines a novel capsid designed to enhance delivery to muscles with our proprietary nNOS-containing microdystrophin. We are currently conducting lead optimization for SGT-003, and we look forward to sharing additional data with you as this program advances with the potential time line to the clinic in approximately 18 months. This slide summarizes data from a dose-response study exploring AAV9, alongside capsid candidate SLB101. As you can see, at all doses, our novel capsid led to increased biodistribution and, ultimately, microdystrophin expression.

We will aim to provide additional program and pipeline updates as we progress SGT-003, as well as other candidates which leverage our strong internal research capabilities. In addition to our internal research and development efforts, we also have a collaboration with Ultragenyx to explore other next-generation opportunities to develop additional Duchenne gene therapies. The companies have been collaborating to optimize candidate vectors that leverage our nNOS-containing microdystrophin construct with an AAV8-like capsid within the Ultragenyx HeLa producer cell line manufacturing approach. I am pleased to share that this is a very productive collaboration that has leveraged each company’s expertise and resources.

Ultragenyx’s leading efforts around vector construction, optimization and creation of the HeLa producer cell line, and in vitro and in vivo screening of the novel vectors, has been expedited by routing expression analytics through Solid’s research team and leveraging our established assets. We expect to provide an update on this program by the end of 2021. As a company committed to improving outcomes for patients with Duchenne, we believe that having multiple ways to deliver our proprietary microdystrophin constructs enhances our ability to make meaningful differences in these patients’ lives. And we are excited to expand our pipeline with additional opportunities.

I will now turn to our Q1 2021 financials. Earlier today, we filed our Form 10-Q for the quarter ended March 31, 2021, which contains detailed financial results and is available on the Solid website. Although I’m not going to review our detailed results during today’s call, I do want to highlight that during the first quarter of 2021, we closed a public offering, including the full exercise of the over-allotment option, resulting in gross proceeds of approximately $143.8 million before deducting underwriting discounts, commissions and offering expenses. This financing further strengthened our balance sheet, and we ended the quarter with $268.5 million in cash and cash equivalents.

We expect that our cash and cash equivalents will enable us to fund our operating expenses into the fourth quarter of 2022. And I’ll now turn the call back to Ilan for closing remarks.

Ilan GanotCo-Founder, President, and Chief Executive Officer

Thanks, Joel, Carl and Cathryn. Before we take your questions, I want to take a moment to review our 2021 priorities and anticipated milestones. As previously announced, we successfully achieved our first-quarter 2021 milestones and, as Joel just discussed, today, we are expanding our pipeline with SGT-003. We remain on track to present additional 90-day biopsy data in the second half of this year from patients seven and eight, who were recently dosed.

The long-term biopsy results we presented today are encouraging and further increase our confidence in our technologies, in our team and strategies for making gene therapy a reality for patients with Duchenne. I’ll close by reiterating our commitment to the Duchenne community and to working every day to advance therapies that improve their lives and address the challenges of this horrible disease. This commitment, for obvious reasons, is a deeply personal one for me. What makes Solid such a special company is that every one of our employees is as committed as I am, and we see these boys with Duchenne for who they are today, kids who just want to go out and have fun with their friends.

We also know what the future holds for them without an effective therapy. And what inspires all of us at Solid every day is the prospect of giving them a different future. This commitment is what guides us through the challenges and drives us to build on our successes. We thank the Duchenne community, our employees and our investors for their continued support and dedication to our shared mission.

I look forward to updating you as we continue to make progress in our clinical and preclinical programs. We’ll now take your questions.

Questions & Answers:

Operator

[Operator instructions] Your first question comes from the line of Joseph Schwartz with SVB Leerink.

Joseph SchwartzSVB Leerink — Analyst

Everyone, congrats on all the progress. My first question is on the longer-term expression data, which — it’s encouraging to see those delayed kinetics. And it seems like they correspond or correlate most closely to six-minute walk and FVC clinical benefits as opposed to NSAA. So I was just wondering how are you thinking about being able to take advantage of this observation, if you agree with that? And try to establish whether these clinical endpoints or a compositive of these, with or without NSAA, might improve the chances to get a microdystrophin gene therapy, such as SGT-001 or three, across the goal line with the FDA?

Ilan GanotCo-Founder, President, and Chief Executive Officer

Great question, Joe. Good to hear from you. I think Carl will start and Cathryn will finish.

Carl MorrisChief Scientific Officer

Yes. Pretty good that you picked that up so quickly. Yes. There seems to be an apparent correlation, but it’s an outer three.

And as you know, you can sort of make any associations you like. I think we’re encouraged by the data overall. There is variability expected in these biological assays. We took some different muscles from different time points.

So — but we are sort of quite sort of happy about it. It’s not unexpected that we would see an increase in expression over time, but we need to get more data from more patients to really sort of start trying to look at specific relationships. I’ll turn it over to Cathryn to talk about the clinical trial and how we might be thinking based on that.

Cathryn ClaryActing Chief Medical Officer

Sure. Yes. Thanks a lot for the question. We were certainly very encouraged by these long-term results.

And I think you asked a question, which really gets to the heart of what we’re thinking about as a company in terms of designing our registration trial. How do we — which outcome measures do we use? How can we find the most robust way to measure functional benefit in patients in such a heterogeneous disease? And as Carl said, this is a small data set so far, but we’re encouraged by it. We — it’s a bit early to start doing correlation analysis, although we’re certainly thinking about that, and we look forward to getting the data on our two additional patients and others so that we can make those decisions.

Joseph SchwartzSVB Leerink — Analyst

OK, great. I appreciate that. And then as far as dosing additional patients in the future, I was just wondering, what does that path look like for you from here? And could you characterize the SAE, which I heard you say was not unexpected but had some complexity? Was this triggered by lab and/or clinical findings? What can you tell us about the last patient to be treated with SGT-001 and the platform?

Ilan GanotCo-Founder, President, and Chief Executive Officer

Cathryn again — yes, keep going.

Cathryn ClaryActing Chief Medical Officer

Sure. I’ll just keep going, yes. So as I said, the patient had an inflammatory response with elements similar to some of our other patients, which is why it was not unexpected. However, the severity of the event was less severe than patient six.

We still are really looking at all the components of it from a causality perspective, the patient course. I — we’re working both internally and with external experts to fully understand it so that we can move forward in a way that will ensure patient safety. You asked about the path to dose the next patient. We are working, of course, with our DSMB.

They’ve reviewed the case. And we’ll be going back to them with the results of our investigation, and they will need to approve dosing the next patient. We’d already built in a minimum of 45 days between patients eight and nine. So while we can’t speculate on exactly when we’ll dose patient nine, I mean, already, there was going to be a bit of a delay.

And then we’re working with FDA as well.

Joseph SchwartzSVB Leerink — Analyst

Thank you very much.

Operator

And your next question comes from the line of Gena Wang with Barclays.

Gena WangBarclays — Analyst

Thank you for taking my questions. I have three questions. The first one was regarding the patient eight’s inflammatory response. Just wondering, any additional color you can give regarding this patient? You did present at the ASGCT showing the 0 positive AAV9 is related to complement activation.

And I think that Pfizer also shared some additional color on their safety, understanding of the safety. So if you can give a little bit more color on this patient and what exactly that inflammatory response was? And what kind of baseline characteristics from this patient, like zero positive, also the platelet count, any other information you can give? That’s the first question. My second question is regarding the SLB101. Did you test in nonhuman primates? What does the safety look like in nonhuman primates? And also which backbone was for — was derived for SLB101? My last question is more the future direction.

You do have your own internal SGT-003, but you also have a rare collaboration. How do you prioritize? Do you see this as internal competition?

Ilan GanotCo-Founder, President, and Chief Executive Officer

Awesome questions, Gena. I think we’re going to start with Cathryn to talk a little bit about the SAE and then she can hand it over to Carl to finish that off and then talk about SLB101, and I’ll talk about the priorities at the end.

Cathryn ClaryActing Chief Medical Officer

Thank you, Gena, for the question. So as I mentioned, patient eight did have an inflammatory response with elements that were similar to what we had seen in some of the other patients. You asked about complement activation. It’s interesting, complement activation is part of the innate immune response.

And we’ve actually seen laboratory evidence of complement activation in all eight of our treated patients. Patient seven had, as we reported before, had some complement activation in lab that did not — it was lower than what we had seen in some other patients. We’re still really evaluating the elements of patient eight. Every patient appears to be somewhat different.

And we haven’t really identified a common factor with our SAEs, but we’re still examining certain elements of it. And we will — once the results of that investigation are done, we can provide some additional information.

Carl MorrisChief Scientific Officer

This is Carl. So yes, the ASGCT poster is highlighting that in the presence of antibodies, AAV, I mean, it doesn’t matter if it’s AAV9 or AAV8, we showed both can activate the complement system. So we think this is an effect that will be seen through — within different programs. So I think that we’re getting a better handle on it, and other companies are seeing that as well.

Regarding SLB101 and SGT-003, the capsid is derived from rational design that we did internally. So rather than going through a computational analysis like a number of companies, we sort of went from the other way and looked at using our muscle expertise to think about how best to target muscles, specifically. And we identified a number of capsids that look promising. It’s very early on in the plan, and we’re still in sort of lead optimization right now.

So we haven’t sort of finalized the candidate. But we plan to be moving into IND-enabling studies as soon as possible once we’ve identified the specific capsid and specific transgenes as well that we’re using. And I’ll pass it back to Ilan.

Ilan GanotCo-Founder, President, and Chief Executive Officer

Just to say that we’re actually making good progress with Ultragenyx. There’s — I enjoy seeing the two teams collaborate. There’s some real complementary skill sets here when you think about doing DMD but with another manufacturing system. And it happens to be that their gene therapy people are here in Cambridge, too.

So I think there’s a lot of good chemistry and very good people involved from both companies. And I think they’ll probably be leading the communication on the next steps there, but we are committed to really helping in any way we can to advance that program. Gena, you’ve heard me say this before. I don’t think they could ever be enough programs there for DMD gene therapy.

There’s just so many patients and such a massive unmet need. And I would just say that there is a potential to consider other musculuskeletal disorders, as well as additional next-generation gene therapies like SLB1 — 003, and Carl keeps confusing me with those numbers. And I look forward to continue to update on the existing and more programs in the future.

Gena WangBarclays — Analyst

Thank you very much.

Ilan GanotCo-Founder, President, and Chief Executive Officer

Thank you, Gena.

Operator

And your next question comes from the line of Salveen Richter with Goldman Sachs.

Sonya BhatiaGoldman Sachs — Analyst

This is Sonya on Salveen. So now you’re currently evaluating what caused the inflammation in patient eight. Do you happen to have any initial hypotheses on why that might have happened? And then our second question was just when are we going to see any additional functional data from patients seven and eight?

Ilan GanotCo-Founder, President, and Chief Executive Officer

Thank you, Sonya. Cathryn?

Cathryn ClaryActing Chief Medical Officer

So thanks very much for the question. So we really — I don’t want to speculate right now on causality because we are looking at several things. As we reported, our principal investigator did deem the event to be drug-related, and it does have some elements that are similar to our other patients but less severe than we saw in patient six. And patient seven, of course, dosed under our new protocol, had a very safe dosing.

So we’re evaluating a number of different factors. And as I said before, we’ll definitely get back to you when we have a better handle on exactly what happened and what some of the causes were. In terms of the functional data, patient seven is approaching a 90-day visit. It will be a while.

We don’t really look at functional data at 90 days to report it because of the steroids still lingering in the system. So it will be a while before there’ll be additional functional data, and we haven’t actually guided to that.

Operator

[Operator instructions] Your next question comes from the line of Gbola Amusa with Chardan.

Gbola AmusaChardan — Analyst

Hi. Thanks for taking my call. I just wanted — a couple of questions about the long-term data on patients four to six. It’s pretty noteworthy stuff.

And I know it’s an equals three, there’s variability in assays, etc., etc., so we can’t make easy conclusions. But could you update us on any hypotheses you might have on what factors could be at play that create a difference for what you see in patient four versus five and six? And then is there anything you can do going forward to encourage results that are more like those seen in patients five and six? And again, I know it’s early days here.

Ilan GanotCo-Founder, President, and Chief Executive Officer

Gbola, it’s good to have you. This is a Carl question, I know, because I asked that to him just two days ago.

Carl MorrisChief Scientific Officer

Yes. We just got these — we just sort of pulled these data in and started analyzing very recently. So it is very early, but we do have confidence in our assays. And yes, given that we’re seeing good results from all these different sort of orthogonal-type assays, it does look it’s very encouraging the way this dose is sort of a good dose, and we’re generating improved responses over time.

It’s not unexpected, I guess, if you think about they’re just sort of continued production over time and then finding sort of more spaces to fill in on the membrane and stabilize the overall muscle. So it’s very encouraging. We’re going to obviously spend a lot of time thinking about mechanisms to look at this. Patient four started, unfortunately — like with all drug trials, you have responders, nonresponders and unfortunately.

Patient four was not as — had lower levels and below the level of quantitation, but still at very detectable levels. So there may be some threshold effect here that we are just not aware of. But importantly, Patient 4 did see — trended with functional improvements that we presented back in March. So I think, even with less than 5%, there’s a sort of really promising results coming out.

The overall sort of increased — apparent increase is something that we’re definitely going to be looking into.

Ilan GanotCo-Founder, President, and Chief Executive Officer

I would just add, Gbola. I would just add that this notion of long-term durability, we got a little lucky here. Because this was supposed to be one-year biopsies that ended up being delayed because of COVID. And because clinics were closed, patients couldn’t show up, the one-year visit ended up being a year later, and now we have two-year data.

I think when you think about gene therapies, as you obviously do all the time, the notion of duration, the notion of continued or even improved durability is clearly going to feature. And in a disease like Duchenne that is so hard to measure the functional outcomes, I’d like to hope that such biomarkers are going to provide us with a lot of confidence, that this is not something that just disappears after, I don’t know, three or six months.

Gbola AmusaChardan — Analyst

Got it. And just another one really quickly. I think, earlier in the call, someone referred to delayed kinetics. And I know we have seen that elsewhere in the AAV space, but the magnitude of change seems greater here for Solid.

And I know it’s apples to oranges and equals three, etc., etc., but what’s the state of art on biological reasons why there might be delayed kinetics? Or is there a reason, an explanation that we can sort of latch on to, to feel like maybe this is a real phenomenon going forward?

Carl MorrisChief Scientific Officer

I’d love to talk to you for a while about this. If the muscle becomes more stable and sort of it’s healthy — healthier, there may be sort of a more consistent production — of protein production that’s occurring, the more nuclei being infused in as the muscle can grow and build and, therefore, every time we get a positive SGT-001-positive nuclei in there, it could produce more protein. Again, it’s all speculation. There’s — kinetically, we generally see stabilization after about 28 days in our preclinical models with sort of a continued but very slow increases.

So we do see a doubling in patient — an apparent doubling in patient six and threefold in patient five, again, apparent. So we don’t know that there could be other things happening. And actually, importantly so, and asked about age, and could age be a factor. Patient four was older.

We really hope not, but the patient flow was about 11 years of age. So that’s something that we really need to be thinking about as we move forward.

Operator

And your next question comes from the line of Maneka Mirchandaney with Evercore.

Maneka MirchandaneyEvercore ISI — Analyst

Great. Thanks for taking the question. Based on what you’re seeing for patient eight, do you think there are any additional potential changes in the protocol that might be able to further decrease the risk of these inflammatory events like changes in the dose of the immunosuppressive drugs or timing or other factors? And what might that look like?

Ilan GanotCo-Founder, President, and Chief Executive Officer

I think, first, obviously, Cathryn will take it. But I’ll just say, Maneka, that, again, we learned so much from every patient. And the idea here is to identify a long-term solution to a pretty serious problem. And I feel that if things need to be tweaked, that’s a great thing, and hopefully arrive at a very happy place at the end.

And other companies are hopefully doing the same. And I’ll have Cathryn add if she’s got some.

Cathryn ClaryActing Chief Medical Officer

Sure. Thanks, Maneka. I mean it’s such an important question and, obviously, safety is really our first concern with these patients. And I mean the really — probably one of the biggest questions we are grappling with right now is to understand the events so that we can potentially modify the risk mitigation profile in a way that we think will optimize safety.

And we’re still really in the middle of that investigation, including consulting with some external consultants who are experts in this area. So we don’t really have — I can’t really tell you what our hypothesis is at this point because we’re still really exploring different options. But we will certainly share that with you if and when we do decide to make protocol changes. And of course, all those need to be approved by our DSMB and shared with the FDA as well.

I think you also asked the question about the doses. And that is one of the things we’re looking at is dosing, but potentially other, other options.

Maneka MirchandaneyEvercore ISI — Analyst

Thank you.

Operator

And your next question comes from the line of Anupam Rama with JPMorgan.

Anupam RamaJPMorgan Chase & Co. — Analyst

Hi, guys. Thanks so much for taking the question. Just a clarification question here. Has the patient eight’s SAE and sort of clinical profile of this patient being shared with FDA and the DSMB? And what are the time lines for feedback from both of those groups? Yes.

Ilan GanotCo-Founder, President, and Chief Executive Officer

Yes. Anupam, absolutely, shared with the FDA and with the DSMB, and we have ongoing dialogues. We’re not really able to project time lines, but that have been shared and discussed.

Anupam RamaJPMorgan Chase & Co. — Analyst

Got it. Thanks so much for taking our question.

Operator

And at this time, there are no further audio questions. Are there any closing remarks?

Ilan GanotCo-Founder, President, and Chief Executive Officer

I mean, look, thanks, everybody, for dialing in, and have a great weekend. And we look forward to talking again soon. Thank you.

Operator

[Operator signoff]

Duration: 44 minutes

Call participants:

Tim PalmerCorporate Communications Manager

Ilan GanotCo-Founder, President, and Chief Executive Officer

Cathryn ClaryActing Chief Medical Officer

Carl MorrisChief Scientific Officer

Joel SchneiderChief Operating Officer

Joseph SchwartzSVB Leerink — Analyst

Gena WangBarclays — Analyst

Sonya BhatiaGoldman Sachs — Analyst

Gbola AmusaChardan — Analyst

Maneka MirchandaneyEvercore ISI — Analyst

Anupam RamaJPMorgan Chase & Co. — Analyst

More SLDB analysis

All earnings call transcripts

This article represents the opinion of the writer, who may disagree with the “official” recommendation position of a Motley Fool premium advisory service. We’re motley! Questioning an investing thesis — even one of our own — helps us all think critically about investing and make decisions that help us become smarter, happier, and richer.



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