Q1 2021 Solid Biosciences Inc Earnings Call

[music].

Okay.

Ladies and gentlemen, thank you for standing by and welcome to the solid Biosciences update call and at this time all participants are in a listen only mode. After the speaker's presentation. There will be a question and answer session to ask a question. During the session you will need to press star one on your <unk>.

Operator: Ladies and gentlemen, thank you for standing by, and welcome to the Solid Biosciences update call. At this time, all participants are in a listen-only mode.

Operator: After the speaker's presentation, there will be a question-and-answer session. To ask a question during the session, you will need to press Star 1 on your telephone. 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.

Telephone 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 and solid Biosciences, Sir you may begin.

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 <unk> clinical trial.

Tim Palmer: 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 clinical development.

Actual results could differ materially from those discussed and these forward looking statements due to a number of important factors, including uncertainty inherent and the clinical development and regulatory process, the extent and duration of the impact of the COVID-19 pandemic and other risks described and the risk factors section of our most recently filed annual report.

Tim Palmer: regulatory process, the extent and duration of the impact of the COVID-19 pandemic, and other risks described in the risk factor section of our most recently filed annual report on Form 10K and other periodic reports filed with the SEC. We undertake no obligation to update any forward-looking statements after the day of this call.

And on form 10-K, and other periodic reports filed with the SEC. We undertake no obligation to update any forward looking statements. After the day at this call with me on today's call are a long day note co founder and President and Chief Executive Officer, and solid Biosciences, Dr. Joel Schneider, our Chief operating officer, Dr. Catherine <unk>.

Tim Palmer: With me on today's call are a long-a-note, co-founder, President, and Chief Executive Officer at Solid Biosciences, Dr. Joel Schneider, our Chief Operating Officer, Dr. Catherine 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 be along to know, Ilan?

And 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 be along for that long.

Thank you Tim.

Ilan Ganot: 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 Duchennemasker disease. First, we 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.

Good morning, and thank you all for joining us today.

The focus on today's call is to provide and update on our current corporate activities as we continue progress along our 2021 corporate goals and.

Our progress means for patients with Duchenne muscular dystrophy.

And I will provide an update on dosing and ignite DMD.

And two patients were dosed this quarter and ignite DMD using extra two feels little one produced with our improved manufacturing and process and I'm doing an amended clinical protocol.

And as previously reported patient seven has been dosed safely and continues to do well.

Ilan Ganot: As previously reported, patient seven has been dosed safely and continues to do well. Today, we are reporting on an additional patient dose. Patient 8 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. Catherine Clary will review this SEAE and the steps we are taking to evaluate its progress.

Today, we are reporting on and additional patients dosed.

<unk> eight experienced a serious adverse events or SAE, but has since been discharged and as of the patients 30 day follow up visit labs' values have either return to normal for continuing to trade the trend towards mobile and.

The moment, Kathryn Clary will review this and see.

And the steps we are taking to evaluate its course.

Following <unk> review of the patient dosing.

Morris will present on encouraging long term biopsy data collected from the first three patients dosed at the two times 10 to the 14 vector genomes per kilogram dose.

Total will also be presenting this data later today at the American Society of gene and cell therapy annual meeting.

Ilan Ganot: Following Kathleen's review of the patient dose, Dr. Carl Morris will present on encouraging long-term biopsy data collected from the first three patients dosed at the 2 times 10 to the 14 vector genomes per kilogram dose. Carl will also be presenting this data later today at the American Society of Gen and Cell Therapy meeting. These data provide evidence of sustained microdistrophine expression for 12 to 24 months postdosing and are potentially supportive of the recently reported positive trends in clinical biomarker and functional data from the Ignite DMD study.

Data provides evidence of sustained micro dystrophin expression for 12 to 24 months post dosing and a potentially supportive of the recently reported positive trends and clinical biomarker and functional data from the ignite DMD study tour knowledge and can I D. M. D is the first and gene therapy trial.

To show durable micro dystrophin expression.

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 <unk> 001 that would be meaningful for patients with duchenne.

Today.

Joel Schneider solid Chief operating officer will share. We are also providing an update on our preclinical pipeline, which includes the nomination of <unk> zero three.

Program as our next development candidate and an update on our ongoing collaboration with projects.

<unk> zero zero suite will combine and novel capsid, and our proprietary and micro dystrophin construct to enable and next generation gene therapy for duchenne with enhanced delivery to muscle cells.

Ilan Ganot: To our knowledge, Ignite DMD is the first Duchen gene therapy trial to show durable microdustrophine 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 SGP-001 that will be meaningful to patients. Today, as Dr. Joel Schneider, Solitz chief operating officer, will share, we are also providing an update on our preclinical pipeline, which includes the nomination of SGP-003 as our next development candidate and an update on our ongoing collaboration with Ultrigenic. SUDD003 will combine a novel capsid and our proprietary microdistophin construct to enable a next-generation gene therapy for Duchen with enhanced delivery to muscle cells.

Data from our novel Capsid program of also being presented at <unk>.

I am pleased with our progress on all these fronts as we continue to generate additional evidence to support for the long term potential of <unk> zero, one while expanding our pipeline of differentiated gene therapies.

I'll now turn the call over to Catherine who will briefly review, our clinics and update and the steps we are taking as we progressed the STG 001 program.

Thank you and lawn and.

Reported in March we resumed enrollment in and Nike empty and and subsequently go to patients and our amended clinical protocol. As a reminder, we're working closely with our data safety monitoring board or the SMB to carefully review all of the data generated with the Belton waiting period, a 45 day minimum.

Between each dosing.

We also previously reported and patients seven dosed at the two <unk> vector genomes per kilogram was dose 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 are sharing the patient eight experienced and inflammatory response, which was classified as a serious adverse event and considered by the investigator to be late and this event is described in our investigators probably sure and is not considered on expected as other patients 30 day follow up visit.

And laboratory values and either return to normal or continue to trend towards normal.

Share the data related to this effort with the FDA and also the ignite DSM B 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 belk and waiting period, a 45 day between dosing patients eight and nine the complexity of this event requires us to carefully analyze all the data for continuing to dose additional patients and ignite DMD and this will allow us to determine what if any changes we might make for the clinical protocol for <unk>.

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 for two six which we believe support the potential of CTO and provide benefit to patients with Duchenne Carl.

Thank you Catherine.

Today I'm excited to share our analysis of the long term biopsy data for patients four to six which provide compelling evidence that a single dose of <unk>.

001, and the <unk> vector genomes per kilogram dose leads to sustained expression of our proprietary micro dystrophin construct.

Many of the neuronal nitric oxide synthase or <unk> binding domain for up to 24 months post dosing.

Ilan Ganot: Data from our novel capsules program have also been presented at ASG. I'm pleased with our progress on all these fronts as we continue to generate additional evidence to support the long-term potential of SDP001 while expanding our pipeline of differentiated gene therapy. I'll now turn the call over to Catherine, who will briefly review our clinical update and the steps we are taking as we progress the SGT-001 program. Thank you, Alon.

The muscle biopsies were collected and patients four to six and taken at 'twenty for 18, and 12 months, respectively post dosing of <unk> one.

For each patient the baseline and the last time quite biopsies were taken from the right quadriceps, while the day 90 sample was acquired for the last quarter and muscle.

Okay.

Over the next few slides I will share with you immunofluorescence and western blot data from the long term biopsies demonstrate micro dystrophin expression remains comparable to.

To the levels observed and the day 90 biopsies for all three patients at this high dose.

Catherine Clary: 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.

And I will then walk you through results highlighting micro district and protein function through the co localization of the dystrophin associated protein beta stock, a glide path as well as and loss.

And finally, we'll look at some morphological analyses of the muscle biopsies that demonstrate overall only minimal muscle deterioration since the day 90 time points with mild active district with pathology observed and the long term biopsies collector.

Collectively these data are potentially supportive of the positive trends and the clinical biomarker and functional data, which we shared and much.

Slide seven shows immuno fluorescence results from patients for through six.

Catherine Clary: As we do with all patients, we are continuing to monitor this patient and will 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 investigator's brochure and is not considered unexpected.

At baseline day 90.

And at the last time point.

As we previously shared the 90 day biopsies share micro dystrophin positive fibers and all three patients that werent seen and the baseline samples.

The longer term data that we're reporting today. So the proportion micro dystrophin positive fibers is maintained for up to 24 months.

Specifically patient for has 10% to 30% positive 5% to 24 months patients five has seemed to have 85% positive fibers for 18 months, while patients six shows 50% to 60% positive muscle fibers at 12 months post dosing.

Catherine Clary: As of the patient's 30-day follow-up visit, laboratory values that either return to normal or continue to trend towards 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 8 and 9, the complexity of this event requires us to carefully analyze all the data before continuing to dose additional patients and ignite DMD.

Okay.

On slide eight we showed western blot data collected for patients for and five and the top panel.

And then patients six and the bottom panel.

As shown in the table on the right hand side patients for micro dystrophin level remains below level, a quantitative and a 5% and level of distress and but it is still detectable out to 24 months.

Patient seismic district and level is seem to be 69, 8% of normal at 18 months compared to 17, 5% at day 90.

For patients six and average level of 23% of normal was found at 12 months post dosing compared to 8% at day 90.

Catherine Clary: 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 4 through 6, which we believe support the potential of SDT-O-1 to provide benefit to patients with Dishun. Thank you, Catherine.

Slide nine summarizes the micro dystrophin expression as assessed by western blot and <unk>.

Of the three <unk> 14, and vector genomes per kilogram patients for up to two years per stores.

The figure on the upper left shows the Western Blot I mentioned on the last slide interestingly.

Interestingly you can see there is an apparent increase and micro dystrophin expression for both patients five and six that both had quantifiable levels at three months, while patient for micro dystrophin expression remains clearly detectable, but below the level of quantitation and a 5%.

Carl Morris: Today I'm excited to share our analysis of the long-term biopsy data from patients 4 to 6, which provide compelling evidence that a single dose of SCT-001 at the 2E14 vector genomes per kilogram dose leads to sustained expression of our proprietary microdistrofen construct containing the neuronal nitric oxide synthase or ennose binding domain for up to 24 months post-dose. The muscle biopsies were collected from patients Each patient, the baseline, and the lost time point biopsies were taken from the right quadriceps, while the day 90 sample was acquired from the left quadricep muscle.

On the right hand side, we show on the immuno for restaurant results from our validated automated analysis for us.

<unk> share measure measurements of stable persistent microstructure and positive muscle fibers out to the 24 month time point and remained 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 share co localization and micro district and positive muscle fibers.

The column on the left shows micro strengthen and Red Middle column shows beta soccer glide Cam and green, while the right column shows. These two images merged with the co localized proteins appearing yellow.

And as you can see these two proteins co localized to the membrane cell membrane, which demonstrates the capacity of our micro dystrophin to recruit dystrophin associated proteins to the muscle sarcolemma.

On Slide 11, we show a similar analysis looking at and loss activity and.

And localization to the muscle membrane.

Again micro strength and as shown in Red on the left while the right panel shows and loss activity using an enzymatic, Spain as indicated by dark purple sustaining at the muscle cell membrane.

Carl Morris: Over the next few slides, I will share with you immunoplorescence and western blood data from the long-term biopsies that demonstrate microdistropin expression remains comparable to the levels observed in the day 90 biopsies, but all three patients at this high dose. I will then walk you through results highlighting microdistropin protein function through the co-localization of a dystrophin-associative protein, beta-sacoglycan, as well as enon.

These results demonstrate both MLS activity and is localization for the muscle membrane aligning with the expression of our micro dystrophin protein.

The continued and loss activity observed in these long term biopsies provides additional evidence of the jabil functionality of our micro dystrophin construct.

The next slide shows histological sustaining of the muscle biopsies from each patient at baseline 90 days and a 12 to 24 months.

Carl Morris: Finally, we'll look at some morphological analyses of the muscle biopsies that demonstrate overall only minimal muscle deterioration since the day's 90 time point, with mild active dystrophic pathology observed in a long-term biopsy. Collectively, these data are potentially supportive of the positive trends in the clinical biomarker and functional data which we shared months ago. Slide 7 shows immuniflorescent results for patients four through six at baseline, day 90, and at their last time. As we previously shared, the 90-day biocytes showed microdestrope and positive fibers in all three patients that weren't seen in the baseline samples. The longer term data that we are reporting today says the proportion of microdistrepan positive fibers is maintained for up to 24 months.

Although these muscle biopsy share variable degrees of this perfect pathology. It is encouraging to see limited disease progression between baseline and.

Long term time points.

And after two years only mild active district with changes and muscle pathology of or observed supporting the role of micro dystrophin and slowing progression of muscle loss.

Yeah.

So overall these new results from the long term biopsies are encouraging as they demonstrate persistent and potentially increased micro dystrophin expression between 90 days and out to 12 months to 24 months.

The middle and progression of muscle deterioration since the baseline provides potential support for the recently reported positive trends and the clinical biomarker and functional data from the unite DMD.

As summarized on the previously reported efficacy heat map.

Carl Morris: Specifically, patient four has 10 to 30% positive fibers at 24 months. Patients five are seen to have 85% positive fibers at 18 months, while patient six shows 50% to 60% positive muscle fibers at 12 months post doses. On slide 8, we show Western blood data collected for patients 4 and 5 in the top panel, and then patient six in the bottom panel.

As a line notice and started the call and I'll be presenting these data on 145 PM today at the CCT Conference My full presentation will be posted to the solid.

<unk> web site once my talk is complete.

Now I'll turn it over to Joe for an update on the preclinical pipeline.

Thanks Carl.

And so growing body of evidence supporting the potential for <unk> 001 to provide benefit to patients with Duchenne is very encouraging and we look forward to generating more data for this program as we dosed additional patients and ignite DMD.

While advancing Sgt's 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 muscular skeletal disorders.

Carl Morris: As shown in the table on the right hand side, patients' microdistrophin level remains below the level of quantitation of 5% of normal dystrophin, but it's still detectable out to 24 months. For example, patient's microdistriven 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 postdosing compared to 8% at day 19. Slide 9 summarizes the microdistrophicot expression as assessed by Weston Blot and IF of the 3-2E14 vector genome per kilogramme patient, for up to two years postdose.

Towards that and we.

We have been actively evaluating a library of novel rationally designed AAV nine based cash flows.

Today, we are announcing our next generation you shed and micro dystrophin gene transfer program.

Called Sgt's 003.

This program is an internally developed preclinical assets that leverages, our broad expertise in gene therapy and muscle biology.

Data presented at the <unk> meeting by Dr. Jennifer Green demonstrate that we have successfully developed a library of novel capsid with increased muscle tropism.

And that corresponds with decreases and liver by distribution and drive improved efficiency compared with 89 in various in vitro and in vivo models.

S. GT 003 is a preclinical candidate that combines our novel capsid.

Carl Morris: 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 microdestrofen expressions for both patients five and six, who both had quantifiable levels at three months. While patient follows microdestrophicine expression remains clearly detectable, but below the level of quantitation of 5%. On the right-hand side, we're showing the immunoflorescent results from our validated, automated, The results show a measurement of stable, persistent, micro-stroke, and positive muscle fibers out to the 20th four months time point. They remain comparable to the level seen in the 1990s.

Designed to enhance delivery on buses with our proprietary and non containing micro dystrophin.

We are currently conducting lead optimization for Sgt's Zero-zero, III and we look forward to sharing additional data with you as this program advances with the potential timeline to the clinic and approximately 18 months.

This slide summarizes data from a dose response study exploring AAV nine alongside casted candidate <unk> 101.

As you can see and all doses our novel Capsid led to increased by distribution and ultimately micro dystrophin expression.

We will aim to provide additional program and pipeline updates as we progress Sgt's zero-zero III as.

As well as other candidates, which leverage our strong internal research capabilities.

Carl Morris: Switching to additional functional analyses of the biopsies, we observed restoration of dystrophin-associated proteins to the muscle cell membrane and showed co-localization in microdistropin positive muscle fibers. The column on the left shows microostrofen in red, the middle column shows beta-sacococcal glycan in green, while the right column shows these two images merged with the co-localized proteins appearing yellow. As you can see, these two proteins co-localized to the cell membrane, which demonstrates the capacity of our microdistrofen to recruit dystrophin-associated proteins to the Muscle Lema.

In addition to our internal research and development efforts. We also have a collaboration with ultra <unk> to explore other next generation opportunities to develop additional duchenne gene therapies.

The companies have been collaborating to optimized candidate vectors that leverage our endoscopy, <unk> and micro dystrophin construct with and AAV eight like half suite within the ultra <unk> Hela producer cell line manufacturing approach.

I am pleased to share and that this is a very productive collaboration it is leveraged each company's expertise and resources.

<unk> is leading efforts are on vector construction optimization and creation of the Hela producer cell line and.

And in vitro and in vivo screening of the novel vectors has been expedited by routing expression and analytics through solid research team and leveraging our established assets.

Carl Morris: On slide 11, we show a similar analysis but looking at Ennos activity and localization to the muscle membrane. Again, Microstropen is shown in red on the left, while the right panel shows Ennoss activity using an enzymatic stain as indicated by dark purple staining at the muscle cell membrane.

We expect to provide and 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 and micro dystrophin construct and.

And our ability to make meaningful differences and these patients' lives and we are excited to expand our pipeline with additional opportunities.

I will now turn to our Q1 2021 and financials.

Carl Morris: These results demonstrate both endless activity and its localization to the muscle membrane, aligning with the expression of our microdistrofen protein. The continued end-loss activity observed in these long-term biopsies provides additional evidence of the durable functionality of our microdistrictment 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 micro dystrophin and slowing the progression of muscle loss.

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 im 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 the public offering including the full exercise of the overallotment 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 and cash and cash equivalents, we expect that our cash and cash equivalents will enable us to fund our operating expenses and to the fourth quarter of 2022 and I'll now turn the call for actual on for closing remarks.

Thanks, Joel call and Kathryn.

Before we take your questions I wanted to take a moment to review, our 2021 priorities and anticipated milestones.

As previously announced we successfully achieved our first quarter of 2021 milestones and as Joe just discussed.

Carl Morris: So overall, these new results from the long-term biopsies are encouraging in that they demonstrate persistent and potentially increased microdestricting 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 in the previously reported efficacy heat map. As Alain 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 Solid Bioscience's website once my talk is complete. Now, I'll turn it over to Joel for an update on the preclinical pipeline. Thanks, Carl.

Today, we are expanding our pipeline with SG 200.

We remain on track to present additional 90 day biopsy data in the second half of this year from patients seven and eight who are recent to dose.

The long term biopsy results, we presented to date are encouraging and further increase our confidence and our technologies and our team.

<unk> and strategies for making gene therapy, a reality for patients with Duchenne.

Okay.

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.

It's horrible disease.

And as commitments for obvious reasons.

As a deeply personal one for me.

What makes solid such a special company every one of our employees.

Coming to those items and we see these boys with Duchenne for who they are today Q2, just want to go out and have fun with your friends.

Joel Schneider: The growing body of evidence supporting the potential for SGT 001 to provide benefit to patients with Juchen 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 Ushend 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 889-based caps. Today, we are announcing our next generation Duchenne Microdistrophin gene transfer program called SGT-003.

We also know for the future holds for them without them effective therapy.

And what inspires all of us at solid every day.

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 seem to have the same community our employees and other investors for their continued support and dedication to a certain mission.

And I look forward to updating you as we continue to make progress on our clinical and preclinical programs.

We'll now take your questions.

Okay.

And as a reminder to ask your question you will need to press star one on your telephone keypad to withdraw your question press the pound key please standby, while we compile the Q&A roster.

Your first question comes from the line of Joseph Schwartz with Leerink.

Leerink.

Everyone. Congrats on all the progress.

My first question is.

Joel Schneider: 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 capses with increased muscle tropis, that corresponds with decreases in liver biodistribution and drives improved efficiency compared with AAD9 in various in vitro and in vivo models. SGT-003 is a preclinical candidate that combines a novel capsid designed to enhance delivery to muscle, with our proprietary and does not contain microdistrict. We are currently conducting lead optimization for SGT 003, and we look forward to sharing additional data with you as this program advances, with a potential timeline to the clinic in approximately 18 months. This slide summarizes data from a dose response study exploring AAB9 alongside CASSID candidate

On the longer term expression data, which.

It's encouraging to see those delayed kinetics and.

And.

It.

Like they correspond or correlate most closely to six minute walk and FCC clinical benefits as opposed to NSA and so.

And I'm just wondering.

How are you thinking about.

Being able to take advantage of this observation if you agree with that and.

And.

Try to.

Establish weather.

These clinical and clients are a composite of these with or without and I say, hey might improve the chances to get micro dystrophin gene therapy, such as SPT 001 or three.

Across the goal line with with the FDA.

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

Yes.

Yes.

Good day, you pick that up so quickly, yes, there seems to be and apparent.

Correlation, but it's another three and as you know you can sort of make any any associations you like I think we're encouraged by the data overall.

There is variability.

<unk> and these biological assays, we took a different muscles from different.

Joel Schneider: As you can see, at all doses, our novel caps led to increased bi-distribution and ultimately microdistrophine 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 Ultrigenics to explore other next-generation opportunities to develop additional Duchengen therapy. The companies have been collaborating to optimize candidate vectors that leverage our ennods containing microdiscuitment construct with an AAB8 like acid within the Ultrogenics, GILA producer cell line manufacturing.

Bob.

And at different time points, so, but we are sort of that.

And sort of.

Happy about it it's not unexpected.

But we would see an increase and expression over time.

But we need to get more data for more patients to really sort of stopped trying to look at specific relationships I'll turn it over to Catherine to talk about the clinical trial, and how and what you're thinking based on that.

Sure Yeah. 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 can we use how can we find them on from fast way to measure functional benefit.

And patients and such a.

A heterogeneous disease and and.

And this is a small data set so far.

But we're encouraged by it.

And it's.

And early to start getting correlation analysis on how we're certainly thinking about that and we look forward to getting the data on our two additional patients and and.

And other so that we can make those decisions.

Okay great.

Great.

And then as far as dosing additional patients and the future.

And I was just wondering what does that path look like for you from here and could you characterize the SAE.

And I heard you say it was not unexpected but had some complexity.

Joel Schneider: I am pleased to share that this is a very productive collaboration that has leveraged each company's expertise and research; Ultrigenics is 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 2015.

This triggered by.

Lab <unk> clinical findings.

And what can you tell us about.

The last patient to be treated with SG teasers for one.

And we'll touch on we can keep.

Keep going.

Yeah, So as I said, the patient and had an inflammatory response and element similar to some of our other patients which is why it was not unexpected however.

Are they already on for the event was less severe than patients six we still are really looking at all the components of it from a causality perspective, the patient core.

We're working both internally and with external experts and fully understand that so that we can move forward and a way that well.

And ensure patient safety.

You asked about the path to dose for the next patient we are working of course with our DSM V and they reviewed the case and we will be going back to them with the results and our investigation and they will need to approve.

It does seem the next patient we'd already built in a minimum of 45 days between patients eight and nine.

While we can't speculate on exactly when we'll dose patient nine and already there was going to be a bit of a delay and then we're working with FDA as well.

Thank you very much.

Okay.

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

Thank you for taking my questions I have three questions. The first one on most of regarding the patient fee income.

Joel Schneider: As a company committed to improving outcomes for patients with Duchenne, we believe that having multiple ways to deliver our proprietary microdistricting construct 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 financial results. Earlier today, we filed our Form 10 Q for the quarter ended March 31st, 2021, which contains detailed financial results. It is available on the solid website.

Inflammatory response.

Just wondering.

And additional color you can give regarding this patient you did presented at TCT.

TCT.

And the seropositive Eni is related to complement activation and I think a pfizer and lost share.

Here's some additional color on bse understanding of the safety.

And I'll give a little more color on this patient and.

Exactly that.

Inflammatory response was and what kind of baseline characteristics from the for patient with zero possible.

And also the.

Clearly call any other information and Kim GAAP.

Joel Schneider: 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 the public offering, including the full exercise of the over-allotment, 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 equivalence will enable us to fund our operating expenses into the fourth quarter of 2022. And I'll now turn the call back to La Land for closing remarks.

The first question and my second question is regarding debt S. L a and b level one day.

Did you test in non human primates, what is the safety look like in non human primates, and also which backbone with for with derive for F. L. B one for one.

And my last question is and what the future direction you do have your own internal <unk> three but you also have a.

Collaboration and how do you prioritize how do you see this as an internal competition.

Yeah.

Awesome questions Geno and I think we're going to start with cash rent to talk a little bit about this and.

And then she can open the call to finish that off and talk about that there'll be one on one and I'll talk about the priorities of yet.

Ilan Ganot: Thanks, Joel, Col, and Catherine. Before we take your question, I want to take a moment to review our 2021 priority and anticipated milestone. As previously announced, we successfully achieved our first quarter 2021 milestones, and as Joe 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 7 and 8 who were recently dosed.

Thank you gena for the question so.

As I mentioned patient did have an inflammatory response with elements that were similar to what we've seen and some of the other patients you asked about complement activation to interest income from an activation as part of the innate immune response, and we've actually seen laboratory evidence of complement activation and all eight of our treated per.

<unk>.

Patient seven had as we've reported before had some complement activation and lab, but did not it was lower than what we've seen and some other patient we're still really evaluating the element of patient eight.

And every patient and appears to be somewhat different and we havent really identified a common factor.

And with RSA East, but we are still exactly are still examining certain elements of it and we will once we have the results of that investigation or debt and we can provide some additional information.

And hi, this is Carl so yeah and.

And the Ace GTT post there is.

And as highlighting that.

And the presence of antibodies to AAV and it doesn't matter if it's AAV nine or eight we share both can activate the complement system. So we think this is a.

And effect that will be seen.

Through with within different programs. So I think we're getting a better handle on it.

And other other companies are seeing that as well.

Regarding <unk> 101, and <unk> three.

The cash that is derived from and rational design and we did internally so rather than going through a computational analysis like a number of companies.

Ilan Ganot: 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 ushant. I 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 disaster. This commitment, for obvious reasons, is a deeply personal one for me. What makes Solis such a special company is that every one of our employees is as committed as I am, and we see these boys with Duchen for who they are today. Kids just want to go out and have fun with their friends.

And we sort of went from the other way and looked at using on muscle expertise to think about how best to target muscles specifically.

And we identified.

A number of cash is that look promising.

It's very early on and the.

The plan and we're still inside 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 trends changed as well that we're using.

I'll pass it back to alone.

Just to say debt.

We're actually making good progress with the trajectory.

Operator: We also know what the future holds for them without 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 Shent 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. Now, we'll take your question. And as a reminder to myself,

And I enjoy seeing the two teams collaborated does some real.

On a complementary skill sets here when you think about doing BMG.

But with another.

<unk> system.

And it happens to be their gene therapy people are getting Cambridge, too. So I think there's a lot of good chemistry, and very good people and wholesome both companies and and.

I think they'll probably be leading the communication on the next steps there, but we are committed.

Really helping and every way we can advance that program. Jim you have heard me say this before I don't think that could ever be nuts.

Total gross debt for.

Operator: To ask your question, you will need to press star 1 on your telephone.

And for.

DMD gene therapy, there's just so many patients and such a massive unmet needs and.

Operator: Number one on your telephone keypad. To withdraw your question, press the pound key. Please stand by while we compile the Q&A roster. Your first question comes from the line of Joseph Swartz with SVB Lering.

I would just say that there is a potential to consider other muscular skeletal disorders as well as additional next generation gene therapies like <unk>.

Zero free cash.

Joseph Swartz: Thank you, everyone. Congratulations 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 the six-minute walk in FEC 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? try to establish whether these clinical endpoints or a composite of these with or without an SAA might improve the chances of getting microdistrophin gene therapy, such as SGT-001 or 3, across the goal line with the FDA. Great question, Joe. Good to hear from you. I think Carl will start and Catherine will finish.

And talk it's confusing me with those numbers and and <unk>.

Look forward to continuing to update on existing and <unk>.

More programs and the future.

Thank you very much.

Thank you Gina.

And.

And your next question comes from the line of <unk> Richter with Goldman Sachs.

Hi, Thanks, so much for taking a question just on your on for Paul.

So I know you're currently evaluating.

Cosby information and patient and do you happen to have any initial hypotheses on line that line is open.

And on our second question was just went out and I'm going to see and additional functional data from.

And part of that team.

Thanks, Mike.

Hey, Thank you Sonya Kathryn.

So.

Thanks very much for the question. So we really don't want to speculate right now on causality, because we are looking at several things as we reported on principal investigators did deem the event to be drug related and it does have some elements that are similar to our other patients.

Yes.

Less severe than we saw on patients and.

And Ah patients have and of course, it does under a new protocol has a very safe dosing. So we're evaluating a number of different factors and as I said before and we'll definitely get back to you and we have a better handle on exactly what happened and what some of the concert tomorrow and.

In terms of a functional data.

Patients seven.

Is approaching a 90 day visit it'll be a while we don't really look at functional data at 90 days are reported because of that alright, filling green and the system. So it'll be a while before and there'll be additional functional data and we haven't actually guided to that.

And again, if you would like to ask a question simply press Star then the number one on your telephone keypad.

Carl Morris: Yeah. Pretty good that you picked that up so quickly, yes. There seems to be an apparent correlation, but it's an out of 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 different muscles from different animals at different time points. So, but we are sort of quite happy about it.

Next question comes from the line of BOMA and Melissa with Chardonnay.

Hi, Thanks for taking my call.

Just wanted to a couple of questions about the long term data on.

On patients four to six you know its pretty noteworthy stuff and I know on equals three theres variability and announced they use et cetera, et cetera, and so we cannot speakeasy conclusions, but could you update us on any hypotheses and might have on what factors could be a plenty that create a difference for what you see and patient for versus five and six.

Carl Morris: It's not unexpected or that we would see an increase in expression over time, but we need to get more data from more patients to really start trying to, you know, look at specific relationships. I'll turn it over to Catherine to talk about the clinical trial and how we might be thinking, you know, based on that.

And then.

Is there anything you can do going forward to encourage results that are more like those seen in patients five and things and again I know it's early days.

Payable.

To help you on this as a call question I know because I asked it up to him.

Catherine Clary: Sure, yeah, thanks a lot for the question. We were certainly very encouraged by these long-term results.

Two days ago.

Yes.

We just got these yeah, we just sort of pulled these data and started analyzing very recently so it is very early but you do have.

Catherine Clary: 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 with such a heterogeneous disease?

Competence and our assays and.

And given that we're seeing.

Good results for from all these different set of orthogonal type assays.

It does look very encouraging the way at this dose and sort of a good dose and where we're at.

And what's generating.

Proved responses over time, it's not unexpected I guess, if you think about.

Catherine Clary: And as Carl said, this is a small data set so far, but we're encouraged by it. It's a bit early to start doing correlation analyses, although we're very excited about it. 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.

Just sort of continued production over time and then finding.

For a more spaces to fill in on the on the membrane and stabilize the overall muscle. So it's very encouraging we're going on.

Obviously spent a lot of time thinking about.

Mechanisms.

To look at this.

A patient for and I started.

Unfortunately, with all drug trials, you have respond as non responders and unfortunately.

Catherine Clary: And then as far as dosing additional patients in the future, I was just wondering, you know, what that path looks 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 traded for SGT-Zer-01? And on the platform, you can, yeah, keep going. Sure, I'll just keep going, yeah.

Patients for was not us.

Had lower levels and below the level of quantitation still very <unk>.

Detectable levels. So there may be some threshold effect here that we are just not aware of but importantly patient flow did see trend.

Trended with functional improvements that we presented back in March so I think even even with.

Less than 5%, there's a set of really promising results coming out.

Catherine Clary: 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 in patient six. We're still really looking at all the components of it from a causality perspective, the patient course. We're working both internally and with external experts to fully understand. 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.

The overall set of increased apparent increase.

And that we're definitely going to be dosing interest.

I would just add bolt on.

This notion of long term durability.

Got it and lucky here because.

It was supposed to be one year biopsy, but ended up being delayed because of COVID-19.

And because you know Phoenix were closed patient couldn't show up the one year visit and that being a year later and now we have two year data.

I think when you think about gene therapy as you hoped for to help us do all the time.

And the notion of duration the notion of continued or even improved.

<unk> is clearly going to feature and and in diseases like Duchenne that is so hard to measure.

Catherine Clary: 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. You know, we'd already built in a minimum of 45 days between patients 8 and 9. So while we can't speculate on exactly when we'll dose patient 9, It was already going to be a bit of a delay. And then we're working with FDA as well.

The functional outcomes and I'd like to hold for that system.

Other markers of Ghana.

Provide us with a lot of confidence that this is not something that's just disappears after on a free of six months.

Got it and just another one and really quickly I think earlier and the qualifying for the delayed kinetics and.

And I know, we have seen that elsewhere in the space.

But the magnitude of change seems greater here for solid and I know, it's apples and oranges, and and equals three et cetera et cetera, but.

Operator: And your next question comes from the line of Gina Wang.

Huidong Wang: of Gina Wang with Barclays. Thank you for taking my questions. I have three questions. The first one also concerns the patient's aid inflammatory response. Just wondering, you know, any additional color you can give regarding this patient. You did present at the ASGCT, you know, showing that seropositive AV-9 is related to complement activation. And I think Pfizer also shares 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 characteristic this patient had, like zero positive, also, you know, the plelic count, you know, any other information you can give. That's the first question. My second question is regarding SLB 101. Did you test in non-human primates? What was the safety like in non-human primates?

What's the state of art on biological reasons, why there might be delayed.

Kinetics or is there a reason and explanation that we can sort and flat time two to feel like maybe this isn't real phenomenon going forward.

But love to talk to you for a while about this.

<unk>.

And if the muscle becomes more stable and healthy healthier than maybe sort of a more consistent production and protein production thats occurring.

And more mine nuclei being used and as the muscle can grow and build on that for every time, we get a positive.

<unk> on one positive nuclei and there it could produce more protein.

And again, it's all speculation there is cash.

<unk>.

And we generally see stabilization after about 28 days and our preclinical models with sort of a continued debt very slow increases.

So we.

We do see a.

Huidong Wang: and also which backbone was derived for SLB 101. My last question is more about the future direction. You know, you have your own internal SGT-003, but you also have a rare collaboration. You know, how do you prioritize, you know? Do you see this as internal competition? Awesome questions, Gina.

Doubling and patients and apparent doubling and patients six and a three fold and patient five again apparent.

So.

We don't know that there could be other other things happening.

Yes.

And actually Ed and putting us on.

Asked about age and credit HP effector patient.

Patient flow was all we really have not.

Patient flow was about 11 years of age so thats something that we really need to be thinking about as we can.

Ilan Ganot: I think we're going to start with Catherine to talk a little bit about the SEA, and then she can end up on the call to finish that off, and then we can talk about S-O-B-101, and I'll talk about the priorities of Thank you, Gina, 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.

Moving forward.

Okay and your next question comes from the line of Monika Merch and Dayni with Evercore.

Yeah.

Great. Thanks for taking the question on.

Based on what Youre seeing for peace and eight do you think there are any additional potential changes and the protocol that you might be able to further decrease the risk and of these inflammatory and then changes in and the dose of the immunosuppressive drugs or timing or other factors and and.

Ilan Ganot: You know, 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 7, as we reported before, had some complement activation in the 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, be able to provide some additional information. And Hi, this is Carl.

What might that look like.

Okay.

Catherine we'll take it but I'll, just say and when it got.

Again, we learned so much for every patient and you know the idea here is to identify and long term.

Allusion to it pretty serious problem for them and.

And I assume debt issue.

Things seem to be tweaks, that's a great thing and hopefully alive at debt.

It's a very big base with yen and <unk>.

Other companies are hopefully doing the same and.

And so Catherine she's got some.

Sure. Thanks, Monika I mean, it's such an important question and obviously safety is really our first concern with these patients and.

They're really probably one of the biggest questions. We are grappling with right now is to understand the event. So that we can potentially modify the risk mitigation profile and a way that we think for optimize safety and we're still really and the middle of that investigation and including consulting with some external.

And sometimes who are experts in this area. So we don't really have I can't really tell you put on when our hypothesis is at this point, because we're still really really Brian different options.

We will certainly share that with you.

And when we do decide to make protocol changes and of course also needs to be a pretty cloudy F&B and shared with FDA as well I think you also asked a question about the doses and that is one of the things we're looking at.

And it does seem potentially.

And potentially other other.

Other options.

Thank you.

Catherine Clary: So, yeah, and the ASGCP poster is highlighting that in the presence of antibodies, AV, and it doesn't matter if it's AV9 or AV8, we showed both, can activate the complement system. So we think this is an effect that will be seen, you know, within different programs. So, you know, I think we're getting a better handle on it, and other companies are seeing that as well. Regarding SLB 101 and SCT-ZER-3, the capsid is derived from a rational design that we did internally.

Okay and your next question comes from the line of and <unk> Rama with Jpmorgan.

Hi, guys. Thanks, so much for taking my question just a clarification question here.

<unk> has the patient eight SAE and.

And sort of clinical profile of this patient being shared with FDA and the DSM B and what are the timeline for feedback on both of those groups.

Carl Morris: So rather than going through a computational analysis, like a number of companies, we sort of went 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 inside of lead optimization right now. So we haven't sort of finalized the candidate, but we plan to be moving into I&D enabling studies as soon as possible once we've identified a specific capset and specific trans genes as well that we're using. I'll pass it on to Alan.

Yes, yes, absolutely.

Absolutely share due to FDA and would it be SMB and.

We have ongoing dialogues.

We are not really able to project timelines, but have been shared and discussed.

Got it thanks, so much for taking our question.

Okay.

And at this time there are no further audio questions.

Are there any closing remarks.

I mean look thanks, everybody for dialing in.

And.

We can and we look forward to talking again soon.

Thank you.

Thank you. This concludes today's conference call. Thank you for your participation you may now disconnect.

Ilan Ganot: Just to say that, you know, we're actually making good progress with ultrigenics. I enjoy seeing the two teams collaborate. There are some real complementary skill sets here when you think about doing DMD, you know, 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, you know, I think they'll probably agree. the communication on the next steps there, but we are committed to really helping in any way we can advance that program. Gin, you've heard me say this before.

[music].

And.

[music].

Ilan Ganot: I don't think there could ever be enough programs there for GMD gene therapy. There are so many patients in such a massive, unmet need. And I would just say that there is the potential to consider other musculoskeletal disorders, as well as additional next-generation gene therapies like SLB-103. And Carl keeps confusing me with those numbers. And I look forward, you know, to continuing to update on the existing existing programs and more programs in the future.

Operator: And your next question comes from the line of Salvin Richter with Goldman Sachs. Hi, thanks so much for taking our question. This is Sonia on behalf of Selvine. So I know you're currently evaluating what

Operator: cause the inflammation in patient aid. 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? Thank you. Hey, thank you, Sonia. Catherine?

Catherine Clary: Um, so, thanks very much for the question. So we really don't want to speculate right now on causality because we are looking at several things. But, as we reported, our principal investigator did deem the event to be drug-related.

[music].

Catherine Clary: And it does have some elements that are similar to our other patients that, you know, 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, and 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'll be a while.

Catherine Clary: You know, we don't really look at functional data at 90 days or so because of the steroids still lingering in the system. So it'll be a while before there'll be additional functional data, and we haven't actually been guided to that. And again, if you would like to ask a question, simply press star, then the number one on your telephone keypad.

Operator: Your next question comes from the line of Bola Amosa with Charday. Hi, thanks for taking my call. Just wanted a couple of questions about the long-term data on patients four to six. You know, it's pretty noteworthy stuff. And I know it's n equals three. There's variability in assays, et cetera, et cetera, which makes easy conclusions difficult, but could you update us on any hypotheses you might have on what factors could be playing that create a difference for what you see in patient four versus five, And then is there anything you can do going forward to encourage results that are more like those seen in patients five? Again, I know it's her. Hey, Bull, it's very good to have you.

Bola Amosa: This is a call question. I know because I asked that to him just two days ago. Yeah, we just got these, you know; we just sort of pulled these data in and started analyzing them very recently. So it is very early. But we do have, you know, competence in our assays. And, you know, given that we're seeing good results from all these different sort of orthogonal type assays, it does look very encouraging that this dose is sort of a good dose and where we're generating improved responses over time.

Bola Amosa: It's not unexpected, I guess, if you think about, you know, they're just sort of continuing production over time and then finding, you know, 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.

Carl Morris: Thinking about, you know, mechanisms to look at this. Patient four, you know, started, unfortunately, you know, like with all drug trials, you have responders and non-responders, and unfortunately, patient four was not as, had lower levels and below the level of connotation, but still very detectable levels.

Carl Morris: So there may be some threshold effect here that we are just not aware of. But importantly, patient four did see trends that matched the functional improvements that we presented back in March. So I think even with a, you know, 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 listening to. I would just add, well, I'll just add that, you know, this notion of long-term durability, we got a little lucky here because this was supposed to all be one-year biopsies that ended up being delayed And because, you know, clinics were closed, patients couldn't show up.

Ilan Ganot: 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, you know, the notion of duration, the notion of continued or even improved durability is clearly going to be important. And in a disease like Duchen, which is, you know, so hard to measure, you know, the functional outcomes, I'd like to hope that such biomarkers are going to, you know, provide us with a lot of confidence that this is not something that just disappears after, I don't know, three or six months. I got it.

Bola Amosa: 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 AV space. But the magnitude of change seems greater here for solids, and I know it's apple to oranges and n equals three, et cetera, et cetera.

[music].

Bola Amosa: But... What's the state of the art on biological reasons why there might be a delay? Is there a reason and explanation that we can sort of watch on to feel like maybe this isn't real? I want to talk to you for a while about this.

Carl Morris: But if the muscle becomes more stable and so it's healthy, healthier, there may be sort of a more consistent production and protein production that's occurring. You know, more my nuclei being fused in as the muscle can grow and build. And therefore, every time we get a positive, you know, SGP 01 positive nuclei in there, it could produce more protein.

Carl Morris: And I, you know, again, it's all speculation. Kinematically, we generally see stabilization after about 28 days in our preclinical models with sort of a continued, but very slow increase. So, you know, we do see a doubling in patient, an apparent doubling of patient six and, you know, three-fold in patient five, again, only apparent. We don't know that there could be other things happening. You know, and actually, importantly, someone asked about age, and could age be a factor? You know, the patient fall was older. We really hope not, but the patient who fell 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 Monica Merchantaney with Evacar. 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?

Operator: I mean, first, obviously.

Ilan Ganot: I mean, first, obviously, Catherine will take it, but I'll just say, Monica. Again, we learn so much from every patient, and you know the idea here is to identify a long-term solution to a pretty serious problem, and I feel that, if you know, if things need to be tweaked, that's a great thing, and hopefully, we arrive at a very happy place at the end. And other companies are hopefully doing the same, and I'll have Catherine add it if she's got it. Sure. Thanks, Monica.

Catherine Clary: I mean, it's such an important question, and obviously, safety is really our first concern with these patients. And, I mean, 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.

[music].

Catherine Clary: 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, those will need to be approved by our DSMB and shared with FDA as well. I think you also asked about doses, and that is one of the things we're looking at, dosing, but potentially, you know, other options.

Operator: And your next question comes from the line of Anupamarama.

Operator: Aniapamara with J.P. Morgan. Hi guys. Thanks so much for taking the question. Just a clarification question here.

Ilan Ganot: You know, has patient 8 SE and the sort of clinical profile of this patient been shared with FDA and the DSMB? And what is the timeline for feedback from both of those groups? Yeah, yeah, hi Anna Pan, absolutely. Shared with the FDA and with the DSMB, and we have ongoing dialogues. You know, we're not, we are not really able to project timelines, but they have been shared and, Got it. Thanks so much for taking our question. Thank you.

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

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

Operator: And thank you. This concludes today's conference call. Thank you for your participation. You may now disconnect.

Operator: For today's conference call, thank you for your participation. You may now disconnect.

Operator: The President, I think of the world. Thank you. Thank you. The President,

Operator: Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. The President, Thank you.

Operator: Thank you. Thank you. Thank you. Thank you. Thank you. The President. Thank you.

Operator: Thank you. Thank you. Thank you. Thank you. Thank you. Thank you.