Q1 2022 Solid Biosciences Inc Earnings Call
Pardon me. This is the operator today's conference is scheduled to begin shortly please continue to standby and thank you for your patience.
[music].
Operator: Part of me: this is the operator. Today's conference is scheduled to begin shortly. Please continue to stand by. And thank you for your... Alexander Cumbo, Bo Cumbo, Huidong Wang, Anupam [inaudible] Music Ladies and gentlemen, thank you for standing by, and welcome to the Solid Biosciences Strategic Business Update and Financial Results Conference call. At this time, all participants are in a listen-only mode. Please be advised that today's conference may be recorded. After the presentation, there will be a question and answer session. To ask a question, please press star 1 on your telephone to get in the queue.
Ladies and gentlemen, thank you for standing by and welcome to the solid Biosciences strategic business update and financial results Conference call. At this time all participants are in a listen only mode. Please be advised that today's conference may be recorded after the presentation. There will be a question and answer session.
To ask a question. Please press star one on your telephone to get in the queue I would now like to hand, the conference over to Kathleen Lally, Vice President of Communications and Investor Relations at solid Biosciences, Ms. Lally you may begin.
Kaitlin Laue: I would now like to hand the conference over to Kaitlin Laue, Vice President of Communications and Investor Relations at Solid Biosciences. Now, when you're made... Good morning. Thank you, operator. Before we get started, I would like to remind everyone that during today's conference call, we may make forward-looking statements, including statements about the company's financial results, financial guidance, future business strategies and operations, and Product Development and Regulatory Progress, including statements about the company's IGNITE-DMV clinical trial.
Kaitlin Laue: 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 FDA. We undertake no obligation to update any forward-looking statements after the date of this call.
Good morning. Thank you operator before we get started I would like to remind everyone that during today's conference call. We may make forward looking statements including statements.
The company's financial results financial guidance future business strategies and operations.
In product development, and regulatory progress, including statements about the company's 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.
Extend 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.
Kaitlin Laue: With me on today's call are Alain Gannot, Co-Founder, President, and Chief Executive Officer of Solid Biosciences, Dr. Joel Schneider, our Chief Operating Officer, Dr. Carl Morris, our Chief Scientific Officer, and Dr. Roxana Doniza-Dradic, Senior Vice President and Head of Clinical Development. During today's call, we will share details of the strategic update the company announced this morning. We'll begin with opening remarks from Ilan, followed by Joel, who will share details of an intended change we'll be making to the manufacturing process for SGT 001. Carl will then review new preclinical data related to FGT003. Finally, Alain will provide an overview of the organizational strategy that aligns behind these two programs before opening the call to questions.
With me on today's call are London.
Co founder President and Chief Executive Officer, followed by our scientists.
Dr. Joel Schneider, our Chief operating officer, Dr. Carl Morris, our Chief Scientific Officer, and Dr. <unk>, <unk> Senior Vice President and head of clinical development.
During today's call, we will share details of the strategic update the company announced this morning will begin with opening remarks from Milan, all by Joe who will share details of an intended change we'll be making to the manufacturing approach for <unk>.
Carl will then review new preclinical data related to <unk>. Your year. Three finally, <unk> will provide an overview of the organizational strategy that aligns behind these two programs.
On the call to questions.
Before I turn the call over to Alon I want to acknowledge that our first quarter financial results have been reported and can also be found on our Form 10-Q , which was filed with the ICC. This morning for opening remarks, I'd like to turn the call over to <unk> CEO along down the line.
Kaitlin Laue: Before I turn the call over to Alon, I want to acknowledge that our first quarter financial results have been reported and can also be found on our Form 10-Q, which was filed at SBC this morning. For opening remarks, I'd like to turn the call over to CEL's CEO, Ilan Ganot.
Ilan Ganot: Thank you, Caitlin, and thanks to all of you for joining us this morning. Solid's ongoing focus on Duchenne has produced two potential therapies for this devastating disease. And today, we will outline our strategy to continue development of our lead program, SGP-001, and to explore the potential benefits of SGP-003's novel capsid to deliver our differentiated microdistribution. This is all supported by a cash position of approximately $180 million at the end of the first quarter of 2020.
Thank you Jamie Thanks, Jamie.
Good morning.
So it is ongoing.
Could you skip detention standards.
Devastating disease.
Good day.
Our strategy to continue development.
Yes.
As you can see with Q1.
Well the potential benefits.
Zero sleeves.
The capsid to deliver some differentiated muscle dystrophy.
This is all supported by a cash position of approximately eight.
<unk> million dollars at the end of the first quarter of 2022.
Ilan Ganot: The Board and Solid Leadership Team remain committed to the progress of both programs, and I'll now summarize our path forward. Following a thorough assessment of currently available alternatives for the manufacturing of HTTP 001, we identified a process that we believe will produce high-quality drug products while narrowing the organization's focus to a single production platform and streamlining our operating structure to a more efficient model. Joel will discuss our revised strategy to advance STQ001 into late-stage clinical development using transient transfection-based manufacturing.
The board and solid leadership team remain committed to the program.
And I'll now summarize.
Sure.
Thank you.
Okay.
So the manufacturing give us <unk>.
Besides the process as we can.
We produced high quality.
While narrowing the organization's focus to a single production platform.
Streamlining our operating structure to a more efficient.
John will discuss these items.
The strategy.
Yes, as you do deals you won.
Stage clinical development with transient transfection based refreshment.
Ilan Ganot: We believe this transition has minimal impact on our timeline for further development through to the potential BLA filing and improves our potential to make a difference for those living with the shrapnel. Our next-generation capsid used in STD-003 has the potential to offer significant advantages for Duchenne gene therapy as well as for the broader gene therapy field for muscle disorders.
We believe this transition has minimal impact to our timelines for the future.
Further development potential.
<unk> BLA filing.
Our potential to make a difference for those living with.
Right.
Second.
Our next generation capsid using cash to do deals.
<unk> has the potential to offer significant advantages.
Gene therapy as well as for the moment.
Gene therapy students muscle disorders.
Ilan Ganot: We will continue to advance towards an IND submission in early 2023 and further de-risk this program and the mobile capital. We expect the clinically-fulfilled concept for HT003 in 2023 will provide further support for our next-generation capsid cluster. As a result of the focused approach on these programs and SOLID's cash runway through Q2 2024, the company will be able to progress through important clinical milestones for both gene therapy programs. I will now hand it over to Joel to go through our SGT001 update in more detail. Thanks a lot.
We continue to advance towards an NDA submission in early 2023, Thanks, Joe This Derisked program.
The disruption.
Do you expect.
Of course, Steve.
In 2023.
To further support of our next generation trough to trough.
As a result of the focused approach in these programs and solid cash runway.
2024, the company will be able to progress through important clinical milestones for both <unk> programs.
Joel Schneider: In March, we released an interim analysis of functional and durability data from the first three patients dosed in the high-dose cohort two years after treatment with SGT001 as part of the IGNITE-DMD Phase I-II study, across all measures, including motor function, pulmonary function, and patient-reported outcome measures. Patients are showing consistent, durable improvement after dosing compared to expected declines in untreated patients. We also shared that patients recently dosed in the high-dose cohort demonstrated microdystrophin expression and localization at 90 days within the range of earlier patients in the high-dose cohort at the same period of time. And finally, all IGNITE-DMD patients continue to do well with no long-term safety event.
I'll now hand, it over to Joel.
Meanwhile, our strategic update in more detail.
Thanks, a lot.
In March we released an interim analysis of functional and durability data from the first three patients dosed in the high dose cohort two years after treatment with <unk> zero, one as part of the ignite DMD phase one two study.
Across all measures, including motor function pulmonary function and patient reported outcome measures patients are showing consistent durable improvements after dosing compared to expected declines in untreated patients.
We also shared a patients recently down in the high dose cohort demonstrated micro dystrophin expression and localization at 90 days within the range of earlier patients in the high dose cohort at the same period of time.
And finally, all 19 D patients continue to do well with no long term safety events.
Joel Schneider: These data are important as they continue to support the potential that Solids and NOS containing microdistrictin is providing durable benefits to patients and warrants further clinical development. We are now focusing on finalizing late-stage clinical and regulatory strategies, supported by a commercial scale manufacturing process. As part of our platform development efforts, we undertook a comprehensive analysis, comparing transient and HSD-based manufacturing processes across a number of factors.
These data are important as they continue to support the potential but solid <unk> containing micro dystrophin is providing durable benefits to patients and warrants further clinical development.
We are now focusing on finalizing late stage clinical and regulatory strategy.
Supported by our commercial scale manufacturing process.
As part of our platform development efforts, we undertook a comprehensive analysis, comparing transient and HFC based manufacturing processes across a number of factors.
Joel Schneider: We collected multiple datasets from different scales of manufacturing to help us compare the processes and to assess how they would scale for production. Overall, our analysis concluded that by developing SGT-001 and SGT-003 using transient production, we believe we can achieve a high quality and highly potent product demonstrating high levels of microdystrophin expression in both our in vitro and in vivo expression assays. We can improve our consistency in product supply yields and have access to a broader supply chain, which is reflective of the adoption of this more commonly utilized manufacturing platform. The turnkey commercially scaled solution will allow us to ease our sole reliance on internal development and manufacturing operations.
We collected multiple datasets from different scales of manufacturing to help us compare the processes and to assess how they would scale so production.
Overall, our analysis concluded that by developing Sgt's 001, and Sgt's zero dual III using transient production platforms. We believe we can achieve a high quality and highly potent product demonstrating high levels of micro dystrophin expression in both our in vitro.
And in vivo expression assets.
We can improve our consistency in product supply yields and have access to a broader supply chain, which.
Which is reflective of the adoption of this more commonly utilized manufacturing platform.
The turnkey commercially scaled solution will allow us to ease our sole reliance on internal development and manufacturing operations.
Joel Schneider: Organizationally, transitioning SGT001 to a transient-based process will bring solid under a single manufacturing methodology, allowing us to streamline our operations. Now, I will walk through the next 12 months for SGT001 as we look to resume dosing in the first half of 2023. Importantly, activities to transition to the new manufacturing process have already begun, with products expected to be available in early 2023, aligning well with our regulatory and clinical activities to support dosing. The transition to the new manufacturing process was a natural opportunity for all to pause and consider how to proceed with clinical development. As part of our strategy, we have decided to conclude enrollment in IgniteDMD.
Organizationally transitioning Sgt's 0012, a transient based process will bring solid under a single manufacturing methodology, allowing us to streamline our operations.
Now I will walk through the next 12 months for Sgt's Zero-zero wall as we look to resume dosing in the first half of 2023.
Importantly activities to transition to the new manufacturing process have already begun with product expected to be available in early 2023, aligning well with our regulatory and clinical activities to support dosing patients.
The transition to the new manufacturing process with a natural opportunity for us to pause and consider how to proceed with the development.
As part of our strategy, we have decided to conclude enrollment in ignite DMD and moving forward patients will be dosed using material from the new process and we have already begun conversations with the FDA to determine the design of a future clinical study.
Joel Schneider: Moving forward, patients will be dosed using materials from the new project, and we have already begun conversations with the FDA to determine the design of a future clinical study. In addition, we will be initiating a natural history study that will support future clinical activity, both for SGT-001 and SGT-003, helping us establish the risk-benefit of our program. There are a number of milestones over the next 12 months that we aim to communicate, such as updates on our discussions with the FDA and additional data coming out of IGNITE-DMD, including one-year biopsies and functional analyses of all patients in Now I will turn the call over to Carl. Okay, Carl?
In addition, we will be initiating a natural history study that will support future clinical activities, both for <unk> and <unk> 003, helping us establish the risk benefit all of our programs.
There are a number of milestones over the next 12 months that we aim to communicate such as updates on our discussions with the FDA and additional data coming out of ignite DMD.
One year biopsies and functional analyses of all patients dose in the program as well as three year follow up on functional data from patients four to six.
Now I will turn the call over to Carl.
Paul.
Carl Morris: Thanks, Joe. Good morning, everyone. I'm pleased to be able to share new data coming out of our Melville Capsule Library Development Program. Let me briefly review our SPT-003 program. This program utilizes a novel, freshly designed capsid that has demonstrated improved muscle tropism compared to AB9 and packages solid, differentiated, and non-spiny domain-containing mycophystrophin.
Thanks, Joe.
Everyone.
I am pleased to be able to share new data coming out of our novel Capsid why redevelopment program.
Let me briefly review our <unk> program.
This program utilizes a novel rationally designed capsid that has demonstrated improved muscle tropism compared to 89 and packages solid differentiated and most binding domain containing micro dystrophin.
Carl Morris: Vismicrodystrophin is the same that is used in SGT001, and as Joel shared earlier, it has been shown to deliver durable and promising benefits to patients in the NIGHT-D&D study. Over the last couple of years, we have shared a variety of data on SGT 003, and it's summarized on this slide. After observing promising data in mouse and human Duchenne muscle cells, As shown on the left, we compared by distribution the microdisturbance expression in dystrophic mice of the novel capsid-1st AAV9.
This micro dystrophin is the same that is used in FCT 001, and as Joel shared earlier it has been shown to deliver durable and promising benefits to patients in the DMD study.
Over the last couple of years, we have shared a variety of data on FCT.
And it's summarized on this slide.
After observing promising data in mouse and humans Michelle muscle cells.
As shown on the left we compared by distribution and micro dystrophin expression of the strategic mice of the novel Capsid AAV mine.
Carl Morris: Improved muscle trophism was observed with the novel CAPTCHA, but it also resulted in an apparent significant reduction in circulating creatine kinase subgroup, RS-89, as shown in the center of the slide. Additionally, we ran an MDX study in wild-type mice to determine if we would see similar changes in the level of expression as seen in the MDX mice. For this study, we used Rapporta CMV, a strict race construct.
Improved muscle tropism was observed with a novel capsid that also resulted in an apparent significant reduction in circulating creating kinase levels plus 89.
As shown in the center of the slide.
Additionally, we ran an in vivo study and wall type mice to determine if we would see similar changes in the level of expression as seen in the mdx mice.
So this study we used to report our CMV and syphilis Comstock as you can see on the right hand side of this page.
Carl Morris: As you can see on the right-hand side of this page, we did observe increased expression in the wild-type mice as well. And when analyzed, we found more targeted expression to the muscles, with lower biodistribution and expression in the liver when compared to AB9. After the promising results seen in human cells and in mouse studies, we wanted to further test the translatability of the increased musculotropism in non-human primates, as well as to have an exploratory look at safety in larger animals.
We did observe increased expression in the wild type mice as well and when analyzed we found more target expression to the muscles with low by distributions expression in the liver when compared to 89.
After the promising results seen in human cells and the mouse studies one of the further tests translate ability of increased muscle tropism and nonhuman primates as well as have an exploratory look at safety and larger animals.
Carl Morris: So earlier this year, we initiated a study using CMV in this HIPAA-raised reported transgene. And there are eight synagogies, my- Four of them, two male and two female, were dosed with the reported construct using AD-9, while the other four were dosed with novel capsules being used in S2P-003. Our goal for the Nublin CAPTCHA program has been to see at least a two-fold improvement compared to 89 in body distribution to skeletal and cardiac muscle.
So earlier this year, we initiated a study using CMV luciferase reported trenching and dosed eight cinema August monkeys.
Four of them two male and female with dose with reported construct using AAV nine while the other small with dose with novel capsid.
Being used in <unk> three.
Our goal for the novel Capsid program is basically at least twofold.
The improvement compared to 89, the bio distribution to skeletal and cardiac muscle.
Carl Morris: What we're highlighting here today is an increase in body distribution greater than the goal of two-fold improvement for both skeletal and cardiac tissue. We also see a promising two-fold reduction in biodistribution to the liver. On the next slide, we similarly observed an increase in SIFRA expression as measured using an activity assay in both skeletal and muscular tissue, tent area, with greater than 10-fold improvement seen in both tissues. And consistent with the biodistribution results, we see decreased expression in the liver of the novel capsid.
While we are highlighting here today was an increase of by distribution greater than the goal a two fold improvement for both skeletal and cardiac tissue.
We also see a promising twofold reduction by distribution to deliver.
On the next slide we similarly observed an increase in the separates expression as measured using activity assay.
Skeletal muscle and cardiac muscle with greater than 10 fold improvements seen in both tissues.
And consistent with the bio distribution results, we see decreased expression in the liver with the novel capsule.
Carl Morris: So overall, these results suggest we may be able to reduce the dose while maintaining expression when compared to AAV9. As we look to next steps for the program, we'll continue R&D efforts on both the Novel Capsule and SGT-003 program for Duchenne, using learning and the promising clinical data from the SGT-001 program. For SGP 003, we are working closely with our manufacturing partner to have product ready to support patient dosing. We are looking to engage with the FDA later this year regarding an IND submission we planned for early 2023. We are very optimistic about the potential that SGT003 holds for patients. The preclinical data continues to suggest that it may be able to improve expression at a lower dose. Therefore, reducing the viral load.
So overall these results suggest we may be able to reduce the dose while maintaining expression when compared to the nine.
As we look to next steps for the program will continue R&D effort on both the novel capsid and execute <unk> III program with the.
Sure using learning and the promising clinical data from the <unk> one program.
The FCC's <unk> three we are working closely with our manufacturing partner to have product ready to support patient dosing.
We are looking to engage with the FDA later this year regarding an IND submission we plan for early 2023.
We are very optimistic about the potential that SPT you are two or three of the patients. The preclinical data continues to suggest that we may be able to improve expression at a lower dose therefore, reducing viral loads.
Carl Morris: The preclinical data continues to suggest that it may be able to improve expression at a lower dose. We will continue to develop this next generation capsid for the Shen patients with DSGT Year 03 program, as well as potentially engage with companies developing gene therapies in other muscle-related disorders. With that, I will hand it back to Alon. Thank you, Carl, and thanks, Joel. We have a lot of work ahead of us, but we have focused our operations to support these two programs, which utilize a single manufacturing approach.
We will continue to develop this next generation captive to the shed in patients with the <unk> III program.
As well as potentially engage with companies developing gene therapies with other muscle related disorders.
With that I will hand, it back to alone.
Thank you Paul and thanks Joel.
We have a lot of work ahead of us, but we have focused our operations to support this key programs, which utilize a single manufacturing approach.
Carl Morris: This has allowed us to streamline our organization structure and reduce our headcount by approximately 35%, which enables us to extend our runway into Q2 of 2024 and achieve important clinical milestones. And over the next 12 months, we will be sharing further data from long-term patient follow-ups, an update on our regulatory interactions for both STP001 and STP003, and potential updates on STP001 CMC and clinical plans, as well as STP003 IMD filing, clinical trial, and dosing plan.
That has allowed us to streamline our organization structure and reduce our headcount by approximately 35%.
It enables us to extend our runway into Q2 of 2024 and achieved important clinical milestones.
And over the next 12 months, we will be sharing further data from long term patient follow ups.
To date on our regulatory interactions for both <unk> and <unk> III and.
And potential updates on the <unk>, CMC and clinical plans as well as strategic suite RMB filing.
Good choice and dosing with clients.
Carl Morris: I also want to mention that, as you may have seen in this morning's press release, Joel will be leaving soon. He has accepted an opportunity to become the CEO of an early-stage, privately-held gene therapy company. Job is staying on through the end of May.
I also wanted to mention but as you may have seen in this morning's press release, John will be leading sites.
He has accepted an opportunity to become a CEO of an early stage privately held gene therapy company.
<unk>.
Okay.
Ilan Ganot: Before we open for questions, I want to take a moment to say thank you. First, I want to say thank you to all of Solid Biosciences' employees for their tireless efforts to bring our treatments to patients. To those who are unfortunately impacted by the strategic reorganization we announced today, I hope you know that your work has made a meaningful contribution to improving the lives of patients living in Dushanbe, and for that, I am deeply grateful. I also want to thank Joel for his eight years of service and commitment to Solid.
Before we open for questions I wanted to take a moment to say thank you.
First I want to say, thank you to all of <unk> employees for their tireless efforts to bring dollars treatments to patients.
So those were unfortunately impacted by the strategic reorganization, we announced today.
<unk> has made a meaningful contribution to improving the lives of patients living with Duchenne and for that I am deeply grateful.
I also want to thank Joe for eight years of service and commitment to service.
Ilan Ganot: Joel's been instrumental in building the company, the teams, and the treatments that are being developed at Solid. I now speak on behalf of everyone at Solid when I thank Joel for his leadership, partnership, and friendship and wish him success with his new job. Finally, I would like to extend a special thank you to the patients, families, and physicians involved in Innovate DMD, thanks to whom we are now in a position to move to the next phases of development. Thank you all again for dialing in. We'll take ask some questions. Thank you. And again, ladies and gentlemen, to ask a question, simply press star 1 on your telephone. That is star 1.
Joe has been instrumental in building the company the teams and the treatments that are being developed in summer and I'll speak on behalf of everyone at summit, what I. Thank Joe for his leadership partnership and friendship and wish them successfully future.
Finally, I would like to extend a special thank you.
<unk> families and physicians involved in getting by Dnb.
To whom we are now in a position to move to the next phases of development.
Thank you again for dialing in.
Take some questions now.
Thank you and again, ladies and gentlemen to ask a question simply press star one on your telephone Daddy's Star one.
Operator: We'll take our first question from Agena 1 of BART. Thank you for taking my questions, Joe. Congratulations on your next journey, and we will certainly. So I have two sets of questions.
We'll take our first question from Gena Wang.
Barclays.
Thank you for taking my questions Joe.
That's all.
Next journey and we will certainly next year.
So I have.
Two sets of questions maybe the first one is regarding the <unk>.
Gina: Maybe the first one is regarding STT-035. So you did show Luciferous reporter gene data. Did you test the microdistrophin transgene in the new capsid? And based on the current data, what would your initial thoughts regarding the phase 1 dose range, like will you be able to go down to the E12 range? My second question, or second set of questions is regarding Sgt.
She did she was the first reported data.
Did you test them micro dystrophin transgene into new caps and are based on the current data book.
Initial thoughts regarding.
The phase one dose range like will you be able to go down to the 12 range.
My second question second set of questions regarding <unk>.
Gina: 001. So now with the new transient transfection phase, outsourced manufacturing process. So do you need to do an additional CNC all comparability study? Follow which is the app.
S. G T. He was doing.
So now with the new transient transfection.
Outsourced manufacturing process. So do you need to do additional.
A comparability study before you fall.
Pivotal study.
Gina: Great questions, Gina. Thank you. I'll have Carl take on the 003 and Joel respond to the 001. Yeah, thanks Gina. It would be great to get down to E12, but I don't think that's possible.
Great questions Gena. Thank you.
Call, they've gone to 003 and Joel to respond to the 001, yes.
Carl Morris: You know, we are looking at doing a, we need, still need to do a dose selection study, and so we hope to drop the dose and, you know, sort of maybe get down by at least twofold. And that is what the goal of the program was always, to get a twofold difference versus 89. And so it appears that we've done that both in mice and monkeys. The second part of your question was about luciferase versus microdystrophin.
Yes, Thanks, Dan.
But it would be great to get that to a 12, but I don't think thats possible. You know we're looking at doing a we need still need to do a dose selection study.
And and so we hope to get dropped the dose.
And so maybe get down by at least twofold and that is what.
The goal of the program was always was to get a two fold.
Difference versus AAV nine and so it appears that we've done that both in mice and monkeys. The second part of your question was around the luciferase and adverse micro to strengthen we didnt dosed nonhuman primates with with with the <unk>.
Carl Morris: We didn't dose non-human primates with microdystrophin, but we dosed them with luciferase, but we did do mice and compared the luciferase and microdystrophin. And so luciferase had a little bit higher signal, but the microdystrophin in the mice was about threefold larger, while the luciferase in mice was tenfold larger.
Destroy them with dosing with the SIF race, but we did do.
<unk>.
We did do mice and compared the luciferase and micro dystrophin as elusive race, it has a little bit higher signal.
But the micro strengthen in the mice was about threefold wildly luciferase and myself 10 full so we think where we're sort of in the right ballpark.
Carl Morris: So we think we're sort of in the right ballpark for the microdystrophin as well. Going into wild-type animals that already have dystrophin, it's a bit problematic trying to administer the microdystrophin and evaluate levels, but this is good. We did it in wild-type mice as well.
Follow up to the micro strengthened as well going into two wild type animals that already have destroyed it's a bit problematic trying to administer the micro described and then evaluate levels.
This is good we did it in wild type mice as well or is it race and it showed quite promising results there as well so as a platform. We think this is sort of a really good first step for us.
Carl Morris: We did it with luciferase, and it showed quite promising results there as well. So as a platform, we think this is sort of a really good first step for us. I would just add, you know, that we had a bunch of internal bars that we needed to cross to get excited about 003. And we crossed them, and we are excited, and we're taking them to the clinic. And, you know, we think there's a lot more potential here outside of Lushen too. And hopefully, you know, very soon, we'll see the patients and see how good it really is. Joan, do you want to cover for 001?
I would just add.
We had a bunch of internal borrowing that we needed to cross to get excited about zero zero to three and.
And we call them and we are excited and we're taking them to the clinic.
I think there is a lot more potential here outside of the Chengdu.
And hopefully you know loosen recruited patients and see how good it really is Joe do you want to cover those are one sure. Thanks for the question on comparability of course, it's all we have a lot of experience in demonstrating comparability between different manufacturing methods. In fact, we just recently accomplished that when we transition to our second generation.
Joel Schneider: Sure. Thanks, Gina, for the question. On comparability, of course, at Solid, we have a lot of experience in demonstrating the comparability between different manufacturing methods.
Joel Schneider: In fact, we just recently accomplished that when we transitioned to our second generation-based HSV manufacturing process. We've already begun to engage with regulators about the path toward dosing a patient's new process and believe that the comparability will need to be demonstrated, that that can be accomplished through analytical methods and perhaps some in vivo dosing to demonstrate comparability overall. But obviously, we have a lot of experience internally with how to demonstrate that comparability, and feel confident that we can have a seamless transition between manufacturing methodologies.
Based HSV manufacturing approach.
We've already begun to engage with regulators about the path towards dosing of patients with new process and believe that the comparability will needs to be demonstrated.
It can be accomplished through analytical methods that perhaps some.
In vivo.
Dosing to demonstrate comparability overall, but obviously a lot of experience internally with how to demonstrate the comparability of appeal.
Confident that we can.
Have a seamless transition between manufacturing methodologies.
Joel Schneider: Maybe I'll just add to this, too, that in the process of switching, we did a lot of analytical work, and so we are pretty confident that the new materials will be at least as good, if not better. Thank you very much. Thank you, Gina.
Maybe I'll just add to this to the.
In the process of switching you know, we we did a little bit a little work and so we are pretty confident that the new materials will qualify.
At least as good if not better.
Thank you thank you Gina.
Joel Schneider: Then your next question comes from Joseph Schwartz with SVB Security. Thanks very much, and I'd like to also add my best wishes to Joel and his next endeavors. I am satisfied that you understand how to best administer SGT001 in a safe and effective manner now that you've wrapped up IGNITE. So I was wondering if you could summarize the key features of the Service Mitigation Protocol, ensuring that patients who receive SGT001 can tolerate it optimally. Hey Joe.
And your next question comes from Joseph Schwartz with SBB Securities.
Thanks very much.
I'd like to also add my best wishes to join US next endeavors.
Sounds like you are.
You understand how to administer <unk>.
Zero, one in a safe and effective manner now that you've wrapped up at night.
So I was wondering if you could summarize with the key features of the risk.
Risk mitigation protocol are for.
Ensuring that patients who receive a G T series or one can tolerate it optimally.
Joseph Schwartz: Thank you for the question. Obviously, we completed enrollment, but we don't wrap up the study because we continue to monitor patients out to five years at least from dosing, and we dose nine and have a number of other patients in the study. But I'll have Roxana jump in a little bit on risk benefit and how we feel about moving forward with those. Thank you, Ilan. Yes, very good question.
Hey, Joe. Thank you for the question, obviously, we completed enrollment we don't drop stop the study because we continue to monitor patients five years at least from dosing and we've those signing up a number of other patients study, but I'll have roxanna I'll jump in a little bit on risk benefit and how we feel about moving forward in dosing.
Thank you Elon.
Very good question. Thank you, we feel very confident and the risk benefit profile of <unk> one based on the nine subjects to date, our trio resolved. So that the patients are experiencing a sustained benefit across all of the functional outcomes.
Roxana Doniza-Dradic: Thank you. We feel very confident in the risk-benefit profile of SGT001 based on the nine dose subjects to date. Our two-year results show that patients are experiencing a sustained benefit across all the functional outcomes in terms of motor function, lung function, and patient-reported outcomes. As for the risk mitigation strategy, we feel very confident that this is the right way forward. We are thinking about finalizing that risk mitigation strategy for the new material, so maybe everything is not going to stay in place as it is right now.
Terms of motor function pulmonary and patient reported outcomes in terms of the risk mitigation strategy, we feel very confident that this is the right.
Wasteful word we are thinking about finalizing.
Finalizing that risk mitigation strategy for the new material, so not maybe everything that kind of thing.
Now, but as you know with previous update we will share that will optimize our accolades the mab regimen and we've definitely optimized R. R.
Roxana Doniza-Dradic: But as you know from previous updates, we've shared that we've optimized our Ecolizumab regimen, and we've definitely optimized our follow-up of the patient prior to infusion and after the infusion in the first couple of weeks through very close monitoring. So we're, of course, assessing that once again to make sure that everything is still applicable for the new material. Okay, thanks. And then what are the next steps for SGT-001 then? When do you expect to get back into the clinic?
A follow up of the patients previous two infusion and after the infusion and the first couple.
A couple of week very close monitoring so we're of course assessing that once again to make sure that everything is still applicable for the new material.
Yes.
Okay. Thanks, and then what are the next steps for US few teasers or one then when do you expect to get back in the clinic and what types of patients will you be focusing on enrolling in the next.
Ilan Ganot: And what types of patients will you be focusing on enrolling in the next? Thank you. Thank you. Thank you. Undertaking a phase 3 at this juncture. Can you help us understand your strategy there? Sure, Joe. I'll take this. It's a quick one.
And the next.
<unk> for two years or one and a few scheduled an end of phase two meeting with the FDA yet.
Are you thinking about.
Undertaking a phase III at this juncture.
Can you help us understand your strategy there.
Ilan Ganot: We've already started engaging with the regulators around the switch. We intend to have material ready for those patients with SCP-001 early in 2023, and all the aspects of the clinical trial design, as well as the number of patients and their age inclusion, are being finalized. Okay, well stay tuned. Thanks for taking my question. Thank you. Your next question comes from Maury Raycroft, with Jeffrey. Hi, good morning, and thanks for taking my questions about the new process. Besides the scaling and streamline process and transient transfection, are there any other fundamental changes we should be aware of? Thanks, Maury. I'll take this one.
Sure Joe I'll I'll take this is a quick one we've already started to engaging with the regulators around this which we intend to have material ready to those patients with the strategic view of zero one early in 2023 and all the aspects of the clinical trial design as well as the number of patients.
<unk> inclusion are being finalized.
Okay, we'll stay tuned thanks for taking my questions.
Thank you Sharon.
Your next question comes from Maury Raycroft with Jefferies.
Hi, good morning, and thanks for taking my questions.
For the new process, besides the scaling and the streamlined process and transient transfection are there any other fundamental changes we should be aware of.
Joel Schneider: You know, one key aspect of this solution that we've identified for the late-stage development of 001 is that it's already at what we would consider a phase three appropriate and commercial scale. We've done extensive work internally on scaling the HCP process, and as we performed our comprehensive analysis between our internal process and external options, we did seek a process that was already sufficiently optimized for late-stage clinical entry and ultimately commercialization.
Thanks Mario.
No.
One key aspect.
Solution that we've identified for for late stage development of zero zero, what is that its already at a what we would consider a phase three appropriate commercial scale.
<unk> done extensive work internally at scaling agency process and as we performed our comprehensive analysis between our internal process and external options. We did seek a process that was already sufficiently optimized.
Joel Schneider: And so we're excited to be able to access that. A couple other key aspects of this are that, of course, transient production is a very widely adopted manufacturing platform, and we think that this will enable us to have broader access to a much wider net of supply chain efforts or supply chain networks.
For late stage clinical entry and ultimately commercialization and so we're excited to be able to access that.
Couple of other key aspects of this is that of course transient production.
Very widely adopted manufacturing platform and we think that this will enable us to have broader access to a much wider net of supply chain efforts.
Joel Schneider: It'll also allow us to, we think, overall improve our manufacturability of clinical supply. And so really, fundamentally, it's a streamlining of our manufacturing behind a single platform for both gene therapy programs. Got it, that's helpful.
Our supply chain networks. It will also allow us to.
We think overall improve our manufacturer ability of clinical supply and so really fundamentally the streamlining of our manufacturing.
Unified.
This single platform for both gene therapy programs.
Joel Schneider: And then I'm just wondering if you can clarify what you mean by a new outsource process. I mean, are there going to be new manufacturing collaborations on the horizon? And how much of a contribution does FORGE Biologics have in the new process? So we're really excited about the work that FORGE is doing for us on SGT003, but simply for diversification purposes, as well as the opportunity to work with a commercially scaled process, we are building a new relationship with a new vendor for the production of SGT001 at those scales. On the aspect of, sorry, actually I'm blanking on the first part of the question.
Got it that's helpful. And then I'm just wondering if you can clarify what you mean by new outsourced process. I guess are there going to be new manufacturing collaborations on the horizon and how much of a contribution does forge biologics happened and the new process.
So we're really excited about the work that Ford is doing for us on Sgt's 003, but simply for diversification purposes as well as the opportunity to work with that are commercially scaled process. We are building a new relationship with a new vendor.
<unk> for the production of <unk>.
<unk> 001 at those skills.
On the on the aspect of sorry, I actually I'm blanking on the first part of the question.
Joel Schneider: Just, I mean, you basically answered it; just anything additional. Yeah. Yeah. Yeah.
Just the E.
I mean, you basically answered it just internal anything additional.
Yeah, Yeah yeah.
Okay got.
Joel Schneider: Yeah, the differentiator there for us is that the HSC process is something that we've worked on extensively internally for the last six or seven years. We are excited to be leveraging external expertise and capabilities to rapidly integrate their expertise into our own around transient production. And so it's really a notion of recognizing the incredible work that our internal teams have done to scale and optimize the HSC process but recognizing that we can now relieve some of those bandwidth constraints by working with external parties, leveraging their proprietary manufacturing platforms, and really focus on bringing our therapy to patients.
Got it.
Yeah. The differentiator there for US is that the agency process is something that we've worked on extensively internally for the last six or seven years.
We're excited to be leveraging external expertise and capabilities to rapidly integrate their expertise into our own.
And transient production and so it's really a notion of no.
Recognizing the incredible work that our internal teams have done to scale and optimize the agency process, but recognizing that we can now relieve some of that of those bandwidth constraints by working with external parties leveraging their proprietary manufacturing platforms and really focus on bringing our therapy to patients.
Joel Schneider: Okay, thanks for taking my questions. Thanks, Morrie. And as a reminder, to get in the queue, simply press star 1 on your telephone. Your next question is from Alison Bratzel with Pipeline. Hi, good morning.
Got it that makes sense, okay. Thanks for taking my questions.
Thanks Mark.
Thank you.
And as a reminder to get into queue simply press star one on your telephone. Your next question is from Allison, Brett <unk> with Piper Sandler.
Operator: Thank you for hosting the call and for taking the questions. So first, just a couple of clarifications for me on IGNITE-DMD, and apologies if you've already covered these. I just want to make sure I'm clear. I guess how many total patients did end up being dosed with IGNITE-DMD? We know nine patients were dosed as of November, so just confirming that's the total number of patients dosed. And then, could you also clarify the cadence for data updates from those patients?
Hi, Good morning, Thank you for hosting the call and for taking the questions.
So first just a couple of clarification for me on ignite DMD and apologies if you've covered these I just want to make sure I'm clear.
How many total patients.
I'm not being dosed on a Nike M D. I think we know.
900, <unk> of November so just confirming that that's the total number of patients dose and then could you also clarify the cadence for data update from those patients I think the prior guidance close to this close to 12 month functional data for patients by.
Operator: I think the prior guidance was to disclose 12-month functional data from patients seven to nine by year-end 22. So, I just want to make sure we should still be. And then, just lastly for me, a clarification on the cash runway.
By year end 'twenty, two so I just want to make sure we should we should still be.
Looking for that.
And then just lastly from me a clarification just.
Just on the cash runway I think the guidance effect.
Ilan Ganot: I think the guidance is that you'll have a runway through Q2-24 through important clinical milestones. Could you just kind of outline the important clinical milestones we should be expecting between now and Q2-24, and just what does that new CASH runway guidance assume for the start of pivotal work? Thanks. Let me try to wrap it all up in a quick answer. With those nine patients, we were always going to dose a couple more. And with this switch, we decided to stop enrollment, evaluate the data, and move to transfection starting early next year.
You'll have a runway through Q2 'twenty for two important clinical milestones could could you just kind of outlined that the important clinical milestones.
Would you be expecting between now and Q2 'twenty four and just what does that new cash runway guidance assume.
For the start of.
Pivotal work.
Yes.
Let me try to wrap it all up in liquid credit.
Those nine patients who were always going to cover more and with this switch we decided to stop enrollment value added data and move to construction starting early next year.
Ilan Ganot: We obviously continue to monitor all the patients that have been dosed, and yes, we will continue to provide additional clinical and biomarker data as it comes in during this year and probably in the future. We are very excited about the durability of the data that we're seeing, you know; we have biopsies out for years that are stable or actually increasing, and we have functional outcomes, especially looking at some of the physical measurements, respiratory measurements.
We obviously continue to monitor all of the patients that have been dosed and yes, we will continue to provide additional clinical and biomarker data as it comes in during this year and probably in the in the future. We are very excited about the durability.
The.
The data that we're seeing.
Our biopsies two years that are stable or actually increasing and we have functional outcomes, especially looking at some of the.
Physical measurements respiratory measurement there is some pretty interesting observations there would we continue to monitor and evaluate the measure and report.
Ilan Ganot: There are some pretty interesting observations there, but we continue to monitor and evaluate and measure and report. The runway will get us to the next two years and a lot of clinical milestones on both programs.
The runway will get us.
The next two years and a lot of critical milestones on both programs.
Yes.
Ilan Ganot: Thank you. Thank you. Our next question comes from Anupam Rama with J.P. Morgan. Please go ahead. Hey guys,
Thank you.
Thank you.
Our next question comes from <unk> Rama with Jpmorgan. Please go ahead.
Anupam Rama: Thanks so much for taking the question. I have, like, maybe just a broader strategic question in terms of you starting dosing for 001 in 2023, and, you know, theoretically, your IND goes in for 003 early next year, and maybe you start dosing patients soon, too. Like, why not just prioritize one and maybe extend the cash weight a little bit longer?
Hey, guys. Thanks, so much for taking the question.
Maybe just a broader strategic question in terms of Youre, starting dosing for zero, one and 2023.
Theoretically youre dosing for three early next year and maybe you start dosing patients soon too like why not just prioritize one and maybe extend the cashway a little bit longer.
Yes.
Ilan Ganot: Good question Anupam, you wouldn't be surprised if it came up internally too. We're not in the business of shooting down things that work. We think 001 has got great data that supports continued development. I can tell you, as somebody with some first-hand experience of this disease, I would love to see that.
The question I Hope I mean, it wouldn't be surprised it came up in total.
Really too.
<unk>.
We're not in the business of shooting down things that work, we think <unk> got great data that supports continued development I can tell you as somebody with firsthand experience of this disease.
I would love to see that.
Ilan Ganot: Touch more patients, if possible. If 003, once active in patients, does show the same effect that we've seen in mice that we've seen in monkeys now, certainly the expression levels and the biodistribution levels of the vector, then that's a great finding. It's a really exciting moment for not just solids but science and muscle diseases too. And at that point, we could make different decisions than we do today. Right now, we are confident that both of these programs deserve a day in the summer.
That's more patients as possible.
0031.
<unk> active in.
Patients does show the same effect that we've seen in mice that we've seen in monkeys now.
Suddenly the expression level by distribution levels of the vector that's a great finding it's a really exciting moment for above just solid, but some science and muscle diseases.
That point, we can make different decisions than we do today.
Right now we are confident that both of these programs do zero.
A data center.
Yeah.
Ilan Ganot: Got it. Thanks for taking that question. Thank you. And with that, we conclude our Q&A session and today's call. All parties may now disconnect. Thank you, and have a nice day.
Got it thanks for taking my question.
Thank you and with that we conclude our Q&A session and today's call. All parties may now disconnect. Thank you and have a great day.
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