Good morning, everyone. My name is Gena Wang. I'm SMCR & Biotech Analyst at Barclays. Thank you very much for joining the seventh Gene Editing, Gene Therapy Summit at Barclays. I would like to first, you know, take this opportunity to thank all the investors, companies, also especially our event team and the corporate access team who made this event possible. With that, I would like to introduce our next presenting company, Solid. With us today, we have Bo Cumbo, our President and Chief Executive Officer. We also have Kevin Tan, Chief Financial Officer. Thank you both for joining us today. Thank you for having us. Yeah. Thank you, Gena. Yeah. Thank you, Barclays. Maybe, Bo, I will start with DMD- Yeah ... programs. I think that we have recently has quite a few, recent, like, new updates, right? We saw the FDA outcome. We anticipate potential first gene therapy approval. Now they actually also mention NOSARs, you know, at FDA, both briefing document and the panel discussion. Maybe, you know, from your end, you know, what do you think now giving current evolving dynamic? Like, how do you see your DMD franchise now, and how do you want to advance your next-gen program into clinic? Yeah. What would be the most efficient way or the most commercially viable way? Yeah. No, thank you very much. Very excited to be here first and foremost. We're very excited about our next generation program. There's obviously a lot of news around DMD right now, and rightfully so. Definitely a high unmet need where we got to get these drugs to these children. You know, obviously, there was an AdCom that recently happened. Ironically, that did not change our current plans at all, regardless of the outcome of what happens. We're focusing on a next-generation Duchenne program in which we're really working on a novel capsid with a novel capsid, the transgene from the SLB001 program, and we have shifted over to triple transfection manufacturing platform. Our goal for this is to create a program that can not only, you know, hit antibody positive children and bring microdystrophin to them at significant levels, but also think about ways we can deliver microdystrophin to children who have antibodies already to these capsids, before being dosed. To older children, how we can look at older populations, you know, ambulatory or partially ambulatory. These are heavier kids. They've been on steroids their whole life, and how do we get a drug to them, diaphragm, the heart, the intercostal muscles, et cetera. Then obviously, you know, there's gonna be children who do not respond, one reason or another, or respond and need a redosing regardless of the outcome. So we're working on ways to approach those children. Now, our first in-house trial will be for antibody negative children. Our goal is to have an IND in Q4 of this year, we will dose our initial patients at the end of this year in Q4 as well. Mm-hmm. That'll be roughly eight to 10 children, antibody negative, somewhere in the range of ages of four to seven years of age, and with multiple baseline criteria that we'll implement as well. We should be dosing at the year-end. I assume giving tenfold improvement, I assume the initial dose were in the 1E13, right? We don't know what the dose is gonna be. We're doing a lot of animal work right now to identify the dose. I mean, in the presentations I've already presented, we went all the way down to 3E13. I think we dosed 3E13, 1E13, 3E14. It was 3E13, 1E14, and 3E14. Those were the original doses we looked at. Ironically, all three of those doses had pretty much 100% across the board distribution in the heart, the diaphragm, et cetera, at day 29. We also saw a significant amount of microdystrophin expression at day four, which was quite surprising to us. It really comes back to the binding capacity of the capsid, and we can talk a little bit about that. Mm-hmm ... this capsid is extremely unique and something that we created in our labs, and we believe that it's gonna bring significant amount of microdystrophin expression to these kids. Going back to your original question, the dose, our preclinical studies show that regardless of the dose, we were getting very significantly high expression. We're continuing to do work looking for a dose curve. With that said, we'll announce the dose when we have it. It'll be later on this summer to early fall. Mm-hmm. Right now, I would expect that 1E14 would be the highest dose that we would need to go to, but it could be easily in the E13s. Okay. Good. Very helpful. Since this is a new capsid, I know you based on some backbone there, do you expect any major differences in terms of, you know, existing AAV-negative patient population to selection, the percentage of patient that could be? Yeah ... utilizing, antibody positive? Yeah. The answer is we do not expect it. You know, we're doing some work with a third party on this right now. Mm-hmm We do not expect, and I'll give an example why. Mm-hmm. One, there is cross reactivity between AAV9 and AAV8, which is, you know, similar to RH74 from an antibody standpoint. And this capsid called SLB 101 is a modified version of AAV9. Mm-hmm. We do not anticipate any differences in antibody, cross-reactivity between AAV9 and... Okay ... SLB 101. Mm-hmm. What we did with SLB 101 is we created it to look at specific receptors. We didn't focus on the antibodies. We were looking at receptor activity within skeletal and cardiac muscle, and we inserted peptides and made point mutations specific for these receptors, all with the theory that binding capacity has a major role in expression and how we can overcome some antibodies. We've done some work on that as well, and our hypothesis is correct. This is why we're getting so much significant increase in micro DNA expression as well as distribution, but more importantly, we're seeing expression after transduction. We're dosing, transducing, and expressing all within a week. Mm-hmm. We can see expression down to four days, now we're doing additional studies to see if we can see it in even before that. We're seeing more expression in four days than we would see at the end of the month with AAV9, with our first construct. Significantly different profile. Mm-hmm. Very helpful. What is the highest dose you used in non-human primates? What is the dose limiting toxicity there? We have not disclosed the highest dose. I will tell you though, it's 2- to 3-fold higher than we anticipate the highest human dose to be. Mm-hmm. As I mentioned before. Mm-hmm you know, be 1 E14 would be the highest dose that we believe that we'd go, most likely it's gonna start in the E13s. Okay. The question more like from the safety perspective. Safety what is the, like dose limiting toxicity? Yeah. What is the highest you dose? Yeah, we haven't disclosed the highest dose in the, in the GLP tox- Mm-hmm ... but it's significantly higher than we anticipate to be in humans. However, we dosed. Mm-hmm ... our non-human primates. We started that trial in December. Mm-hmm. That trial concluded in mid-March. Mm-hmm. From the time of the study start to the time of animal take down, all the animals did very well. There were no unscheduled sacrifices, it went as smooth as we anticipated it. We did not see anything in the trial that would give us concern. However, I do not have the tox report yet. I will get the tox report very soon. I'm hoping within the next couple weeks 'cause we did end the trial mid-March. I don't have a full tox report to provide anybody. Mm-hmm. Okay, good. Then, since you know, the phase I initiation will be very soon, I'm pretty sure you thought about the prophy regimen. Yeah. Any thoughts on Soliris prophy? I think, you know, we're gonna let the animal studies dictate sort of how we think about it. Based on what we've seen to date, because this capsid is also liver-detargeting, if you think about it from a dose standpoint, even if we end up at 1 E14, that's significantly lower than Solid's original 001, which was 2 E14. It's also liver-detargeting, about 1 to 2-fold liver-detargeting. You're going to get, you know, the impact to the liver should be about a quarter of the amount that you had with the original 002 program or 001 program. With that said, we're gonna let the animal and data dictate it. Right now our current regimen will be steroids only. Mm-hmm. We will look at it to see if we want to augment this with, you know, Sirolimus or something else, but we'll decide that later. Mm-hmm. Okay. Very helpful. I know you do have a Ultragenyx collaboration- Mm-hmm ... with your, construct. Any update there? Any, you know, do you think a wide will still be a good backup, strategy at this point? There, you know, we have not disclosed any of the relationship, the partnership with Ultragenyx, publicly. They've been a very good partner. We're constant communication and collaboration with them. We're all rooting for the children, you know, the first. Any program that can help, you know, make a difference in these kids' lives, that's what we're all trying to do. They've been a great partner. Their program's their program. They have. I don't know what their timelines are, and we don't discuss them. Okay. Yeah. Okay, that's fair. Then now go back to manufacturing. Yeah. I think that's another thing that raised during the AdCom. Yeah. Maybe discuss a little bit your triple transfection based manufacturing. I know, you know, change from. Yeah ... previous HSV. Regarding the yield and also maybe one very technical aspect, like% of full capsid. Mm-hmm One last is the manufacturing capacity. Yeah. Mm-hmm. There's a lot there. you know, manufacturing CMC was core to us, you know, from, you know, on both sides, both AavantiBio as well as Solid. Now they're all combined together. Mm-hmm. You know, the team is a world-class team now. I mean, really, top to bottom, led by Paul, who, you know, previously was at AavantiBio and then before that BridgeBio, has really put a unbelievable team in place and process in place and we've been building our own platform since the announcement of the merger of the two companies. Really has already taken, you know, shape and we're seeing robust changes into the process. We feel very comfortable that our current process, even heading into phase I, can be very similar to what we expect further down the road. From an empty to full ratio, you know, while I will not, you know, announce the exact number because the numbers can fluctuate, but it's greater than 80% full. We had that with all our programs, even, you know, our FA program, and BAG3 and all these other programs that we're working on, greater than 80% full. We feel that if we can stay above 80%, then from a variability from batch to batch, you're going to get a very, you know, comparable conclusion there. To be determined as we move forward, but our process was very robust, not just for this Duchenne program, but for our other programs. Truthfully, we are probably on the cusp of making some great strides just on our manufacturing platform, regardless of the program. We have, you know, this is a triple transfection platform with Duchenne. Mm-hmm. We also have dual plasmids. Mm-hmm. as well as a single plasmid platform. The dual plasmid platform is getting significantly higher yields, lower cost because you're using 1/3 of the material. Most likely will end up in our BAG3 program because it's moving relatively quickly. just on from a platform standpoint within the company from a manufacturing side, we've made great strides. You asked about yields. We haven't disclosed the yields but, you know, one of the issues that when you think about why you started with HSV, you went with HSV originally back in the day because of yields. We've made such progress with the triple transfection and now the dual transfection platform that we're getting equal yields, if not higher yields than HSV, but without all the residual issues that you have with HSV platforms. We're very excited about it. From a scalability standpoint, when you think about Solid's original SGT-001 program, they're roughly at 250 liter. We're already at 1,000 liter. We have the ability to scale higher. Just within our own organization, within our headquarters, we have, you know, almost 22 liters, 10 liters, 50 liters, 250 liters, and 500 liters. Our process development team can scale up to 500 liters within our own headquarters, which is unheard of for a small mid-cap company like ours. We're extremely excited about manufacturing in general, when it applies to our Duchenne program, we feel very confident in our first in-human dose. Very good. Now switch gear. We have a few more minutes. You do have a tons of cardiac pipeline assets, and you have several, you know, planning to move to clinical development. Maybe, you know, talk about your differentiated capsid and also the reason to select the key, you know, the lead indications there. In cardiac? Yeah, cardiac. Yeah. When we were building out cardiac, our cardiac platform. We have roughly four to five programs that are in active development one way or shape or form. BAG3 is that lead program, but we have others that are moving up relatively quickly. We, you know, from a commercial strategy standpoint, a corporate strategy, we wanted to make sure that we approach something that had very clear clinical endpoints, something that you could hit relatively easy, or see relatively easy in a short period of time. Hopefully, some of these programs won't even have to go 52 weeks out because you can look at the cardiomyopathies and arrhythmias, et cetera, in a six-month study or less. All of them have a high unmet need. There's no underlying cure for these programs, for these disease states. You're taking beta blockers or other medications, and with a high mortality. Really high unmet need. While we have not disclosed the other programs, they're all significant. When you think of BAG3 has roughly 29,000 lives in the United States, and that's, you know, all lives that have been diagnosed. When you look at the people who are, you know, banging down the door looking for a drug right now, it's as big as Duchenne. You know, you would be talking roughly 10,000 patients that need treatment right now. Once you're in BAG, you have, or once you're symptomatic with BAG3 and you end up with cardiomyopathy, you're gonna end up in heart failure. 25% mortality once you're symptomatic in the first year, 50% by year five. There is no treatment for this. We are taking a modified transgene as well as a promoter that I have not disclosed, and I won't disclose it today either. RH74. RH74 is our capsid. As I mentioned before, this was on a triple transfection manufacturing platform, but we've made such progresses in our manufacturing platform in general, we might be moving this to a dual plasmid manufacturing because we're getting better yields, better purity and lower COGS. We're excited about this program. Our other programs, we're gonna announce up at a conference either late this year or early next year, and we'll announce our entire pipeline. You'll see, in three years or less, I believe that we'll be one of the most significant cardiomyopathy companies in biotech. That's good. Maybe any thoughts on, you know, data update from these programs? Pre-clinical data. Yeah. Initial R&D finding. From the Duchenne program, as I mentioned, our tox study is completed. Mm-hmm. We have not really thought about when we're gonna present that data, if we're gonna present that data. We're gonna file an IND later this year. I think everybody will be just focused on first in human dosing, but we'll. Mm-hmm. consider it if it's, if the investor groups really believe that it will make a difference, we'll consider it. As far as BAG3, we're going into non-human primate study later this year. We ordered the non-human primates in February. Unfortunately, they're backordered, and we are set to get them somewhere right around into Q3, early Q4, and that'll start the Dose-range finding. We'll move into, as soon as we finish the Dose-range finding, we'll move into IND-enabling tox and manufacturing next year. We'll be pushing for the IND, you know, in a short period after that. The other programs, they're in mice. Mainly, like, one of our programs for Hypertrophic cardiomyopathy, we have 20 different constructs that have been made, different promoters, different capsids. All of these are going head to head against each other so we can have what we believe will be the best in class program, 'cause there will be competition in that disease state. The other program for dilated cardiomyopathy, we haven't disclosed, but we're doing the same thing, multiple different constructs, different capsids, different promoters, and, you know, working on a mouse model there. With that said, I think, we're very excited about the whole platform with cardiac as well as our cardiac capsids. We have a cardiac capsid library that's going into second round non-human primates and pigs in this summer, over the summer, and then third round at the end of the year. That's gonna be, we're gonna use these capsids not only for non-dilutive financing, but as well as, our pipeline. Mm-hmm. Well, very helpful. Maybe last question for you, Kevin, the cash. Yes. Yeah. Gena, that's always top of mind for most biotechs these days. We ended Q1 with $185.5 million in cash. We are guiding the street that takes into 2025. Okay. That will be sufficient to support the initial-. Absolutely. phase I. Oh, yeah. study with DMD and Okay. And move everything else forward as well. Okay. Yep. Good. Well, thank you very much, and we look forward to the dinner tonight. Yeah. Thank you so much, Gena. Thank you, Gena. Okay. Thank you.