Good afternoon, everyone. Welcome to Barclays Global Healthcare Conference. My name is Gena Wang. I'm a Senior Biotech Analyst. It is my great pleasure to introduce our next presenting company, Solid Biosciences. With us today we have Bo Cumbo, President and Chief Executive Officer. Bo, maybe before I dive into the questions, do you want to give a very brief overview of the company?
Yes. Thank you, Gena, and thank you, Barclays, for the invitation. Yeah, it's our Solid Biosciences, we are precision, precision genetic medicine company. We're focused on neuromuscular and cardiac diseases. We also have multiple platforms that we work on, both cardiac, and skeletal capsid library, as well as a manufacturing platform that we develop different plasmids for, like dual plasmids for manufacturing expansion. So it's a great company. We work on about four or five different programs, both in neuromuscular and cardiac diseases, and one of those which our DMD program's moving into clinic right now.
Okay. Great.
Thanks.
Maybe before I ask you specific questions.
Yes.
I will ask you about the recent licensing deal with Armatus Bio.
Yeah.
You know, so maybe, like, how much data did they see? And then, you know, what is the, you know, the regarding the upfront payment, and is there any contingency upon certain, say, milestones?
Yeah.
Mm-hmm.
Now, we're very excited about this deal. This is the first one of many that we're hopeful deals that we'll be working on, to get our capsids out, as well as our plasmids. It's not just gonna be capsid, but it's gonna be our plasmid, our dual plasmid. But they got to see our preclinical data. We gave them an MTA first, so they got to play around with the capsid, actually do work with it, and see if the results that they were gonna get, in their hands matched what our data showed. And it did. And they felt very comfortable moving forward. It's, you know, typical milestone-driven. You know, it has an upfront. We did not disclose the upfront. And I'll talk about our strategy as well, because I think it really does matter.
And there will be milestones and, you know, mid-single digit royalties along the way. So we're very excited about it. You have to understand what our plan is. Our plan is to get our capsids, our multiple capsids, as well as our plasmid, our dual plasmid, out to as many companies as possible. If you understand the life cycle of genetic medicine, you know it takes a long time. The most important thing in our companies, you know, outside of myself and all the other gene therapy companies, is time. You do a lot of work upfront, making the capsid, doing the mouse work that you need to do, then the non-human primate. That work typically takes two to three years. You don't wanna go backwards in time.
And so, you know, what we try to do is we try to give our capsid at a moderate upfront. Moderate upfront. And then try to incorporate it into as many platform programs as possible. So this is the first one. We have other companies that are excited about our capsids, and we're just gonna continue to try to get it out.
Does that also apply, you know? I do know you also have a platform regarding the AAV, you know, capsid engineering.
Yeah.
Does that also apply to, say, the hard tissue target?
Yeah.
Or capsid engineering?
Yeah. It applies to everything. We're gonna. We're focused on getting our capsid and our dual plasmid.
Mm-hmm.
which will increase yields 2-5 times for gene therapy. We're gonna get that out to as many companies as possible. And, you know, these smaller companies, they don't have the $10 million, $15 million that they can pay upfront. So it's a limitation. It's a bottleneck for these guys. And so, we work with them, make sure that we can get it in their hands, get it into the trials, and that way, long term, our goal is to get our capsid in as many programs as possible, and then get our, our dual plasmid in as many programs as possible as well. We'll make royalties off that as well.
Mm-hmm.
The dual plasmid's very, very interesting. You know, the biggest limitation in gene therapy is COGS. With our dual plasmid, we can increase yields, you know, 2-5 times. So, for example, if somebody ran a 200-liter batch on a program, any program, and they get, you know, 10 patients out of that 200-liter. By switching from a triple transfection to our dual plasmid, they're gonna go from 10 patients to 20 patients, up to 50 patients. COGS are gonna dry up dramatically and decrease. And that, that's gonna open up also for companies to use their dual plasmid and get it into a lot of populations that are really, really small. A lot of companies don't go into truly orphaned drugs, like, you know, sub-100 to 1,000 patients, because of the risk and the cost of goods.
If I can change that for them and get their disease program, it's gonna open up for a lot of other diseases. We're very excited about our plasmid.
Mm-hmm.
As well. You'll hear more about that.
Okay.
We just filed all the IP in the last month.
Okay. On the other hand, I think it's very, you know, a noble way to share, you know, your early discovery with other companies. On the other hand, you know, will you limit the indication so that you also you know, the major large indication will be in-house?
Yeah. I mean, we'll keep it for Duchenne. We'll keep it for CPVT. I mean, you know, we'll keep it for those two indications, at least. Probably most likely BAG3 as well. But, you know, we'll get it out to everybody else.
Mm-hmm.
If you looked at the license last week, it was also nonexclusive. I think that that's something that you should take a look at, because I, I do plan on getting it out there to as many people as possible. I'm not gonna try to limit it to, to one company.
Mm-hmm. Okay.
So the data's really good. I mean, like, you look at our Duchenne program, for example, you know, you're getting, you know, 2-5 times different biodistribution in the quad, the gastroc. But just as important, the diaphragm. The diaphragm is, like, 5-10 times greater. And diaphragms are hard to dose. So, when you think about some pulmonary indications that people can go into, it really does open it up.
Okay. Good. So now your DMD indication.
Yeah.
I do know you put a,
Yeah.
Earnings release this morning. Maybe a little bit update.
Yeah.
On the program.
Very excited. You know, your first biggest hurdle in getting a drug to the clinic is the IND. The second is the IRB approvals. And we're excited to announce that we got both IRB approvals done last week. Both Nationwide Children's Hospital, as well as UCLA, were IRB approved. And that opens up a lot of a lot of doors for us. And that was our biggest hurdle. That's what we were waiting on. It took about 60 days longer than we anticipated, because the sites, UCLA and Nationwide Children's Hospital, they had some staffing issues to fill the IRBs. If you know about IRBs, they're separated from the PI. You know, it's a separate entity. So you can't you know, you have to work with the IRB, and you have to in our trial, it's gonna be obviously in Duchenne, so and it's gene therapy.
So you need a neurologist. You need an immunologist. And it's hard to schedule these. It took about 45 days, 60 days longer than we anticipated, but we got them done. And they're, they were approved as of last week. You're not allowed to recruit for patients until you get IRB approvals. So Monday, we started now talking to patient advocacy groups. All the physicians at UCLA and Nationwide are now talking to other physicians because of the IRB approvals. So we have scheduled our site initiation visit in April. That's the next step. So you do IRB approvals, then you go to site initiation visit. That activates the site. Then the sites can. It's basically you're training the site on your drug. And then they start recruiting patients, screening patients, getting them in trial. So this was a huge step for us. We're very excited.
Now we can start really moving forward.
Mm-hmm. So there any stepping up. The stacking phase for the first patient, second patient.
Yeah. The FDA mandates 30 days.
Okay.
So we have to wait 30 days in between patients. So you dose your patients, you know, on day one, whatever day one is. And you're not allowed to dose your patient till 30 days, your second patient till 30 days. Typically, you know, it's not gonna always be 30 days. You schedule the patient. You have to work with their schedule to get them into the hospital and dose. But at a minimum, it's 30 days. And most likely, it's gonna be a little, you know, a little delayed.
Mm-hmm. Okay. So, maybe I think of this will be the new capsid.
Yeah.
Moving to the clinic, right?
Yeah. Yeah.
Maybe talk about a little bit about the backbone capsid, you know, safety profile, and now how the preclinical data look like.
Yeah.
You know, with the engineered version, and what are the key data points you would be looking for for the human safety?
Well, you know, this capsid's very cool. Like.
Mm-hmm.
We took this capsid, and we modified it. It was an AAV. It was a parental AAV9. And we modified it to where we add peptides for endocrine receptors, across the capsid. And we noticed when we first made this capsid, we wanted to increase the binding capacity and the speed of transduction for this capsid. And we noticed in our early preclinical studies that we were seeing expression in as little as four days. And that's something we typically have never seen before. We work with a lot of other capsids. We work with all of them, AAV9, RH74, AAV8. You don't expect to see expression typically in four days. And we weren't seeing just a little bit of expression. We were getting, like, 50%, 75% in the heart, the diaphragm, in four days. We repeated that study 'cause it was a little shocking.
And we also took a look at 2 days. And you can actually start seeing expression in 2 days and 4 days. We then took that same capsid, and we went into a study with IVIG. And we were looking at, so we dosed mice with 0.5 mg/kg of IVIG, 1 mg/kg, and 1.5 mg/kg of IVIG. And then we dosed the microdystrophin on top of that to see if it could, you know, it could go through the IVIG. And it did. We're getting a significant amount of expression, even in the face of IVIG. So the capsids acted very different. We also noticed that dose curve was hard to find. We had to go all the way down to 2E12 to get a dose curve. And we've presented that data.
At 3E13, we're maxing out at 100% microdystrophin expression. Then we went up to, I think, 5E13. Then obviously, 1E14, 3E14. There was a debate internally, you know, do we start in patients at a lower dose? 'Cause we were already at 100% microdystrophin expression at 3E13. Do you go down to, you know, 5E13 and start your dose? But we wanted to put the best foot forward. We looked at our safety profile. In non-human primates, we dosed it all the way up to 3E14. The FDA did not have one single question in our IND regarding safety. All the animals did very, very well. There were no mortality events. There were no unscheduled takedowns, no alteration of any kind of immunomodulation. The animals did very well.
So with that safety data in hand, you know, and with Sarepta and Pfizer and RegenxBio and everybody else out there, we were like, "You know, let's put our best foot forward and try to help these kids. And so we went 1E14. We're gonna see what happens.
Mm-hmm. So with 1E14, can you remind me, do you do, prophylactic Soliris?
No. We just use prednisone.
Mm-hmm.
Just prednisone. We bump up the dose, I think, 2 days before we dose patients, and then we taper down 30 days after.
Mm-hmm. So any concern there given the AAV9 history?
Based on the animal data, no.
Mm-hmm.
You know, you know, I mean, I think, you know, the gene therapy field has changed a lot. It's not just AAV9 that you need to think about. You need to also think about manufacturing. CMC plays a major role in SAEs and potential SAEs. When you have a, you know, lower full-to-empty ratio, you're dosing these kids at a VG to KG basis. So, for example, Gena, if I had, like, a 50% full ratio.
Mm-hmm.
You know, and I'm dosing you at 2E14, I'm really having to, you know, if I wanna get you to the VG to KG, I'm really dosing you at, at 4E.
Mm-hmm.
So this is where full-to-empty ratios come into play. I think, Solid has one of the highest full-to-empty ratios of any of the groups that I work with, that I've seen. We're on a very consistent basis, 77%-81% true fulls. And I think it's very important to understand what I mean when I say true fulls. You can lump in, you can look at true fulls. You should look at true fulls, partials, and empties. Some people lump partials in with empties. Some people lump them in as fulls. We don't believe that they're active. We lump them in as empty. So 77%-81% on a batch-to-batch basis is pretty consistent on a true/full basis. If we lumped in partials, you're talking 98%-99%.
So when you think about it from a safety profile, when you're going up to VG to KG, you're really not having to increase too much. And then other companies have had that problem. And I think early days and the reason I bring this up is, you know, early days in gene therapy, you did not have a ratio like that. You were probably 50%-55% at best.
Mm-hmm. Mm-hmm.
So it matters.
Okay. So, you know, with such a high full capsid, true full capsid, and, is that, like, how scalable that is? Like, if, you know, we wanted to do the commercial scale?
Yeah.
Would that be easily translatable?
Yeah. So we use cesium chloride, right?
Mm-hmm.
A lot of times, cesium chloride is hard to scale because you're having to take that step to, you know, titrate out the drug that's full.
Mm-hmm.
We automated it. We created equipment on our own, and then we worked with a third party to make this machine scalable. We have multiple CDMOs that actually want to buy this machine now. And it's all automated. So we take it out of the controller's hands. It's now it goes down. It siphons out the exact same amount every single time of the true fulls. You can do multiple vials at the same time. And it's very exciting because we can now scale up cesium chloride, you know, purified drug. I think we're the only company that I know of that does it.
Mm-hmm. Yeah.
I'm selling the machine to the CDMOs as well, so, so.
That could be side business.
Yeah. But it's innovation. I mean, look, we're very focused on delivery.
Mm-hmm.
When you think about gene therapy, delivery is critical. There are three flavors of delivery. It's your capsids. It's your CMC. It's your promoters. We own two of the three platforms, capsids as well as manufacturing.
Mm-hmm.
We make, we put a lot of effort behind it.
Actually, since you mentioned promoter, you know, does this have a muscle-specific promoter?
Yeah. CK8. Yeah. We use CK8.
Okay.
We haven't disclosed the promoter in BAG3 or CPVT.
Okay. The backbone for the cardio program, is that the same or different?
You mean the capsid?
Capsid. Yeah.
For CPVT, it's AAV8.
Mm-hmm.
For BAG3, it's RH74. But there, there's an asterisk on the BAG3 program. I didn't have SLB101 at first. And so we've been dosing up multiple sets of non-human primates with different constructs to pick our lead candidate. And if SLB101 looks like what it looks like in Duchenne, then we might switch.
Mm-hmm. Okay. So now, with the third patient, do you think it's realistic later this year or 2025 you will share the data? And, what kind of data will you be sharing?
Yeah. So.
With the initial data?
Everything is still on track. We.
Mm-hmm.
You know, we knew that the biggest hurdle was first getting the IRB approvals. We got them last week. Ecstatic about that. Now we can start the process and talk to patients. We expect 3-4 patients to be dosed. You have to wait 30 days in between dosing. So over late summer, we can announce that we've dosed our 3-4 patients, announce that we've hopefully, knock on wood, done this in a safe manner. That puts us on a timeline of Q4 to announce our data. What are we gonna announce? We're gonna have all the data. So we'll have, you know, CK data. We'll have Titan, you know, we'll have NSAA, dystrophin-positive fibers, mass spec, the gamut of data that you would expect.
Mm-hmm.
We'll release that Q4. I mean, we might hold it to a conference that's right after Christmas. But, you know, we'll, it'll be in that timeframe.
Okay. Good. So, you do mention, like, the quite a lot of different measurements.
Yeah.
Maybe starting with the protein level.
Yeah.
We did see already a few in a different program showing their protein level. What will be your and I'm very happy to hear you will also measure using mass spec because that's also mass spec western, you can get a better understanding of a true protein expression there, right?
Yeah.
What kind of a threshold you will be looking for? I know this is the first dose.
Mm-hmm.
But what you are looking for regarding the.
You know, realistically, we're gonna be focused on dystrophin-positive fibers to make the choice on how many fibers we're getting to.
Mm-hmm.
To move the program forward. You know, the methodology on Western Blot, you know, it really changes from company to company. You know, what antibody you're using, how long are you exposing, what's your standard curve, what's your, the amount of protein you're putting in wells. It varies greatly.
Mm-hmm.
Mass spec will give us a direction. And then, dystrophin-positive fibers using Flagship as a third party will help us understand how many how many fibers are we actually transducing, expressing. And if we're happy with the number there, we're gonna move forward with a global trial. We're filing CTAs first half of this year.
Mm-hmm.
UK.
Mm-hmm.
As well as Canada. Then Italy is coming third. If we're happy with the data at the end of the year, then we're gonna announce that we're going into a global trial.
Mm-hmm.
We're already working with the thought leaders, Dr. Muntoni, Dr. Mercuri .
Right.
McDonald, you know, all the right people, to help us set up these trials and to move forward.
When you say, like, you know, global trials, are you thinking about, say, accelerated approval path, or you want to do traditional, like, say, controlled study and moving forward?
Yeah. No, it's a great question. I think you have to think about it both ways.
Mm-hmm.
I think you can lean into accelerated approval in the United States and, you know, I'm using a surrogate and marker microdystrophin. Ex-US, you need to hit a clinical benefit, which means you need to have a, you know, placebo control trial.
Mm-hmm.
So what you have to think about is what are we trying to accomplish? Well, we're gonna lean into an accelerated approval process in the United States using a surrogate marker. So what does that trial look like? It's gonna look very different than what you're gonna have to have for the ex-US.
Mm-hmm.
That's gonna be a double-blind placebo control trial with a clinical benefit so you can get reimbursement. Otherwise, you're not gonna get reimbursement. It's gonna be very challenging. So, you know, we're not going to think about it as one-size-fits-all, especially in the world that we're living in today with the regulatory agency that we have, which it's I'm grateful for. So, we're gonna lean into accelerate approval US and then do the right trial, XUS, to hit a clinical benefit, get reimbursed.
Mm-hmm. Okay. That's very good. And that actually, I think, at the protein level will become very important, right?
Yeah. Protein level becomes that's what Dr. Marks has stated publicly. Yes.
Yeah. Yeah. And then what will be the, let's say, initial, like, the threshold you will be looking for that you think it will be competitive enough for you to warrant further development?
Yeah. Yeah. So, I look at DMD, as I mentioned before, dystrophin-positive fibers, if we can get to that 40% where you're close to, you know, expressing 1 out of every two fibers at, you know, roughly 40%, I think that's gonna, that can give you enough expression to hit a clinical benefit for these kids.
Okay. So positive fiber, I felt a kind of low threshold, 40%. I felt, like, a lot of.
Dr. Chamberlain has mentioned.
Mm-hmm.
That, you know, if you have one positive fiber, it should provide a benefit and structural benefit for this fiber that's beside it. So that's why we're looking at that. Of course, we want higher, but we'll see.
Mm-hmm. Regarding the protein expression and.
You mean, like, a mass spec or?
Yeah. Like a mass spec or.
Yeah.
And then you can still, like, draw the linear correlation and then come up with percentage of protein.
Yeah. It should be determined on that. We have not announced that yet.
Okay.
Yeah.
Okay. Good. I know we are running out of time, but quickly, from the initial, say, safety profile you gained from this, how would that translate to, say, your cardio program? Because you also have a suite of other, you know, the new capsids coming to clinical development.
Every program's different, right?
Mm-hmm.
I think it will give us a lot of confidence in the capsid.
Mm-hmm.
But it will also give us a lot of confidence in the manufacturing platform because I do think the empty-full ratios matter.
Mm-hmm.
Especially when you're, you know, you're dosing, you know, pretty big doses. And our platform, our CPVT drug, which is scheduled for IND filing and submission in Q1 of 2025, I mean, this, this drug, you know, we're very excited about. 20,000 patients in the United States, highly fatal. They get diagnosed five to 10 years of age, 40% mortality in 10 years. There's not another company in the space. Our manufacturing material is at the highest purity of any drug that we actually make internally. And, so we feel very confident about the purity of the drug. And I think it's gonna, you know, lean into that. I that program has the chance to change Solid forever.
Mm-hmm.
You know, it's a major, major market, high unmet need. The global, we're doing an ad board in the next couple of weeks. The global KOLs are all over it because this can change the course of the disease. Right now, there's nothing.
Mm-hmm. Very good.
Yeah.
Well, thank you very much, Bob.
Thank you.