Good afternoon, everyone. My name is Gil Blum, and I am a Senior Analyst here at Needham & Company. I'd like to welcome you for joining us today at the final day of the Needham Healthcare Conference. It's my pleasure to have with me today Bo Cumbo, President and CEO of Solid, and Gabriel Brooks, Chief Medical Officer of Solid. They will discuss their ongoing efforts in DMD. With that, Bo, you can continue.
Yeah, thank you very much, Gil. And thank you, Needham, for inviting us to the conference and to allow us to present. We really do appreciate it. I'm going to be making a number of forward-looking statements today. Please, everybody, the slide deck will be up on our website. Please take a moment to look at forward-looking statements, as some of my statements might change over time. All right. Listen, Solid Biosciences, we're very grateful that everything's coming together. We're trying to pioneer, really, the next generation of precision genetic medicines. It starts with our neuromuscular programs, not only for Duchenne, but also for Friedreich's ataxia, and then followed by very unique cardiac programs in CPVT, as well as TNNT2. We also have an entire department focused on delivery.
We believe if you're going to be a true next-generation pioneer in genetic medicine, you really need to make sure that you focus on delivery. Delivery is everything, whether it's capsids, it's promoters, CMC purity, immune modulation. We have a whole division that focuses on that. Today, I'll spend most of our time talking about our DMD program, and I'll touch on our FA program, as well as our cardiac programs. Here is our pipeline slide. We are moving things forward at a pretty reasonable clip to date. Let's dive into DMD. It is the next-generation Duchenne program called 003. Now, we fundamentally believe that Duchenne is a muscle integrity and dysfunction disease.
Therefore, if we want to give not only ourselves, but our investors, as well as families and KOLs confidence in our program, that it's having a benefit, we view the world as how can we preserve muscle integrity by looking at a host of different biomarkers and signals so we can shore up the muscle. If we feel that we can shore up the muscle, but not only the heart, but also skeletal muscle, then we believe that over time, we can actually change the course of this disease for these little boys. That is how we looked at the world. We built this program, this 003 program, eyes wide open, and rebuilt it from ground up. We started with our next-generation program, started with our construct design, our microdystrophin transgene. It's unique.
It's the only one of its kind where we have two different hinges. We have the most flexible protein that is out there, as well as the nNOS binding domain. We believe nNOS plays a very, very unique role and important role in Duchenne. We have this R16, R17 binding domain. When you have R16/ R17, you're able to recruit for alpha-syntrophin. When you're able to recruit for alpha-syntrophin that binds to the R16/ R17 domain, you can recruit nNOS. When you see nNOS activity, you can see a whole host of different events, whether it's reduced inflammation or fibrosis. Also, in Becker's, you can actually see that patients that have naturally occurring nNOS end up having longer ambulation and a better outcome. That's why we focus so much on this program, on this transgene. We also recreate our capsid.
It's the only capsid of our kind. After I go through the presentation today, you're going to hopefully believe what I believe is that SLB 101, this muscle trophic capsid, is the best skeletal and cardiac transducing capsid on the market that's been dosed in patients to date. Hands down, that's what we believe. We also have these RGD peptides that have been inserted into our capsid. These RGD peptides actually bind to two integrin receptors that we've been targeting. We know that these integrin receptors are upregulated in both fibrotic or inflamed or Duchenne-type tissue. That's why we believe that we were going to see such a benefit. We did see that benefit. It has an increased binding capacity. That means it really binds to these receptors very, very quickly. It transduces within two to four days. You see expression.
It transduces very quickly, and it increases expression. We also have another aspect of our program that's not listed on this website, on this page today. That's CMC. We believe that we have some of the most pure product that's out there from a full-to-empty ratio greater than 80%. We think that that matters. I'll talk a little bit about that at the end of this presentation. Today, I'm going to be talking about the first three boys from a dystrophin standpoint. However, in this presentation, we have six patients' worth of safety data that we'll go through. You can see the weights and the ages of the boys and approximately how long these boys have been dosed at the time of this presentation. Dosing has been well tolerated across the board.
There's been no SAEs, no SUSARs, no TMA, no aHUS, no hospitalizations, no third agents utilized outside of steroids. Very clean program, and we're very, very excited about it. Top line, what did we see with these boys? This next-generation program, we believe, hands down, has the best data that is out there, whether it's microdystrophin expression, which is the top line. I'll show you more data in a second, whether you're looking at Western blot or mass spec. It's the highest numbers with the mean at 110% for Western blot, 108% for mass spec. That translated down to how many positive fibers. It's the most robust data to date that we've seen from a dystrophin-positive fiber standpoint with the mean at 78%.
It is going to be quite interesting when I show you the data, how uniform it goes from vector genome copies to Western blot to mass spec to dystrophin-positive fibers to the dystrophin-sarcoglycan complex coming together, and then all these muscle biomarkers. We look at muscle biomarkers. This should give us a sense that from a muscle integrity standpoint, that we're doing something within the body of these children. We look at it from three different types of biomarkers: the acute phase of muscle damage, the chronic phase of muscle damage that's less variable. If we can shore up the acute and chronic phase, then we believe that embryonic myosin heavy chain will come into play. That is the muscle maturation phase of our biomarkers. We are having an effect on all three aspects of it.
It all starts with, can we get our capsid and our program to the muscle? And look at our vector genome copies per nucleus. It is very, very high, depending on the patient, pretty uniform across the board. When you look at the data that I am getting ready to present, it really starts with the copies per nucleus, the VCN, and it really translates very nicely down to dystrophin-positive fibers, Western blot, et cetera. As you can see here, top line, Western blot is on the left-hand side, Mass spec is on the right, some like Western blot because you can roughly compare to other programs, others like Mass spec because of the sensitivity. It really does not matter which one you like here. They are both the most robust and highest numbers that have been published. That translated extremely well down to dystrophin-positive fibers.
We fundamentally believe that if we are going to change the trajectory of these little boys' disease, you need to get greater than 50% of the positive fibers out there and really change the course. Now, of note, this is our intermediate biopsy. This is the first biopsy after being dosed. Most programs, when they show you positive fibers, and I think positive fibers really do help tell the story of what's going on within the muscle, most of the programs have a baseline biopsy, an intermediate biopsy, either at 8 weeks or 12 weeks, and then a biopsy at 52 weeks. You typically see fiber count, positive fiber count, go up from that intermediate biopsy to the week 52 biopsy. We are already starting at almost saturation levels at week 12. We believe that that will go up over time. We are very, very excited about this.
We also took it one step further, and we said, "Okay, now that we have positive fibers," which you see on the left-hand side over here, that's the same page that I just showed you, the same slide I just showed you on the left-hand side. Now look at the middle. How does this put the entire dystrophin-sarcoglycan complex together? How well does it put together? I don't believe that we've ever seen numbers this high of the entire complex coming together when we're looking at positive fibers for beta-sarcoglycan. Those two, the positive fiber count as well as the whole complex coming together, translated to the first time ever of seeing nNOS production or nNOS activity at levels that we're seeing here or levels, period. No other program has been able to show it.
Whether you're looking at thinking about fibrosis or blood flow or inflammation, this is where nNOS can have an activity. We fundamentally believe it's having an impact on these little boys, especially in the heart. I also want to call out, look at the baseline values. These assays are extremely well done. They're tight. You don't see high baseline values. Matter of fact, if you go read publications that are out there looking at baseline positive fibers for normal Duchenne boys, this falls right in line. These assays are really good assays. We threw the last line in for a change of baseline in case there was any confusion, in case anybody thought we were talking about changes from baseline. No, we weren't. We're strictly talking. We're all numbers up top. We just put that in for clarification.
Now, as we know now that we have the highest level of vector genome copies per nucleus, that translated down to the highest levels of protein, just raw protein, whether you're thinking about Western blot, whether you're thinking about mass spec, it didn't matter which one. That translated to dystrophin-positive fibers. We believe positive fibers really helped shape the story about can you get to clinical benefit. That led to the whole complex coming together. Now we want to ask ourselves, are we doing all this for nothing? Can we shore up the muscle? Can we increase muscle integrity, resilience, and preservation? We look at three different types of biomarkers. You have your acute biomarkers, which are going to be ALT, AST, CK, lactate dehydrogenase. They can be pretty variable. That's why you tie the acute phase to the chronic phase.
The chronic phase is more of the cardiac troponin I or titin. Titin is only released into the serum when the muscle is decomposing. It is less variable. This gives you a good play between acute and chronic muscle damage. Of note, you look at this slide, you say ALT, AST, that is a liver enzyme. Not in Duchenne, it is not. ALT, AST is a great biomarker for skeletal muscle damage in Duchenne. Some companies cannot use ALT, AST as a biomarker because they dose gene therapy and you have increases in ALT, AST. Not with our program. ALT, AST has been declining. We actually saw with our capsid in both mice as well as non-human primates that our capsid was liver de-targeting. We hoped to see that play out in our human subjects. We did see that play out.
ALT, AST only go down with time. We feel very comfortable using these biomarkers. Now, here's the results. The results look very promising. We're seeing across the board, both the acute, chronic, and muscle preservation phase, muscle maturation phase, all the biomarkers head in the right direction. There was not a lot of variability between patients, and they all pointed in the right direction. It gave us a lot of confidence in these biomarkers. These are the acute phase biomarkers. As I mentioned before, they can be variable. You tie CK back to titin, and CK can be the acute phase of muscle damage. Titin can be the chronic phase of muscle damage. It's less variable. They both head in the right direction across the board.
Now, once you shore up the muscle and you feel like you're having confidence that you're doing something in the body, you look to embryonic myosin heavy chain. Very important in Duchenne. These muscle fibers are often in an immature state that lead to persistent levels of embryonic myosin heavy chain due to constant muscle injury and incomplete repair. It actually depletes the entire satellite cells, the satellite cells. What you want to see is you want to see a major reduction in embryonic myosin heavy chain. You know that the muscle is maturing for the first time in Duchenne, and you're able to hopefully see a benefit. That's exactly what we saw. That'll be over on the right-hand side. We saw the decrease in embryonic myosin heavy chain.
To my earlier points on the left-hand side, thinking about sort of the waterfall of effects, you saw vector genome copies. Then that led to positive fibers or high levels of microdystrophin expression, whether it's Western blot or mass spec. Positive fibers led to the dystrophin-sarcoglycan complex coming together, led to nNOS activity, which you see on the left-hand side. The acute phase of muscle injury led to the chronic phase of muscle injury, which you see titin in the middle. Now we're shoring up muscle and muscle maturation phase, which is on the right-hand side of embryonic myosin heavy chain. No one has ever shown this complete of a data package in Duchenne. It gives us a lot of confidence that we know now we're doing something in these little boys' bodies. We're hopefully shoring up the muscle. We're shoring up preservation and muscle integrity.
That is going to lead to a clinical benefit as long as we design the clinical trial correctly and think about the right patient population, the right endpoints, the right baseline criteria, as well as the length of time to get to that benefit. We have taken into consideration all this. Now, something that we were hoping to see, we did not know. We had some hints in preclinical data, is that we would have an impact on the heart. On the left-hand side, what we saw in preclinical models, we saw two things. First, which is not on this side, we saw that our capsid, because of this increased binding capacity that I mentioned earlier, was getting expression in the mouse heart up to 75% by day four. Unheard of. It was such a high expression by day four.
We took a look at our capsid in human cardiomyocytes. This is the data that we saw. We saw a 20-fold increase in expression versus AAV9. We thought to ourselves, we should really take a look at these little boys' hearts via echo and see if it's making an impact. Now, too early to tell with patient number three. We waited till day 180. Day 180, and Dr. Brooks can talk a little bit about this in the question and answering, is when you start to believe that there are going to be long-term benefits and remodeling starts to happen in about day 180. That is why we showed the data here. You can see that there is a change from baseline. It looks like in all three of the patients. We are going to have more data from other patients going forward.
We also looked at, sorry, one second. We looked at serum troponin in these kids. We had two boys out of the six that had elevated serum troponin at day one, at baseline. Actually, three different measurements prior to dosing we looked at to make sure the readout was correct. Three different pre-dose baseline criteria or baseline measurements of troponin in these boys. We had two boys. This is patient number three. Patient number three had a 36% reduction in troponin by day 90. We're very pleased with that. We hope to see more patients with decreased troponin over time. Trying to, there's the slide. Sorry about that. I had a problem with my computer. This is the safety. I showed you all the dystrophin data on three boys, but this safety includes all six.
We had no SAEs, no SUSARs, no TMA, no aHUS, no hospitalizations. We did not have to use any third agents of any kind outside of steroids. Our most common AE was nausea. We do observe thrombocytopenia. We had one grade 3 thrombocytopenia. All thrombocytopenia, by the way, resolved by day 14. We did not use eculizumab. We did not use sirolimus. We just used steroids. We had no hospitalizations or no intervention of any kind. We feel very, very comfortable with the safety program to date. Now, I'll kick it over to FA. We got this IND open, and we announced this IND in January. We're very excited about FA. We're doing something that no one has tried before, which is combat both the CNS as well as the neuromuscular and cardiac manifestations of the disease all at once.
There's roughly 5,000 patients in the United States. I think we all watched Reata move their program forward. We're really excited about this program because we believe that it can be disease-modifying for the majority of the patients suffering from FA. Now, we're doing something very unique. It's the only dual-route administration to combat the neuromuscular and cardiac manifestations. We're actually dosing the patient both IV as well as IDN, or intradentate nucleus administration, going right to the source of the problem to make sure that we can deliver the drug directly to the patient. What we're doing, we're doing something pretty unique with our program here. We're using a pressurized catheter approach where we can deliver the medicine right to the dentate. We're using gadolinium in our program.
We'll be able to see day one via MRI, did we get the program, the drug right to where we want it to be into the dentate. We're very excited about this program. We dosed a lot of non-human primates over the course of many, many programs to make sure that we really are getting the drug right to the area that we want. We actually looked at both dosing IV only, IT only, IV IT, as well as IV IDN. We landed on IV IDN because if you really want to get to the Purkinje cells and the cerebellum, you really need to make sure that the drug is guided. You could use a capsid approach that crosses the blood-brain barrier, but it's going to go everywhere.
It is not going to be really specific to the dentate nucleus, which is exactly where you need to get to. That is why we landed on this approach. We are opening up sites over the course of the second half of this year, and we should be dosing at the end of the year. The study design, we have multiple different cohorts. We are going to be focused on cohort one, obviously, looking at non-ambulatory patients and really is to evaluate safety and tolerability of not only the infusion, but the gene therapy program itself. We will continue to move forward looking at ambulatory patients as well as ambulatory and non-ambulatory patients, and then going younger into the patient population as we gather more data. Now, cardiac program, we will start with our lead cardiac program, CPVT, catecholaminergic polymorphic ventricular tachycardia. This is a huge unmet need.
We're the only drug of its kind going into this disease state. This is a pretty big population. While you might not think you know of these kids, you probably have heard about children that have just passed away suddenly from arrhythmias. This is mainly caused by mutations in the RYR2 or CASQ2 genes. It really disrupts this calcium release, and it triggers abnormal contraction and relaxation that lead to arrhythmias. What we're trying to do is absorb the calcium, the excess calcium, so we can actually restore a normal rhythm, which is on this slide here. We're very excited. Our preclinical studies looked fantastic, and we could see a clear dose response in these patients in the mice with no negative safety profile.
We will be filing this IND in the first half of this year and hopefully dosing patients in the second half of the year. If all goes well, when you think about the three programs that we just talked about, we will continue to dose patients in Duchenne up to 20 patients by the end of the year, 30 patients by end of Q1. We will be meeting with the FDA later this fall to talk about our Duchenne program, accelerated approval, as well as our registrational trial, confirmation trial that's going to be going on ex-US. We should be dosing patients in FA. We will be filing our IND for CPVT in the next couple of months, hopefully dosing patients in CPVT at the end of the year. We will have three programs in the clinic, one of which have a registrational trial underway.
We also spend a lot of time on delivery. We believe that if you're going to be the leader in gene therapy and leader in the space, you really need to focus on delivery. We spend a lot of time on CMC from a purity standpoint, as well as capsids and promoters. Today, I'll just spend a little time here on manufacturing. We identified very early that while a lot of companies were talking about yields, we wanted to make sure that we had the most pure product out there. Purity to us is how full capsids versus empty capsids, what's the percentage? We think about it from really three different areas. We know that if you have a high empty ratio, a lot of empty or partially empty capsids, you're really dosing a patient at a vg/kg standpoint.
You're going to have to increase that dose pretty dramatically so the patient can get a true full vector genome copies. As you increase that dose to get up to that high levels of full capsids, you end up causing side effects. We spend a lot of time on purity. We have greater than 80% pure product or full to empty capsids in our Duchenne program, up to 90% in our cardiac programs, and very excited. We also know that it clearly will change your COGS. More importantly, as you increase your full to empty ratio, it also increases your protein expression. I think that that's one of the reasons that we have such a great program in Duchenne, not just because of the capsid and the transgene, but also because of the pure product.
Now, I already mentioned these near-term milestones, but we're actually very pleased with where we are to date as a little company, roughly 100 employees doing all this great work, both in neuromuscular, cardiac, capsids, and the pipeline. With that, I think I will turn it over to Gil, and we can go from there.
Thank you very much, Bo. I do want to remind the audience that they can ask a question through the ask a question box. Maybe just starting relatively at a high level, some changes in the agency and the FDA. Peter Marks was a big proponent of gene therapy. How is the company navigating this?
Yeah, it's a great question. We get this question a lot. Obviously, Peter Marks leaving the agency is a blow.
I do think that the philosophy of regulatory flexibility has been really within the agency at all levels of the agency, not just at the higher levels like the Peter Marks of the world, but all the way down to the reviewers of the division in multiple different programs, whether it's rare disease, oncology. I think that philosophy is pretty wide-standing within the agency. I doubt that we're going to see major, major change there. I also do take a lot of comfort in watching McCarthy's comments about rare disease. I think Senator Cassidy talked about it the other day, making sure that there was regulatory flexibility for these rare orphan drugs. While there's a lot of uncertainty because Peter Marks is no longer there, I do take a lot of comfort in knowing that broadly within the agency, there's a lot of people that want flexibility.
There's flexibility that wants from McCarthy, flexibility that's wanted from Senate Republicans that are making public statements. Now, as far as impact to us, I would call on Dr. Marks or some of the other people within the agency. Realistically, my team, the teams, the regulatory teams, the clinical teams, they're dealing with the division. They're dealing with everyone, the reviewers. That has not changed. We have not seen change. It has not impacted us to date. Maybe it will in the future, but to date, it has not. We do not anticipate it too. I also think about just myself, my career.
As I think about the history of working with multiple different companies and thinking about restructuring, you typically do when you come in and you restructure an organization, you do restructure managers, you restructure the admins, but you do not ever really restructure and want to harm the workers, the people that are doing the day-to-day work. I do not think that that is going to happen here. I also think about time to stability. When I think about change, whether it is in the FDA or whether it is in a company, the first three months can be unstable as you are putting in new staff, new leaders. Month four is always better. Month five is better. Month six tends to be the end of it. The company and what I am referring to as a company transformation, typically stable at month six.
The great news about us is we're going to be working with the agency in the fall for our Duchenne program. It is not anytime right now immediately. I expect everything to be stable.
That is very helpful. Another topic that we have gotten a lot of inbounds on, which is one of your competitors recently saw a patient death. This is through known toxicities of AAVs. I mean, the death is still pending investigation, but it appears in line with previous toxicities that we have seen. I would appreciate your two cents here as it relates to your own product.
I am going to turn this one over to Dr. Brooks, but I do want to say from the bottom of our hearts, our thoughts and prayers go to the family and to the families that have been affected. That is what I will say, and I will turn it over to Dr. Brooks.
Yeah, thanks. And Gil, that's absolutely right. I mean, I think first, it must be really tough for that family, and our thoughts are with them. The prospect of benefit for these patients with an AAV gene therapy always has to be balanced with the known risks. The way that we have come to SGT-003 and reimagined what AAV gene therapy can do is to focus on how can we make the most tropic capsid for the tissue that needs that transgene, which is muscle, and avoid organs where we could see safety liabilities like the liver. In addition, as we reimagine what AAV gene therapy could be, we also thought very carefully and innovated around downstream purification. Bo has spoken about how if you minimize the amount of empty capsids, that means that you're minimizing the overall particle load that the participant and patient is facing.
What we're very gratified to see with, yes, an early data set, but with one that's showing a remarkable safety profile, not least of which because we do not see any enzyme elevations, liver enzyme elevations, any hepatic injury elevations. That is novel. We know that there are other innovators in this space that are using really profound immunosuppression. Our approach is really to have changed the capsid to focus on the organs that we want to transduce and to avoid the liver. That is what we're gratified to see with glucocorticoids alone. We're seeing a very clean profile from a myocardial. We don't see myocardial injury. In fact, Bo is pointing to actually we are seeing myocardial potential early signs of myocardial benefit.
From a liver standpoint, what's remarkable is that we see that this happens to our experience shows that we're not seeing liver injury, which is really remarkable.
Another key topic is path forward for DMD programs with an incumbent placed. I mean, it sounded like the agency is very much open to accelerated approvals. I don't think that's changed. From a commercial standpoint, we do hear sometimes like, "Okay, why do I need three of these?"
Yeah, look, I mean, I would argue a little bit differently if we were competing against Sovaldi and HCV where unmet need has been solved. This is a very different scenario here where there has not been a cure. The unmet need has not been met. While we're making a lot of progress in Duchenne on multiple fronts, whether it's gene therapy, exon skipping, etc., the kids are not cured.
Therefore, the unmet need has not been met. We also know now that safety can be improved. There are a lot of paths forward. There are drugs. There need to be choices for children and families who have a child, any child in a rare disease, not just Duchenne, any child in a rare disease. Choices for KOLs. All drugs are a little different. I believe that the agency has made it very clear, and they have spoken publicly that accelerated approval is going to be on the table not only for us, but also for Regenxbio. It should be. It should be. Families should have choices. KOLs should have choices. Until we cure, and I mean really cure this disease, the unmet need has not been met.
Maybe a follow-on as it relates to product differentiation. This is slightly hypothetical. I mean, you're starting to see some level of signal in the heart. Is this what you would have expected given the nNOS domain? Because that's a bit of an angle.
Gil, I appreciate that comment. I'm a trained clinical cardiologist, and I'm a multimodality imager. I had a lot to think and to say about the way that we should be monitoring the heart. Let me be very clear. We were dedicated to the safety of every single participant that chose to be our partner in taking this drug. For that reason, we were assaying very closely the troponins and also looking at structure and function of the heart through echo. That's the principal reason. We're really grateful to share with you and all of the folks online that not only did we not see injury, but we saw promising signs of potential early benefit.
Now, you asked about the cadence. Should we expect such an early robust response? I will share. I was not expecting to see something so soon, except potentially, and this is a speculation, that maybe it's the improvement in myocardial blood flow because now you have nNOS properly localized, and that may be the reason that we're seeing this early benefit. It's something that's not been seen before. We feel now very much compelled to follow even more closely the heart health of all of our boys. We are exactly doing that, especially in the older populations where they have a lower ejection fraction, where they're starting to have mild decline in function of using cardiac MRI in these boys so that we can have a much more precise measurement of structure and function. We are very pleased and gratified to see the accrual of this data.
Yeah, I think that moment of opinion, but I think that's a potential key differentiator. If you continue to see signal and can add that as a secondary endpoint, that would be very meaningful. I believe anything that you could add to the label on those lines because no other therapy has shown any benefit.
Absolutely. Heart function. We know that we meet these boys at different places in their Duchenne journey. Some of them are ambulating. Some of them are now no longer ambulatory, but upper limb function is so important to their lives. Cardiomyopathy touches each and every one of these boys. It is urgent that we address the cardiomyopathy of these boys. We feel very grateful to be able to explore SGT-003 and how it may affect the heart health of these boys. Maybe a couple of questions outside of DMD.
One as it relates to your FA program. Any concern about overall total exposure? I know that giving the drug both IV and into the CNS directly, there's always bleed out of the CNS. I'm just wondering how you're thinking about it.
Yeah, look, this is exactly why we did. I feel bad highlighting how many non-human primates we studied. This is exactly why we did what we did with multiple different programs. We had like four different programs that we looked at. We looked at different routes of administration: IV, IT, IDN, IV, IT, IV, IDN. It is exactly for the question and the answer to your question, why did we do that? Our goal, it starts with the goal. Our goal is to change every patient's life that is suffering with FA and to get to all the different aspects of the disease.
Some patients have neuromuscular or CNS only. Others have with cardiac. Some happen early, some happen late, some more severe. How do we change the course of a four-year-old and also change the course of a 40-year-old? It goes back to making sure that we can get drug to the areas that you really need to, not only where they are in the disease, but hopefully down the road very early in the disease. We dosed a lot of non-human primates, making sure. The dose is minuscule. We have not disclosed the dose. When everybody sees what our dose will be in our clinical trial, you'll realize the off-target or worries about overexpression are probably you should not be concerned. We're going to have to dose patients to find out. We don't have a lot of concern because of all the work we did preclinically.
Gil, very, very quickly, we are targeting exquisitely the area in the brain that is responsible for the ataxia, the dysarthria, and the poor bulbar function. The doses that are used for that targeting is minuscule. The overall systemic dose is actually quite low in terms of what needs to get to the heart to help preserve function and to see myocardial mass reduction. In terms of the intradentate nuclear injection, it's a minuscule amount of virus. The total exposure is very, very low.
I think it's very important to understand how we're dosing this. Gabriel is using a pressurized catheter. I mentioned this. It's using gadolinium. We're going to be able to know day one, did we get it to the right location? Because you're going to be able to see it on the MRI.
I think that's critically important because I know that we're going to end up having competition down the road that's going to use one of these neurotropic caps that they're going to say, "Well, it's going to get across the blood-brain barrier." That's great. Where's it going? Where's it going? It's going to go everywhere because once it crosses the blood-brain barrier, it's going to literally go everywhere. We want to make sure that we're getting it right to the areas of concern and get it to the Purkinje cells. That's why we're doing it this way. I think it's going to pay off for us long run.
We are at time. I want to thank you both for attending today. It's been a very enlightening conversation.
Thank you for you guys very much. I really appreciate it.