All right. Good morning, everyone. I'm Lisa Walter, Senior Biotech Analyst here at RBC Capital Markets. Thanks for joining us at RBC's Inaugural Ophthalmology Conference. This morning, we have gene therapy pioneers, MeiraGTx, and joining us today, we have Alexandria Forbes, CEO of Meira. Zandy, welcome. Thanks so much for joining us today. How are you doing?
Thank you very much for inviting us.
We're happy to have you. Zandy, you know, Meira has been a pioneer here with locally directed gene therapy approaches, and Meira has a very broad and diversified pipeline. Can you maybe start us off by giving us a brief overview of the company and the key therapeutic areas of focus?
Yes. You're right. We are unusual in the diversity of the therapeutic approach. The indications that we target, our therapeutic modality is genetic medicine, and our initial programs have all involved the local delivery of very small doses. That isn't only for gene replacement in the eye. It is gene replacement, but we have a program in Xerostomia following head and neck cancer, which is in a pivotal study, a large population, an unmet need, that affects many, many patients who've been treated for head and neck cancer with radiation. That, as I said, is in a pivotal. We also have a phase III program in Parkinson's, which circumvents the need for dopamine by changing the genetics of neurons in one tiny locus in the brain.
We've recently done a partnership with, a completely innovative, AI company, where we have been able to look into the brain of the patients we've treated in two positive sham-controlled studies and actually show that we're changing physiologically the circuitry and the neural environment in the brain in a disease-modifying way. This idea of local delivery in small doses really underlies our pipeline. We have our own internal manufacturing, which is arguably the best and broadest in the world with the most advanced process.
That underlies the late stage of our programs because we are essentially a commercial-ready platform going from the process developed with over 20 capsids and viral vectors all the way through Plasmid manufacturing, even under our GMP quality systems, to flexible scale, scalable single-use philosophy facilities, one in the U.K. and one in Ireland, both fully licensed for production and a commercially licensed QC facility. We release. That knowledge of regulatory agencies of our manufacturing for the past nine years allows them to look at our products and think of them as pivotal programs like our Xerostomia program, which the FDA told us was pivotal. We did not request based on our manufacturing. We can move things into the clinic very quickly without the delays that you may have if you have external manufacturing. We also highly optimize our vectors.
We may optimize capsid, promoters, sequence in a way that increases potency by three logs or more, which decreases dose, decreases cost of goods, decreases the potential for safety issues. We have also developed in-house a way of driving the production of any protein, an antibody, GLP-1, GIP, glucagon from a DNA template that can be delivered in any way. We deliver DNA templates to the muscle. You give a pill, and the template is read and protein, the therapeutic protein produced in the body. We have got incredible data in metabolic disease, in CAR-T, and in a whole range of different biologics. Again, after local delivery to the muscle of a very potent vector and the proteins produced when you take a pill daily.
Zandy, thank you so much for the overview of Meira, and thanks for touching on the Riboswitch program I hope to touch base on that maybe towards the end of the conversation here. Maybe my first question or second question for you is another big picture. You know, given we've had this shakeup in the regulatory environment with the FDA, and we now have Peter Marks leaving as the head of CBER, what impact is this going to have on gene therapy development? Is this maybe going to be a negative across the board? Is this going to be more of an indication-specific issue, or is it just too early to know what the impact is going to be to drug developers like yourself?
I can give you my feelings with respect to Meira, if that would be helpful, but I don't know if I can speak for the industry and every gene therapy or non-gene therapy company. I would say from our experience, we have very strong relationships with the FDA around CMC, okay? Number one. The FDA, CMC groups have seen over the last nine years every filing for every indication based on manufacturing that's come out of Meira. That is very important. That is not limited to or even anything to do with Peter Marks. I don't know that that would change. I think we have an AI component to our manufacturing that I feel the future-looking FDA may be interested in. Our new JV partnership, HalogenAI, is well equipped to help us discuss with the new FDA, right?
From a CMC perspective, we are in a very, very good position. We have just received licensure from multiple agencies globally. From an indication-specific position, we have three late-stage programs. We do not see a particular impact, negative impact on the loss of Peter Marks. In fact, we continue to have a very good dialogue with the agency. The meetings that we have are still treated with excitement by them. The data that we have in our AAV-AIPL1 program is still viewed by the FDA as it was last week. If anything, I think this new administration, this new FDA may well keep the notion that the FDA wants to be seen to approve drugs that have a really big impact on patients' lives. That is what we need to think about, right?
The drugs that we have discussed, our GAD drug and our Xerostomia, but our late-stage, our AAV-AIPL1 drug for blind kids has an impact that is completely, you cannot argue it. We had a call just yesterday with Mike Michaelides and some, you know, other groups. It's really, really clear that everyone who sees this, you have a blind baby who can now see, read three lines on a chart. I think that this is something that not only the FDA, but the global regulators, including the MHRA and other jurisdictions, by the way, that we've been speaking to, are keen to approve, to show that these sorts of treatments can transform people, children's lives. That's what we're all wanting to do, right? We, the agency, investors, ultimately, that's what you want to see.
In the products that we're discussing at the moment, we have very transformative effects. Parkinson's is the same, right?
Zandy, it sounds like what I'm hearing at the end of the day, good data for an unmet medical need, that is kind of what is going to matter in the drug development business, regardless of administration changes and regardless of changes of personnel. Good data and helping patients is what.
Our relationships, our good relationships with the FDA may even have improved, right? Peter Marks left and was fantastic. That doesn't mean that the FDA isn't filled with people who remain, who are dedicated to the approval of drugs that make a big difference. I would say our communications with the agency in the last week have been extremely positive. It's not despite disaster at the FDA, good data will always win. Let's just stand back and consider that maybe the FDA actually has people that remain that also have a similar view to Peter Marks, and even the new people have a similar view, right? We have not experienced any negative interactions with the agency recently.
That's helpful to hear that your interactions continue to remain positive.
Absolutely. I think we have to just sit back and wait and see what happens. From our perspective, from this company, we have had in the very recent past positive interactions with the FDA that we would have expected whatever had happened.
Got it. That's very helpful, Zandy. Maybe we should talk about the AAV-AIPL1 program or LCA4. Can you give us an overview of this program? I know that this study, this program was advanced under a specialist license in the U.K. and you successfully dosed 11 patients, all of whom showed a response to the gene therapy. Can you walk us through some of the key points of this program?
Yeah. You described it well. LCA4 is one of the most, if not the most, severe forms of inherited retinal disease in that children born with a mutation in AIPL1 actually are blind. What that means is they can perceive whether there's light or not, but if you move a hand in front of them, they can't see that there's a hand. It's called no hand movement. These are blind children. By the time they're four years old, almost always in the literature, the entire retina has degenerated. This is a population of children that's rare and rapidly degenerating. Very hard to do a clinical study, but a severe need.
There is a license that we have because of our strong manufacturing in the U.K. and most importantly, our quality systems that allow us to release material for use outside of the ability to do a clinical study. It's called a specialist license for manufacturing. We made AAV-AIPL1 material available in the U.K. under our specialist license, and it was used to treat four children at two hospitals in the U.K., four children in one eye only. This was up to four years ago. Every one of those blind children gained vision. The data on each of those four children, and the other eye completely degenerated to nothing. They're now about three to four years out.
With this data, we made available every last bit of AAV-AIPL1 that allowed seven more children to be treated in both eyes, again, by hospitals in London, pediatric physicians. Every one of those children went from completely blind to having vision. The data from the first four was published in The Lancet about a month ago, and we released the data from the remaining seven kids. We have 11 children all treated between one and four years old, blind that can see. The level of vision, just so you understand, from a clinically meaningful perspective, is not only they sort of can see vaguely. They can read, they can see colors, and they behave like normal children interacting with the world. Whereas previously, when you're born blind, there's some autistic-like behavioral issues in young kids. It was transformative to these kids.
We spoke to the MHRA, who told us, do not do anything, try to do a study. We will accept this clinical data on those 11 children. It is so unprecedented for approval under exceptional circumstances. We talked to them about the CMC because we are manufacturing in-house. We agreed with them on an expedited CMC package, which we are currently putting together and will file this year in the U.K. We also had informal discussions with the FDA. They agreed informally that the data was exceptional, and they requested that we file for a meeting to discuss moving forward, which we have done. We continue to be in dialogue with them around that in a positive way. We have also discussed with other agencies in the world who are interested in approving things in gene therapy, maybe to make a precedent, right? Also, very positive on the clinical data.
The thing that allows this to be approvable is our underlying manufacturing. We have had very strong responses from global agencies and also potential partners about this particular treatment, really because the size of the effect is so massive. The age at which you treat is so young. Therefore, the lifelong benefit is so enormous. One more thing about this disease, AAV-AIPL1, it is rare. Yet, because kids are born blind, you can find every child who has AAV-AIPL1 with newborn testing. We are in dialogue with the newborn testing groups globally, approval of the drug. When a drug is available, this will go on the newborn testing panels. You do not have to go out and find a child who one day will become blind. You test an infant, and they have AAV-AIPL1, and they are immediately a candidate for treatment.
The younger you treat, the better, and the better for the long-term outcome and the durability as well as the effect. This is really, it's like a Zolgensma for the eye in a way. We're super excited. Not just us, you know, Mike Michaelides, the professor at Moorfields, he said he could retire based on this. This is something he never thought he would be able to do in his life. You can see the videos of the kids. It really, really is transformative. It's amazing to have been able to use the specialist license and treat the kids so young and have a vector that had such a massive effect.
Thank you. Thank you for walking us through that, Zandy. It is definitely amazing to see 11 out of 11 children having a response and such a dramatic response as you've described. It sounds like you are on the verge of or scheduled a meeting with the FDA. Is that fair to say?
No, we're meeting with them.
Okay. Got it. This program, you have a rare pediatric disease designation for this program, correct?
Yes, we do.
That could potentially, if approved, provide you with a priority review voucher?
That's correct. Yes, it would.
Got it. Okay. Excellent. We will look forward to more updates there as you progress on the regulatory path and as you make progress in the U.K. and in the U.S. I also want to talk about your XLRP program. I know this is partnered, well, it is more in J&J Janssen's hands now, but can you just remind us about the economics for X-linked retinitis pigmentosa, the economics with the Janssen partnership, and what milestones does Meira still remain entitled to here?
We sold this program back to J&J, and we have one more pair of milestones for the first patient treated in the U.S. and the first patient treated in Europe. It's around $285 million on each of those. I can't remember the split, I'm afraid, but there's a one-time payment on approval in both jurisdictions. First patient treated, similar to approval in both jurisdictions. That's it. We sold them the program, and that was part of the sale price. We are no longer collaborating in a clinical sense. However, we also are the commercial manufacturer. We entered into a commercial manufacturing agreement with Janssen. We are currently working with them preparing documents for the CMC section of a BLA. That is ongoing as we speak. We will be the manufacturer of this product when approved.
Janssen is planning to present data from this program sometime in 2025. Is that correct? From the pivotal study as we shared in 2025?
At least in their last earnings, yes.
Got it. Okay. Excellent. Zandy, before we maybe talk about some of your systemic diseases that you're going after, are there any other ocular programs investors should be aware of?
We have a lot of Ophthalmology programs, RPE65, phase III ready, two CNGA3/CNGB3 in phase II. We have three IND ready programs, RDH12, a number of them. We have a preclinical, could be in the clinic in six months, Stargardt's program, which seems to be superior to others that are potentially going into the clinic. We're not moving those forward at the moment, but we have had partnering interest from them. We have rare pediatric vouchers, I think, for three or four of them. We have another Specials ongoing, again, with a charity for BBS10, and that will be initiating, I think, later this year.
Yes, we've got a lot of viral vectors already for the clinic, a lot that have been in the clinic with positive data in the area of ophthalmology that we've put into a little ophthalmology business with all our technology, our AI-driven promoters, our intravitreal capsids. We've got intravitreal capsids, which appear to be better than 7m8. We've got delivery devices, right? We've got ophthalmology business, which is being separated out, and we are in discussions around different aspects of that business.
Got it. So lots of innovation from MeiraGTx on the ophthalmology front. That's really helpful. I do want to touch on your systemic programs and the time that we have. Xerostomia, remind us what stage this program is in and what are the next catalysts? For those who aren't aware, what is the unmet need in radiation-induced Xerostomia?
Okay, just one thing, just to be really clear. We have no systemic programs. The entire history of this company is based on local delivery of small doses. We do not do systemic doses, just so that everyone's clear, okay?
I apologize. I tend to think of the eye and the rest of the body. The rest of the body is just systemic, so I apologize for using the wrong term, but you're absolutely right. You're a local delivery-focused gene therapy company. Xerostomia is delivered directly to the...
One of those is in the salivary gland, and the other is in the CNS. Local delivery to the CNS and local delivery of small doses to the salivary gland. Xerostomia is for an indication which is very severe and very common. Around 30% of patients cured of head and neck cancer, disease-free, remain with severe Xerostomia. They can't make saliva. We use a water channel, a vector-carrying water channel that we cannulate. We literally just put a little tube into the opening of the salivary duct, the parotid, and put AAV, AQP1 is the water channel. What we've seen in our phase I, again, is unprecedented improvement in Xerostomia symptoms as well as water flow in patients treated with AQP1. We started a phase II.
That phase II was deemed pivotal by the FDA, who wrote to us six, nine months after we filed and told us that. We then filed an RMAT based on our phase I data. We received an RMAT at the end of last year, and we are now working with the FDA to ensure that our phase II pivotal program is, in fact, completely shored up that if positive, will support a BLA approval. That is where we are. We have completed enrollment in low-dose cohorts, and we are looking at initiating the high-dose cohorts that we talked about last year.
Got it. Thanks, Zandy. We should also talk about the Parkinson's disease program. You had this very interesting deal with a healthcare AI company, Halogen. It was just announced a few weeks ago. Can you remind us about the deal that this involves and why is Halogen the right partner to advance the GAD program?
Yeah. First of all, the GAD program is targeting all those patients with Parkinson's disease who no longer respond adequately to dopamine, right? The dose gets too high. They get Dyskinesia, whatever it may be, which is essentially all Parkinson's patients post five years after treatment begins. We are in an unusual position. We've done three clinical studies with this product. It is the delivery of a very small dose into the subthalamic nucleus, a nucleus of the brain that is responsible for controlling motor output. It's one of the circuitry issues with... It's one of the nuclei involved in motor circuitry. What we have shown, again, is unprecedented, which is in two studies with a sham control, one, we showed a statistically significant improvement in motor symptoms in UPDRS in our phase II, and similar data in our phase I bridging study that we released last year.
We have two studies with sham controls that give positive statistically significant UPDRS. That's the standard clinical endpoint for Parkinson's. No gene therapy, no cell therapy, no growth factor therapy has ever worked against a sham. We have very strong data. We're moving this into phase III, and we looked at partnering this with a strategic partner. We obviously looked at Halogen, and the partnership with Halogen provided two things. First of all, like a pharma company, we got an upfront to Meira that allows us to finance Xerostomia and Riboswitch and all of the things at Meira. Number two, the phase III program in GAD is 100% financed. We formed a JV with Halogen, which has up to $230 million that will support the GAD program and other pipeline products. That's number two. Number three, Halogen has unique AI.
There's a huge amount of AI that can really, really help every aspect, I believe, every aspect of drug development, clinical development. Indeed, Meira has used AI spectacularly to develop our promoters, right? What made us do this partnership with Halogen was because their technology is somewhat different from the generative large language models like ChatGPT, and it is specifically developed for looking through the heterogeneity of clinical data, which is essentially one of the issues with doing clinical studies and seeing by modeling the differences between individuals and individual measures, you can see outside of the requisite heterogeneity, which exists in life, to actual effects and improve study design, but also see effects that may be masked by what other AI sees as noise. This isn't selecting patients that the drug will work in.
This is looking at real data through a lens of a massive data space, latent space, and being able to look at what changes have really happened. Yes, using HalogenAI's technology, we have really de-risked the phase III program with UPDRS as primary endpoint, right? Statistically. What we also were able to do is we looked at all of the brain scans from our two phase II studies, which we'd done, and we'd seen patterns that were correlated with improvements in movement specifically.
When we did that with HalogenAI's technology and in this huge data set that they had, we were able to see robustly, really strong statistics and really robustly, actual physical changes in the circuitry of the brain in Parkinson's patients, not in that were physically different from sham-controlled patients, that reflect a change in brain circuitry in patients that aren't responding to dopamine that allows them to move. Amazing. The first time that anyone's shown a physical disease modification in a really robust way in a sham-controlled study. We looked at the Nigra, which is not where we treat, and we were amazed to see, or we were very happy to see, that we saw changes in the Nigra that suggest that there's a disease modification that could potentially slow degeneration.
Using this technology, started looking at other regions in the brain, such as regions involved in mood and cognition. We were able to demonstrate that treating with GAD, so changing this circuitry and downregulating this hyper-glutamaturgic situation in these patients, actually has effects throughout the brain, not just on movement. This is incredibly powerful to be able to use an AI, which is the only AI that really models heterogeneity and can look clearly at real anomalies, and to show potentially for the first time that our treatment for Parkinson's is disease-modifying, that actually physically changes the brain with a one-time treatment of a very small dose. One thing I just want to mention, as I keep saying this word, locally delivery, small dose, you have to remember what that does for cost of goods, because people are always shocked when we say this.
Cost of goods for all of our treatments, locally delivered, very potent, is in the single-digit thousand dollars, which is one of the reasons we are able to go after large indications with a transformative effect and potentially have a price that enables us to really get a good benefit-cost analysis for patients.
Got it. Zandy, thank you for mentioning the COGS here and walking us through what AI could really bring to the Parkinson's disease program. We are at time, but just on the Riboswitch program, can you remind us when is this anticipated to enter the clinic?
We're currently in another one of our discussions with the FDA. We are entering into dialogue with the FDA about a platform approach to how we take this into the clinic. That is ongoing now. We have a couple of indications we're discussing with the agency, but our target is to be ready for an IND at the end of this year.
Thanks so much, Zandy. We'll leave it there. Thank you so much for joining us today and for your time, and hope you enjoy the rest of the conference. Thanks, everybody.
Thank you very much.