All right. Good afternoon, everyone. Thank you for attending our eighth Genetic Medicines Conference. My name is Daniil Gataulin. I'm one of the senior biotech analysts here at Chardan. It is my pleasure to introduce our next presenting guest from MeiraGTx. We have Zandy Forbes. Zandy, welcome.
Thank you.
So the format for this session is a fireside chat, and, as always, if anyone in the audience have any questions, feel free to raise your hand, and, we'll make sure to get to you. With that, I think we're gonna go ahead and get started. So Zandy, if you could spend a few minutes and, introduce the audience to Meira, please.
MeiraGTx is a genetic medicines company. We started in 2015, to be able to treat not just inherited diseases, in fact, rather not inherited diseases, but much larger indications using DNA in a similar way to Moderna uses RNA. In order to do that, we believed, and in fact, it's true, that one really needs to be able to control messenger RNA production from any DNA template, which over the last nine years, we have been able to achieve in a much more robust and granular way than we expected. We look to a future pipeline where we're able to deliver any natural biologic or antibody peptide hormone via a small molecule that's oral, a small molecule of our choice, and a DNA template, which encodes exactly that biologic.
And we're applying that particularly to places where the therapeutic is an agonist, such as the short-lived agonist in metabolic disease, both the incretins, the myokines, leptin, as well as receptors that are currently tonically active, such as in CAR T. So that's our future. Our pipeline will be in the clinic next year, for example, with our first metabolic disease programs. What we started the company around was the technology that existed at the time, and we decided to focus on local delivery of small doses that we manufacture in the eye, in the salivary gland, and in the brain. And as a result of that, and a number of other factors, all of our clinical programs have actually been successful.
So we're currently in a situation where we have our collaboration with Johnson & Johnson, which they bought out the lead program last year, with Phase III data in a very large inherited retinal disease indication sometime this year. We have a Parkinson's program about to go into Phase III , with the best sham-controlled data ever shown in Parkinson's gene or cell therapy, and our data from bridging study about to read out in the next month. We have a xerostomia program, which, because we manufacture, the FDA has deemed pivotal in a dose-ranging pivotal study, which we are intending to file in 2026. And in between those two bookends, we have our own manufacturing, which allows us, when we file an IND, to file with commercial material. We manufacture plasmid to GMP. We have two GMP facilities, one of which will be a commercial facility next year.
The others are GMP for clinical, and we have our own clinically licensed QC. We're in a very unusual position where global agencies have vetted our infrastructure and our process so that when we file an IND, we don't get questions, but rather the last time we did, they wrote to us and told us, "You're so good at manufacturing, this is a pivotal study," which saves years in clinical development. Our vectors, which is important when you think about cost of goods, are highly optimized. The capsids are optimized, the promoters, the enhancers. We have non-coding sequences that we now insert into our vectors. When you think about optimization, we tend to optimize the potency of our vectors by three to four logs. Why is that important? It's not just important to make your drug work and to make it safe, which it does.
It's important because when you have potency that's three to four logs greater than your original vector, your dose is three to four logs less, your cost of goods are three to four logs less, and you've actually got something that you can deliver to a million people, not just a hundred, and you can charge a reasonable amount with a good margin based on that cost of goods, which of course is further lowered because we manufacture everything in-house. So we have late-stage clinical programs in large, non-inherited indications, all the way through to a completely transformative technology, which allows us as a pharmaceutical industry, to now really think about how you most effectively deliver agonists, short-lived agonists, and receptor agonists, that will be going to the clinic towards the end of next year.
Got it. Thank you, Zandy. That was a great, great intro. A lot to unpack here, so let's go program by program. So I'll start with XLRP first. As you mentioned, you're advancing that program into Phase III with Janssen, with data expected sometime later this year. Can you remind us about the trial design for this ongoing Phase III program, and maybe highlight some of the previous data that give you the confidence in this program?
The trial design is untreated. Well, patients are treated in both eyes, 'cause it's pivotal. There's an untreated group, and two dosing groups that are randomized. The primary endpoint is BCVA, because that's clinically meaningful, considered so by all regulatory agencies, and secondary endpoints include retinal sensitivity, which is what physicians recognize, as well as PROs, which is clearly what patients and other groups, advocacy groups recognize. So it's, you know, there was a lot of iterations and discussions with global agencies around that design and around those endpoints.
With respect to efficacy, we have shown in a large PhaseI , II some people call it 3, but a large Phase I , II study with an expansion, that we cause significant increase in retinal sensitivity, that we cause improvements in blindness in the dark, and a maze that was a different maze. We've now got a validated maze accepted by the FDA. Also, patients have told us and their physicians, and part of this is in PROs, that they can now see better, they're more independent. What we expect is to have similar data in this particular study, and of course, we have the anecdotal, you know, "I can now see. I can now navigate. I now have improved retinal sensitivity," anecdotally out of this study, and we're expecting the data.
We don't know when, but maybe towards the end of this year. The last patient was treated at the end of the Q3 last year. It's a 12-month endpoint. We don't have visibility any longer-
Mm-hmmI
Into the data release of that study. That's up to Johnson & Johnson, but we expect it, you know, however long it takes them to analyze this data after the end of this quarter.
Got it. And can you remind us of potential remaining milestones related to this?
So we sold back, or they bought out this program, and we received already $115 million. There's $285, which is basically most of that, the large majority of that. I think there's $30 million that is not, is based on first patient treated in the U.S. and Europe. So it's. That's it.
Got it. Okay.
In addition to that, we entered into a commercial manufacturing agreement, so that is a manufacturing agreement where we're now paid to manufacture on launch for Johnson & Johnson.
Okay, yeah, and that was my next question. In terms of potential revenue upside, can you-
That would be the revenue.
Mm-hmm.
And obviously, we can't disclose-
Sure
Johnson & Johnson's launch projections, but, they're good.
Mm-hmm. Excellent. Okay, with respect to your other ophthalmology program, LCA4, so you recently announced that the company was awarded the Innovation Passport designation by the UK for that program, which provides a number of potential benefits, including a more accelerated approval for that program. Can you talk about LCA4 and what that designation means, and your potential next steps there?
This is a disease where children are born blind, and by the time they're four years old, their entire back of their eye is gone. So there's absolutely nothing to do that you can do for them. It is the most aggressive of all inherited retinal diseases. They are blind when they're born. What that means is, if you wave a hand in front of them, they can't tell. They can tell whether it's light or dark, full stop. So we, I mentioned our manufacturing, have a specials license because we manufacture for clinic and commercial. And in the UK, that allows physicians to treat patients with material from our licensed facility outside clinical trials.
We designed and made an AIPL1, LCA4, gene replacement therapy, and we made that available through our specials license to doctors in the UK. Eleven children were treated under the age of four, between the ages of one and three. Every single one of those children can now see. So 11 out of 11 went from blind to seeing, and we talked to the agency after we got this passport, Innovation Passport, and they said, "Do not apply for conditional approval. Don't even think of doing a study. Come and talk to us about marketing authorization under exceptional circumstances." So that's what's happened over the last few months. That is what we are doing next month, and we also applied for a rare pediatric voucher. We will be going to the FDA.
We're working with a great gentleman who used to be head of the Cell and Gene Therapy Division, to see how we can actually get this drug approved globally and give access to these patients who are born blind. I mean, it's the best data ever in ophthalmology, in gene therapy, probably because you treat people when they're one year old. Right? You don't have to wait till they're 19 and then start treating them. So that's really exciting.
Got it. Yeah, we'll be watching the progress closely-
Yeah
And, yeah.
Rare pediatric vouchers are going up in price.
Yes, we saw that, too.
Yeah.
Got it. Okay, in the interest of time, let's move on to the next program, so radiation-induced xerostomia.
Yeah.
So you have an ongoing Phase II . You presented data from Phase I in the program. So before we talk about those data, can you talk about the condition first, and what is the medical unmet medical need there?
So this is completely untreatable condition. Nothing works. When patients receive head and neck radiation for head and neck cancer, all of them have xerostomia. They cannot produce saliva. About 30% of them, two years after they've been cured of head and neck cancer, still cannot produce saliva. 70% can, they take sialagogues, and they're okay. 30%, they don't produce saliva. Sialagogues don't work, there's nothing you can do. What this means is they can't breathe properly, they can't exercise, they can't eat, they can't speak, they can't sleep. It is really bad. Their teeth fall out, and there's nothing that can be done. No drugs work. So, these patients are all in the care of physicians. They're returning to the physician once a year to see if their cancer's back.
They all have reimbursement of some kind because they've already been cured of head and neck cancer, and they're all sitting there with this as their worst problem. We input locally, distill into the salivary gland, an AAV2 that locally delivers aquaporin that makes those salivary glands permeable to water. We showed in the phase 1 study that we had a massive impact on the quality of life measure that is the validated measure of xerostomia. And when I say massive, what is considered a clinically meaningful change, which the drugs that have been approved for lesser xerostomia don't even reach, is an eight-point change. We saw a 17-point change from baseline. In addition, we saw, with the same profile, an improvement in saliva production. We had what physicians and patients considered transformational data. We initiated a Phase 3, and filed the FDA CMC documents.
We were allowed to open, no questions, and nine months later, the FDA wrote to us and said, "Well, if you manufacture like you do," which obviously.
Mm
We did because we've manufactured it, "we consider this pivotal.
Mm.
So suddenly, we're in a situation where our Phase II is a pivotal study. We're enrolling now. We're adding an extra dose. We will complete enrollment of the initial doses, and then the higher doses towards the beginning of next year, late this year, early next year, and we intend to file this, if the data is strong.
Mm-hmm
In 2026.
Got it. Okay, makes sense. And in terms of the administration procedure itself, is it something that physicians need to be specially trained on, or is it something that could be done in dental offices or oral surgeon offices?
Oral surgeons and dental can be trained in a couple of hours. You just go to a dentist to have this done. It's literally open the mouth, insert a catheter into the opening of the parotid, and instill in the product.
Okay. And, in terms of the phase 11, can you comment on the enrollment progress and-
We don't talk about where and when the enrollment is. We currently have, I think, 23 of the 30 sites. It may be more, maybe 25 of the 30 sites open. We have sites in Canada, U.K., and the U.S., and enrollment is going up and up.
Got it. Okay, fair enough. All right, let's move on to your next program.
Parkinson's . Parkinson's. Yeah, let's talk about that. So you have an AAV-GAD program there. Can you talk about that program? And, you mentioned some very, very impressive data early in your introductory comments, so if you could expand on that.
Yeah, so Parkinson's is really interesting and probably the most misunderstood of our programs because people still think gene therapy is global delivery of something that's addressing the very early disease mechanism. We address Parkinson's in a disease-modifying way. We change the circuitry of the brain to circumvent the need for dopamine. We're not trying to give dopamine back, which is hugely difficult, or after patients are not responding to dopamine, and we're not trying to modify the disease at its unknown source so it never happens. Also very difficult. Rather, in Parkinson's disease, one of the issues is this tiny nucleus in the brain, the subthalamic nucleus, is hyperactive. If you put electrodes into the subthalamic nucleus with electricity, switch it down, you can move again. What we do is the exact same delivery-...
As deep brain stimulation, we put a very tiny local dose of the enzyme that converts glutamate to GABA. Glutamate is the hyperactive neurotransmitter. GABA is the quieting neurotransmitter. And in doing that, literally the smallest dose we know used in gene therapy, it costs a few hundred dollars for us to make. You are able to switch down the subthalamic nucleus, and we've demonstrated we re-circuit the brain, and we have a statistically significant benefit on UPDRS, which is the standard approvable endpoint in Parkinson's, against sham. Sham is the highest standard in an interventional study, and no other gene or cell therapy or growth factor has ever shown a benefit against sham. They're all single arm that fail when they're controlled.
We have just finished a bridging study where we manufactured, in our commercial way, material for this, a new manufacturing process from the old one, as we've done for all of our products, and the data from that will be coming out in the near term. That was a safety study, but it was sham-controlled, 'cause the FDA wanted that, so we have a two-dose, sham-controlled, very small safety bridging study that will be giving data in the next month, and that allows us to go to the FDA and initiate a phase III.
Got it. Okay-
With commercial material.
Got it. Okay. With a few minutes left, I wanted to take a pause and see if there are any questions in the audience. All right, so I know we just have a few minutes left, and I definitely didn't wanna miss talking about Riboswitch platform. So can you talk to us more about that platform, recent developments, and next key milestones in that for those programs?
So the Riboswitch platform has the word "switch" in it, which everyone asks me, "Does this turn on, turn off? Can you turn off? Can you turn on?" Don't think of it as a switch. We have developed a control cassette that we can put into any gene. We can CRISPR it in, we can put it in AAV, we can put it in lenti. When that control switch, right, or cassette, is put into any gene, it completely blocks messenger RNA formation. We then give an oral small molecule. That small molecule activates on a one molecule per one messenger RNA basis, messenger RNA formation from that template. So we're able, for the first time, through an oral pill, to deliver in vivo, in the body, any protein peptide hormone that can be encoded by DNA. So where have we done this?
We have made and regulated the templates for every large pharma's antibody. Put the template in the muscle, take a pill, you can cure breast cancer in a mouse. You could add Dupixent. You can do whatever you like, really easy. We have controlled hematocrit with a template for EPO, growth hormone, PTH, all multiple different small hormones and peptides. As I mentioned, the place where this is most powerful has been where you're delivering the native short-acting forms of peptides and hormones, which have to be short acting to work well. GLP-1, biggest drug in the world, is only a drug because the pharma industry managed to make it long acting, right? In fact, better drugs are PYY, Amylin, and combinations. But Amylin, in 2004, couldn't make those long acting, so they went for GLP-1.
We can make any combination of gut peptides, put the template into the body, take a pill, and you make the combination. What we've discovered, which everyone in this room, and at Novo, and at Lilly should have known, is that when you deliver the short-lived hormones and peptides in a daily way, not through injection, which is why they didn't do short-lived, but with a pill, you get massively increased efficacy. You get weight loss, which way supersedes anything you see with the synthetic long-acting peptides. Because when you're dealing with a system that is homeostatic, the controllers of that system, GLP-1, GIP, glucagon, myostatin, leptin, they have to be short acting, because they're responsive homeostatic systems that respond to the environment. Every time a receptor is switched on, the body switches it off.
So when you have long-acting synthetic peptides, you're switching things on, but you're switching them off. For the first time, our data shows the power of being able to deliver long-acting, short-lived. sorry, short-acting peptides in a physiological timeframe using a pill. And we've done this for CAR T, and our CAR T are four times more potent. We can manufacture. There's no exhaustion more, markers. They're not cytot- they are four times more cytotoxic, one-third the number of cells, gives you complete cure, head-to-head with Carl June's approved anti-CD19. So this platform allows us to deliver any biologic, but it's the first time the pharma industry is actually able to control the delivery of agonists, and it opens up a huge world of what you can actually do, with the information that we have in biology, frankly.
Got it. Okay. All right, thank you, Zandy. Obviously, there is a ton more to talk about, but unfortunately, we're out of time for this session. Again, I really appreciate you coming over and.