Good morning, everyone. I'm Lisa Walter, Biotech Analyst here at RBC Capital Markets. Thanks for joining us at RBC's Ophthalmology Conference. This session, we have Alexandria Forbes, President and Chief Executive Officer of MeiraGTx. Zandy, thanks so much for joining us today. How are you doing?
Well, I'm doing very well. Thank you for inviting me to speak today.
Well, it's a pleasure to host you this morning. Zandy, maybe just to kick things off, can you give us a big picture overview of the company and give us a sense of where things stand with the ophthalmology programs at MeiraGTx?
Okay, that would be fine. We are quite a broad company in that we currently have three late-stage programs that have come through this company. Two are in the eye, which are both for inherited retinal diseases and one is partnered with J&J, one is partnered with Lilly, and both are awaiting filing with global regulatory agencies for approval. We also have two late-stage programs which are not in ophthalmology, but large indications and not inherited disease. One is in xerostomia two years after patients have been treated with radiation, so this is severe long-term xerostomia, an intractable and very unpleasant condition. The second is in Parkinson's. Both of those are in a phase II and a phase III study. That's in Parkinson's starting this year.
In addition to that, we support our programs with our own internal manufacturing, which gives us very good costs of goods and speed with regulatory agencies. We have highly advanced optimization technology from capsids promoters and all sorts of different tools we can make to improve the potency of our vectors by up to three logs, again, reducing the dose that we need. We have a platform which is now a mechanism for delivering any protein that can be encoded by transgene using small molecule oral inducers.
One time delivery of a DNA template and daily oral pills that can deliver you any antibody, Herceptin, PCSK9, any peptide, EPO, GLP-1, GIP, or combination of peptide, which is extremely powerful today as we're starting to find hosts of smaller proteins and peptides that could be used as therapeutics if they could be delivered in their native form or in a form that allows them to be dosed effectively in the body without having to be made synthetically and long-acting outside the body first. That's the broad range of the company. One more thing I forgot to mention, which is the entire company was built using only locally delivered small doses of AAV. That's how we got to our indications rather than large intravenous doses.
The delivery of small local doses has an impact on safety, on the cost of goods, and is really one of the reasons that all of our programs so far are now late stage and has been successful, we think.
Got it. Well, definitely a lot to unpack. A lot going on at MeiraGTx at the moment. But I you know, this is a ophthalmology conference, so.
Yeah
I'm gonna focus on those programs first. Maybe just on an inherited retinal disease, Zandy, MeiraGTx has a lot of experience developing gene therapies for the IRDs. There's a XLRP program, LCA4, and you also recently launched a program for BBS10. Can you maybe tell us broadly why inherited retinal diseases are attractive areas for clinical development and maybe also why gene therapies are well positioned to succeed in these disease areas?
Inherited retinal diseases obviously result from mutated genes, and therefore intuitively one of the best ways to treat them, like many inherited diseases, is to replace the gene. There is a long history of being able to safely deliver genes to the back of the eye using AAV. When I mentioned that at MeiraGTx we only use small doses locally delivered, the eye is clearly a place where you only require very small, very local gene delivery, and it has the benefit of being able to actually look into the treated eye and be able to see the effect of what has happened. In addition, there are many, many different endpoint measures of vision, visual function, retinal function that allow you to have quite a detailed look at the effect of your gene therapy.
If you are focusing on small doses locally delivered and safety. Then the eye is a great place for inherited and also larger indications, and that is one of the areas we focused on. It's the only area actually we actually look at inherited diseases. Our other areas of focus are outside inherited for large indications like Parkinson's, like xerostomia, and like pain and ALS, and all those programs that are preclinical for us. One more thing about expertise in the eye, the inherited retinal disease space is a very small one. There are probably between 30 and, I'm gonna say 50 leading sites in the world with KOLs who see probably over 80% of the known patients. When we went into this area, ophthalmology, it was actually the foundation of the company.
We did a partnership with UCL and the Moorfields Eye Hospital, and the Moorfields Eye Hospital is arguably the largest catchment hospital anywhere in the world for inherited retinal disease, and one of the centers from which this expertise emanates. Through that acquisition of the spin-out from UCL Moorfields, we gained relationships with those in the world who are most experienced with these diseases, both identifying them, genotyping them, and understanding the endpoints that will really show how the drugs have worked if they have. That has been key in our success, is that relationship and our deep connections with those thought leaders.
Zandy, that's very helpful to know and understand, and I don't think I appreciated how small the IRD space is and you know how few KOLs there are out there. I think that's really helpful.
Yeah. Well, and there's one other thing is that there are hundreds of IRDs, right? The same doctor at the Moorfields will see patients with all of them. You don't have a KOL for RP and a KOL, a different KOL for LCA. Those physicians have seen all those leaders in those centers, who run those centers, have probably seen all of those IRDs and we work with Mike Michaelides at the Moorfields, and I believe he probably sees, I think it's around 70 IRD patients a week. It's a lot, and that's both children and adults. Those KOLs are very few, relatively in the world, with very concentrated knowledge of a vast array of these different diseases, and they're real experts. Right.
Zandy, there's kind of some synergy, I guess, if you're working on one IRD, it almost makes sense to look at other indications as well. Is that fair?
I think that's fair, and that's not only sort of academically, but also from clinical trial perspective. The phase III study with Johnson & Johnson was at 30 sites in Europe and the U.S., and that included, like, those leaders through the relationships with Mike at the Moorfields, and those very same physicians will be the physicians that treat and prescribe these multiple gene therapies. From an academic all the way through to a development and commercialization, there is a lot of synergies between each of the different diseases.
Got it. That's really helpful. Zandy, I do want to talk about the XLRP program. I think many investors listening in, you know, are familiar with this. This is, of course, partnered with J&J, and we had the phase III readout last year, and this really did show some promising trends. I'm just wondering if you can share any updates on this program.
This is owned by Johnson & Johnson. We sold it back to them, and we are the commercial manufacturer. We agree, as do many of those KOLs, particularly the ones that were in the study, that the data that was presented was extremely promising and showed that in the eyes of these thought leaders in the FFB, that this therapy was having a very positive impact on these patients' lives. We know that the data actually was meaningful, and we are waiting to hear J&J's strategy for getting that to patients.
Got it. Maybe more broadly, were there any learnings from the XLRP pivotal study that you are taking with you and applying to your other inherited retinal disease programs?
That's an interesting question. There were many, many learnings from all of the studies that we have done, and many of those KOLs have done, that led to the phase III. Those are things like the surgery technique had been developed through multiple studies that we, the Moorfields, Mass Eye and Ear had done. That went into this phase III. The steroid regimen, and that was presented a few years ago, when it went into the phase III, almost obliterated, you know, the inflammation that had previously been seen in some of these studies. Those sorts of logistical learnings actually supported the phase III in RPGR, as well as the surgical training. I said there were 30 sites. There were two surgeons trained at each site.
We now have 60+ surgeons, fully trained, who were involved in this study, who are ready to deliver IRD therapies. As was presented, there were virtually no surgical issues, safety issues in this study. I think we have, through the last decade, learned how to safely and effectively deliver inherited retinal disease therapies to the back of the eye. That's applicable to any indication you might want to do. It was applicable to AIPL1, to the specials programs that we're now doing, and any phase I, phase III that may be done in the future.
Got it. It certainly sounds like we've come a long way since Luxturna.
Yeah
... which gained approval in 2017. I do wanna touch on the LCA4 program with that has now been partnered with Lilly. Can you remind us where this program stands as well as the Lilly partnership?
This is an ultra-rare. Unlike RPGR, which is one of the commonest RPs, this is one of the rarest LCAs. It is caused by a mutation in AIPL1. Infants are born blind, so they can hardly see a hand moving in front of their face. Through our specials license, which allows physicians to deliver a potential therapy to children, 11 children were treated under the age of four with this viral vector replacing the AIPL1 gene, and all 11 gained sight. Lilly have licensed this to commercialize and get it to patients globally. There was $75 million up front, plus additional milestones, $135 million based on various global approvals and largely U.S. approval and a PRV.
Now, PRV has been extended, so we now know that approval in the U.S. will give a PRV, even if it is in October and not September this year. That is a decreased risk in one of those milestones, and we work with Lilly weekly and daily to help in supporting them as they file for various approvals with regulatory agencies globally. They're very focused on patient access to this particular drug for a very aggressive disease. They've got a very strong, large team working on this.
Got it. Thanks for reminding us about the PRV. I think that's very helpful. Maybe let's talk about the BBS10 program. You just recently launched this. Can you share a little bit more background? Is this a subset of the Bardet-Biedl syndrome population?
Yeah.
Can you share a little bit more detail maybe on the prevalence and what your approach is here?
Okay. I mentioned the specials license. The specials license is actually a manufacturing license, and we have a commercial manufacturing facility in the U.K. with commercial license, QC in Ireland. In addition to the commercial licenses for our facility, we also have something called a specials license, which allows us to manufacture for particular patients that a physician wants to treat because there's no other option, even if the drug has not been in patients before. The BBS 10 program arose through a patient advocacy group, through parents, a particular couple who had a BBS 10 child, who supported MeiraGTx to design and make a BBS 10 viral vector, to manufacture it, and release it under our specials license for children who had BBS 10 to be treated by physicians in the U.K., if they thought it was suitable.
That's how the specials come about. Indeed, we're looking currently. We have another request for specials from, again, a charitable organization, and the same path can be followed. It's how AIPL1 got its data. We have started treating the BBS10, or physicians have started BBS10. We can supply that, and we are looking into the design and manufacture of another IRD treatment for potentially supplying under specials. It's a very unusual and sort of license and process, and we're very willing to take, you know, on board some of these extremely rare damaging diseases and supply under these conditions, particularly when parents or philanthropic groups come and request that from us.
Zandy, is the specials license just a program in the U.K., or is there a FDA equivalent as well?
At the moment, there is no FDA equivalent. The specials license is related to manufacturing, and it's related to the physician being willing to use a drug that has never been in people before, right? The system in the U.S., let's just take out plausible mechanism for the moment, allows patients to be treated without clinical data if they do not get to enroll, they're not appropriate for an ongoing clinical study. The material has to be released to the, you know, to FDA requirements. It's slightly different, but there are mechanisms for getting material to patients in the U.S. who are not eligible for current studies, but it's a different situation. This is a U.K. license.
Got it. Understood.
Just one thing, in the AIPL1 case, the patients who were treated, these children who were blind, came from seven different countries. You're not limited in who can be treated, but the physicians can only request material to be used in the U.K. that are manufactured de facto in the U.K. at our facility.
Got it. Patients could travel to the U.K. to be treated, but they don't have to be from the U.K. Is that how to think about it?
That was the case for the AIPL1. Very rare, and patients came from seven different countries all over the world. Even the U.S., patients came from. Yeah.
Data that's generated from the specials license, you can use or can you use that to support a potential filing down the line, with the FDA or EMA or other regulators?
An important question. That data needs to be collected in a way that it can be presented appropriately to the FDA, and this is physician-led studies. If you can present that data and verify that data, yes, it can be used to support global approvals.
Got it. Very, very helpful to understand that. Zandy, there's some other programs going on with MeiraGTx that are ophthalmology related. I, you know, see one for Stargardt, wet AMD, dry AMD. Can you share some additional background on these programs? Are they using similar approaches as the Inherited Retinal Diseases, or is this something a little bit different?
We do have quite a deep pipeline that has been developed over the years of inherited retinal disease programs that are moving towards IND. In that collaboration with Lilly, the deal with the AIPL1, they also took on two other gene therapies for other inherited retinal diseases, not as rare as AIPL1. One is literally ready for IND, so those documents are being transferred to Lilly. One is pre-IND, we can manufacture, and we do manufacture for AIPL1 in the near term for Lilly. Yes, we have IND ready and pre-IND ready programs. We have a very deep, and that involves use of organoids, retinal organoids, and this was actually the group that came from UCL who developed retinal organoids with the Japanese many years ago.
That allows us to do two things very effectively in our optimization. Number one, very, very good intravitreal capsids that came from a monkey screen, a nd what happens in humans, but you have two ways of getting as close as possible. Capsids that really do reflect what is needed in the human. Secondly, also using retinal organoids, we have a very large promoter platform, which is very powerful in the eye because we use retinal organoids and AI, and we have been able to develop strong, small, very strong, very cell-specific promoters that for different cells in the eye. Why I mention both of those things is because Eli Lilly, who obviously have seen all the ophthalmology companies out there, also got the rights to use both our intravitreal capsids and our promoters in vectors addressing Lilly targets.
That's five targets, and we don't know what they are. Lilly will move them forward using our capsids and our promoters from our big 200,000 promoter library. We do have very strong technology all the way from, you know, the very building of a vector right out to phase III development.
Zandy, very interesting work on the intravitreal capsids. Can you maybe give us an idea about how these might be a different versus what other folks have developed?
Well, we have for many years been looking at intravitreal capsids as many people have, and we have tested head-to-head with AAV.7m8, which is gold standard, right, many intravitreal capsids from many private and other companies. Meanwhile, we did our own screen where we first of all, it was a screen replacing different pieces of the capsid and screening in NHPs, and then taking our best hits and testing them in human organoids as well. We did the same comparisons as we have done for other capsids, intravitreal capsids that we ended up not using and versus AAV.7m8.
The data that we have, we selected capsids that were looking superior in those assays, monkey and organoid to anything else that we'd seen, and our gold standard was AAV.7m8. We, you know, can infer only that these are very good intravitreal capsids, and we can use them in our larger indications, wet AMD, dry AMD, glaucoma, etcetera. We actually did a screen for glaucoma-specific capsids. It's a whole other story for the front of the eye, and promoters as well. We'll just go with the intravitreal for now.
Got it. Well, very interesting. It'd be very interesting to see a glaucoma-specific capsid as well. That would be a very novel innovation.
It's ciliary body.
Got it. Ciliary body. Got it.
Yeah.
Got it. Maybe just in the couple of minutes we have left here, I do wanna touch on some of the non-eye programs. So, xerostomia, can you maybe just briefly remind us where this program is right now and maybe what the opportunity is here in radiation-induced xerostomia?
Thank you. Radiation-induced xerostomia, this is not at the time of treatment. It is radiation-induced xerostomia, which is durable for after two years post radiation treatment. It's very severe, and it's actually a rather large market. We have redone our market research, and this is a multi-billion-dollar global and even U.S. opportunity. The coverage and the pricing is strong, and the number of patients each year is high. This is actually a very large market opportunity with a very low cost of goods and a manageable price that we think we can get from, you know, we've got 90% to 90%+ coverage in our surveys at least. The study is a pivotal phase II that the FDA has agreed in writing is one that can support a BLA as a single study.
It is completing enrollment as we speak, and we are targeting filing for approval in this quarter next year with the aim of actual approval by or around the end of next year to launch in 2028.
Got it. Thanks for that. We are almost out of time, Zandy, but is there anything you wanna touch on with either the Parkinson's program that's partnered with Hologen AI, or anything you wanna flag with the Riboswitch program?
Riboswitch, we are in multiple communications with the FDA to prepare for an IND filing later this year for a program in leptin that we have very long-term data on. We have three small molecules, GMP manufactured, ready for the clinic, one of which is going to be used in the leptin. In addition, we've talked about using this for pain in the past, and we have increasingly strong preclinical data in neuropathic pain. As we are discovering more peptides, short-acting molecules that are involved in cardiovascular, metabolic, blood pressure-type systems in the body, all of which are responsive, we recognize that we have a mechanism for the first time for readily dosing the body with effective doses of peptides, proteins, and hormones, which can't be taken out, synthetically manufactured to be long-acting and put back.
We're very excited, you know, AI discovers this should be able to turn them into drugs very rapidly. We'll be in the clinic with our first this year. Pain is looking really good, and the target generation through this is, at the moment, the only way that you can deliver many of these metabolic and longevity related homeostatic proteins.
Got it. Thanks, Zandy. Well, I'm afraid we're officially out of time. Thanks so much for joining us today at our Ophthalmology Conference. It has truly been a pleasure to have you.
Well, thank you so much, and I will speak to you soon.
All right. Thanks so much.
Talk to you.