Good morning. I'm Geulah Livshits, and it's my pleasure to introduce our next participant. We have Dr. Zandy Forbes, President and Chief Executive Officer of MeiraGTx. Again, the format for the session is a roughly 25-minute fireside chat. If you have any questions during the session, feel free to type them into the question box, and we'll try to ask them on your behalf. So with that, Zandy, thanks so much for joining us from Paris. Can you start by giving us the latest on Meira's manufacturing and CMC capabilities, and then touch on how those fit into Meira's overall company strategy?
Thank you, Geulah. Thank you for inviting me to speak today. Meira is unusual for a sort of small gene therapy or genetic medicines company in that we have one of the broadest capabilities in gene therapy manufacturing, which means we have both a process and a process development team who's worked over the last eight years to develop a platform process that we have manufactured many, I think up to eight different viral vectors to GMP. So we have huge data lakes which allow us to fit any new vector to our platform in a one- to two-month period of time and then take it into GMP. We transfer it into DMP, which is very rapid. Now, with respect to GMP manufacturing, we have a plasmid facility.
We have two viral vector facilities, and our most recently built facility is a QC facility, which we actually built last year, and we now have both a clinical and commercial license for that because it was very, very difficult to have all of the QC testing for release and stability on our clinical batches done using the current CROs. And we are launching a product with J&J, and we couldn't be limited by outside testing on the release of material for launch. So we have extremely broad capabilities and multiple GMP facilities that really address every single step in the manufacturing process. And finally, because we have that and because we've worked with J&J on a process for a BLA for commercialization, when we initiate an IND, we actually have a process that is commercial ready. It may need a bit of scaling.
It may need a few new things, but we generally start an IND with something that can be commercialized, which is extremely important for expediting any clinical development plan. We have great relationships with global regulatory agencies. We've worked with them not only on multiple phase I and phase II studies, but in preparing for a BLA for a commercial product. They now know us very well. We know them very well in what they need for a commercial product. This has led to us being able to cross-reference all our CMC documents and INDs. Most recently, we are in discussions with the FDA. They propose that using our material from our facilities, if we do certain QC assays, they would consider one of our phase II studies in xerostomia as potentially pivotal because they deem that material appropriate for a pivotal study.
Again, this is extremely important because if you don't use material that is the commercial manufacturing and the commercial presentation for a phase II or a phase III study that you want to base approval on, it may not be considered pivotal. And so in multiple areas, our manufacturing has been incredibly valuable to the company and to our partners like J&J, who we sold our program to last year, but we then entered into a commercial supply agreement with them. So long introduction, but it's quite a lot of parts that make up this broad capability.
Great. So maybe let's follow up on that last point first. As you mentioned, last year you had the asset purchase agreement with J&J for the XLRP program, and that also incorporated a manufacturing agreement to produce the commercial supply. So can you expand a little bit on that, where you are in terms of readiness to manufacture the commercial material and also just general color on how that worked out?
The phase III study enrollment was completed in the third quarter of last year. It's a 12-month endpoint. J&J is moving towards BLA based on the 12-month data from that study, if the study is successful, which we certainly hope it will be. We, as with J&J, are currently completing what's called PPQ, which is all of the different batch manufacturing that shows the FDA that you can consistently and repeatedly manufacture material within the parameters that you say you can. That's ongoing this year, and it's that that will eventually get filed into the BLA. That's where we are, and we're working on that with J&J right now.
Do you have the capacity to potentially provide similar manufacturing services for other potential partners as kind of an additional revenue stream while also continuing to advance your pipeline?
Yes. So we have two facilities. If, for example, we fully supply J&J with their maximal launch requirements, we would not completely fill the UK facility, and we have total capacity in Ireland. So with these two facilities, and given that each of the suites in the facilities is itself scalable from 100-2,000 liters, we have a huge amount of scalability at our fingertips to use for other potential partners. And definitely, we can fully supply our own clinical and potentially commercial needs. Now, what's important here is we, even at small bioreactor size, both of our late-stage programmes, xerostomia and Parkinson's, use small locally delivered doses. And there are lots of reasons for that, but one of the consequences of that is, like the eye, the doses are low, there's less capacity needed, and very low cost of goods.
We have capacity for Johnson & Johnson at a very strong launch. We have capacity for all our clinical needs and potential commercial needs. We have capacity for other partners to manufacture because of the sort of elasticity of how we've built the different facilities. By the way, having plasmid, we have very high capacity. There we can even supply other guys with plasmid.
Great. You touched on this a little bit, but what kind of feedback have you received from regulators and/or other stakeholders or experts in the space regarding your manufacturing facilities, either for XLRP or for your other programs?
From regulators, we have, I'm pretty sure, over the last seven years, we've had very similar feedback to lots of companies who receive feedback on their CMC. It is complicated, and we, you know, the first IND, I think eight years ago, we'd use HEK293T, and the agency said, "Take T out of there." So, you know, T antigen went. That was very early on. Suspension. We do suspension. We learned about, as we bought QC in-house, every single assay is validated and shown to the FDA. So we have a lot of experience. Potency assays. One of the very, very important aspects of your FDA interaction as you're moving something through clinical development. And we actually had our preclinical team and our organoid team.
That group is now expert in developing potency assays in the format with the parameters of the FDA demand for a commercial, you know, not just for a clinical supply, but for commercial supply, cell-based assays. So through iterative interaction and through cross-referencing, we've had increasingly positive, and that means less feedback from regulatory agencies. And it's important that we are able to cross-reference. They like to see that other reviewers have looked at what we do and agree with that current reviewer. And so our last several INDs, there was no clinical hold. We were allowed to start. And then most recently, the interaction around, you know, our material being considered pivotal, that came from the agency.
We were able, because we worked on our assays in-house, we were able to readily, in a three week period of time, which is the reply, the exchange of answers time, we were able to, you know, answer affirmatively. And that was very valuable. So from the agencies, we've learned a lot, and they've become more and more comfortable with us. And we have recently had a full, I will call it audit, but it was an analysis of all our facilities in London and in Ireland by a group who is one of the leading consultants in gene and cell therapy manufacturing called Dark Horse. And they gave us incredibly positive feedback. They told us that they had not seen anything in the world that was as broad and comprehensive, and we got highest rating on every single thing.
I think there was one demerit on every aspect that they looked at. But that was really gratifying because you never know when you think something is really good, and people tend not to believe you when you say that. But they were very rigorous. They spent almost a week looking at everything, interviewing everyone. And they did say, you know, you know, one of the, you know, whatever large pharma they'd come from in manufacturing, this is what they would have built, and they haven't seen anything as good anywhere in CROs, pharma, or biotech. So it was really good. I was pleased.
No, absolutely. That makes sense. So I guess touching on the, I guess, the radiation-induced xerostomia program, where you talked about how you reached alignment with the FDA regarding what would be needed to make that pivotal. So this program does use a different capsule in different route of administration versus XLRP. So can you talk a little bit how you utilize the learnings from your other late-stage programs to streamline both the advancement to late-stage of the existing programs and also to streamline the IND process for new assets? And you touched on this a little bit, but it would be great to have a little bit more insight on that.
Yeah. This is actually really important, Geulah, and we haven't talked about it actually before, but it's one of the things that's missing in the industry today. We actually have big pharma companies, well, large biotech companies and CDMOs coming to us at the moment about a platform process. Now, most companies and many companies have a lead product, and they manufacture that, right? And they develop a process around that. We developed a process using multiple capsids, using multiple genomes within capsids. An example is AAV2, for example, we use for both GAD and for xerostomia. And yet the genome makes AAV2 capsid a little bit different depending on what's inside it. So we have massive, massive amounts of data. We've done many, many GMP runs and literally thousands and thousands of smaller scale runs, tens of thousands.
With that data on so many capsids and so many vector genomes, we're able to very rapidly look at the parameter, do an experiment with a new vector that comes in, look at where it comes out on titer, empty to full, lysis time, all of those parameters that you look at at upstream and downstream, and very rapidly analyze what the range of different things we can change at each of those different three steps. Super fast, we can get to what is more likely to be the best case process on that platform to go to GMP. Sometimes it takes a little bit more tweaking. We now, of course, like everyone, use, I'll call it machine learning, but we obviously use different algorithms, and we've got, you know, a data scientist who makes this even faster.
It's really the fact that over so many years we've developed a process using multiple products, not just one. So we were able to actually make the AQP1 vector to the quality that was made using an adherent cell line at Rentschler, which is where the Zolgensma product was initially made, where they double-spun it and just did a whole load of weird stuff. We were able to put those required parameters into our platform process. And even though it's suspension and even though it's a very different process, we were able to achieve the incredibly high full ratio and yield that had been achieved with a very, very different and sort of somewhat deviated from process.
Going forward, what kind of optimization do you then need to do on a product-by-product basis?
Sometimes not, because what you do is you bring it in, you do your standard process, and you look at the parameters of where it sits, and you add a bit of this, you add a bit of that, you change the separation parameters, and you're not really changing much. As you scale, you look at cell depth, you look at the cells, but as you understand the behavior of your cells, you again go back to your machine learning, and you can start to look at how cells and plasmid interact with each other and how that scales. So from an IND to commercial changes, you often have to do things like, what's the vial, how do you fill it, you know, what exactly is the polysorbate solution, you know, the formulation has to be the presentation that's going to be used commercially.
There are things that are major changes, and there are things that are tweaks and scales, and you can do the latter and tell the FDA, and they'll say, that's great, you know, incorporate it within these parameters. Or you can have discussions with them about, this is a major change if you've added a whole new step, right, or you've changed your cells. And then what do you have to do?
We have our own cells that we licensed many years ago, so we have master cell banks, we have our own cells that the entire process was built on. So we're not going to be making those major changes, but when we start, we try and make the process as optimal as possible for that vector in that capsid so that any changes going forward will be considered minimal changes. I don't know if minimal is the right regulatory word, but not big changes that require an additional study.
Got it. It sounds like you've obviously dedicated considerable resources to this over the last several years as you've been advancing your program. Currently, about how many employees at Meira are focused on manufacturing?
I'm going to say it's 180, 200, something like that. It's a lot. That's across five facilities from MSAT, plasmid, two viral vectors, fill and finish, and QC.
Great.
Supply chain warehousing.
Got it. Great. And so maybe just jumping to a different topic, what is the significance of the Specials License that you have in the U.K.? You recently talked about that in the context of an ocular therapy that you guys have developed.
Well, we've seen recently how valuable a Specials License can be, and I think it's unique. I'm not sure, but I believe it's unique our facility. So in the U.K., there is a program, I'll call it, called Specials. And this is for rare degenerative diseases where there is no treatment. And what the specials means is that a physician is able to prescribe an unapproved drug with no human data, so only mouse data, if they believe from that data that this has a high likelihood or some likelihood of benefiting a patient with such disease. Only if the material is manufactured in a licensed facility with a Specials License. That means that the drug may not work or it may work, but they have to guarantee that from a CMC perspective, it's absolutely licensed to go into people.
Given our facilities have GMP licenses, we applied for a Specials License. And the first Special that we did was for a rare, one of the most aggressive of the inherited retinal diseases. It's called LCA4 AIPL1. And in this disease, children are born blind, so they can't see anything more than whether it's light or dark. And by the time they're, you know, four years old, their retina is totally degenerated. So we manufactured the material. First of all, we made the vector, AIPL1 vector. We manufactured the material, designed the vector to treat these patients, manufactured the material and made it available under the license. And three different centers in the U.K., these kids were treated, eight children were treated, and the results were absolutely shocking in that every one of the children subsequent to being treated had acuity. So they could actually see.
Different degrees, but they went from blind to having vision. We and the physicians at Moorfields and Great Ormond Street have never seen anything like this. It could possibly be because they were so young. So their brain's plastic, their retina is, it was very rapid and very profound effect. Based on that data, we are filing with the U.K. for an ILAP, which is a path to potentially getting these sorts of drugs where you can't actually do a controlled study because there's no way you can not treat a one-year-old who's going blind completely and to try and get this approved because it's such strong data.
We have another specials in IRD. We are looking to work with one of the leaders in rare obesity in the U.K. in our MC4R obesity. We've got a BDNF vector under a specials license. It really allows you or allows physicians access to appropriately manufactured material that they can give access to their patients to if they see fit that can't really be accessed through a clinical trial. It's been very, very successful so far in that first one.
Got it. So kind of another external signal of applications of your manufacturing. Great. So I see we're just about out of time here. So I'd like to thank you again, Zandy, for all the insights here.
Thank you very much, Geulah.