MeiraGTx Holdings plc (MGTX) May 13, 2026 Conference Transcript

Started here. Thanks for joining this session with Mira GTX. My name is Alex Stranahan. I'm senior biotech analyst here at Bank of America covering Mira. And I have the pleasure of introducing Zandi Forbes, welcoming her back to another Vegas conference. Zandi is the chief executive officer of Mira. Thanks for being here, Zandi.

Thanks for inviting me.

Yeah, great. Well, Well, maybe just to start off, you know, at a high level, you've materially repositioned Mira over the past 12 months. You took back the Bodevec rights from J&J. You secured the halogen collaboration to fully fund the Parkinson's program.

You got BTD for xerostomia, I guess. what is sort of the the single most important de-risking event that you think um the market hasn't fully appreciated for the company over the next 12 months i'm not sure what the one thing that the market has not fully appreciated could be could be many things um but i would say that buying back rpgr from j&j has been the most de-risking thing we've ever done at the company um and it's a i'm getting it approved globally is a real focus for us and since we did that i don't know 10 days ago two weeks ago um we actually have some quite senior people from j&j who may have been working at other places come and join us or speak to us and it puts us in a really good position to move super fast and you know that drug came from us and the people who worked on it at J&J are very keen to get it approved and it's really great to have their help well one of them Penny Fleck led development of the whole therapeutic area and she's now working at Mira as of this week so that's I think the most transformative thing we've done this year

and kind of liberating now to be able to talk about the program how you want and push it forward how you want uh yeah yeah yeah um and I mean you were always going to be the manufacturer of of Bodevec maybe maybe we can just talk at a high level I think that the commercial scale manufacturing is maybe something else that's underappreciated. You guys sort of have an industry-leading, vertically integrated manufacturing capabilities for gene therapy within the company.

I guess, how central is that manufacturing capability to sort of the valuation and the story that you're trying to build for Mira? so we we didn't necessarily build the breadth of our manufacturing infrastructure on purpose we we did it over 11 years because it was absolutely necessary to develop genetic medicine drugs in a timely fashion so it does two things number one we have a platform process and that allows us to start an ind with essentially similar to commercial material super super important in gene therapy and has been very important for us number two is that as our own manufacturer everything from the process to the gmp facilities all the way through to QC. So every single assay, we have commercial license and we cross-reference everything with the FDA. So the FDA and we are very familiar with what's required in a CMC section. And we did initially for J&J, now for ourselves, full PPQ for RPGR. So we're also familiar with what's needed to file a cmc section of a bla or maa those are very valuable and really important from a time perspective and a regulatory perspective and um and i think that having manufacturing in-house is probably one of the number one de-risking things you can do for any ind it it's difficult though because you've got to build it over many years but for us that's what it's done we we wouldn't have four late stage programs that we could file with our own manufactured

material unless we've done it ourselves we'd probably be three years later in each program right and that's you know fixed costs that have already been you know put in place and yes yeah And, you know, beyond, you know, hitting the clinical endpoints that you hope to in your clinical studies, and we can talk about xerostomia next, but when you do go to file with the FDA, you've already kind of checked a lot of the boxes on the non-data components around CMC, et cetera, right?

Like you're ready for commercial scale. yes so yes so our programs another reason i think we've been largely successful in all of our programs getting them to late stage is they are small doses and locally delivered we never do large systemic doses so that means that we start essentially at commercial scale some things for really big indications like parkinson's we increase the bioreactor size but we we have single use so we can use the same suite for a 100 litre or 200 litre or a thousand litre bioreactor so we built manufacturing to be um scalable within one space we've got lots of suites but it's that was under the guidance of regulatory agencies so we start with something that is a commercial close to commercial ready process at a commercial ready um scale and and again that's extremely important because what is the biggest part of any bla or ma is a cmc section and it's not only the biggest part of the bla or maa it's the biggest part of the ind it's the biggest part of your phase two um ind amendment of your phase three meetings so throughout the regulatory process you are iteratively learning what's needed on the same process with the same manufacturing from the agencies and in fact you just mentioned xerostomia the one of the reasons that's a pivotal program it started as a phase two is we obviously manufacture it ourselves and it's a it's really high yield so we don't have to go to massive scale but we manufactured ourselves and filed our cmc section with the phase two um ind amendment and started you know no comments in 30 days so we started and six to nine months later the FDA wrote to us and essentially said that if we manufactured within the parameters that we'd written they considered the study pivotal so without us asking because of the CMC that they reviewed that is what made that study pivotal then we got an RMAT then we got alignment written alignment with the FDA on the clinical side and then we got breakthrough. And then we got three-year data.

Yeah, right. Maybe we can, you know, unpack that a little bit further. And I know that the PIVOL study, I think it completed enrollment recently.

It's finishing now. Yeah.

Okay. BLA filing, I think you're targeting for the first half of next year. Yes. You aligned with the FDA on the primary endpoint as the XQ Pro and saliva flow. yeah yeah um saliva flow is the the key secondary um i guess uh you know when when you think about um what good looks like from the study maybe you can just walk us through sort of the powering assumptions um and you know uh how important this this patient reported outcome metric is so xerostomia is a patient reported disease condition it is not correlated at all with

actual saliva volume it is it results from too little saliva produced in the mouth of whatever individual you're talking to but one individual could have xerostomia with 10 microlitres um or five you know a minute for five minutes another with a mil so the actual volume of water doesn't correlate with the symptoms i.e the definition of xerostomia the xq is a xerostomia specific uh PRO we also have other PROs in there which we also had in our phase one and um and this XQ is the one that is most most focused on questions related to what are normally the symptoms of xerostomia such as sleep eating swallowing how dry is your mouth those sorts of things so it's it's a pretty standard pro for xerostomia which is only possible to detect by a pro however clearly there is some need in the face of a pro to have an end point or some measure of the actual mechanism of the drug and the actual mechanism of the drug is you create more saliva. So the secondary endpoint is the actual volume of saliva that you produce per minute when you spit into a tube for five minutes. And that's another very standard way of measuring saliva flow.

Okay. And, you know, you're testing for, I think, active dose cohorts here. Do you expect or do you hope to see a dose response or, you know, is it more of a hedging strategy?

And do you think the label could end up covering one dose or multiple so this started as a phase two right and so we were doing multiple doses because our phase one had cohorts of three people and while there was some incredibly good response there was some much smaller responses and we showed that in the three-year data we showed pay patient data every time point individual patient data at every time point over three years. So, there was no dose response that we were able to determine. So, there was no correlation with vector genome, titer, with total vector genome, with volume of gland. And so, we had a lot of patients with very good responses, but no way of predicting how that related to dose if it does at all because you're simply making the gland cells permeable there isn't that much of a dose response even in the potency assay because once the cell is permeable because it's got aquaporin channels on both sides of it you add twice as many aquaporin channels it's permeable still so there's not that much of a dose response even on a monolayer in vitro so the phase two has four different doses against two placebo arms separate placebo arms and the the study is designed and powered that any single dose cohort no particular one in no particular order that beats the pooled placebo is a win and it's 95% powered to be successful with the current patient numbers.

Okay do you have an expectation you know from the survey work that you've done or from the phase one what what the placebo arm could do I mean these patients they obviously can't make saliva on their own so I imagine the the level on the PRO is going to be quite low, but any sort of quantitation you can provide for the placebo expectation?

So it's an excellent question. And it is the question that we have thought about a lot. These patients are patients who remain with xerostomia for the rest of their life and only get worse. It's the 30% of patients after radiation, three years after radiation, that have not recovered 70 percent recovered of the radiation there's erostomia 30 percent do not and of those 30 percent that are moderate to severe 85 percent don't respond to sialagogues right so those those sialagogues by the way have a 25 percent placebo rate so these patients aren't even responding placebo wise unless the 15 percent that supposedly do respond is a placebo response right so so you're looking at a population the natural history is they only get worse they don't respond to a drug that has a placebo response however you always worry about the placebo response and how much of your massive efficacy is related to placebo. When we showed the three-year data, if you look at that, patients gave the same response each year for three years in a PRO, even though they were treated three years before and they did the questionnaires 12 months apart it's super difficult to imagine that is placebo in addition that wasn't only the best responders but similarly the middle responders were a bit more variable but the level of response was maintained over three years again it's hard to see a mechanism that a pro which they tend not to work after like 12 to 24 months gives the very similar data at three years from one year however we given that there's no known placebo we had a very high effect size and i say high because it was a massive decline in the xq so in the cohort which treated both sides there was a minus 21 improvement minus 10 is is transformational and so the bilateral and unilateral had a minus 17 we used minus 17 as our effect size and we powered to have success we powered for a nine point difference between placebo so that leads you even with 17 a big placebo response with 21 it's more than transformative right so that's how we powered it and it will nevertheless would be successful if the other assumptions are correct at a six percent sorry a six point change so we designed it as conservatively as we could we gave the placebo a transformative improvement we'll see right but we did what we could to to use that big effect size which we think is real okay okay and

you know you mentioned the three-year durability data this could i guess potentially be transformative with how prescribers perceive treatment of this disease which is mostly symptomatic relief right now with a one-time therapy I guess from your latest work you know speaking with prescribers or payers you know how are they viewing kind of this durability piece is this maybe one of the key items for adoption and how does this sort of feed into your approach to pricing and coverage so when we've recently spoken to positions and payers it was one of the key elements which changed the view of this drug so we it had been a drug that had a big improvement on xerostomia

and physicians were very keen on using it however when we presented the three-year data it sort of changed in the minds of physicians to what was noted is really simple safe virtually painless procedure one time and a durable disease modifying impact on a condition that is otherwise lifelong so those were the words that started coming back and payers also looking at that durability data gave a considerably higher price now we have not done payer negotiation work obviously we don't have our phase three data and we gave a conservative number in our presentation of 150 000 the range when we were asking with that target product profile was 100 to 250 so we will wait for the phase three data and and then have pricing negotiations but i will say that for both rpgr for botavec and this product we think that small sales forces that are really targeted are very much within what we can do however our focus right now is patient access that from both in both of these diseases particularly in europe is the key thing that we're focusing on seeking there are incredibly good payer access groups that will go to the meetings with you and you know someone got Novartis that pricing for Zolgensma right and and we want those people to help us it's it's the most important thing to us is exactly that the negotiation of pricing us and for botavec obviously europe right right that makes sense and maybe that's a good segue to talking about botavec you mentioned kind of a sales force and a commercial approach that you can maybe wrap your arms around on your own i guess what was the rationale for um you know regaining the rights and self-filing versus maybe finding a new partner there so um botavec was you know born in mirror and the founders of the company some of the founders of the company actually developed that drug and the people at ucl who developed those drugs now work for mirror so we have great familiarity with botavec from its birth now Now, one of the reasons we initially did that deal with UCL is its close association with the Moorfields Eye Hospital and one of their lead IRD physicians called Mike Michaelides is also one of the founders of this company. and he as a consultant guides us on clinical development now why I say that is the Moorfields is arguably the most important hospital in the world for inherited retinal diseases Mike Michaelides alone himself not including the other physicians there sees a hundred IRD patients adults and children each week and that is some physicians see that number of patients in a year and it turns out that there are about between 30 and 50 individual physicians in in japan europe UK and the US who have under their care 80% of all IRD patients and 32 of them were in our phase three study because Mike Michaelides called them and asked them to be and Mike and each of those physicians has the phone number of the other physicians so from a sales force perspective we currently have you know we can call mike can call or someone from mirror can get in touch with most of the physicians that have under their care most of the rpgr patients in us europe uk and japan and in this past year as j&j has not moved this forward there has been an escalating cry or outpouring from those physicians and those patients to get it approved so as i mentioned earlier finding the patients is not the most important thing for the launch the most important thing for a fast launch is to make sure it's paid for and the value of changing those patients lives and actually improving their vision when that before this drug it wasn't thought to be possible that value is recognized and we want to do it fast so you know there are some things we can do which

is we have the patients and the physicians listening to us um we need to get payers to agree to to pay for the drug right and obviously the the fda as well is another stakeholder um And we listened to the presentation for J&J on the Lumios study, and I think the feedback at that presentation was very positive from the patients and the patient advocacy groups within XLRP. I guess, how are you sort of approaching the submission package in terms of the totality of evidence from the study? How do you sort of package that for the FDA?

And is there precedence in rare genetic disease that supports this approach? there's number one there's precedent in many diseases of a trend in a primary and very strong secondaries being approved for full approval number two there is a precedent in the only gene therapy for a blindness that results in dim light vision failure and that is luxturna So there are precedents for both. Luxterna is the closest. Luxterna also failed its primary maze and they spent about a year doing post hoc analyses and were able to show in a 20 patient crossover. So only 10 placebo patients or untreated patients in quite a confounded maze, they were able to show a difference between treated and untreated and they got approval. They did not have strong secondaries. So that's a good precedent. In addition, the FDA's job is to make sure the risk benefit that is provided to patients makes sense. and on the lux sterner label there was an issue which is a degeneration of the central retina and it was put on the label and and physicians were not supposed to treat the central retina now that lux sterner degeneration has been seen out in the community and is very well known as a side effect toxicity issue with luxterna because it's so well known every one of our 135 patients that have been treated were looked at at every appropriate time point with fluorescence looking at structure to see if there was such a toxicity so when you ask about precedent we have a precedent where a very similar disease, albeit fewer patients, got approval for a very similar type modality of therapy with way less data. We've done three studies with different controls with not even a trend in the primary to start with and not the very strong secondaries. Our two secondaries are now accepted by not just the Europeans, but the FDA subsequently has accepted LLVA as an endpoint and as a primary endpoint. And what is also important is when you have an endpoint that doesn't meet significance as primary, it's useful to show that that's because the tool isn't sensitive, not because patients fail to see in the dark. And for us, there is a very strong response, pre-specified as a quite highly ranked secondary in the low luminance domain of the extreme lighting PRO that met with incredibly high significance. and it measures how you function in the dark but when the questions were looked at separately the p-value for mobility in the dark was 0.001 so that shows you that these very same patients who were treated have a big difference in their mobility in the dark and it's the same domain as the maze so we also have a discussion that indeed this was highly variable and with this number of patients wasn't sensitive enough to show the change in vision in the dark and mobility in the dark that was shown with this very well validated commonly used endpoint which is a PRO And that was all pre-specified.

Okay. Okay. Very, very helpful. Maybe the last question, just in the minute we have remaining, I think you guys have done a great job driving value from the pipeline through partnerships over the past 12 months. You have the Lilly collaboration with LCA4. You've got the halogen collaboration for Parkinson's. I guess, how do you see these, the DD activities, I guess, progressing over the next 12 months? And I guess, when could we see maybe a partnership from Riboswitch or somewhere else?

That's an interesting question. We are focused on getting Riboswitch and riboleptin into the clinic this year. and we have discussed with the FDA, we can do both small molecule and riboswitch in a first-in-man dose-finding study, which is great. So the material is being made, currently optimized, so it's commercial-like. So when will we do a partnership in riboswitch? I don't know. We speak to many companies all the time about all of our programs. And, you know, there are some companies that are interested in multiple of our programs. And as we move towards commercialization to potential launches in multi-billion dollar markets in the next two years, you become interesting not only to investors, but also other companies, larger companies. and you know we have many meetings many discussions and we get to know companies and we consider their offers and and also talk to them about things we might like to do so it bd goes on but i can't say we're about to do a deal tomorrow okay so i guess we'll stay tuned yes stay tuned yeah but um i guess we'll leave it there uh thank you zandy for the excellent

discussion and thanks everyone for your attention. Thank you.

Thank you very much, Alex.