MeiraGTx Holdings plc (MGTX) Earnings Call Transcript & Summary

Great. Good afternoon. Before we jump in, Zandy, I will read our candy dandy research disclosure. So for important disclosures, please see the Morgan Stanley research disclosure website at morganstanley.com/researchdisclosures. If you have any questions, please reach out to your Morgan Stanley sales representative. Great. My name is Jason Russell. I am Managing Director with the Morgan Stanley Healthcare Banking team. Delighted to be joined by Zandy Forbes, Dr. Zandy Forbes to be very clear. And really excited to have Meira at our conference. There's a lot to talk about. You -- 6 clinical programs, I believe across various TAs, Phase 3 trial enrolling, big partnership, manufacturing, wholly owned manufacturing site and then Riboswitch which is really exciting. So I want to cover it all. Let's try and jump in. Maybe just start with some high-level perspectives on MeiraGTx, a brief overview of the company, your vision. Let's start there.

Yes. So thank you for inviting us. I'll give you an overview first of or first of all, the strategy when we formed the company in 2015 and how we've built on that until today and since our IPO. So when we formed the company, we took the approach that we were a gene therapy company, rather than a specific therapeutic target company or disease area company or even rare disease company. And the reason for that is, there are many excellent scientists and groups throughout biotech and pharma who really do have expertise in particular therapeutic areas, so there is neurodegenerative disease or particular rare diseases. But there's a new technology, which is genetic medicine and really that isn't an area that there's any expertise in the world in genetic medicine. So we planned to really be a company that focused on genetic medicine and gene therapy as a therapeutic modality. And when we put together our pipeline, it wasn't focused on the therapeutic target alone, but really on those targets which have human proof of concept in the diseases that we thought they would work in. In all cases, our clinical programs use small dose and locally delivered to immune-protected areas for many reasons, including avoiding some of the issues of high dose and safety and immune activation that we've seen over the last 5 or 6 years in gene therapies and that delivery problem. So our program so far are 6 as you've mentioned, we have not had a clinical failure. We have moved our lead program from an IND with our partner, Janssen to pivotal program, expecting a BLA filing in 2024. We have 2 other programs with Janssen in Phase 2, one initiating treatment at the end of this year and other the beginning of next year. We have 2 internal programs. One is completing its Phase 1 dose escalation readout at the end of this year. It's an open-label study. We've been presenting data over the last 2 years and we'll have the final data in our Xerostomia program at the end of this year. We're discussing with regulatory agencies, what sort of trial design we need in our Phase 2 to potentially have that as a pivotal program and that will be starting at the end of this year, that study. And in addition, we have a program in Parkinson's disease, which avoids many of the issues in Parkinson's to do with dopamine. It essentially changes the circuitry in the basal ganglia in such a way that you are able to have more normal movement in the same way that you normalize movement in deep brain stimulation. And in all of those cases, we deliver very small doses to very local regions and have quite significant impact on the disease or the condition. So in addition to that and one of the things that has allowed us to move all those programs forward is that we focused on internal manufacturing. So we currently have 2 viral vector production facilities, the GMP approved -- GMP approved production, we're the commercial manufacturer for our Janssen collaboration. So we're currently doing PPQ and ramping up for a potential launch should the BLA be successful in 2024, 2025. So we have a lot of experience in manufacturing process, as well as the infrastructure to manufacture. And in order to supply commercially for manufacturing, we bought plasmid in-house. So we have a plasmid production facility for GMP and we're currently completing our QC facilities, so that we are able to release material for commercialization. Some of you may know, there's a big problem in the vendors in the QC houses in the world today. And when we were looking at supply chain for this -- earlier this year with our partner, Janssen, it would not be possible to have the projected launch that we hoped for by relying on the entire global QC supply at the moment. So we have bought that in-house and that we expect to have commercial licensure at the beginning of next year. And in addition to those things, we've developed a lot of that technology that hasn't been available or wasn't available when we formed the company in controlling genetic medicines, in promoter development. And one of the things that you mentioned is our Riboswitch. We're in a position now in vivo in any gene we've tried from antibodies to peptides and hormones, we can precisely control the dose a gene therapy produces its protein very precisely via a dose of an oral small molecule and that oral small molecule is of our choice. So we can screen oral small molecules that may be blood-brain barrier penetrant or may accumulate in tissues of interest to be able to very precisely control genetic medicine. And this ranges from in muscle, in the CNS, we are now able to for example very precisely controlled CAR-T activation by regulating the CAR. So that's a quick overview.

Okay. Great, a lot to unpack, but that's great. I think the thing that I took away the first thing was locally in small doses, which is pretty unique when you compare it to what most of AAV gene therapy has been attempting to do. Maybe a good segue to the eye.

Yes.

So before we go to the specific program, you mentioned the Janssen relationship. How did that come about? How is it going? What's in it for Meira? How do you feel about that relationship going forward?

So how the Janssen collaboration started is that we -- when we formed Meira, part of that formation was the acquisition of a company out of University College London and the Moorfields Eye Hospital, where they not only -- we received or we licensed a large portfolio of inherited retinal disease gene therapies, but we also gained a collaboration with the Moorefield Eye Hospital. So that gives us global leading clinical expertise in many of these rare diseases. And we had quite a lot of interest from large pharma in partnering in the area of inherited retinal disease. Now Janssen was one of those potential partners. They did a really good job in diligence. And also they were willing to pay 100% of all clinical development and clinical manufacturing, which we're currently really benefiting from because we are in a Phase 3 program, which is fully supported by a very large pharma. They have huge amount of infrastructure. The retina for Janssen is an area that they're very interested in being leaders in. So these programs are not sort of secondary programs to even Janssen, who is a large company, but they are designated as extremely important programs in Janssen. So we have a very tight collaboration with them across the board from clinical operations to regulatory, which is really expedited and increased the quality of the trials we've been able to do, as well as our interactions with regulatory agencies and have the benefit of them paying 100% for these clinical trial development, so we could potentially file a BLA and potentially have approval. They will commercialize these products without us having to spend on those particular program. And we are the commercial manufacturer. So we've learned a lot about how you commercially manufacture, not how you manufacture for Phase 1, which has hugely improved our own manufacturing capabilities. We get to 20% top line royalty globally, untiered and we work very closely hand-in-hand with large teams at Janssen moving these programs forward. And we have very positive data so far. We have released top line data from our last RPGR study, randomized study, randomized eyes that showed benefit, significant benefit across multiple different measures in RPGR that will -- was released this top line earlier this year and we now have a late-breaking oral presentation at AAO on October 1st.

Great. Well, just on the relationship with Janssen. I mean, it really does -- we see all kinds of flavors of partnerships and relationships in our industry, but it really seems like a huge win for Meira to have that experience. So congratulations.

Yes, it's changed the company.

Yes, no doubt. Maybe on XLRP for a moment. So you mentioned the data, you mentioned AAO. Let's talk -- Phase 3 is enrolling, is that correct? Can you just give us a little bit of a flavor of what does the Phase III look like? Are you guiding to the timing of results? How should we think about that?

So the Phase 3 is to treatment arms, so a low dose and an intermediate dose, the identical doses presented at AAO that were the randomized arm in our expansion phase of the Phase 1/2 versus an untreated control arm, so or randomized and the endpoint is 12 months. The primary endpoint is a functional vision endpoint, which is a maze, which has been discussed widely with European agencies and the FDA and we have modified the maze to be in line with those discussions as a primary endpoint. The secondary endpoints are including retinal sensitivity, functional vision, visual, all of those PROs, all of those supported endpoints that you will see in our AAO presentation, in our press releases from earlier this year. Janssen is expecting a 2024 filing and hopefully, approval thereafter.

Okay. Wonderful. And then maybe just one clarification on the control arm, they're untreated or is it sham?

No. So -- so it's [indiscernible] so you can't do a sham yet because of the surgery. So you can't really mess around with these men's eye assortment. You can't mess around with these guys eyes. So it's untreated, which is standard in inherited retinal disease.

Okay. Understood.

Yes.

Okay. I want to make sure to just have time to get to a few other topics. But just while we're on the eye, any other programs in that area that you'd like to just comment on?

So Janssen has taken over the INDs for our -- for 2 other programs, 2 different achromatopsia. There's a study starting treatment at the end of this year, as well as beginning of next year in each of the achromatopsia. And we also have a pipeline of preclinical programs partnered with Janssen in the inherited retinal space. We have our own preclinical programs using that vectorology technology and injection technology in the large indications, not partnered with Janssen. So we have dry AMD, wet AMD, uveitis glaucoma clinical -- sorry, preclinical programs, research programs in those large eye indications, as well as research in different suprachoroidal delivery and different types of capsids to get different parts of the eye. And none of that is associated with Janssen.

Okay. Very interesting that they would start in the smaller indications and that you've been able to maintain those larger order opportunities.

Yes.

Great. Maybe shift to another area, so Xerostomia program. On the indication itself, probably not as familiar for some people. So help us understand why is it so important?

It is -- so Xerostomia means you can't produce saliva. And our first indication in Xerostomia is radiation induced Xerostomia. So this is not an inherited disease. We do have orphan status, but it's not ultra-rare. This is a condition that occurs in almost all patients who are treated with head and neck cancer. So we treat Grade 2/3 Xerostomia, which is a very severe condition where even 2 years after you've been cured of head and neck cancer, your salivary glands still are unable to function and produce saliva. In our orphan status documents, there are about 178,000 patients in the U.S. and we've recently had a report done by LEK on the global market. They're between 400,000 and 500,000 patients in the big market in Europe, Japan and the U.S. and 10,000 to 20,000 patients a year in the U.S. who are new Grade 2/3 xerostomia patients a year. This is very unusual for gene therapy market. It's not genetic and it's got a big incident population. I mean, prevalence very big, but orphan status is under 200,000, an incidence is a real market. It is one where these patients are out there unknown because all of these patients have in the past 2 years before potential treatment have been cured of head and neck cancer. And they are coming back to their positions at least annually and having been cured, they now complain to their position. Well, you got rid of my cancer, but I've got Xerostomia. So it's a really good market. And as for the cost of goods, like all of our current clinical programs, the dose is very low. So it's [ 1E12 ] per patient or [ 4E12 ] per patient on both glands depending on gland volume. And we manufacture ourselves low cost of goods. And we've been looking at pricing and through our LEK report, it looks like the potential price in the U.S. is higher than we had anticipated. We were modeling 50,000 per onetime treatment, potentially a little bit more than that and even that kind of amount in global market. So this is a really interesting market from a commercial perspective, from selling as well as pricing. And in our data that was presented last year and the year before, which will be presented in full in December, these open-label Phase 1 studies, we've seen really strong benefit in the endpoints that have been used to approve other drugs for Xerostomia in PROs. So we're really enthusiastic about this and it's a complete unmet need. The patients with Grade 2/3 Xerostomia don't respond to the other drugs that are available. So they are sitting there with nothing to do. And we're going to be talking to regulatory agencies about how we make the next study one that can support BLA.

Very interesting. I think the incidence point that you make is a really strong one because in most of the indications where AAV gene therapy is traditionally being considered, we all imagine that commercial model, the spike and the drop off. So that's a potential path to a more normalized type biotech, biopharma revenue curve.

Yes.

Interesting.

And our gene regulation technology actually allows us to start addressing many indications like that from obesity to osteoporosis to any of the antibody treated diseases. So when we formed the company, it wasn't about being a rare disease company, but it was about developing genetic medicine to treat not only inherited diseases, not only rare diseases, but potentially having better treatments for some of the larger diseases that are out there.

Very interesting. Okay. So updated at the end of the year, I assume -- will that include guidance on the next step?

So we're hoping to meet with the FDA from now until the end of the year and we'll have not only data, but we'll also discuss potential design of the study, which we hope to initiate by the end of the year.

Okay. Thank you. Sorry, I missed that.

Yes.

Wonderful. Well, I know there's a lot more to cover on programs, but just circling back on the manufacturing capability. So where is that?

We have a GMP -- our first facility has GMP approval, I'm going to say for 6 years and we are waiting for our third biannual inspection. So that's where we're producing current clinical material for all of our programs in Janssen. We have a second even larger scale facility in Shannon, Ireland. We also have a process development facility where we develop our platform process and fit new vectors to it in London. And our plasmid facility is in Shannon and our QC facility in Shannon and currently fill and finish in London and fill and finish is coming in Shannon.

Interesting. Okay.

It is very broad manufacturing footprint.

And on the plasmid, I mean, that effectively means no Aldevron, right? So...

We didn't buy from Aldevron anyway.

Okay.

Because until recently Aldevron wasn't as high enough quality for GMP use in Europe where we started. So we bought from Biome and some of the European smaller houses. Even from Aldevron, it's hard to get slots and very expensive. So plasmid costs were about 40% of the cost of a batch and QC another 40%. So we initially did this for the plasmid for cost as well as time. And that actually turns out to be why we had to do QC because the QC houses just a complete disaster.

Interesting. Great. So your -- and maybe this doesn't matter. Have you -- is your Phase 3 product for XLRP, is that including using puro plasmid?

We manufacture RPGR plasmid, so that has been manufactured by us. But going into the BLA, we ordered from by reliance. So it isn't part of our BLA because we had to fix that process for PPQ right now. And it was better to use what we've been using for Phase 1, et cetera, at that point.

But in the future, we get...

Correct. Yes, we could get that approved, we could get that into manufacturing.

Okay. Understood.

Yes.

Okay. Maybe just on the capabilities front, you mentioned in the intro, some capabilities around vectors, I think, promoters as well? And so what are your efforts there?

So one of the issues in gene therapy in general has been -- well, there's been safety issues and there's been a focus on licensing in programs for the clinic, largely from academia. And these haven't been fully optimized in a systematic way. So we've built multiple platforms for optimizing every aspect of the vector, not only capsid, but also promoters. We've got 4 different promoter platforms, ranging from bespoke promoters to high throughput screening of every 300 basis of the genome, all the way through to AI-driven in silico screening. So we've got large numbers of different size promoters, enhances regulatory elements for controlling the expression or the RNA production of many of our genes in liver, in muscle, in CNS, in eye, even in kidney. And when we optimize our vector sequence, that also includes every single base, every single base for expression, for lack of immunogenicity, for durability. So we really focus on a whole toolkit for tissue specificity, as well as general efficacy of a viral vector. One of the ways we address safety is by increasing the potency of our viral vectors. And if you can increase potency by one or 2 or even 3 logs, which we do for our viral vectors, you drop the dose to such an extent, you can now avoid some of the side effects that we're seeing caused by high doses. And then aside from that, we also have our gene regulation, which is using Riboswitches not transcriptional control, that overlays on optimized expression in cell-specific, cell-level specific ways.

So let's go there. I know you're really excited about that capability. So small molecules, controlling protein, the expression, therefore, the protein production. But just walk us through it a little bit, breakup.

So in any genetic medicine today, we had technology, we put a gene in and it expresses in that cell from that promoter for the rest of time, for the rest of the life of that cell, whether it's delivered by [ Lenti ], whether it's additive, whatever it is, right? But what we've developed is a way we have inserted, I will say, into the central dopamine, a new function for going from going from DNA to RNA to protein. Now in using our switch, you go from DNA to RNA to RNA plus small molecule to protein, right? So on a one-to-one basis, we only get RNA messenger RNA formed in the presence of one small molecule. So we're able to very precisely control exactly how much of any gene is made at any time point, based on the dose of a small molecule and it's not just a small molecule. We can now screen for any small molecule -- small molecule libraries and find new small molecules that can regulate new [indiscernible], new Riboswitchs that we design and randomize. So we currently have in vivo the ability to precisely regulate the amount of Herceptin, the amount of PTH, the amount of EPO, the amount of GLP-1, GIP in a mouse. We can control glucose. We can control calcium. We can control many of those metabolic disease or the diseases are controlled by peptides, we can precisely control those levels in vivo in animals by dosing those animals with different levels of small molecules of our choice.

When do we get to the clinic?

So the small molecules, we currently have 2 that are looking really safe that in pre-IND tox at the moment, so in NHP tox. And depending on availability of NHPs, we're moving those into the clinic over the next few quarters into side by studies in man, healthy volunteers.

Sure. I think could be really revolutionary on a number of levels. So, great. Okay. Last question. I ask this to everyone. It might be part of what you've already covered. What is it that makes Meira special compared to every other biotech or every other gene therapy company, what is it that really makes you special?

I think we -- the experience of the management team and our history as scientists, investors and other experience a lot of the management team has had has led to a company that is not one product, it's not one idea, it's not one program. We've really built a comprehensive company, a real business where we built manufacturing because that's what's required to actually move a pipeline forward. We built promoters and we built regulation because that's what is required for a future in genetic medicine. We chose programs not because we were expert in the eye, but because we had data and we thought those were the most likely to work with the programs today. So as we built Meira, we made it multilayered and we really thought about risk as well as innovation in a way that has built a company that so far we haven't had clinical failures. We have been extremely -- we're in a position where we've got the broadest manufacturing arguably than any CDM, right? Not because that was RA, but because we had to do that to be a successful genetic medicines company. So I think we are unusual in the way that this management has thought about building a company rather than taking a program and developing it, which is another successful way of building companies, but we have been very thoughtful and diligent in how we spend our money and in what we've got for that. And in trying to mitigate risk while having the biggest possible potential for our pipeline in the future.

Wonderful. I think we're going to have to leave it there. Dr. Zandy Forbes, thank you very much.

Thank you very much for having me.