MeiraGTx Holdings plc (MGTX) Earnings Call Transcript & Summary

Hello, everyone. Welcome to day 2 of the 2020 Bank of America Healthcare Conference. My name is Alec Stranahan, and I'm an analyst from the biopharma team here at BofA. This session with MeiraGTx will last approximately 30 minutes and will be conducted in the fireside format. If you are accessing the event through the Veracast platform, you will have the options to submit questions at any time throughout the session. Your questions will remain anonymous. And with that, it's my pleasure to introduce Alexandria Forbes, President and CEO of MeiraGTx. Zandy, are you there?

Yes, I'm here. Thank you very much for inviting me to speak at your conference.

Great. Well, maybe before we get into our questions, I'll just hand the floor over to you to give some brief context about the company first.

Thank you, Alec. So MeiraGTx is a gene therapy company. We formed about 5 years ago with the view of taking advantage of this new therapeutic modality, not only to use gene therapy for gene replacement or for rare diseases, but to take gene therapy technology, optimize it and use it for rare diseases but also apply it to treat larger indications. And in setting up the company, we wanted to have vertically integrated platform that allows you to manufacture, design and optimize your vectors as well as clinical programs which we now have entering in late-stage clinical development. And all of those things fit together to allow you to rapidly develop gene therapies to multiple different targets, both rare and more common diseases. And I think Alec is going to ask me some questions about some of our programs now.

Okay. Great. So maybe we could just start by talking about your clinical program for X-linked retinitis pigmentosa. So this program has obviously been a major focus as it's one of your lead programs and it's also a major component of the Janssen partnership. And while I'd argue that there's much more to your company than just the Janssen partnership or the rare eye disease programs, maybe we could first talk about RPGR as data from the Phase I/II trial's expected this year. So maybe you could briefly introduce the program and where it is in development currently.

So thank you, Alec. The RPGR program is -- has completed the dose-escalation phase of the Phase I/II study. The expansion phase, the randomized, untreated, controlled expansion phase is ongoing and we will be presenting data from the dose escalation in the second half of this year.

Great. So I'd assume, ahead of the readout, many will be looking at the 6-month data published at the end of February by Nightstar. So maybe you could just speak to the differences between your product and Nightstar's for this indication. And given the clinical endpoints of retinal sensitivity, et cetera, do you think it's fair to ultimately compare the results we'll see later this year for your program to the Nightstar study? Or do you think we should wait for a larger pivotal study?

So the Nightstar data, and I believe they're presenting as we speak at the ASGCT conference that data again, it comes from their dose escalation, and they looked at perimetry endpoints, in particular, to show that replacing the RPGR gene has an impact on retinal sensitivity. That's what we know from the Nightstar data. We, Meira and Janssen, will be presenting data from our dose escalation, where we also look at perimetry as one of the endpoints we look at. I agree that I think discussions with regulatory agencies around the world through -- with us, and I'm sure other companies, have indicated that perimetry in this indication is a useful assessment. And readouts from perimetry and analysis of perimetry may be used as primary endpoints in clinical studies. So I agree that there is an ability to look at maybe Nightstar data and say there are some responses and our data, when you see it, and assess the types of perimetry data that we present to you. We actually, as a company, as you've seen with our RPE65 study, we use a wide range of assessments when we do our clinical studies in Phase I and Phase II. So we don't necessarily show the identical type of perimetry or the same type of analysis as Nightstar. So there are many different -- there are several different ways of measuring perimetry, different machines, MAIA machine, which is what the data that Nightstar and AGTC had presented. We have used the Octopus machine and the MAIA machine. You can analyze perimetry just by looking at the mean sensitivity of the eye or you can use algorithms that's been developed by Dick Weleber at the Casey Institute to use all of the data that you collect from those perimetry machines in a Helio Vision. The optical machine is a very robust way of collecting data. It internally determines the reliability of the subject and each piece of data. So while you will see broadly perimetry from all of the companies, we may each present different ways in which that perimetry is calculated, assessed and presented.

Great. And along those same lines of clinical endpoints. Your RPG (sic) [ RPGR ] program does have prime designation in the EU. So how would you say the greater access to regulators is sort of informing your thinking around what kind of endpoints you may include in a more registrational study and sort of what do regulators view as the most meaningful endpoint within this indication?

So yes, we are in discussions with regulatory agencies, both here and in Europe, around this and our other eye programs. And I think in general, the discussions of the use of perimetry and how it's used have been very helpful in informing us of what would be preferred primary or secondary endpoints in future studies, but we haven't yet made public what those are for us. But we've had very helpful dialogue with agencies globally on that point.

Okay. Great. And maybe turning to the Janssen partnership component of the program. Could you speak to the nature of the partnership? Obviously, a lot of the focus is on the financial contribution, such as the milestones, the 20% royalties on net sales and having Janssen support all of the clinical development for the rare eye disease programs. But could you maybe speak to sort of what are the lessons you've learned with working with Janssen sort of how that partnership functions on the day-to-day? And how you may be applying those lessons to other programs outside of the partnership?

Yes. That's -- interesting question. So this collaboration, when we did it obviously was financially very helpful for Meira and allowed us to accelerate and really robustly move forward our inherited retinal disease franchise or platform, I would say. So from that perspective, it was useful. But much more transformative to the company has been the incredibly close collaboration that we've had with Janssen across the development spectrum. So I would say that we worked as a very close team from manufacturing through clinical operations, through regulatory into medical affairs, areas that Meira did not have experience in. And Janssen has been a real collaborator so we work in teams with a group from Janssen, a group from Meira working together as one organization. And I would say that, that collaboration has transformed the company from a Phase I/II gene therapy company into a company that is fit to support pivotal and commercialization of drugs. And Janssen has really helped, overseen and collaborated in showing us what is required and that's a lot. Globally, regulatory agencies require a lot to have something ready for a BLA, ready for approval, from the quality systems all the way through clinical operations, everything. And I think -- we're actually really grateful to the Janssen teams that have come on board and worked with us as one group in moving these programs forward. So it really has transformed the company in our capabilities, not only in the IRD programs to allow those to be accelerated and successful, but taught us as a company what we need to know to apply -- to take forward our other programs into later-stage development.

Great. And that's actually a nice segue into my next set of questions around your manufacturing capabilities as it's not only important to the regulators to have confidence in the quality of the gene products coming out of your labs, but I'd imagine that's also a driver of the Janssen partnership to begin with. So how would you say having a commercial-scale GMP production, pretty much from day 1, will benefit the clinical development of your pipeline candidates, both from a regulatory and a commercialization perspective?

So manufacturing for gene therapy is a big focus and rightly so. And as the first gene therapies have got approved, and particularly the AveXis drug, and drugs for DMD and hemophilia are in late-stage development, one of the first issues is this capacity issue. Can you make enough of your product to first treat your clinical trials and then supply the market? Because that's obviously required for approval. So there's been a lot of focus on companies building their own internal capacity. Now -- which is important. What I would say is, more important when you're building a gene-therapy company, is to actually build very flexible manufacturing using a platform process, which supports Phase I/II, but from the very start of your manufacturing process, for your first clinical trials, you use the process that will ultimately be used for pivotal and commercial. And so while Meira, when we first formed, immediately built a state-of-the-art manufacturing facility, the nuts and bolts, we spent a lot of time considering, in building that facility, what the regulatory agencies would prefer to see for a commercial product. So our facility -- the quality systems have been built to support commercialization. And in addition, and equally, if not more important for gene therapy is the process that you use. So we've spent a lot of time and energy on building a manufacturing process that can be readily applied to any viral vector we bring in. And the earlier you do this in the development of that viral vector, the better. Now all of the material manufactured by us in our facility, whether it's for a Phase I study or a pivotal study, uses broadly the same platform, which means that anything coming out of our facility does not have to go through bridging to create a new process to scale it. We have physically scalable single-purpose facility and a scalable platform process. And all of that means that very quickly, you could move through your clinical development into your pivotal trials without having to do extensive comparability between Phase I and pivotal. In addition, one more thing I'll say is that the actual vectorology, so the vector-construct platform that we've put together, and the optimization of our vectors prior to them going into an IND also feeds into manufacturing. So as you can understand, if you have a vector and it is -- you managed to make it through promoter, capsid, gene engineering, a thousandfold more potent than it may initially have been, that essentially drops your cost of goods, drops your dose a thousandfold conceptually. So our vectorology also feeds into our manufacturing requirements and ultimately, the dose and the cost of goods. So all of these elements of gene therapy are very closely linked, and all of them have to be optimized in order to produce ultimately a pipeline of gene-therapy products, which are manufacturable, high-quality, efficacious and lower cost of goods, all of which are important, if you're starting to treat not just rare diseases but potentially diseases that address a larger population.

Perfect. And having all those capabilities in-house, you mentioned that you're building out your plasmid production currently and the other components are also sort of vertically integrated within your capabilities. How does this compare to other companies that are maybe at a similar clinical stage? And could you maybe point to some examples of approved therapies from Spark and AveXis and sort of what's had to be done for those therapies that maybe weren't so integrated at their early stages?

I don't know enough to speak specifically about Spark and AveXis. But I would say that at this stage, in the life of the gene therapy and AAV industry, I'll call it, some of those successful early products actually were developed in academia, they were shown to work and manufacturing was built and developed specifically to manufacture those viral vectors, specifically at a capacity required to suit the market, to supply the market. And they have done and they've been approved and they're successful drugs. What I would say is, looking forward into the next 10 years, there are ways that we can optimize all aspects of gene therapy, which is the aim of Meira. And that lies in the promoter technology, in capsid technology, in protein engineering, in many different things to improve potency, to improve delivery as well as manufacturability. You mentioned our plasmid. If we look at cost of goods, for an example, and you look closely, the cost of your plasmid is a large part of your cost of goods. The cost of your QC to release the commercial material is another large part of your cost of goods. So at this point, Meira is addressing that, bringing plasmid in-house as well as looking at alternatives for plasmids as well as building cell lines, our producer cell lines, using maybe synthetic DNA, bringing our QC in-house, validating it in-house, all of those aspects, which you don't necessarily see from the outside, are ones that we focus on with the eye to being able to produce high-quality, commercial, material across a wide range of different viral vectors that can ultimately be commercialized and is less expensive than the processes that are being -- that are at scale today.

Perfect. And you mentioned commercial-scale manufacturing. So what would it take to reach scale for manufacturing for all of your current therapeutic candidates? Or are you already there? And how will a second GMP viral vector manufacturing facility you're planning in Europe feed into your overall strategy longer term?

So yes, so manufacturing scale is -- all of our products are -- and the manufacturing runs that are done are scaled for the need. So all of the products we currently have in the clinic and one of the reasons we chose to start our clinical development pipeline in these indications was not only efficacy because there was proof-of-concept but you'll notice that all of our gene therapies, whether it's IRDs, in the eye; AMD, in the eye; whether it's our Parkinson's program, local delivery; whether it's xerostomia, local delivery; local delivery in joints -- we acquired a company last year -- all of those use small doses. So we do currently have the process and the capacity to scale up any of those in our current facility for commercial -- to supply a commercial market. Our second facility will allow larger bioreactors. One thing I should just point out. Our facilities, we have a single-use philosophy. So there's no fixed bioreactors in any one of our production suites. So scalability means that we can use 80 liters, 100 liters, 250-liter bioreactors in the same room, sequentially, shut the room down and change the scale of that room. Our next facility will be equally flexible, but the size of that bioreactor that could be used will go up to 500 to 1,000 liters. So this allows us, having both of these facilities rather than to only get to large-scale volume, it allows us the increased flexibility to produce clinical material, all of which is of the process and the quality systems for supporting a commercial material. So I don't know if I've explained that, and that's the difference between our manufacturing approach, I think, to some others in that we have this flexibility, which allows us to produce many different viral vectors for clinical or commercial and at the same time, rapidly scale up because of the single-use philosophy to a commercial market scale.

Okay. Great. Well, maybe for the last 5 minutes or so, we can shift attention to some of your other clinical programs outside of eye diseases. So maybe just to start, we can talk about your AAV-GAD program for Parkinson's. So this program was actually brought into Meira through an acquisition you guys did back in October of 2018. Could you maybe touch on how the clinical data drove your interest in this asset? And what your plans are for continued clinical study over the coming months?

Yes. Thank you, Alec. So this is our most advanced program. And we are very excited about the data that has come out of this program so far. This program was developed by Matt During and Mike Kaplitt who actually were the pioneers in developing both growth factor and dopamine gene therapies, and having thought and looked very carefully at the ways in which you can address Parkinson's disease with gene therapy. They devised the treatment with GAD of the subthalamic nucleus as what they thought would be the most successful and safest way of treating Parkinson's disease with a gene or cell therapy. And we have Phase I dose-escalation data and importantly, a Phase II sham-controlled study where statistically significant difference in UPDRS was shown. This is the only gene therapy or cell therapy that's ever been shown to have a statistically significant benefit against sham. The mechanism is one that is very well-validated in Parkinson's disease. It's well-known that there are 2 ways basically of treating Parkinson's disease. One is to address the dopamine pathways by replacing dopamine, and you can do that with drugs or you can do that -- there are attempts through gene and cell therapy. And the other way of addressing Parkinson's disease motor symptoms is to address the hyperactivity of the subthalamic nucleus, which occurs as a result of the dysregulation of the basal ganglia when dose signaling is not appropriate. And this hyperactivation is what we addressed in the same way that deep-brain stimulation addresses it. So we actually, in a onetime treatment, deliver to the subthalamic nucleus, the enzyme that converts glutamate to GABA, and that GABA within the subthalamic nucleus essentially calms it down, the hyperactivation that normally occurs is because of the reduced GABA input to the subthalamic nucleus, a very well-validated mechanism. When we restore GABA to the subthalamic nucleus with a very local delivery of the enzyme that creates GABA, and we have a good effect versus sham on the motor symptoms, and in addition, a number of other endpoints that were secondary endpoints in that clinical study. So we feel we've got very compelling data for a mechanism that's been well-validated through other areas. And we're moving forward into a later-stage study towards the end of this year and next year.

Okay. Perfect. And we only have a couple of minutes left, and there are many other programs in your pipeline that I'd like to talk about, including your xerostomia program, RPE65 and also your wet AMD program as well. But maybe we could just spend the last question on your xerostomia program as this one should have data, I believe, in the second half of this year from the Phase I/II trial. So maybe you could talk about how your gene therapy is unique in terms of mechanism of actions or the unmet need in this indication? And also how investors should frame their expectations around the trial readout?

Thank you. So yes, this is a very interesting program. Again, not gene replacement, but solving a problem that is otherwise not solvable without gene therapy. So when people have radiation to cure their head and neck cancer, they all lose the ability to produce saliva called xerostomia. And it's a major problem. 30% to 40% of patients after 2 years, when the salivary glands have recovered, still have very low or negligible levels of saliva, which is a very severe condition. So we treat patients who are coming in, see their oncologists or their dentists at least once a year to make sure they don't have cancer and still had this untreatable lack of saliva. The reason for this is because the cells that allow water to flow through the salivary gland are very sensitive to radiation. So essentially, those salivary glands have lost their permeability to water. We took the genes to aquaporin-1, a nonpolarized water channel that is used throughout the body, we put it into the ducts of the remaining salivary glands. And when it transfects those glands, those cells become permeable to water and water can again flow through salivary glands into the duct and into the mouth. This has been shown in a previous study in man using adenovirus. We now use AAV2, which is not immunogenic, and deliver the aquaporin-1 to the salivary gland. We have 2 studies, 1 with our collaborators at the NIH, a dose-escalation study, and a multicenter study in the U.S. and Canada ongoing, which Meira is doing. And we hope to have data from some of those subjects who've been treated unilaterally with aquaporin-1-AAV2 in the second half of this year. The market is a very interesting one because of those patients have grade 2, 3 xerostomia, 2 or more years after curing their head and neck cancer, I'll call it, there are about 170,000 of those patients in the U.S. today. So we do have orphan designation, but you can appreciate that for gene therapy, that's a large market. And also with 50,000 patients having head and neck cancer every year, there are about 5,000 to 10,000 new patients a year with this sort of xerostomia. So the dose is small, it's a noninvasive delivery that can be done by a dentist or a head-and-neck doctor. And this is really an unmet need that the patients haven't been incorporated in the health care system and are sitting there, waiting to be treated, keen to be treated, and it's a very debilitating quality of life as well as health risk with oral infections, loss of teeth, inability to eat, sleep, talk. So it's a very severe indication. And we're hoping to have some data on saliva production later in the year from both of those studies or at least one of them.

Okay. Perfect. Well, thank you. Unfortunately, that's all the time we have with you, but we want to thank you for the comprehensive overview of your business and for taking the time to participate in our conference, and thank you to those on the line as well for your interest.

Thank you very much, Alec.

All right. Thank you. Take care.