MeiraGTx Holdings plc (MGTX) Earnings Call Transcript & Summary

Thank you, everyone. My name is Gena Wang. I'm SMID cap biotech analyst at the Barclays. I first hope that everyone stays healthy, and I would like to thank all of the participants, investors, companies and, especially, our event team and the corporate access team who made this virtual health care conference possible. With that, I would like to introduce our first speaker today, Zandy Forbes, Chief Executive Officer from MeiraGTx. Zandy, I hand over to you.

Thank you, Gena. And again, thank you to Barclays for making the virtual conference possible. I'm Zandy Forbes, I'm the CEO of Meira Gene Therapy. And I'm going to give a very quick overview of the company and then Gena and I are going to go into a Q&A. So I think you have our slides. I bring your attention to the forward-looking statements here listed in Slide 2. And moving to Slide #3, which is an overview of really the structure and strategy of MeiraGTx. We're a gene therapy company and somewhat unusual in that we were founded with the aim of really using gene therapy to optimize and develop therapies for a wide range of different indications to cost effectively treat diseases that are serious. And we have approached this in a way where we've built a company that we have next generation technology, which allows us to switch genes on and off. That was some of the foundational technology, which is still in research, but has now worked in vivo in animals. And one of the first things that we knew we needed to have a fully integrated gene therapy company is manufacturing capacity. So we have our own facility in London, which is both scalable and flexible and as well as the infrastructure for manufacturing. We have spent a huge amount of time and money, more than any aspect of R&D, on developing a manufacturing platform that enables us to manufacture AAV, not just one single AAV, but a variety of different AAV vectors to a level that is appropriate for pivotal studies as well as commercial. So all of the material that we make in our facility is not simply for Phase I studies, it's GMP that we have developed on this platform appropriate for pivotal and commercial. And in putting together the company, we -- as well as having a viral vector engineering toolbox, we have a diverse pipeline with 6 ongoing clinical programs. So first, if you go to the next slide, Slide 4. This is an outline of our facility in the U.K. We have designed this. I think it's unique in that it's been designed for high capacity, but also flexibility to be able to produce multiple viral vectors in one year to enable us to have GMP material to start a number of different clinical studies. So we have 2 cell feeder rooms, 3 viral vector suites, each has their own handling unit. And those suites can be used for different viral vectors at different scales. We also have on the far right-hand side, we have our own fill and finish and QC is the uncolored area around the top. So this allows us to be flexible enough to start all our studies, but in addition, should programs become commercial, we can also scale up and produce all the commercial material for our current programs from this facility. On the next slide, this covers the 3 therapeutic areas that we first entered into. Ocular is one, and we have a pipeline of clinical and preclinical programs in rare inherited disease, which is partnered with Janssen. So currently, Janssen pays 100% of our clinical development. And of those programs which get approved, we have a 20% royalty, and we get paid for manufacturing. The Janssen collaboration only covers for our eye disease, and we have our own internal program in larger eye disease such as wet AMD, dry AMD, DME, and we also have a program to eventually regulate gene therapies in the eye. In neurodegenerative disease, our lead program is in Parkinson's disease, where we have Phase II sham-controlled data, addressing a different aspect of the disease from dopamine, it circumvents dopamine, which uses GAD to improve GABA production in the subthalamic nucleus. We have research in ALS and pain and another -- a number of different neuro applications. And our third silo is in the salivary gland, where we have 2 ongoing clinical studies in radiation-induced xerostomia, and we could use that same viral vector to improve saliva production in Sjogren's disease. And we have a preclinical program looking at regulation of genes in the salivary gland. Slide 6 shows an outline of our current 6 programs. As you can see, our most advanced program is the neurodegenerative disease Parkinson's program. Our eye programs partnered with Janssen are in and completing Phase I/II programs and you'll hear more about those this year. And our salivary gland program has 2 ongoing studies in radiation-induced xerostomia. With respect to our early work in gene regulation, this platform is unique. We use RNA shape to regulate genes, and we do that with small molecules binding to aptamers, which mean that we switch off the ability of RNA to be translated in our switch. And when we add a small molecule, we release that and RNA is available to be translated. Importantly, this switch allows you to retain the gene regulation through specific promoters, which is very important, both to get high levels of expression or appropriate levels of expression as well as cell-specific levels of expression and our overlay of our riboswitch technology allows us to maintain both promoter as well as small molecule regulation. On the final slide, Slide #8. This is just a quick review of some of the key milestones for 2020. AAV-RPGR program for X-linked RP is ongoing, and we'll be reporting data from the Phase I/II study this year. The salivary gland program, the 2 studies are ongoing. The enrollment in both, study at the NIH and our own multicenter study, is accelerating, and we hope to have data by the end of this year in that program. Parkinson's disease, we will be filing an IND in the second half of the year, having initiated manufacturing in our facility. And with respect to manufacturing, we have our current facility up and running producing Phase III compatible virus, and we will be building a second viral vector manufacturing facility, initiating construction in the middle of this year with plasmid production we anticipate in-house by the end of the year and the full facility probably up and running by the end of 2021. So that's all I have today, Gena, and we can move into our discussion.

Thank you, Zandy. That's very helpful. I just wanted to start with gene therapy in the eye, the delivery, route of delivery since you have so much experience with all different kinds of eye programs. And also I'm pretty sure you are very -- follow very closely the latest wet AMD gene therapy data that give us some understanding about intravitreous versus subretinal surgical procedure for eye disease. So wondering, what is your latest thoughts on these 2 delivery routes for gene therapy in the eye?

Well, I think, undoubtedly, if intravitreal was able to be used as a dose where the transfection could occur without inflammation and would be effective, that would be more convenient and easier for physicians. So yes, intravitreal delivery would be ideal. However, I'm not sure that we have yet the ability to transfect throughout the retina using intravitreal gene therapy without some risk of inflammation. Now in some conditions, where you don't need cell autonomous expression, like AMD, where you're producing a source of a viral -- a source of a therapeutic protein, you don't need to transfect the whole retina. So for developing intravitreal, that is a reasonable place to start because you can use things such as potency of your molecule, potency of your virus as well as delivery as well as controlling the potential flip for inflammation, all to get a balance, which may allow intravitreal delivery. In the AMD space, I think Regenx has certainly shown that you can have an impact on the disease and on the number of injections needed. I think that data is clear and they do use subretinal injection. And Adverum's data starts to show that there may be a possibility of using intravitreal injection as well. I'm not intimately familiar with either company's data, no more than any of you, but that's, what I would say, the take-home messages from what we're seeing out there in the current studies.

Okay. That's very helpful. So based on these data, like, would you thinking -- maybe one step back, regarding the inflammation, we did see quite some inflammation through intravitreal delivery. So like what do we know about effectiveness of oral steroids versus topical steroids to treat the eye -- the gene therapy in the eye?

I don't know person -- I don't know that there's really good data head-to-head against oral in gene therapy versus topical in gene therapy. But we do have a large number of tools, both oral, intravitreal, topical. And what I would say is that we are developing protocols which involve duration, the time at which you take off steroids, the types of steroids that you give. And I'm not so sure that only oral, only topical or other different methods of being a prophylaxis for inflammation are yet fully ironed out. But we do have a lot of tools that can actually block the potential of inflammation. In addition to that, obviously, there's what do we do if inflammation does occur despite the prophylaxis when people come off steroids. And again, there are a number of different protocols, and there are a number of different tools that can be used. And again, uveitis experts are looking at what the best way of preventing, blocking, stopping, ameliorating any inflammation that does occur using all of those tools available. So I'm sorry, I can't be more kind of prescriptive in saying, if you do A, B and C, you won't see inflammation. But I think all of the companies working in gene therapy are looking at how to combine the various different tools available. First of all is prophylaxis. Because ideally, we don't want the inflammation to even occur. And part of that is, obviously, the potency of your vector as well as your delivery.

Okay. That makes sense. Zandy, so based on the current data so far, I remember in the past, you were saying you were contemplating either intravitreous or could be subretinal for your wet AMD program. So after current data, what is your latest thoughts of your approach?

Yes. So we actually are on a drug for hitting VEGF, is an antibody, a fab fragment against the receptor. So it's a bit like CYRAMZA. It doesn't hit the ligand, it hits the receptor. And so in our animal models, head-to-head with EYLEA, for example, this molecule is -- when delivered through gene therapy, is as effective, if not more potent than the ligand-hitting VEGF inhibitors. And we have that, and we've done studies and animal model studies and NHPs with subretinal delivery. However, rather than moving straight into the clinic with that potent molecule and delivering it subretinally, having seen Adverum's data suggesting there's a possibility for intravitreal delivery, we are spending this year developing an optimized vector, so optimizing expression as well as the molecule that we're expressing, but also looking at different ways of delivery, including intravitreal and capsids that are more appropriate for intravitreal as well as different ways of controlling inflammation. So that's what we're doing now to see if it's possible to really deliver intravitreally using all these different aspects of optimization for AMD.

Okay, very helpful. And now move to your Janssen's partnership programs. First one is the RPGR for X-linked RP. First, want to congratulate you on the PRIME designation. I'm just wondering, did the EMA saw all the data? And at what level they saw the data, the clinical data?

So we filed in our PRIME the data on the dose escalation, and that's what they saw. And they gave us PRIME with -- as a result of seeing that data.

Okay. So I understand it's in your partner's Janssen's hand, but wondering when can we see the data? I think previously we should expect sometime last year. When should we expect you to see -- expect to see the data now?

We're expecting to release that data sometime later this year.

Okay. Are there any specific, like, second half this year? Or any -- a little bit more granularity on the timing?

Not really. No.

Okay.

We haven't said yet where we're going to release the data, I'm afraid.

Okay, okay. Following that, just wondering how is Janssen as a partner so far? I think when -- after you signed the agreement, we have seen quite a lot of delay in sharing the data. We understand Janssen is a big company. They have a different strategy. Just wondering, how is the clinical trials progressing for these partner programs, including RPGR and CNGB3 and CNGA3?

So I would say that there may have been a very -- I wouldn't say a delay in data. We aren't releasing some of the data that as a small biotech company we may have released. However, the partnership with Janssen has been really transformative for the company, in that not only do we have clinical op support, MSAT, the manufacturing support, and financial support, clearly, for clinical development, but we also have the expertise in how you actually get something to BLA rather than how you open a Phase I/II study. And this has been really important for this company in rapidly getting to a point where we have the infrastructure, and we understand what needs to be done to actually get a drug approved, rather than have a drug in clinical development. So the partnership with Janssen, from our perspective, has not only provided the money, but really we've had a step change in how the company operates in clinical development and manufacturing to really be ready for getting something approved and in pivotal studies. So it's really accelerated our clinical development and the quality of our clinical development rather than delayed anything. While some biotech investors may not like that we don't release data until we have full data, and it's appropriate for the program, I would say that there's very good reasons for that from a competitive standpoint and from other standpoint, the patient standpoint. And Janssen has really been instrumental in helping us in all our programs with them, accelerate them at very high quality.

Okay. Okay. Good. And regarding the CNGB3, just wondering, what would be the next steps and the potential regulatory path?

So CNGB3, as you know, the patients who enrolled last year, they -- I think all patients reached their first end point of everyone hitting 6 months at the end of 2019. We are continually collecting data in a 3- to 6-month on every patient, analyzing that data and preparing how we move forward in additional studies in A3 and B3. And the 2 programs do feed into each other, but not absolutely. But we are progressing both of those as expected and receiving data every 3 to 6 months from those studies.

Okay. And then...

A3, I should just say, is currently still enroll -- I mean the A3 study is enrolling in pediatrics. The B3 is complete. And we're looking at the data as it becomes available.

Okay, okay. And then the timing for data presentation?

We have -- no, we haven't decided with Janssen when that data will be put together for presentation.

Okay. Okay. So that's very helpful. The -- maybe we'll move to the Parkinson's disease. I'm wondering, have you met with FDA regarding the Phase III trial design?

So we met with the FDA in a pre-IND meeting because we acquired this, and we need to open an IND and they don't have a mechanism for meeting to discuss pivotal studies until you have an open IND. So we are manufacturing material to pivotal study quality grade at our facility, like all our material this year to use as we file the IND. Once we've opened the IND, we -- with that material, we will discuss the ongoing trial design with the FDA at that point. We would like to beforehand, there isn't a mechanism though.

Okay. Okay. So based on the Phase II experience, what could be your proposal to the FDA that will be the potential end point that you will prefer based on the current Phase II data?

Well, so first of all, this is -- to be clear, this is not addressing the duration of dopamine activity. So we aren't looking for on-drug improvements, okay? So there's a very, very big difference of what we're actually doing. We're looking at what happens in this disease in a way that you look with deep brain stimulation. So in our sham-controlled Phase II, we saw a statistically significant improvement in UPDRS motor scores as well as a number of other scores. Now UPDRS is what was the primary end point. We have the statistics on it. And we, in addition, have a PET data, which we think can augment the UPDRS data. But our current Phase II and what we're thinking about in continuing studies is UPDRS is an end point that we're very interested in. And that is overall change in UPDRS versus a control. It is responders changing in UPDRS by a certain amount. In our Phase II study, we saw a statistically significant improvement in response when response was defined as UPDRS change of 9. Now that level of a 9-point change was prospectively set in this study based on a 25% improvement over the baseline UPDRS. And we saw a specifically significant benefit compared to sham. Now subsequent to that study, a paper has been published looking at what changes in UPDRS are clinically meaningful. And a clinically meaningful change of 5 to 6 points -- a change of 5 to 6 is considered a good clinically meaningful change. A change of 10 points is extremely -- is considered extremely clinically meaningful. So by choosing our 9 point, which is 25% of baseline, we actually had shown an extremely clinically meaningful improvement in UPDRS. So we're looking at how you look at response, what's very clinically meaningful in the field, and that will feed into the type of end points, which we'll be using in our next study.

Okay. That's very helpful. We're running out of time, but I would like to ask one last question regarding your manufacturing. Just wondering, what do you need to do from a manufacturing perspective in order to move to the late-stage studies of your gene therapy?

A lot of it is QA. So we have a single-use philosophy. We have a -- as many as 2-unit operations as possible. There are 3-unit operations. But really to be in Phase III, you have to have very robust quality, QC and validation. So everything has to be highly validated, repeatable, and the data has to be very clear and correctly documented. So a lot of being ready for commercial is, in fact, QA and documentation of a process that really is reliable and reproducible.

Okay.

The quality documentation is absolutely critical.

I see, I see. Okay. Well, thank you very much, Zandy. Thank you, and thank you, everyone, for participating.

And thank you, Gena. I'll speak to you soon.

Yes. Talk to you soon. Thank you, everyone. This concludes our call. Bye.