MeiraGTx Holdings plc (MGTX) Earnings Call Transcript & Summary

Hey, everyone, good morning. Welcome to day 1 of the 2022 BofA Healthcare Conference, and thanks for joining the session with MeiraGTx. My name is Alec Stranahan. I'm Vice President and Senior Biotech analyst covering Meira here at BofA, and I'm pleased to be joined by Zandy Forbes, who's the President and Chief Executive Officer of Meira. I believe Zandy is going to run through some slides to start, and then we'll get into the Q&A. So with that, Zandy, over to you.

Thank you, and thank you for inviting me to speak to this exclusive group. I hope that what I show you today will impress you enough to run away and tell your friends how amazing Meira is. So we are a gene therapy company and very unusual because of the way we were set up. We started in 2015, not to focus on a particular indication, but rather on the capabilities that are required for any gene therapy company to have a clinical pipeline and commercialize as well as a pipeline that we chose because it was the lowest risk pipeline that we thought was available at the time. And indeed, our pipeline so far has not failed in a single indication. So we chose our pipeline, which currently has 6 clinical programs a pivotal program with our partner, Janssen, because those were programs where there was human proof of concept, small doses immune privilege, and we were able to manufacture those doses some are in rare diseases, inherited diseases, other are more like tissue engineering and 1 is in Parkinson's disease. Importantly, we set up manufacturing. We bought and built our first facility when we founded the company. We now have 2 GMP facilities, in-house plasmid production, analytics for full commercial QC with a commercial manufacturer for our partner Janssen and we're currently preparing for a commercial launch after BLA in 2024. In addition, many of the vectors you see today in the clinic are suboptimal. They came from academic institutes. They may have a promoter that's useful. They may have a capsid that's useful, but they are just at the edge of efficacy. And we've built in-house at Meira, our vector and capsid optimization that optimizes every single base and the capsid so that we can reduce dose by increasing potency and increased safety. So we have a pipeline of programs that are pre-IND that are really fully optimized. And by increasing potency and reducing dose, you tend to be able to overcome the issues of safety that we're seeing today. In addition to that, over the last 7 years, we've built in-house and invented in-house, a completely new technology for precisely controlling any genetic medicine with an oral small molecule. And that sounds far-fetched, but rather than going to an academic institute, we and the scientists of Meira actually thought completely differently about how you control genetic medicines, and we have invented a way of inserting into the central dogma the production of message, the requirement for 1 small molecule. And so we can have different small molecules to different genes and we can precisely control how much of any gene in cell therapy, in any context is switched on at any time with an oral pill. This is our pipeline, which I mentioned. IRDs are some of our lead programs. Our pivotal program with Janssen is in a large inherited retinal disease, RPGR. And as I mentioned, we're planning for the commercial launch of that after BLA filing in 2024 should the pivot will be positive. Parkinson's disease. We're finding -- we will be starting an IND opening study with our own material. We have positive Phase II data versus sham the only Parkinson's programs to have that. And the xerostomia program, we presented positive data from our dose escalation study last year. Completed dosing in that study, I'll be presenting full data at the end of this year and starting a large randomized study by the end of this year. RPGR, our lead program, a large indication for IRDs we presented from our dose escalation, and we had some data last week even [indiscernible] positive retinal sensitivity and positive retinal function, positive functional vision as measured by going through maze as well as many, many measures that show that when we treat with our drug in our Phase I study, we're able to improve the vision of these patients. This is, as I mentioned, the lead program with our collaborator, Janssen, and this allows us -- our deal with Janssen allows us to move this to commercialization without having to pay anything else ourselves, which is clearly important at this point in the capital markets. So the deal involves Janssen pays 100% of all clinical development we codevelop. So we have the full support of Janssen's entire infrastructure and operations as well as all the financing for manufacturing as well as clinical trial. So we have a top line 20% royalty on approval and we're the commercial supplier. We had a $30 million milestone at the beginning of this year, and the pivotal study is very unusual for someone in IRDs because of the support of Janssen, and this is one of their lead programs. We have a large 30 or more site program globally. We filed our material -- our CMC material with more than 10 global agencies. So we know that material manufactured at Meira with Meira's quality systems with Meira's facility and process is fit for not only a pivotal, but for moving towards commercialization. We've had those discussions with global agencies. The pivotal trial is ongoing, Janssen's time line for filing the BLA is 2024 with potential approval coming shortly after that. Now this is really important for CMC because as you can see with monthly releases with CMC issues, CMC actually allows you to develop drugs. We have the broadest viral vector manufacturing in the industry. What does that mean? We have a process, which is a platform process for manufacturing that we can use for all of our different AAV viruses and it's flexible and scalable. In addition, we have multiple facilities, 2 viral vector facilities so we have scale to launch commercially of even very large indications. We, in addition to that, have bought in-house plasmid production. So we have plasmid production capabilities, which 20-fold exceed our own current clinical needs and very few companies have GMP plasmid production. And you'll probably have heard the issues with analytics. So not only do we use our preclinical groups to develop analytics. But for the launch of our first Janssen program and all the ones that follow, we have bought full analytics for release and stability of a commercial program in-house at Meira. Currently, it's actually impossible to launch a product in the commercial environment because of the analytics from CROs are reliable enough to -- in a timely fashion launch a drug. So we brought all of that in-house as well as fill and finish. So we have multiple GMP facilities that have capabilities that are currently preparing not just for clinical supply but for commercial supply. Our second program, Xerostomia, huge unmet need, very, very big market for gene therapy. Here, we re-paralyzed the salivary glands of patients who totally lost salivary function because they've been treated for head and neck cancer. This is post being cured for head and neck cancer. So each patient is coming back to see their oncologists to make sure they still don't have cancer, and this is their worst problem. We finished our Phase I dose escalation. We actually added to that with a bilateral dose escalation, which completed dosing in 1 quarter in the first quarter, and we'll be going into a larger, randomized Phase II study by the end of this year. And we'll present data from that full study that I just mentioned the dose escalation at the end of this year [indiscernible] that we presented last December. And in Parkinson's, many people have tried to treat Parkinson's with cell therapy and dopamine mechanisms. Here, we take a completely different approach. And what we've done is we've used a neurotransmitter that blocks the hyperactivation of a tiny part of the brain, the subthalamic nucelus, and we carve it down with local injection of an enzyme that makes GABA. And in this way, the brain rewires and motor symptoms are diminished. And we've shown this in a positive Phase II trial. It's actually the only positive trial ever done in gene therapy, growth factor therapy or cell therapy that's had an effect in Parkinson's versus sham. We've made new material with our process in our facilities, and we are opening an IND study now in this indication. So I've told you about our pipeline, our collaboration with Janssen, which has given us the infrastructure and the financing to build out all of our manufacturing, our QC, our quality systems as well as in-house develop these proprietary vectorology, which allow us to build a new pipeline as we move forward and actually use these capabilities that many companies don't have, which allow you to manufacture and move forward with new products. Just pictures of our various manufacturing facility, it's scalable, it's flexible. We can produce many different viral vectors in a year. During COVID, for example, not only did we build a GMP plasmid facility, but in our other facility, we managed -- we manufactured 5 different clinical products, whereas -- and this is when you couldn't get filters. So we have very strong supply chain, manufacturing, which is fit for clinical but also commercial and scalable. And I said, GMP plasmid as well as QC/QA downstream, which is turning out to be essential for being able to start anything. I'm not going to do that. So we focus as well on every aspect of vectorology. Promoters, you'll know companies like encoded and Synpromics that cover one promoter platform. So rather than that, we have 4 different promoter platforms ranging from hand-made promoters in Organoids through medium throughput designing promoters with known elements and screening encoded database, et cetera, with our promoters to high-throughput barcoded promoters engineering, where we looked at every 300 base piece in the genome and found promoters. And what's very, very successful now for cell-specific promoters and single cell analysis is our AI platform. So with this, we have literally a promoter that is 17x stronger than the current promoter used in DMD products. We have multiple muscle specific promoters. We have liver-specific promoters. We have neuronal promoters, and we have multiple constitutive promoters, which are manyfold stronger than CAG. And why use CAG, is if you look at both gene therapies that are approved, Zolgensma as well as Luxturna, completely different. What promoter do they use? An optimized academic CAG. This is not the way to move forward with a fully optimized platform of gene therapy products. And finally, our gene regulation. This is not an on-off switch. This is a precise way of controlling with a pill how much of any genetic medicine is present in the body at any time. I'm not going to show these. We presented all of our data, but in a dose responsive way, we can switch a gene on in a mouse at any time with this oral pill. This is very, very precise. Here are 5 mice with an unregulated gene. Here are 5 mice with the same gene, but our regulation cassette at 1 dose, look, every mouse produces the same amount of the product. A very -- I'm not going to do that one. Here is an example -- actually, you know what, I'm just going to go back. Here are an example of our molecules that we already have regulated, which are activated with an oral pill. Every pharma companies favor antibody. We can put, for example, HER2, PD-1 within the CNS and activate it with a small molecule. We have, in vivo, precisely controlled hematocrit with a pill with EPO, human growth hormone with little mice, we can control how big they are. PTH, we can precisely control serum calcium GLP insulin, GLP-1 agonist. And just as a final thing, which I love you all have seen Lilly's data in a 4-month period of time, we created a vector that produces the natural forms of GLP-1 and GIP and you can activate it with a small molecule pill, which we've done here in a mouse, and you will see that these are the control mice, 1 with no drug, 1 with no construct. And what you will see is that when you activate -- sorry, I need a pointer, but these are the ones that are activated -- so this one has a constitutively active GLP-1, GIP. This one is the one that's regulated. And you can see, you give the mouse a pill, it produces the exact right amount of GLP-1 and GIP at the right time, bam, it's got completely clear post-prandial regulation of glucose. This is an incredibly powerful technology that you can use in many ways. You can look at this on our Analyst Day. And this is our company. So derisked pipeline, which has allowed us to build end-to-end GMP manufacturing. We've focused on our future pipeline in next-generation vectorology, a transformative gene control technology. And to support all this, we've got in-house end-to-end manufacturing that every gene therapy company needs to actually have a pipeline, and we've brought it all in-house.

Okay. Fantastic overview, Zandy.

2 minutes too long.

Really applied by a lot of exciting stuff going on for sure. But maybe in the Q&A, maybe we can just start with manufacturing. I think Meira is really a company that's differentiated itself compared to others by having really sophisticated manufacturing from day 1. So I guess how has this sort of helped in the company's growth in terms of feeding forward into the other programs, keeping all of that intellectual advancements in-house? And could you just speak to the commercialization piece?

Yes. It's really interesting because when we started the company, the first thing we did is build a manufacturing facility. And I will just say one thing, is we have these facilities and I'm a very risk averse like worst-case scenario-type of person. And when we built our facilities, we insisted that we bought the land and the buildings. So we're currently. I'm very happy to say, in a 100% possession of the actual facilities and actual land. So just that is probably worth more than our market cap, right? So we saw the value of manufacturing. When we started, there was a big push to have scalability. You saw companies like BioMarin, unable to supply their trials, but really to be a gene therapy company with more than one product, you need to have not only scalability but flexibility. So we worked with the regulatory agencies globally to design our first facility that has single-use philosophy, every room different air handling and was built as what the regulators want. And then we were in discussions with several large pharma companies about partnering our inherited platform and in IRDs. And I think the ability to manufacture clinically in-house was really important. And in doing the collaboration with Janssen, we obviously collaborated with a partner who while not experienced in gene therapy at the time is extremely experienced in launching drugs. So through that partnership, not only do we have financial support but we learned what it meant to be a company that's not producing clinical material but is actually producing material for a BLA. And we've had iterative discussions with our partner, Janssen, who's got a very big team that works with us with global agencies around every aspect of our studies, but the CMC aspect is clearly critical. So that when you -- when we see people from the FDA speaking, it's very much what we've built over the last 3 years in order to support these Janssen programs, which have allowed us to turn from an early clinical stage company into a company that actually can commercialize gene therapies. And that's really important because the process is important. We're one of the leading process development companies. We beat the test almost all the new technologies. We're developing producer cell lines. We work with Janssen, who is really good on knowing what you see is required and how you validate and what's required for BLA. And as we've seen issues in the industry, in plasmid quality and supply, we brought that in-house. Now as we're looking to launch is a very clear that bringing QC in-house, which we decided to do during lockdown because the supply is actually essential, if you'll go to supply any amount of gene therapy. So our partnership with Janssen has really been instrumental in allowing us to learn how to be a company that produces commercial top quality viral vector. And I think that's quite unusual. And in a time frame that's allowable. So just on the analytics. Just one story is, last year, in the second -- third quarter, we were releasing a product and we had an infectious tighter assay with a particular vendor BioReliance. And we asked for the time frame, they said, "Well, we'll give you the full report in November 2022." Now that -- you just can't run a trial. You can't plan anything with that sort of time frame. So along with our partners, we brought it in-house, we released that product some months later. So it really is a massive problem. And we've added a lot of capabilities and we've learned a lot from agencies and our partners.

Right. Right. very forward thinking, and obviously, it just grows in importance as a bit more...

Absolutely. I mean we didn't imagine that when we started, but it's been essential to actually have a pipeline that moves.

Right. And it's a beautiful building, too. I think that was the first time I saw...

One in London's underground. One in Shannon's, yes, beautiful tulips everywhere.

Well, maybe we can talk about the Riboswitch platform as well. And this is something that if valued on its own, would be a huge IPO. And I think it overcomes a lot of limitations of historical attempts as well. And like you said, it's not just a non-off switch. There's a whole gradation depending on the concentration of the inducers. So I guess in the simplest terms, could you just talk about the Riboswitch platform? How does this feed into your future pipeline aspirations? And how does it really differentiate you as a company?

So the Riboswitch platform is a unique technology, which has been, I'll call it, holy grail of genetic medicines. How can you precisely control how much gene is on at any one time. And one of the big issues with this is that it's been extremely hard to be able to switch genes on from zero. And that means that the dynamic range, the range between on and off tends to be very low and not useful. So what we did at Meira is that rather than keeping trying to switch things on, we stood back and went okay, how can we completely switch RNA formation -- message formation off. So we've designed a cassette that if you put it into any gene, this is in a cell, it's -- wherever you want it, will completely block messenger RNA formation. And then we designed a way of splicing that block out when a small molecule bound to that cassette. So as a consequence of that, we have a switch, a control mechanism, which is extremely high dynamic range. We can combine -- we can do switches a 10,000-fold dynamic range, right, to undetectable to fall on and we can do tenfold dynamic ranges. But in literature, a good dynamic range is tenfold. So you can see this is completely transformational. In addition, 1 small molecule, I said, makes on messenger RNA. So there's incredibly precise control of the amount of RNA with the amount of the drug. So we're in this position where we can now control the amount of any genetic medicine by an oral pill. And we can screen our cassettes so that each cassette a particular aptamer that binds a specific small molecule. So this is really important technology. And what we're looking at using it for now is things like biologics across the blood-brain barrier. If you put an antibody like I mentioned, we've regulated PD-1, PD-L1, Herceptin, you put the antibody or an anti-amyloid within the CNS, you can switch it on with a pill to the right dose at the right time, and it doesn't have to cross the blood-brain barrier. And the dose, as you know, up from serum into the brain is at 0.5% maximum. Other areas are being able to have things like oral insulin, oral PTH and use the natural form of the drug. Most importantly, one of my favorite examples is the gut peptide. We've all seen the huge success of Lilly's dual agonist, GLP-1, GIP. And the obesity, diabetes industry has attempted for 3 decades to really use gut peptides to effectively address metabolic diseases. That's extremely hard. We -- there's a peptide called PYY, which if you can add it to GLP-1 and GIP hugely increases its efficacy. However, it needs to be infused because it's so short lived. I showed you the efficacy in a glucose challenge in a mouse of GLP-1, GIP but we also have a triple combination with PYY. So we can currently make any combination of small short-lived peptides and switch them on with a pill. And this is incredibly powerful for a whole arena of medicines, which haven't really been tractable as drugs because they disappear so quickly, like PYY, but things like metabolism, aging, fat, general cognition there are peptides, which are very involved in these sorts of diseases. And this allows you to incredibly quickly put combinations together and test for efficacy. And so in those areas where we haven't been able to make drugs, this is the first time that we can really use those sorts of molecules for a therapeutic benefit in the most effective way.

Right, right. And I think the data from Lilly on tirzepatide was pretty impressive, not just in diabetes, but obesity alone and the market opportunity combined is at least $10 billion and going back to the table, there's obviously many, many more applications. So I guess as you're taking the technology forward, how do you prioritize there? And what are the next steps in terms of clinical development?

So we have libraries of small molecules and we select those which have good PK, good safety. We're currently taking 15 of those through preclinical talks into pre-IND. We hope to have an IND for that first small molecule by the end of this year, but we have libraries following. So by next year, we'll have first-in-man studies, dose escalation studies of our small molecules and we'll be able to look at exactly which drugs we put into the clinic with those small molecules, and we'll be doing pre-IND combinations during next year.

Okay. So I guess just to end, what would be the top 3 things to look out for over the next 12 months from the pipeline that you're most excited about?

Number one, we have data from our RPGR expansion study in the next 6 weeks before the end of June. Number 2 is we have enrollment of that pivotal study, and we're preparing for a commercial launch. Number 3 is our Xerostomia data. We showed positive data for the first 3 cohorts. We'll be presenting data on that study at the end of this year. we'll be starting a Phase II study in xerostomia at the end of this year. We will be initiating our IND opening study for our new GAD material in the next few months. We're having lots of talks with partners about promoters and switches and our whole vectorology platform. Actually, we were surprised at the number of incoming calls about muscle promoters, for example, which we hadn't quite realized, were so unoptimized so far. So there's a lot of discussions about how we can use our broad technology and partnerships with others to speed forward its use in the clinic.

Okay. Very exciting. Well, with that, I think we're up on time. So thank you so much for the discussion and for participating.

Thank you. Thank you very much for having me.