Apellis Pharmaceuticals, Inc. (APLS) Earnings Call Transcript

Okay. Great. I think we have everyone in the live session. So again, to the second panel that I'm moderating for the day, this is entitled Ophthalmology - Seeing 20/20 in 2020. I'm Yigal Nochomovitz. If you're interested in asking questions, you can either just e-mail me directly, yigal.nochomovitz@citi.com, or there's a feature on the showcase virtual app where you can submit a question via chat. So just feel free to do that. So it's my pleasure to have with me this morning 4 distinguished guests, all CEOs of their respective companies: from Aerie, Vince Anido; from Aldeyra, Todd Brady; from Apellis, Cedric Francois; and last but not least, from ProQR, Daniel de Boer. So welcome, all gentlemen. Thank you very much for taking the time to chat with us today.

I think what I'll do is just as a -- just very preliminarily, if each of you could give a very brief 1- to 2-minute overview of each of your companies just to level set, so that everyone has a sense as to what you're doing because some may not be familiar. And then in answering that question, if you could also just comment on what you think is being least appreciated by the Street in each of your respective pipelines. So Cedric, do you want to kick off?

Sure. Happy to. Thank you, Yigal, and thank you for putting me on a panel with these distinguished co-CEOs. It's good to be on an ophthalmology panel. So Apellis is a company that is focused on the complement pathways and has 2 key programs in advanced clinical testing. One is in a nonophthalmological field called the paroxysmal nocturnal hemoglobinuria, which is a rare disease of the bone marrow, where we administer our lead compound, pegcetacoplan, subcutaneously twice per week to control that disease. We then take the exact same molecule, which controls complement factor C3 and use that to do intravitreal injections, either monthly or every other month in -- for the treatment of geographic atrophy. In GA, we have kind of an interesting -- or in macular degeneration, I should say, there's an interesting story over the past 20 years where obviously, with the anti-VEGF, we can control the leakage associated with the wet form of macular degeneration, but there's currently nothing on the market. And up to our Phase II results, everything had really failed to control the progression of the dry form, which is like a forest fire in the back of the eye, where the retina gradually disappears. In it's pure form, that is something that affects 1 million patients in the U.S. It's also worth mentioning that patients who are on chronic anti-VEGF use are at very high risk of developing GA as well, about 98% over 7 years. We have fully enrolled 2 Phase III clinical trials of 600 patients each. And we will have a readout in Q3 of next year.

Very good. Todd, do you want to give us the highlights quickly?

For sure. So Aldeyra is, like Cedric's company, an immunology company. We have both ocular and systemic programs. Our ocular programs seem to be at the forefront these days. We -- our lead molecule, reproxalap, have 2 Phase III trials, one in dry eye disease and one in allergic conjunctivitis. We have another Phase III program in retinal disease called proliferative vitreoretinopathy. And then most recently, we've announced that our systemic immune-modulating agent, ADX-629, where we're beginning shortly 3 trials, one in COVID, one in asthma and one in psoriasis. What is the least appreciated, I think, is allergic conjunctivitis. It's everyone's favorite disease to dislike. But what's amazing is about 1/3 of the world has allergic conjunctivitis. There hasn't been a new mechanistic approach in decades. We think we will be the next novel entrant in allergic conjunctivitis, in about 40 to 50 years actually, and at dry eye disease, which has more recent entrants. But an exciting time for reproxalap and an exciting time for folks like myself that suffer from anterior ocular inflammation.

Great. Daniel?

Yes. Happy to, and thanks for inviting me to this panel, Yigal. So ProQR Therapeutics, we are developing medicines for inherited retinal diseases. These are genetic diseases that cause typically congenital blindness, so vision loss that starts in childhood and gets more severe over the course of the lifetime of people. There's about 3 million people in the world with these types of diseases, and only a few thousand of them have treatment available to them. We are developing a platform of RNA therapeutics for these inherited retinal diseases. We think we can target many of these inherited retinal diseases, and we currently have 3 drugs in clinical studies and the fourth one to start clinical studies soon. All 4 of these programs will have clinical data over the next, let's say, 12 to 18 months, including a pivotal readout on our lead program for Leber congenital amaurosis. So a lot going on.

Great. And Vince, do you want to tell us just the highlights on Aerie's commercial franchise and the pipeline?

Sure. And again, thanks for the invitation. Our company, Aerie, has 2 products on the market for the treatment of glaucoma here in the United States. Rhopressa was launched a couple of years [ ago, ] Rocklatan, a combination of Rhopressa plus latanoprost, a major prostaglandin here in the United States, we've launched about a year or so ago. We're gaining quite a bit of traction. And the great news is that we've got a lot now of managed care coverage in the U.S., which is critical to the success of the products. In addition to that, we have a growing pipeline. We have a number of products that are just now in the process of reading out. Most recently, we introduced the data for our 1105 -- AR-1105, which is dexamethasone insert for the treatment of diabetic macular edema. We had great results there. We did get the -- we knew that the product worked. We knew dexamethasone worked. The issue was can we deliver it for 6 months, and we were able to do that, and that's a critical time line from a retinal physician's point of view. We have another retinal program, which is AR-15503 (sic) [ AR-13503 ] which is for a Rho kinase Protein kinase C inhibitor for wet AMD. That will read out sometime in the middle of next year. Last fall, we acquired a company from Spain that had a unique treatment for dry eye, and they had completed a Phase IIa trial, which is very exciting. And so that program, which is designated as 512, for us, we'll start its Phase IIb clinical trial here in the United States later on this year. On a global basis, we continue to progress. We had great result in our Phase II trial in Japan and moving into Phase III trials there before the end of the year. And in Europe for -- at Roclanda, which is Rocklatan here in the United States, approved sometime towards the end of the year, beginning of next year. And that's a follow-on to the fact that Rhopressa was approved sometime towards the end of last year. So it's exciting time. And what's really unappreciated right now for us is the revenue ramp for Rhopressa and Rocklatan in the United States. Clearly, like everybody else, we got hit by COVID towards the end of March this year. And as of last month or just a few weeks ago, we're back to the pre-COVID revenue levels. And so we're excited about the prospects, and we've put an awful lot of new things out in the market that allow us to progress a little bit more quickly.

Perfect. Thank you all for the introductions, and everyone's working on relatively different indications. So I'd like to move into a bit of a more thematic discussion around some of the challenges and opportunities in developing drugs for ocular conditions. And maybe we could just start out with a conceptual question, which I'm sure all of you have thought about at great length, and that is how do you effectively design your Phase II or early stage program such that it's properly designed to support an effective Phase III program? I'd love to hear your thoughts. Cedric, do you want to give that a shot?

Sure. I'm not sure that there's a straightforward answer to that question, Yigal, because it's highly individual, of course. But I think, at least from our perspective and then kind of, I guess, more narrowly focused on geographic atrophy, it was very important in GA, where the end point is an anatomical end point and where there had been so many failures that we would have a Phase II that would give us the confidence and the ability to raise the money needed to run a Phase III clinical program. Trials in ophthalmology in general, I believe, are very expensive because of the imaging and are also very difficult. I mean there are lots of failures. So I think when you come out of the Phase II, it is important that you come out of that with great confidence and with good data. And in my opinion, it's important that between Phase II and Phase III, you don't make a lot of changes. I mean I think often, when you -- it's tempting, right? You're going to go, "I see something there post hoc, their post hoc" and then I redesign my patient population for Phase III. That, in my opinion, is a mistake. So I think the redeeming message here is when you start your Phase II, think through all the way to registration and make sure that you're ready to get everything funded and do it in a staggered way.

Makes a lot of sense. And Todd, do you want to offer your thoughts?

Yes. I think what's key for a novel approach is to assess a variety of end points, especially in your first Phase II trial. In fact, we have a rule here at Aldeyra. For the first Phase II, we don't declare a primary. The primary is safety. Because if you have a novel agent and a novel mechanism, you don't know precisely how it's going to work. And you have a variety of secondary end points, all of which have to be clinically relevant, the FDA would have eventually approved. And then in your next Phase II trial, run that, pick your best, power the trial and run it with the primary at that point. But I think the key is a variety of choices for your first Phase II trial and then some ability to demonstrate the clinical relevance of those end points and some regulatory precedent that those end points will be accepted. I tell people that at our company, I don't want to -- I want to hear the term precedent once. I don't -- I'm not a big precedent guy. We've been very successful with the agency with new end points. An example is RASP as an end point, which is how our drug works, the target of our drug. As long as you're able to put forth the agency good data to suggest that your end point is meaningful and relates to the disease, I think it puts the company in a good position in terms of future trials.

Okay. Great. Dan or Vince, do you want to add anything to the question around development, transitioning from...

Yes. Sure, happy to add. I think for us, it's slightly different since we work in rare diseases. So typically, our development programs are much leaner, and we don't pull out a typical Phase I, II, III. We use a lot of adaptive trial designs where we typically combine Phase I and II, and then we do a combined Phase II/III adaptive pivotal study for registration. I think across the board, we try to derisk the programs early. So work with strong translational models that can predict what we will see in the clinic such as we, in the early clinical studies, can refine and confirm that we need see that, understand what patient population, what subset of the population is most likely to respond to those end points and enrich the population in the pivotal study for that particular subgroup for the -- that relate well to the end point as you fix to register the drug. So I think for us, it's -- the Phase I/II is really a learning exercise to inform the Phase II/III. I think broader than that, we are developing a platform. So all of these drugs are targeted to a certain mutation but are targeting very similar disease phenotypes. So whatever we learn from one disease, we can apply to the next. And with that, we really refine how we look at the end points that we select for our clinical studies.

Okay. Very good. Vince, did you want to add anything?

Yes. Just a bit. So for us, it's very different, depending on which segment of ophthalmology we're chasing. So for example, in glaucoma, the kind of trials that you have to run using intraocular pressure decreases as the metric are relatively straightforward. In fact, if you run them pretty much in a standard way, every product that has achieved success in Phase II has ended up getting approved. And so it's a great track record. Unfortunately, we're also in dry eye, which is a huge market. But what we know there is that as soon as you complete one study and it's successful, there is no guarantee that if you replicate that study that the Phase III will be successful. And so in a Phase II trial for the drug that we're starting later on this year, we're not only chasing some pretty standard end points, which are well validated and you [ sought ] the agency quite a bit for approvals, but we're also backing up the truck with almost every secondary end point that we can find for the treatment of dry eye because of some of the -- the folks have already said, you're really still at a real research mode at this point. And what you're trying to do, elucidate what exactly it is your drug really can do that's unique and different. And then so that when you get into your final Phase III design, you've got the -- you put your best foot forward.

Great. And in terms of trial design, I just want to focus a little bit on end points. All of you have already touched on it a little bit. But how do you balance the decision process in terms of focus on more of the anatomic versus more of the functional, obviously, visual outcomes. Are there certain points in development where anatomic matters more than visual and vice versa? And can you just comment on the strategy to blend those 2 end points to produce successful value proposition?

Sure. The -- if I take a look at our retina trial that we just completed for our 1105, our dexamethasone insert, what's really interesting is when you talk to the retina physicians and you do have to do functional changes like decreasing in the thickness -- the macular thickness and things like that. But ultimately, the FDA and other agencies look at visual acuity changes. But what's interesting is the doctors decide whether to keep the patients on drug or not, if they see that decrease in the macular edema upfront. And so for them, while it is somewhat validated but not totally correlated, visual acuity change will occur if upfront they see a decrease in the macular thickness. And so we do spend an awful lot of time reading that out because it does help to get the physicians on board faster because they'll say, "Well, if I saw that, then I'm bound to keep [ this pacing on ], I think the drug is working."

Got it. Cedric...

Yes. I think, yes, building on that, we use the imaging methodologies more to support the visual outcomes as well. I think it builds a lot of confidence when you see the 2 combined. I think they could give earlier signals in the anatomy of what you're doing to the retina. But eventually, you will likely approve the drug based on vision outcomes. So we typically do study them, but there are secondaries. I think for us, as we are purely focused on these inherited retinal diseases, we define our end points based on the disease phenotype. So some of these diseases like retinitis pigmentosa have much more of a peripheral vision loss where we look for several perimetry measures, where for more central vision loss diseases, BCVA is the outcome measure. So we really have that defined by the disease phenotype. And it's -- therefore, differs a little bit program to program.

Yes. I agree with that. I think it depends. I mean visual acuity is really foveal acuity, right? And when you have diseases like GA where you have foveal scarring, visual acuity slows down or goes -- you lose visual acuity deceptively slowly compared to the visual function loss that you have. I mean I'm personally very excited about kind of the new methodologies to track visual loss through interaction with cell phones and electronic devices. I think in the future, we're going to see much more of that where through adaptive designs and through adaptive studies, you can actually see populations' behavior on the phone maybe correlate with visual function loss in a more astute way than once every couple of months visual acuity measurement.

Great. Todd, did you want to add anything?

I think in the anterior segment, it's all about subjective versus objective. So imaging is probably an example of an objective end point. But the FDA requires, if your primary end points -- you have a subjective component but you also match those with an objective component in the case of dry eye disease symptoms and size. I do think there are some examples of anterior segment diseases where you can get away with signs only. So Schirmer's test in dry eye, maybe [indiscernible] staining might be another example. But in general, I think the FDA's looking for the concordance between subjective and objective. And I can tell you that Dr. Chambers' position is typically, if there is not a symptomatic component to your drug, an improvement, something that's meaningful to the quality of life of the patient, we're going to look very carefully at your package. And in some cases, that will be [indiscernible]

Well, you mentioned the FDA interaction. Maybe we could talk a bit about how best to work with the ophthalmology division of the FDA and designing trials to best support approval. What are some of the "classic pitfalls" that one should avoid in approaching the agency? And just what does that partnership look like with the ophthalmology division to really bolster chances of success?

Yes. Our approach, Yigal, has been frequent communication with lots of data. So I think it is often difficult for a regulator to opine on a position that you may have or proposed without data. So we've typically, on a frequent basis, come to the FDA typically with Type C meeting request, asking about certain items but supported by data. And I mentioned RASP, that's a great example where we've generated data on RASP and how that relates to anterior segment inflammation. And then the FDA, typically, in the case -- in this case, in vision, is very receptive to proposals as long as you have data to back that.

Cedric, any words of wisdom in terms of FDA [ interaction? ]

I'm not sure about that but that seems that -- I agree with Todd. I mean we interact with multiple divisions at the FDA, and I have to say the ophthalmology division is probably the most easily approachable. Dr. Chambers, without any commitment -- but he's someone who you can easily talk to at conferences, who will share his opinions, who will -- who's open-minded. I mean I remember specifically in geographic atrophy, because of the kind of the relative weakness of visual acuity as an end point there, went through a whole process, in collaboration with the NIH at that time, to determine whether measuring the area of atrophy should be acceptable as -- or and the loss of retina as measured by SDOCT or autofluorescence should be acceptable as an end point. And at the end of that process, his famous statement was, "I think we can all agree that a dying retina is a bad thing." And that was -- and hence, the end point became acceptable towards registrations. So I think it's an example of, to Todd's point, a very pragmatic division within the FDA, which benefits all of us, very open and...

Yes. I couldn't agree more. I think that, Yigal, involving the agency early and lots of communication, really building that partnership, that helps to a align the minds on how you can arrive at a package that proves sufficient risk benefits to show that patients can benefit from the therapy. With both the EMA -- with both the FDA and EMA, I think it's really important to also engage EMA early. And I think in that context, the data has to tell the story. So we work with lots of predictive translational models where we, early on with clinical data -- with preclinical data, can already predict what we think will happen in the clinic and building that relationship out with continuing to fill that pipeline with data and have that data during discussion is really building that relationship and the partnership.

And Vince, did you want to throw in any comments on FDA interaction?

Sure. The -- yes, we're benefiting from the fact that it hasn't been all that long that the ophthalmology group had its own FDA group to call on, which was -- is very encouraging. And certainly, interactions today are more positive than they were, say, even 2 or 3 years ago where they were reporting up the line with transplant at one point or dermatology in the early days, et cetera, et cetera. So the fact that Dr. Chambers is his own boss right now is a huge deal for the industry, and a lot of folks work very hard to make that happen. I think the interesting component about Dr. Chambers, and I think that Cedric actually called it out is he's really easy to talk to. He offers his opinions and the like. And then so the balancing out for companies and for CEOs is simply, if you listen to what he says, there is no doubt that if you follow what he says and your drug works, it will get approved. The balance is in today's environment, where we're also having to consider all sorts of other factors, not the least of which is getting it on formularies and making sure you have the differentiation right so you can justify whatever pricing scheme that you're coming up with, it's really making sure that you have enough data in those studies in order to be able to do that. And so again, it's a very open environment. And certainly, it's a welcome change from what we saw even just 2 or 3 years ago.

Good. Well, let's move on to more of the practicalities of delivery of ocular medicines and compliance. Obviously, each of you are taking a different approach, some commonalities, but different approaches to delivery, whether it's eye drops, intravitreal injections or sustained delivery. Could you just talk about, in that context, how you think about managing compliance risk in terms of adherence to medication and what you can do to assure adherence in the case of drops, in the case of the intravitreal injections and the extent to which you think that sustained delivery approaches sort of represent the next frontier in ocular medicines?

We have both eye drops as well as inserts that we can use for small molecules for retinal diseases. And we purchased a company a few years ago called Envisia that had the -- had the ability to take polymers, to mix them up with small molecules, and we can change the shape and the size to determine exactly how much drug we want to deliver over a certain period of time. So for retinal diseases, we were able to do that. We had 2 very different delivery scheme setup for our phase -- our recent Phase IIa trial on our dexamethasone insert. They both work, but they worked a little bit differently. One loaded up the eye a little bit faster with dexamethasone. The other one extended the activity out over a longer period of time, which is the one that we ended up choosing because it matched what the doctors needed. On the eye drops side, it's typically pretty hard to overcome the benefits of a once-a-day eye drop. You start looking at 2 and 3 times a day, compliance drops off pretty quickly. And there's an awful lot of folks that have chased all sorts of delivery systems. And I think the balancing act there is can you get enough drug, when you're sending out such small amounts, can you get them off through the surface of the eye so that they have some activity. And in some cases, we've seen folks that have tried that. And then certainly in the glaucoma space, it's been awfully hard to get the same effect using, say, a topical extended delivery system like a punctal plug or something like that versus just simply loading up the eye with one eye drop that makes it through all the corneal enzymes and gets off to the site where it has its activity. So we like the approach. Once-a-day eye drops, if we can, or take it out of everybody's hands and just do the inserts for retina that last about 6 months.

Got it. Cedric, what about -- what are your thoughts on delivery and compliance, given that you're testing the every month and every other month intravitreal injections for pegcetacoplan in GA?

Yes. I think -- so it's very interesting, right? I mean the -- I'm going to call it the elephant in the room here is also the retinal practices, which have shifted an important source of revenue towards the whole infrastructure that they needed to build to support all of the anti-VEGF intravitreal injections. And so there's, on one hand, obviously the need for these less frequent injections because at the end of the day, that's -- that is what benefits patients and what we should all be focused on but also balancing that out with kind of the needs of these retinal practices. And I think that it's a complicated balance. At the end of the day, the less frequency you can do an intravitreal injection, the better it is. So I'm personally really looking forward to being able to do less frequently with our drug. I'm looking forward to anti-VEGF approaches that can do that less frequently. Hopefully, in the future, some of the genetic therapies that are out there will materialize as well. Yes, that's -- I think it's a no-brainer, but it is logistically and practically not as straightforward as it may seem.

Got it. Got it. Did anyone have any other thoughts on that?

Yes. I'm happy to comment there. So we are fortunate that our medicines have a really long half-life. So although we deliver them through intravitreal administration, we do that very infrequently. So with the stability of these medicines, we can dose maybe once or twice a year, eventually with these newest therapies, which is obviously, yes, great for patients and good for compliance as well. So I think we have a favorable profile with the drugs that we use. I think across the board, patient convenience is really important because they do need to actively participate in taking their therapy. So making sure that this is done in a way that's -- is convenient for patients is really important.

The final thing, Yigal, I would just add is compliance is proportional to a patient's assessment of need, right? So if a patient is losing their vision, in the case of the diseases that Daniel's working on or Cedric's working on, I think they're motivated to get injections. In the case of PVR that we're working on, I think there's a series of injections after retinal detachment occurs. Patients are motivated not to lose their sight. I think where it gets tougher is diseases where patients aren't feeling any changes in their life. Their eye isn't burning. There's no pain. They're not losing their vision. That's where compliance becomes more of an issue. And I think in our anterior programs with dry eye disease allergic conjunctivitis, these patients are in pain. I mean they're constantly chronically, persistently disturbed. And so they're motivated to take eye drops, and many of them take eye drops hourly in that case. So I think it really depends on the patient's assessment of -- maybe as a medical community, we can do a better job of convincing patients that they need to be compliant. But I agree with Cedric, I look forward to the future where some of these delayed-release and these technologies become more forefront of therapy.

Well, you bring up an interesting point, Todd, in terms of early-stage ocular disease, lack of symptoms, lack of pain, no observable changes to vision but there is a latent disease there. I think geographic atrophy would be a good example of that in the -- at least in the early stages. So with that in mind, we'd love to hear everyone's thoughts in terms of better surveillance for early prognostic factors, early risk factors that can detect ocular [ degeneration ] at an earlier point in time and catch things earlier. What are you seeing in the field on that front? And how are you taking advantage of earlier detection potentially to leverage your -- each of your drugs in your pipeline?

That is the next frontier, right? I mean in geographic atrophy, specifically. I'm super excited about kind of new ways with artificial intelligence to be able to predict in patients what their retinal -- for receptor cell loss is going to be if they don't do anything. And hopefully, in the future, we can correlate that to treatment effects as well because, I mean, for example, with exudative macular degeneration, you have the instant gratification of giving an anti-VEGF injection and seeing the retina dry up, right, which is magical for the patient and for the physician. You instantly notice that difference. In GA, the first year, you're going to adhere to your therapy. But after that, beyond that, you need something to know that your commitment to that therapy is actually helping you as well. And especially with elements that happened in the periphery of your vision, it's not always easy to have a good view on that, no pun intended. So I think that we have more and more insight into that. There's a very exciting presentation that's going to come up at AAO from a couple of companies on that as well that I'm looking forward to. And I think, specifically, in macular degeneration then, the next frontier, of course, is intermediate AMD. Why wait until your retinas degenerating if you can prevent that from happening in the first place?

Other thoughts on early detection?

Yes. For us, it's slightly different. It's fully focused on genetic testing. There's a lot of people that are diagnosed clinically with one or the other form of a retinal vision loss. And many of those don't actually know what disease they have or what kind of gene is affected in them or even what mutation they have that -- and without knowing that, there's no way to know if you -- if there's a therapy available for you, if you could participate in a trial. So for us, that's really important. And to that extent, we have partnered with My Retina Tracker at the Foundation Fighting Blindness to help execute a genotyping program in the U.S. that makes genotyping available at no cost to patients that are diagnosed with an inherited retinal disease, and we're exploring similar efforts in Europe. So I think for us, it's fully focused on genotyping.

Great. And for Daniel, Todd and Cedric, I just have a sort of a precommercial question. I know, of course, Vince, you're already a commercial stage company. But for the other 3, could you just talk a bit about what early steps you're taking or maybe not so early steps you're taking to prepare for commercialization for your -- for the respective indications that you're going after? How are you assessing the market, preparing your marketing research so that you're best prepared to -- for launch once you're finished with clinical development. Cedric, do you want to start since you're already in the Phase IIIs for GA?

Yes. Thank you, Yigal. So we are -- so we have a fantastic Chief Commercialization Officer, Adam Townsend, who is fully working on that heavily already, right? I mean we'll have a readout in Q3 of next year. We're, of course, optimistic in all our subjectivity that, that will have a fantastic readout. And after that, filing in the disease in a specialty like that is a big undertaking. And then going into the retina, specifically, geographic atrophy, I think, is really interesting because, quite frankly, it is what retina specialists see most of the day, each day in their practice these days. So beyond kind of the responsibility of hopefully bringing the first therapy for that condition to the market, there's also the opportunity to find a special place within the practice and kind of hopefully being good stewards of what our industry and our therapy stand for in those practices. So it's a big commitment and a lot of investment but, I think, well worth making.

Very good. And Todd, how are you preparing for dry eye in AC?

So it's disease specific. So the anterior disease, as you mentioned, there are -- it's a -- sort of a question we have to continue to consider internally, which is who provides for these drugs, right? It's a broad segment of the health care provider community that goes all the way from ophthalmologists to nurse practitioners and community medicine doctors and so forth. So how best do we optimally exploit the commercial landscape? And that could be with a partner. I think the good news is there's ophthalmology in the anterior segment. As Vince knows, you can launch. I think there's a couple of companies that are planning to launch dry eye therapies on their own. It's feasible. It's not 10,000 reps. And I think a lot of awareness has been raised by other companies shier perhaps in terms of making people aware of dry eye disease and hopefully, that happens with allergic conjunctivitis as well. So some of our work has been done for us, assuming we want to launch internally. I think for the retinal disease, PVR, that's feasible for small companies. There aren't that many retinal physicians that treat this disease. I think for a small group of physicians relatively to target, that's in the realm of feasibility for small companies. So that's something that we're considering very actively for internal launch.

And then Daniel, in terms of preparations for those LCA10 and [indiscernible] to a...

Yes. No, our commercial preparations are in full swing. We hired a head of commercial last year as we're in the midst of a pivotal study. So I think for us, it's, yes, very similar to what we heard before, I think the advantage of an inherited retinal disease is that this field is very concentrated. So there's maybe 30 real specialist sites between Europe and the U.S. So building a commercial infrastructure towards those is very doable for a company at our stage. And for us, it's now mostly focused on building the awareness, doing all the research, educating and building the right genotyping infrastructure to make sure that the patients are genotypes and know what disease they have such that if and when our therapy gets approved, they are -- can immediately benefit from it.

And Vince, not to leave you out of the discussion, maybe talk a bit about just some of the lessons you've learned. Obviously, you've graduated to being a commercial stage company. So what have you learned in terms of the Rocklatan and Rhopressa launches that you're applying on a go-forward basis?

Well, the biggest challenge, at least in the United States today and in Europe, it's got its own challenges, is the whole pricing mechanism and how are you going to get on formularies, et cetera. We chose to bring inside a group that does nothing but contract with managed care. It's roughly about 8 or 9 folks. They do both national contracting and local contracting. And we've been [indiscernible] over a 2-year period now, Rhopressa is pretty much got covered by both commercial and Medicare Part D plans. And so we think that -- and it took us about that long to get it all set up with the right rebate structures, et cetera, et cetera. Rocklatan, actually, we were able to accelerate a little bit because Rhopressa was already under contract with many of these companies and -- or managed care entities. And so again, that's moved along pretty nicely. And so -- but the next phase is making sure that there's a great length between the managed care organization as they sign the deals and this field sales force. In glaucoma, we have roughly about 100 sales representatives that cover, I'll call it, about 14,000 prescribing physicians. And so the big thing is understanding which managed care plan most impacts that particular practice and make sure you get that message across. And if you could -- were able to do that, then you get the pull through. And so we saw that very recently. We signed probably the largest Medicare Part D plan in the country, represents about 17% of all managed care -- I'm sorry, all Medicare alliance under managed care. And we were able to double our market share within that plan from May to today because we were able to generate that pull through. So it was a tough lesson to learn, and it took us a while to get it right, but I think we're on the right track now.

Perfect. And maybe just in the last minute or 2, we could just do a quick lightning round. If everyone could comment on what investors should focus on, what's the next big data catalyst, the regulatory catalyst or other catalysts for each of your companies over the next, say, 6 to 18 months? Just real quick. Cedric?

So -- well, in geographic atrophy, we have to wait until Q3 of next year for the readouts. But in the meantime, at EURETINA, in the beginning of October, we're going to have a very interesting update on the FILLY trial, which is now relatively old trial, but we have a new analysis that was done there that is really fascinating. We then will present our data on the 1-year follow-up in our proof-of-concept study in C3 glomerulopathy. The abstracts become available on October 9 and will be presented at ASN. We then have the -- in PNH, the 48-week completion of the data at the end of this year. We also have, in the near future now, the filing of the NDA and the EMA filings for our PNH program. And then next year, I think the 3 big things to focus on at Apellis are the readout in GA, of course, the launch in PNH and the other indications where we're going to use this product and then the preclinical work that is going to come to maturation.

Very busy. Very busy indeed. Vince, what about for you?

So for us, over -- between now and, say, at the end of the year, we continue to have great progress on the commercialization here in the United States in both Rhopressa and Rocklatan. And so like I said, we're back to pre-COVID levels. So we're -- I think we're in the right frame of mind to be able to move that forward pretty quickly. We will start the 5 -- 012 dry eye trial before the end of the calendar year. So that's pretty exciting for us. Likewise, we'll start our phase -- first Phase III trial in Japan for Rhopressa. And so we do expect and had great discussions with potential partners that will get involved with that. And hopefully, we'll be able to sign a partnering deal in Japan, mainly for commercialization but also for development before the end of the calendar year. So we do have an awful lot of things, both on a commercial as well as the pipeline side that are coming over the next few months.

Todd, you've got some pretty important catalysts coming up.