Apellis Pharmaceuticals, Inc. (APLS) Earnings Call Transcript & Summary

Good afternoon. I'm Andrea Tan from the biotechnology team at Goldman Sachs, and it's my pleasure to host a fireside chat with Apellis management team. With us, we have Cedric Francois, Co-Founder and CEO; Adam Townsend, Chief Commercial Officer; and Tim Sullivan, Chief Financial Officer. Thanks so much for joining us today.

Thank you so much, Andrea.

Great. So maybe to start, just as a high level overview. If you could provide one of the complement cascade and why targeting C3 is so important? And then maybe provide some thoughts on how to think about that in the context of competitors who are looking at C5 inhibitors?

Sure. So first of all, thank you so much for inviting us here today. It's really a pleasure to be with you. So Apellis is a company that is focused on the complement cascade, as many on the call probably know. The complement cascade is a highly complex interacting network of enzymatic proteins, hundreds of millions of years old, best comparable probably to the clotting cascade and kind of at the nexus of that cascade sits complement factor C3. Why is that important? Because there are 3 pathways by which complements can be coactivated. All 3 of these pathways converge on C3 and from there then the myriad of effects that ensue from complement activation happen. And I mention that because if you think about the effects, so the downstream things that happen in complement, those you can kind of simplistically split into 2 areas. One are the effects from molecules like C3a, C5a, et cetera, that play an important signaling rule in the immune pathways. The other one is the formation of the so-called membrane attack complex, which creates hosts in cells. And bacteria, that's obviously a good thing. In pathogen, that's a good thing. In our own cells, not such a good thing. And in a disease like paroxysmal nocturnal hemoglobinuria, where cells can die from the formation of that membrane attack complex, that is also a bad thing. Now C5 inhibition was kind of the first therapeutic modality in that complement cascade that came to bear with this drug called Soliris. It's a life-saving therapy in PNH because it saves red blood cells from forming these membrane attack complexes. But now that we are further along about a decade beyond that and now that we understand the complement's pathways much, much better, we've come to understand the therapeutic potential beyond PNH. And when you think about it in that context, going after C3 is kind of the in all and all out of controlling that complement cascade when it gets out of control in a therapeutic context. Now when we entered into this field about a decade ago, obviously, that was a question. It was like, okay, wow, such a central point. Can you do it? Can you control the complement cascade there? And secondly, if you do, is that going to be something safe to do? Now what we have found out now, especially illustrated by the disclosure of our Phase III results in January in PNH is that, yes, you can control C3 systemically. And yes, you can do it safely. And that is very important because if you now go back to how the complement cascade works, it is truly the perfect point in the cascades to control that myriad of conditions. Because if you become more specialized and you go either downstream at the level of C5 or you go upstream within the 3 activation pathways, that may sound like a good idea if there is a safety concern by going after C3. But from what we know now, that doesn't seem to be the case. And the flip side to that is if you become more specialized and you go in more specific points, you may miss out on the efficacy. So right now, we feel very good with our systemic program, where we control C3 all over the body and do that chronically. We have patients that have been on our drug for 4 years or longer now. We feel very good about the safety profile, and that opens up the window into all of these indications.

Perfect. And then maybe just as you think about the competitive landscape for C3 inhibitors, how is pegcetacoplan differentiated?

So again, from a mechanistic and a safety perspective, it is product candidates, I should say, a drug candidate that stands out truly from an efficacy perspective and also from a safety perspective in the sense that really has been remarkably safe for us with approximately 150 patients' years behind us. Now it is a drug that is given twice a week subcutaneously, self-administered at home with what we call a subcutaneous infusion. And I think Neulasta, quite frankly, just something you have to get used to, it takes 2 times 30 minutes per week. We schedule it Wednesday and Sunday or Thursday and Sunday but patients can choose. And you could say, well, there's improvements possible on that, right? Hopefully, in the future, we can do this less frequently or in other circumstances, what if you could give something like this orally? That would, of course, be better than giving a subcutaneous injection. And in that context, within the field of complements for many years, people have tried to look for solutions that wouldn't involve injections. And specifically, oral products have been in development, but it's worth noting and important to note that those products, rather than controlling it at level of C3, had to go upstream in what we call the alternative pathway, one of those 3 pathways of activation. And there, with the pill given twice a day or 3 times a day, it looks like you can control that pathway of activation with the convenience of having an oral product. And we view it as an important kind of contributor to the field of complement, but it is still very much a question mark, and we'll find out how that unfolds. Whether there's a trade-off to be made in terms of efficacy, and quite frankly, in a disease like PNH, where exquisite control of complement is really important and can be life-threatening if you don't do it, whether there's a trade-off on the safety side as well. So that remains to be seen. But it's a very exciting field in general, and we look forward to where it's going to go.

Got it. And then is there a mechanistic rationale, do you think, for combining your C3 inhibitor with other complement inhibitors? Or not so much given the factors you've mentioned here?

The very short answer to that question is no. So we have -- what we do with pegcetacoplan is we kind of control the complement cascade at 3 points around C3. So on one hand, we prevent C3 from becoming activated. And even if it then becomes activated, we still inhibit kind of the enzymatic activity that it's -- within that case display. And then the next step of enzymatic activity as well. So we don't have kind of a full knockout point where we try to destroy all types of activity. We have kind of 3 points and if you think about it simplistically, 90% of these ends up with 99.9% control, right, that give us that very, I'd say, buffer enzymatic way of inhibiting an enzymatic cascade. If you do that and you have the proper levels of the drug, you don't need any other complement inhibitors in that mix.

Got it. That makes sense. Now maybe we can just dive right into the pivotal PEGASUS trial that you just announced the results back in January. We're expecting an update tomorrow at EHA. Maybe just to level set, can you help us understand the unmet need that still exists right now, just given that Soliris and Ultomiris are being used in the treatment paradigm today?

Yes. Thank you. So that's a really, really important and good question. The bottom line is that now that we are, I guess, close to 15 years after the introduction of C5 inhibitors like eculizumab in PNH, it is now becoming very clear that when you control C5 in patients with PNH, you do not control the disease properly. And that is reflected in the fact that patients with PNH on C5 inhibitors continue to suffer from anemia, often are transfusion-dependent in spite of the fact that their bone marrow works as hard as it can to compensate. And the reason for that is that there are 2 sources of red blood cell destruction, of hemolysis, in PNH. One is called intravascular, the other is called extravascular. And with intravascular hemolysis, you should think of red blood cells exploding in the blood stream. And that is related to that membrane attack complex we were talking about earlier. And if you give a C5 inhibitor like eculizumab, you can do a really good job of preventing cells from exploding. And that is a life-saving intervention in PNH, very important. On the flip side, though, it does nothing about controlling this extravascular hemolysis. And what that refers to is red blood cells become overloaded with complements. And when they go through the liver and spleen, they get eaten up quite literally by phagocytes in these organs. And that essentially means that these patients, sure, they don't have exploding red blood cells, but they have very low red blood cell levels compared to what they could have if you control the extravascular hemolysis. That was always complicated to understand what is the contribution of EVH in this disease? Sure, they are anemic, but is that related to the bone marrow and you cannot measure EVH directly. So it was kind of an unknown. And one of the great things about the PEGASUS study, beyond the fact that we believe it establishes a strong case for efficacy and for the benefit that our drug will give is that it truly showed how much there is to be gained by patients with PNH, when they are on treatment with a C5 inhibitor, when you then also control extravascular hemolysis. And that, I think, is truly what in January, we showed. We're very excited about the data that we will announce tomorrow as well.

Perfect. So maybe let's dive into that. If you could walk us through that trial design, some of these key results, what were you most excited by? Were there any outcomes that you were surprised by?

Yes. So when we went into the PEGASUS study, we kind of took a big leap of faith, all packaged into one trial. We did something that had never been done before. We decided to give the active drug to our control group for 1 month and then take it away again. And the reason why we did that is manifold. We said, look, if we're going to go into the field of PNH where at least in the developed countries, most patients who need to be on treatment are already on treatment with a C5 inhibitor and they're taking a life-saving therapy. How can we make it as easy as possible for physicians and patients, right, to make a transition to what we believe is going to be a much better drug and do it in a way that is safe and where you don't take any chances. And the best way to do that is to rather than say, switch over and see what happens. And then maybe you have to go back and how is that going to work? No. You don't have to do that. For 1 month, you take the drug on top of what you're already taking. You will, and that was a leap of faith. We believed and we showed that you experienced the full benefit of controlling extravascular hemolysis over the course of 1 month. And if you then switch to monotherapy, you keep that benefit. And we show that you keep that for 4 months when we had to readouts of the trial. Conversely, if you discontinue pegcetacoplan and you go back to where you were before that happens. In 1 to 2 months, you're exactly where you were before, and that can be done safely as well. So that's what was very important about this trial. So it showed the benefit and ensured that, that can be done safely in a real-world setting.

Perfect. So I guess maybe just diving in a little bit about some of your secondary endpoints, and I'm sure we'll see a little bit more of this tomorrow but one of the points on LDH correction, you had a positive trend there, but it didn't reach significance. Can you just speak a little bit more about that finding? How much of a sticking point you think that might be with regulators or physicians moving forward?

Yes. So I'm going to start with the second part of your question. It's not a sticking point with regulators. Because LDH in the very first place is an important safety parameter. When you have intravascular hemolysis, LDH is an enzyme that gets released from these red blood cells when they explode. So it is in a very essential way, a biomarker of intravascular hemolysis, not extravascular hemolysis, which is why, obviously, with C5 inhibitors, it's a great way of looking at the work, right? Now we wanted to evaluate -- or to statistically establish noninferiority in our study. But because of the variability on the LDH levels, especially when you have hemolytic events, et cetera, the data was not there. The variability was too large to be able to statistically establish that. But that doesn't matter. What matters is how well is LDH controlled? Not, is it better or noninferior compared to eculizumab. And what we showed with pegcetacoplan as you will see tomorrow at EHA is that we had really remarkable control of LDH. And I think I can already say that from the data that we had in January, numerically better than what you get with eculizumab, which is extraordinary because you have patients coming into the study on maximum control of C5, many of these patients were on higher doses than normal. And in spite of that, they continue to have LDH levels that are really not where they're supposed to be. So more about that tomorrow.

Perfect. We look forward to it. So maybe just in terms of the filing strategy here then, you recently completed your pre-NDA meeting. Maybe if you could just provide some insights into the nature of those discussions, how you came to the agreement that hemoglobin improvement would be an approvable endpoint. And then also, how you're thinking about filing time lines, both in the U.S. as well as the EU?

Yes. So in January, when we announced the data, we also announced a letter that we had received from the FDA, which didn't say that the hemoglobin or hemoglobin superiority would not be an approvable endpoint. What it did say is that the delta of what that improvement needed to be was not preestablished. Now the discussions that we have had with the FDA, we're always in the range of like, should it be 1 gram, should it be 2 grams, and there was no clarity around that. With 3.8 grams per deciliter of superiority, we felt very confident going into these regulatory discussions, and that is exactly what materialized. So it was obviously our obligation to inform -- fully inform the Street. We are a very transparent company in that sense. But we always felt that this was going to go well and it did. So we are now preparing for the FDA submission in the second half of this year. And tomorrow, we will also give an update on the time lines for the [indiscernible].

Perfect. And then maybe as you think about the commercial outlook, maybe a question for Adam here. You have prior experience launching Spinraza. What learnings are you taking from that as you look to commercialize pegcetacoplan? And then maybe can you speak specifically about some of these early launch preparations that you might be working on right now?

Yes. Thanks, Andrea. So one great learning is it's such a privilege actually to collaborate with physicians, patients and the PNH community all over the world. We try incredibly hard to do our best to understand the impact of the disease to all of these patients. And we are laser-focused at Apellis to put the patient in the center of everything that we're doing when it comes to the launch of pegcetacoplan in PNH. Every thought that we give as we look to commercialize is around how can we meet those unmet needs in this disease? And that was a great learning for me on previous rare disease drug launches. With that laser focus on how we can help patients and everything that we do to make that happen, was a huge, huge learning. So we live and breathe that every day. Second part of your question, we've been preparing for the launch for over 1.5 years commercially now. So I was the first commercial employee at Apellis. And we've been building a really strong team in the U.S. and the Europe. We're lean. We're nimble. We're agile. It's got a different feeling to my previous organizations. It's great. We're ready to go. So we're progressing all activities to prepare for launch. And tomorrow's EHA date is just another step in that pathway to launch.

Perfect. And then maybe you could share from your early conversations that you've had so far with physicians, how much of a lift do you think it's going to be to educate them and the community about this drug given Soliris and Ultomiris, but then also how, I guess, receptive are they to switching their patients?

So when the data came out in January, we were obviously compliantly in talking about our data through medical affairs. And we've been educating the PNH community about us as Apellis and also the unmet need that exists. One consistent piece of feedback we get from patients is, and we use the term, the new normal. Prior to a PNH disease, they felt like you and I did. And then post, they don't feel as good, and they call it the new normal. So we're shining a light on how we can potentially elevate the standard of care. A 3.8 gram increase in hemoglobin can have dramatic impact from a patient perspective. So we started to have all of those conversations. We're actually having them virtually now. So we pivoted very quickly to a virtual engagement and every physician that we've been presenting our data to and every PNH community advocate that we've been talking to has been really impressed with our data. So I think people are looking forward to it to actually get commercial use within this product.

Perfect. And then can you remind us, you have a subcutaneous administration injector under development right now. How important is that in order to drive commercial uptake with the patients? And what is it going to look like if it's not ready upon launch? How does that impact the uptake curve then?

Yes. Great question. So actually, all of the work that we've done with physicians and patients, they point to the efficacy and the safety data being the main driver for wanting to ask for a switch or for a physician to want to switch a patient. We get really positive feedback on our device for injecting pegcetacoplan. We've actually spent some time with some of the patients in our study. And there was this lovely lady who we spoke to, actually, wears the device strapped around -- on a strap on her body, when she cooks, that's some of the freedom that the at-home or anywhere you want administration has some great advantages, and particularly even more advantageous in this world of COVID, right, having the flexibility for being able to administer in the safety of your own home is huge for us. So we took the decision actually very early on that we would launch with commercially available devices. We wanted physicians and patients to have the easiest of transitions and allow them to get access to the drug as quickly as possible. You also said we're working on this amazing device, which is a needle-less device, which you attach to your body and it administers the drug and then sends a ping to the cloud to know that you've done it. And on purpose, we decided that we wanted to launch that device after we were commercially launched. It gives us a great opportunity to build strong relationships with patients, offer amazing patient service. And then also gives us an opportunity to really show the world just after launch that we can bring innovations to these patients. So that's our plan. Feedback on that plan has been really good from a patient perspective.

Great. And then, can you provide your initial thoughts on how you might price the drug, particularly in the context of the existing therapies? And then, as you look forward to pegcetacoplan being used in other indications, would you expect to utilize maybe the same pricing, understanding it is still early?

Yes. No, great question. So actually, when we did some really robust pricing research post the January data set from PEGASUS. And we've been talking to payers in the U.S. and also ex-U.S., we have an amazing medical affairs team, but also market access team. And we're looking at putting the patient in everything that we do. So we want to make sure that access to APL-2, pegcetacoplan in PNH is as seamless as is possible for every PNH patient that wants to switch. And part of that is how we'll be thoughtful in price. So we'll look at making sure that we don't slow access down. And at the same time, we looked at all of the future indications, some of which we're not remotely public on. And we draw a line in the sand with our PNH pricing, and that will help us scale as we go to more and more indications. So when we choose a price, we'll make sure that it has the ability to be that price that goes into multiple other indications. It was a really thorough plan.

Great. And so then maybe turning to your other pivotal trials. So you have one on the PRINCE study that's evaluating the drug in treatment-naive patients. Maybe if you could just remind us on the trial design here, an update on the status, how COVID has been impacting the time lines here?

Thank you. So that is -- this is a 1-month study. It's -- sorry, it's almost -- what am I saying. Sorry, this is a 6-month study in treatment-naive patients. So this study, quite frankly, originally, was organized for us to be a backup should the data from PEGASUS not be sufficient for filing. As a secondary purpose, should there be any label limitations, this is kind of the standard bearer for a treatment-naive label. So we could have a supplemental NDA to expand on that. And of course, it also ends up giving us more data as we move forward into the future. So it's a trial that continues to build on our excitement, and what we see in patients with PNH. It's a study that we have said would be fully enrolled by the middle of this year, and we do expect it to be fully enrolled this month, in line with that guidance. COVID, obviously, delayed us in the completion of enrollment, but we were ahead of schedule, and now we are pretty much exactly where we had said we would be. So that's kind of -- we're very excited about PRINCE. It doesn't teach us much more than what we kind of learned from PEGASUS but under the current context. And I want to make, if you don't mind, Andrea, make a small correction on the enabled device. It is not a needle-less device. So there is a small needle, but there's no manipulation of the needle that is necessary. So just that as a small back up on Adam's comment.

Maybe just a follow-up on your comment there about this potentially being the confirmatory or the follow-up trial, do you expect that any of this data will be available to be included in the regulatory submission package? Or is it just too early for that right now?

It's too early for that right now, but we do not believe that we will need the data from PRINCE in order to file or in order to get approval, I should say.

Perfect. So maybe if we can move now to your second indication for this drug in geographic atrophy. Maybe as a big picture, if you could speak a little bit about the indication, what's the mechanistic rationale for targeting C3? And how should we think about your approach compared to others in the field?

Yes. Thank you. So this is an extraordinary program for us. 1,200 patients, close to being fully enrolled now. We're literally weeks away. And those 1,200 patients will then read out in the second half of next year. Geographic atrophy is the advanced dry form of macular degeneration. Most people are familiar with the wet type, for which we have the anti-VEGF drugs like Eylea, Lucentis, et cetera. The advanced dry form on its own affects 5 million patients globally. It is also almost the inevitable outcome in 98% of patients after 7 years of treatment with anti-VEGF. And it is without a question, the most observed or biggest problem that retinal specialists face today. Everything in clinical trials had failed until our Phase II clinical trial came along. It was a large Phase II clinical trial, where we met all of the endpoints that we were looking for. We feel really good about those data. And should that drug get approved, we will be alone and the sole solution for these patients for a long period of time. It's a program that I think it's hard to understand. There have been so many failures. Some people call it the Alzheimer's of the eye. But we've obviously analyzed our data in 100 million different ways, and we feel very good about what we have there. In terms of kind of the mechanism behind it, without getting into too much detail, we believe it is absolutely critically important to control complement at the level of C3. Many other complement factors have been tried at different points that have failed. So we have an understanding or we believe that an understanding as to why that is the case. But what stands out are the data there, and we look forward to completing that trial and reporting it.

So maybe just digging more into that. If you can just walk us through what you did see in your prior Phase II trial? How meaningful those results were? And how we should think about potential read through to your Phase III? And how much similarity there is between the 2 trials?

Yes. So we had 3 groups of approximately 80 patients each, a sham control, patients receiving an intravitreal injection like an anti-VEGF monthly and patients receiving intravitreal injection every 2 months. We met our primary endpoints where we showed that over the course of 1 year, there was a slowdown on the progression of GA by 30%. What does that mean? Well, you can measure how many retinal cells you lose over time and anatomically. And you can then determine if you can slow down the rate at which you lose these retinal cells. That is the approvable Phase III endpoint. And when we did our Phase II clinical trial, we were very careful to make that basically a Phase III like trial, completely imaged after the 2 large Phase IIIs that at that time Genentech/Roche was running with a drug called lampalizumab. So this trial was built to be literally something that we could copy and paste into a Phase III setting, which is pretty much exactly what happened. And I'll talk in a minute about what the differences are, which are minor. But most importantly in the readout, we met the primary end points. We had a dose response between the monthly and the every other month group. Then we saw kind of an accelerated or an improved effect from month 6 to month 12. So there was more of an effect from month 6 to month 12, then from month 0 to month 6, with close to a 50% slowdown in the monthly dosed individuals and 33% slowdown in patients dosed every other month. Then we stopped dosing for 6 months. And indeed, the lesions start growing faster again. But there's no catch up or a bounce back or whatever, even after 18 months in spite of 6 months of nondosing, still statistically significant. And then I'd say, for me, one of the most exciting pieces in the context of efficacy is that we have a lot of patients who had bilateral geographic atrophy. And whereas in all the other analyses, we look at one eye per patient compared between groups. We could now look at the treated eyes compared to the control eyes, which were not treated, the brand-new set of control eyes. And there, too, in the monthly-dosed individuals, statistically significant slowdown, but most interestingly, also from month 6 to month 12, an increased effect compared to from month 0 to month 6. So you put all of that together and it is -- it's really exciting for us, and we look forward to repeating that in Phase III. Now talking about the differences between Phase III and Phase II, this is the same patient population. The same way of measuring these lesions. The same reading center that measures it. A couple of differences are that we bring more quality into today. So we measure these -- the loss or the progression of GA every 2 months, whereas in the Phase II trial, it was 0, 6, 12 -- 0, 2, 6, 12 and 18 months. So more images, which will allow us to benefit more from the mixed effect model that we use, which accounts for missing data. We also -- when we have patients who require anti-VEGF treatment because they may develop exudations, we make sure that there is no investigator bias, which in the Phase II, very clearly and almost certainly led to an imbalance in and the need for anti-VEGF treatments. In the Phase III, that bias is eliminated. And should patients develop exudations, we continue to treat them with pegcetacoplan, whereas in the Phase II, these patients stopped receiving their injections. And then the last piece is that in the Phase II clinical trial with the primary endpoint analysis, we did what is called a square root transformation. So rather than taking the absolute area of atrophy, we took the square root to compensate and be able to compare patients with large lesions to patients with small lesions. It's a correction for the PR Square. That is not something that the FDA wanted in the Phase III. They said just use the absolute lesion sizes. Now post-talk in the Phase II that makes no difference, taking square root versus absolute. So again, we feel very confident about what we will see in the Phase III.

Perfect. And then maybe if you could help us understand. So many trials here have failed due to the sham control. Are there any steps that you're taking to mitigate this risk here? Or is that a concern based off of what you've seen from the Phase II?

Yes. So that's a fabulous comment that you make, right? I mean the sham control is arguably the most important group in all of these studies. And what do we know about sham controls? Well, we know the average rate of progression in sham controls from all the historical studies that are out there. The most importantly, probably being the 2 large Phase III clinical trials that, again, Genentech/Roche did, which was close to 2,000 substance, right? The drug didn't work, but it gave us a really good natural history of the progression. The second piece is that from all the studies that we know, patients with GA tends to grow linearly. So the rate of progression over 1 year is a linear progression. And the last piece then is that in patients with bilateral geographic atrophy, eyes tend to progress at identical rates. And so what -- to get back to your -- sorry, I'm trying to remember your question.

Just if there are any steps to mitigate the risk of seeing a response from the sham group?

Yes, sorry. So the sham control group in our study in the FILLY trial was almost identical, exactly what we had predicted in our statistical analysis plan. And I will say it is one of the most important things that we have to hang our hat on because as we move into the Phase III, what we saw in Phase II was a true reduction in the growth rate compared to the sham group, of course, but which was reflective of the natural history. And it's important to contrast that with the Phase III clinical trial that Genentech/Roche ran with lampalizumab. They did that after their Phase II clinical trial, which was called MAHALO. And in that MAHALO study, the sham control had moved faster than you should have expected. And the active arms were basically moving in line with what you would have expected from natural history. Now, of course, that was a warning sign at the time, Genentech/Roche decided for many reasons that it was worth a risk going into Phase III. But in retrospect, that is what was wrong with that Phase II.

Got it. So maybe just very quickly since I know we're coming up on the hour here. Can you briefly talk about your APL-9 program, the genesis in developing the asset and maybe just the potential there that you see?

Yes. So APL-9 is a mini-me of APL-2, exact same mechanism, exact same structure, 2 cyclic peptides that control C3 linked by a polyethylene glycol. The size of the PEG is difference between APL-2 and APL-9. It's 40 kilodaltons for APL-2, it's 10-kilodaltons for APL-9. And that means that APL-9 is ideal for administration intravenously. So you can very quickly control systemic intravascular complement activation under certain conditions where that is needed. Now the first indication or the first field that we are taking this into is in genetic therapies, where when you introduce AAVs that probably lengthy, et cetera, these viral particles start activating a ton of complement in intravascular compartment. That, on one hand, reduces the transduction efficiency. So you need a lot of these particles to get your effect. On the other hand, that complement activation can have deleterious side effects. As we have seen in many of these programs, especially in Duchenne muscular dystrophy, we believe that we can address both of these issues by preconditioning or pretreating patients with APL-9 and keeping their complement system under control, while the AAVs are being introduced. Now we also just started a trial in COVID-19, where we believe that the massive complement activation associated with these viruses does have an important impact on thrombosis and specifically the thrombotic microangiopathies that it's becoming very clear, are heavily associated with the mortality and kind of the second phase of the disease is something that we're hoping to control with complement.

Perfect. So maybe just one last question, and Tim, I'll pull you in here. Can you just remind us what your current cash position is, anticipated runway and then the upcoming milestones?

Sure. So we ended the quarter on March 31, with a little under $650 million in the bank. And then we did a convertible notes offering of around $330 million, which net of fees got us up to close to $930 million, which is a substantial amount of capital. And what that positioned us to do was to get through not just our 2020 milestones but our 2021 milestones and into the first half of 2022. So that really is about as much as we guide on a cash run basis. But in terms of the milestones, at least for 2020, we obviously will be presenting the 16-week PEGASUS data tomorrow. We have the 48-week top line PEGASUS data in the second half of the year. We'll give you an update on the PRINCE trial enrollment and also the 2 Phase III GA studies, the enrollment there. And we'll be discussing future indications. Cedric will -- and the team will unveil sort of our plan for pegcetacoplan and beyond what is known today, sometime in the near future. And then most importantly, what that cash runway gets us is through the launch of PNH and also through the readout of -- comfortably through the readout of the DERBY and OAKS GA study.

Perfect. With that, thank you so much again, everyone, for joining us.

Thank you very much.

Thanks so much.

Thanks, Andrea.

Thank you.

Bye.