Hello, and welcome to Apellis Pharmaceuticals First Quarter 2022 Earnings Conference Call. . It is now my pleasure to introduce Senior Vice President of Investor Relations and Strategic Finance, Meredith Kaya..

Good afternoon, and thank you for joining us to discuss Apellis's first quarter 2022 financial results. With me on the call are Co-Founder and Chief Executive Officer, Dr. Cedric Francois; Chief Commercial Officer, Adam Townsend; Chief Medical Officer, Dr. Federico Grossi; and Chief Financial Officer, Tim Sullivan.

Before we begin, I would like to point out that we will be making forward-looking statements that are based on our current expectations and beliefs. These statements are subject to certain risks and uncertainties, and our actual results may differ materially.

I encourage you to consult the risk factors discussed in our SEC filings for additional detail. Now, I'll turn the call over to Cedric..

Thank you all for joining us today. 2022 is off to an extraordinary start at Apellis as we continue to execute across each of our key priorities. Starting with intravitreal pegcetacoplan for geographic atrophy, or GA, we've made important progress as we prepare for the NDA submission later this quarter.

We completed the pre-NDA meeting in January, and then in March, we shared 18-month data from our Phase III DERBY and OAKS studies determining that longer-term treatment with pegcetacoplan resulted in an increasing benefit to patients with greater amounts of retinal tissue saved over time and a favorable safety profile.

Additionally, these data showed improving effects in DERBY that were comparable with OAKS starting at month 6.

Just this week at ARVO, we shared additional 18-month data analyses that showed that pegcetacoplan reduced lesion growth in patients with extrafoveal lesions and in patients with foveal lesions, further supporting pegcetacoplan's benefits for a diverse population of patients across the GA disease spectrum.

Collectively, these data reinforce the potential for pegcetacoplan to become the first ever treatment for the millions of patients living with GA, a relentless disease that is a leading cause of blindness worldwide. Turning to EMPAVELI in PNH. The launch is off to a strong start in 2022, with approximately $12 million in U.S.

net sales despite the initial headwinds due to the Omicron variant. We remain focused on further establishing EMPAVELI as a first-line treatment for patients living with PNH. Our aim is to ensure that all patients with PNH, regardless of their baseline hemoglobin levels, have the potential to benefit from EMPAVELI.

The leading indicators for the launch remains strong with positive physician and patient feedback, a favorable patient mix, high levels of compliance and positive recognition by payers. Globally, we are thrilled to see our partner Sobi begin to bring EMPAVELI, known also as Aspaveli in certain countries outside the U.S. to patients worldwide.

Beyond PNH, we are seeking to advance EMPAVELI as a transformative therapy for rare complement-driven diseases. In the first quarter, we completed enrollment in our potentially registrational Phase II study in amyotrophic lateral sclerosis, or ALS, with top line results expected in mid-2023.

Additionally, Sobi dosed its first patient in a Phase II study in hematopoietic stem cell transplant-associated thrombotic microangiopathy or HSCT-TMA. Together with Sobi, we now have 2 late-stage clinical programs underway and remain on track to initiate 2 additional programs in the second quarter.

Combined, these opportunities could address the needs of as many as 35,000 patients per year in the U.S. alone, significantly expanding the opportunity for EMPAVELI. We are also advancing complement inhibition as a novel approach to enabling adeno-associated viruses or AAVs.

In collaboration with Spark Therapeutics, we look forward to sharing in vitro data with APL-9 at the upcoming Annual Meeting of the American Society of Gene and Cell Therapy later this month.

While early, with additional clinical investigation warranted, these in vitro data further supports our hypothesis that complement, and specifically C3, plays an important role in anti-AAV responses, and that targeting C3 has the potential to help mitigate the safety and tolerability concerns associated with AAV delivery.

Finally, we are continuing to progress our early stage pipeline with 3 INDs expected over the next 18 months, including APL 2006, APL 1030 and our SiRNA program, and continue to make great progress in our partnership with Beam Therapeutics.

On the finance side, we ended the first quarter with close to $1 billion in cash, providing runway into the first quarter of 2024. This strong financial position allows us to head into our NDA submission and potential launch from a position of strength in otherwise challenging market conditions.

We look forward to building on our momentum as we further cement our position as a leader in complement across multiple therapeutic areas. And let me now turn the call over to Adam for a commercial update.

Adam?.

Treatments are needed and needed now. More than ever, we believe that pegcetacoplan is positioned to meet the significant unmet need, and we are committed to working to bring this therapy to as many patients as possible as quickly as possible. Our commercial team is preparing for a potential launch as early as the end of the year.

We have onboarded several of the key leadership positions in medical affairs, sales and marketing and market access within the U.S. and additional leadership positions globally. We are initially focused on those retina specialists who manage the majority of GA patients.

We also continue to make strides in our near-term launch initiatives, focused on disease state education, KOL and payer engagement activities. In the EU, we remain on track to submit our MAA in the second half of 2022. We look forward to providing more detail on our commercial plans as we prepare for launch.

I will now turn the call over to Fede to review our clinical developments.

Fede?.

Thank you, Adam. Submitting the NDA later this quarter is one of our highest priorities. As Cedric mentioned, we are excited to share the 18-month data from DERBY and OAKS, which showed continuous and clinically meaningful benefits to a diverse and broad group of patients over time.

As highlighted on this slide, both monthly and every other month's treatment with pegcetacoplan continue to reduce GA lesion growth compared to Puan at 18 months with all nominal P values below 0.05 in both DERBY and OAKS.

This means that there was a larger absolute difference between pegcetacoplan and Sham in GA lesion area than observed at month 12.

In an effort to understand how the treatment benefit evolve over time, we then look at the effects with pegcetacoplan at 6 months intervals and found that the payment effect in DERBY were comparable to OAKS during month 6 to 18.

Pegcetacoplan in both studies continue to demonstrate a favorable safety profile as shown in the FILLY study and the 12-month top line DERBY and OAKS data readouts. Additionally, and most importantly, the combined 18-month data showed the potential for improvement treatment effects over time.

Then, earlier this week at the ARVO Annual Meeting, we and our collaborators had 10 presentations, including 3 oral presentations, showcasing our leadership in the data. In one of our presentations, we share 18-month data.

We showed that pegcetacoplan continued to demonstrate a reduction in GA lesion growth in patients with extrafoveal lesions and an improved effect in patients with foveal lesions.

In the combined DERBY and OAKS data, monthly and every other month treatment with pegcetacoplan reduced extrafoveal lesion growth by 26% and 21%, respectively, and reduced foveal lesion growth by 13% in both arms. Nominal P values were all below 0.05.

This additional data reinforce the potential of pegcetacoplan to slow the progression of GA across the disease spectrum, which is critically important given the better geneity of this patient population.

We are excited to potentially bring a therapy to all patients with GA with an additional opportunity to treat early in disease progression and save as many photoreceptor sales as possible throughout the course of the disease.

We're also excited to present the 18-month fellow eye comparison at an Apmedical meeting and expect the results to be generally consistent with what we saw at top line. We're also working to deliver on the broad platform potential of EMPAVELI to advance our disease franchise, which includes 4 late-stage studies in multiple complement-driven diseases.

In addition to what Cedric mentioned earlier regarding our LS and HSCT-TMA studies, we also expect to dose the first patient in a Phase III study in immune complex membranoproliferative glomera nephritis or IC-MPGN and C3 glomerulopathy or C3G in the second quarter.

Our partner, Sobi, remains on track to initiate a Phase III study in colablutin indices or CAD in the second quarter. We're excited to share our continuous progress across this rare disease programs. Let me now turn the call over to Tim for a review of the financials.

Tim?.

Thank you, Fede. Since we issued a press release earlier today with the full financial results, I will just focus on the highlights for the first quarter of 2022. Total revenue was $14.4 million, which consisted of $12.1 million in EMPAVELI net product revenue and $2.3 million in collaboration revenue from Sobi.

R&D expenses were $90.9 million, G&A expenses were $51.2 million, and we reported a net loss of $138.9 million. As of March 31, 2022, Apellis had $965.3 million in cash, cash equivalents and short-term marketable securities, excluding the additional $50 million milestone received in April from Sobi.

Our cash balance reflects $380.1 million in net proceeds from our offering in March. We expect our current cash balance to fund our operations into the first quarter of 2024, including the ongoing EMPAVELI launch, the global launch of pegcetacoplan in GA and further development of our pipeline.

We remain confident in Apellis's financial future as we continue to execute on our upcoming milestones. I will now turn the call back over to Cedric for closing remarks.

Cedric?.

Thank you, Tim. We have made excellent progress over the past few months and look forward to an exciting rest of the year.

By year-end, we expect to have further cemented our position as a global leader in complement with 2 commercial products and a robust pipeline encompassing multiple late-stage rare disease programs and additional pre-clinical programs heading into the clinic.

We look forward to building this momentum throughout the coming year and to updating you on our progress. And let us now open the call for questions.

Operator?.

. And our first question comes from the line of Madhu Kumar with Goldman Sachs..

I guess our first one relates to the European filing strategy for pegcetacoplan.

How should we think about that? And do they need to see the 24-month data, both in terms of GA lesion growth and in terms of functional assessment division before you kind of formally start the process of filing for approval in Europe?.

Mel. Great to hear you. So we are meeting with the rapporteurs in Europe, and those interactions are going very well. Our plan continues to be to file in the second half of this year. And as you mentioned, the 24-month data is something that will be updated in that package.

The functional end points, I want to again point out that the expectation there should not be to see something statistical, it never was. The European regulators want to understand what the functional relationship is with the full receptor cell death that we measure with the anatomical endpoints. So all of that will be included.

And again, the second half of this year continues to be our guidance..

Okay. One more question maybe on GA market size.

So a question you kind of have been getting more recently is, what fraction of GA patients are functionally legally blind in one eye? And how does that affect kind of the treating decision versus patients who have functional vision in both eyes? Like, can you answer looking at that question? And what are you hearing out there?.

Yes. Mel. So the number there is around 40% of patients, so it's a very high number of patients who are legally blind in one eye and affected by GA in the fellow eye. That is particularly a target population that is of interest for many retina docs because, of course, those are the patients that are most at risk of catastrophic bilateral vision loss..

And our next question comes from the line of Jon Miller with Evercore..

I guess one on -- let's start with cash runway.

I guess into '24 seems to get you well into the launch, but what's the likelihood that that can get you to profitability? And given the new runway, how have BD priorities and discussions shifted since the recent raise?.

Jon. I'm going to hand the call over to Tim..

Sure. Jon. So with this recent capital raise, as you said, our runway does get us into the first quarter of 2024. And in terms of that, there are a lot of assumptions out there that could fluctuate that kind of target of profitability one way or the other, so we're not guiding to profitability based on that time frame.

However, I don't think that capital really gets us a comfortable cash balance if we get to profitability, so we're going to continue to be thoughtful about what that potential financing that would get us there looks like. We're looking at approaches that may include that royalty partnerships or other financing vehicle.

But the good news is that we have a very strong cash balance right now. And we can take our time to figure out what makes sense for the company..

Great. That makes sense. And then maybe one more follow-on on the 24-month data we just were discussing.

When we think about FDA, if they get that 24-month data later this year, what's so likely that constitutes a major amendment pushes at the PDUFA?.

Yes. Jon. So like that is very, very small and would be based on surprises, right? So we have, of course, amply discussed this in anticipation. And the reason why the 24-month data is not something we need to wait for is because we don't expect to learn anything new between month 18 and 24.

So of course, when we have the data, we will communicate it, but it's not scheduled to be a major amendment..

And our next question comes from the line of Philip Nadeau with Cowen and Company..

A couple more on regulatory. In terms of an FDA panel issues, do you think the FDA would want to hold on? And if so, what would they hope to learn? And then second, on the timing, we noticed on Slide 13, you suggested an approval is possible this year.

Our understanding of the regs at the FDA is they have 2 months to accept any filing, and then even with prior review, it's 6 months after the acceptance for the PDUFA. So it seems like even if you were to file today, the 2023 PDUFA day would be likely occurs.

What have you heard from the FDA that gives you some confidence that the approval could actually come before the end of this year?.

Yes. Phil. So 2 great questions, I'm going to start with the second one. So the 6 months from the time of acceptance is a time line that depends on a new chemical entity.

But because pegcetacoplan is already approved in the different products, of course, it is no longer a new chemical entity, and that would be in 6 months from the time of filing rather than acceptance. So as it relates to the -- and that will, of course, put us at the end of this year still, even if it were to be at the end of the second quarter.

Now as it relates to the FDA panel, we are operating under the assumption that there will be one. We will be ready to have one. It is, of course, potentially the very first approval in this very important new indication.

I think when we think about what could be discussed during a panel like that, I want to remind people that the way in which the MDA is being submitted kind of the centered runs with 4 cornerstones, right? The first one is safety. The second one is the biological activity of the drug.

Does it work? And that is premised on meeting the primary endpoint in 2 studies. FILLY and OAKS, and then on the fellow eye analysis in patients with bilateral GA. The third chapter of the third cornerstone is then what is the real effect size? Because between the 3 studies that we have, we have an effect size ranging from 12% to 29%.

And with the covaried analysis clearly, at one year, clearly sits around 20%.

Then the fourth cornerstone is, what happens going into year 2? And of course, that was one of the foundational principles of including the 18-month data as well where we want to understand what is the long-term impact of treatment with this drug in the disease that people will have for years, if not decades.

So in the context of an outcome, should there be one? Kind of the only subject that is really kind of an interesting one is what does 20% at one year mean? What does kind of the continued benefits over time mean for patients in terms of safety for receptor cells? But we do not believe that other than that, there are many controversial elements in the submission..

So it sounds like you think a panel would go into that major subject of kind of what's the clinical significance of the data or even of the results that you've shown? Is that -- am I interpreting what you're saying correctly?.

Yes. And the question was if you have a panel that would be discussed, and I think that would be kind of probably what we predict. Now we have done a ton of research on that, of course, in the preparation for the launch.

A general consensus among physicians is that 20% is clinically meaningful, so it's also not a subject that we believe will be problematic for us..

That's very helpful. ..

Our next question comes from Steve Seedhouse with Raymond James..

This is Timur Ivannikov on for Steve Seedhouse. So just a question on G&A. I think you've talked about the importance of educating retina docs.

And assuming the drug is approved, what do you think will be the best way to communicate the benefit of pegcetacoplan if a patient doesn't really see a change in symptoms over a year or maybe the symptoms are worse, but it's not really clear whether the drug is helping?.

Yes. Timur. I think it's a very important one, right? I mean, I would say that what most resonates with retina doctors is when you talk to them about the area of saved retina, right? I mean, that's a very tangible thing to look at, right? I mean, it's not a percentage slowdown or whatever. So how much retina is actually being preserved.

And we disclosed the number with the 18-month data of OAKS, for example, where at one year, a 0.41 square millimeter of retina was preserved compared to the Sham whereas at 18 months, that was already 0.66 square millimeters.

And you could say, well, what is a square millimeter in the retina? Well, think about it this way, approximately or even less than 2 square millimeters is responsible for all central vision. So what we need to read charting, which determines visual acuity. So there's a lot of retina over the course of, we could say, 1.5 years.

A lot, but in the picture of a treatment with GA, a very short period of time..

Okay. Got it. And then maybe just a quick follow-up. In terms of fast progressor that you've talked about in DERBY.

On the other hand, do you have people who are best responders who are deep responders? Do you have patients who did not really progress at all on GA? And if you do, what is the distribution of those patients across the studies?.

Yes. So those are deep details that over time, we will talk about more. It is very rare for a patient to not progress at all. That can occur, of course, but it's rare. And it goes in distribution, right? It goes from very fast to no progression at all. How exactly that pans out, we will, in due time, publish.

But what's important is that we have many variables that can drive how fast these patients progress. And so it's easy for a study to be out of balance because you can quite frankly not stratify the study properly in GA to really be well balanced. So sometimes, you can get lucky.

In FILLY, for example, we probably were lucky in terms of the distribution of the patients between Sham and active. Plus in DERBY, we got -- we were unfortunate, right, in the sense that, as you mentioned, these rapidly progressive patients were disproportionately allocated to the active's monthly arm..

And our next question comes from the line of Chris Howerton with Jefferies..

Team, this is Combis on for Chris. A couple of questions for us.

What were your takeaways from the DERBY extrafoveal subgroup analysis? Were you surprised to see every other month performing better than monthly in that group? And I guess, just any general broader takeaways in GA from that finding? And then as a second question, thinking about kind of function and how pegcetacoplan will impact patients' visual function.

What's the most high fidelity functional measure in GA? And kind of like, what's the most practical way to measure function? Would something like a digital Amsler grid be practical and easy to implement to measure visual function?.

Thank you, Combis. So let me start with the extrafoveal question. So hereto, by the way, the 12-month data on extrafoveal that we also disclosed, I believe it was at Retina Society in the beginning of October, right? And so it's a continued -- we do have an inverse dose relationship there.

But one that will be interesting to see how it continues to progress over time, right? And there, you see the true manifestation of what I mentioned earlier, which is that in DERBY, in the monthly arm, not in every other month, but in monthly, we have this rapidly progressing patients, right? So they have -- they are at a disadvantage compared to the Sham and they're even at a disadvantage compared to every other month.

But what's very interesting, and that's beautiful to see, is how over time, that compensates, which we also clearly disclosed in the 18 months update that we gave in March. Then as it relates to function.

So one of the big problems that we have in geographic atrophy, but in the retina in general, is that measuring function is very difficult and incomplete in the retina, right? So you can see a visual acuity, for example, which is the best known. Well, that only measures your central vision.

To read the chart, what you need is the central person of your vision, and you could read the chart looking through a straw if you wanted to.

But if I told you to run across the street, looking through a straw, of course, that gives you an idea how poor of a measure for function that really is, right? We then have some visual questionnaires that can be helpful again to understanding how functional evolves, so they're also incomplete.

Reading speed is another one, but that one, too, varies widely within the same patient, right? I mean, your reading speed in the morning is different from the evening, for example. And then microperimetry is a really interesting one.

It's an intense examination, takes several hours where we sign a laser with different frequencies in the back with several spots. But again, there, the number of spots you can test are limited. So all of these things have their limitations, and they can provide the contextual context.

But what is important, and this is the reason why the FDA and every regulatory organization that we deal with has accepted the anatomical endpoints of autofluorescence over time, is that it measures directly how quickly retinal cells die, right? So yes, it's an anatomical endpoint.

But with almost -- with close to single-cell resolution, right, we can measure how quickly patients are actually losing for receptor cells, which is directly correlated to vision..

And our next question comes from the line of Colleen Kusy with Baird..

So can you talk -- I think in the 18-month update, we did see some of the slope analysis.

I guess, do you have a sense of this view on the slope analysis? And would they care about the entirety, so like 0 to 12 or is it at 18? Or could that be more heavily weighted towards the later slope to say, months 12 to 18?.

Colleen. That is a really great question. So again, kind of going back to the way which our primary endpoint is measured, right? We look at lesion size reduction over time. That is what we agreed on with the FDA, and that is the way we do the primary endpoint analysis. However, in secondary analysis, among many other things, we do a slope analysis.

And the slope analysis gives you exactly the same outcome as you get for the measurement of loss over time, but close to exactly the same. You make it a very important and that will be a really critical point, which is also slope can be measured in various ways. You can go from, for example, over 1 year from 0 to 12 months.

You can go from 0 to 6 months, 6 to 12, or you could even go from 12 to 18, the way we did it at the 18-month time point. That is important because the slope gives you an idea of what to expect over time and how consistent the measurements are among each other.

So it is a contextual tool to understand what the long-term impact of treatment is on patients.

And what we showed with the 18-month data in March is that if you take it through this piece-wise linear slope analysis from 0 to 6, 6 to 12 and 12 to 18, that these effects seem to be compounding, right? And if I have geographic atrophy today, it's not that important how bad my disease was 2 years ago or 18 months ago.

I care about what it is like now because that is what I will know likelihood carry forward as long as I stay on treatment, right? And in that sense, the 12- to 18-month data looked very good with data. Much more consistent between DERBY and OAKS now, for example, at the beginning of the study..

Great. That's really interesting.

And on a potential GA launch, I guess, how much focus will be on retina specialists that are already seeing probably more advanced GA patients? And how much focus will be on educating optometrists or general ophthalmologists on referring earlier stage GA patients to specialists?.

Yes. Colleen. I'm going to hand that one over to Adam..

Colleen. So as a quick little reminder, right? So we'll target around 3,000 retina specialists and some optometrists as well, right, to drive patients who are unaware that there's a treatment to a retina specialist. So our focus is on the target list of about 3,000.

But an interesting piece of information, right, about 900 retina specialists do about 85% of all of the intravitreal injections for. So really, really concise group of physicians that do the bonus of the injecting. So it's a very easy target for us to go and introduce ourselves to and start to build commercial relationships with.

As we said on the call, we started to onboard several of our leadership positions across commercial, medical affairs, sales and marketing. And interestingly enough, we've -- we started our high-level leadership sales position recruiting, and we had over 400 resumes come in for those positions.

So you can see the interest within the industry on the potential excitement around our RGA launch. So hopefully, that answers your question, Colleen..

Yes, it does..

Our next question comes from the line of Derek Archila with Wells Fargo..

Maybe just shifting gears to PNH and EMPAVELI for a sec, just 2 questions. I mean, first, I guess how has the EMPAVELI patient mix trended in terms of naive versus C5 switches since launch? So that's question number one.

And then second question, I guess, can you talk to what the competitors are doing in this market right now? Are you starting to see some more counter detailing since you've been in the market for now more than several months? That would be helpful..

Derek. This one, too, I will hand over to Adam..

Yes. Derek. So not a surprise we're finding that C5 inhibitor switch patients continue to be the majority of our EMPAVELI starts. And as a reminder, there's 1,500 C5 treated patients within the U.S. and 150 treatment-naive patients, give or take. And again, consistently, 75% of the switches are coming from ULTOMIRIS patients.

And that just tells you the benefit that people see of a C3 treatment over a C5 treatment. We are also seeing patients with hemoglobin levels near normal that have experienced the benefits of EMPAVELI. Patients from this group will still potentially suffer from systems such as jaundice and fatigue.

And so we're seeing that the high levels of hemoglobin are now entering the market and asking to switch and switching to EMPAVELI. We continue to see treatment naive patients come in as well to EMPAVELI and they're also benefiting from the significant increase in hemoglobin.

So as we get later into the launch of this year, I expect us to continue to build on that C5 switch population. To continue to drive higher hemoglobin patients on C5 to C3 to EMPAVELI, and I expect the treatment-naive patients to also increase.

So I think we're getting a whole mix of patients within the market that are benefiting from switching to EMPAVELI. Now the second part of your question, competitors and what we're seeing. So one thing I'll say, Derek, is we are laser-focused on executing our plan.

And for me, that's best practice as we launch into these older rare diseases to make sure that we offer the best solutions for EMPAVELI patients and also hematologists and oncologists that are willing to put patients on EMPAVELI.

So we try and make sure that when we hear about competitors and everything that's happening in the market that we just stay true to our plan, which is we want to elevate the standard of care for PNH patients.

So we have not surprisingly seen more action and noise from various companies, but again, we are determined that we have the best products and we believe that we can have the best impact on patients, so we're going to continue to execute our plans.

So we tend to listen to the noise, ignore it and stay focused and true to what we wanted to execute in the market..

And our next question comes from the line of Yigal Nochomovitz with Citi Group..

Cedric and team. Cedric, I had a question on effects for extrafoveal. So obviously, in extrafoveal, the data are very, very strong for both OAKS and DERBY. Though portfolio, the situation, as you know, is a bit more complicated since the data looked really good in it but not quite good in DERBY.

Though, of course, on a pool basis, figures shows a very solid nominees in fact at 18 months.

So with that being said, what is your level of confidence you can get claims to full yield in the label? And more to the point, how much do critical extrafoveal claim, given that these patients already have irreversible central vision loss and more retina docs will have more opportunities to save vision that they can start treating patients with the extrafoveal lesions..

Yigal. So that's a very good and important question, because I think it's worth briefly speaking about this extrafoveal involvement. So fovial lesions are lesions that, as you know, sits centrally and have affected the fovea and therefore, have a dramatic effect on it.

As opposed to extrafoveal lesions where the central vision is preferred but a lower rate per second. Newly diagnosed patients with will get diagnosed initially with extrafoveal lesions because there is, for reasons that we don't fully understand, the foveal is often protected until the very, very end of this progression.

So it is a fair assumption that fovial patients you should think of as more advance compared to extrafoveal patients, particularly the earlier ones. Those advanced patients, even when fovial becomes involved, however, can still rely very heavily on whatever retina is available to them outside of fovia.

So those patients, when they get to that time point, you don't want to stop closing or treating. If anything, you want to -- you may want to consider being even more aggressive because these patients are the ones that are really using the most quick. So to your point, in DERBY, the extrafoveal patients, they did not show a lot of defect.

In books, they, once again, the most fascinating to some. Over time, that seems to -- so we're going to continue to follow that, but a way in which study was done on the primary endpoint is being based on base capacity, foveal as well as extrafoveal.

And once you start diving into the treatment, they have to be careful with the fact, of course, that you're doing with smaller patient populations where retinas can have a big. So to be continued, but our filing will be on all patients with geographic atrophy, foveal as well as extrafoveal..

Okay. Great. And then just on the dosing regimen for pegcetacoplan in GA. So as you know, there doesn't appear to be a clear dose response between monthly and every other month. As for example, the extrafoveal every other month and monthly dose responses are inverted between OAKS and DERBY.

So I'm just wondering, is there any credence to the argument that the agency should only approve every other month, given comparable efficacy to monthly and an incrementally cleaner safety profile on new onset CMD? Or do you disagree with that assertion and believe both schedules merit approval?.

Yes. So we -- look, we're very excited about every other month dosing schedule right. I think especially for patients with extrafoveal lesions at the beginning of the disease, we want to preserve as much retina as possible.

If you end up getting 80% to 90% of the benefit of monthly injections by doing every other month, that is desirable if you start early and you want to get as much as possible over the long run. . So we think that is a very important piece of our filing. There's also the 18-month data that we have.

So not just 12, but we have the full data package on the 18 months, both on safety as well as on efficacy. And then, of course, as we discussed earlier, kind of the improving effect profile that we see on these foveal patients as well over time.

So I think that in terms of the dosing regimen, both doses we believe, have the data necessary to get approved. We do not believe that the safety profile warrants limiting the label, and we would like to provide as much as flexibility as possible to the physicians.

So -- and importantly, again, you don't get the full benefit, right? Touching as I did in the previous question on that every other month versus monthly inversion in DERBY. That is related to the fact that we had rapidly progressing patients in the multi-arm.

So if you look at the totality of the data, monthly has a slight benefit over every other month without the data..

And our next question comes from the line of Eliana Merle with UBS..

Just in terms of the GA sort of commercial landscape and any sort of pre-commercialization kind of analysis that you guys are doing.

I guess, what data do you have or sort of what kind of your latest understanding of sort of the number of patients that might be undiagnosed today? Just given sort of no available treatment, so maybe not an incentive to actively diagnose? And how you're thinking about that just as we all kind of run sort of the standard kind of model in terms of the number of patients that might be out there with GA?.

Ellie. I will hand that one over to Adam as well..

Ellie. So a quick refresher. So obviously, 5 million GA patients worldwide, 1 million alone in the U.S.

Now in our discussions with retinal physicians, we've -- we've got to a level where a lot of retina physicians believe that that number is actually greater than 1 million patients because of patients that might not make it to their retina center or to injecting ophthalmologists or something like that.

So I think if you speak to the experts within the field, they'll tell you that number could be higher than that.

So for our -- in all intents and purposes, we are focusing on that $1 million and working at various ways, including targeting certain optometrists and ophthalmologists, to allow that drive of the patient now that there's a potential treatment on the horizon to enacting retina specialists.

We're also exploring various ways through digital footprint, disease education and awareness to really make it known to patients through various channels that they could and should potentially go and see their retina specialists or injecting physician. So we've looked at a lot of those type of activities. We have plans around that.

We do think it's going to be important to make sure that we can drive patients to injecting physicians. So hopefully, Ellie, that answers your question..

Your next question comes from the line of Joey Stringer with Needham & Company..

One on PNH. So that you've added based on your start forms 25 or the last -- over the last 2 quarters. Just curious if you see this sort of sort of reaching sort of a steady state? And were there any impacts on start forms in -- COVID-related in 1Q? And just on the compliance rate, remains quite high.

Do you still expect this to remain this high? Or where do you see the compliance rate sort of leveling out -- it?.

Joey.

Adam?.

Yes. Joey. So I think we believe that we're going to see consistent growth quarter-over-quarter in an ultra-rare disease like PNH. It's incredibly encouraging that we continue to see that demand.

Especially to your point, Joey, in light of the COVID-19 restrictions, which thankfully, we're seeing now as we exit the first quarter, lifting a little bit and access is improving, for sure.

So that allows us to get back into physicians' offices and train patients more frequently face-to-face I do expect some fluctuation when it comes to start forms, right? This is our first January, February and March for an approved product in EMPAVELI, right. So we're learning the seasonality, we're learning the impact.

But I'm pleased with the consistent demand that we're seeing when it comes to staff falls. Another good metric for everyone to think about is we continue to see REMS certifications programs increase. So we had over 170 physicians sign up for our REMS program. That continues to grow. And that's another good sign for everything that's coming there.

So more to come. I expect the demand to continue everything we're hearing from physicians and patients points in that direction..

And our next question comes from the line of Laura Chico with Wedbush Securities..

I kind of wanted to follow up on one on the commercial side for GA. And I think you discussed this a little bit, but what is the capacity of the system in the U.S.

to treat IVT or to handle IVT injections by ophthalmologists and retinal specialists? I'm just trying to understand how many patients could feasibly be treated more at a peak period, but as we're ramping up. .

And then kind of related to that, what would be the time line to obtaining a J code? And just curious how that might impact uptake during the period prior to issuance of the J code..

There are two excellent questions. I'm going to hand it over to Adam, but very briefly on the capacity level.

I think one of the things that is really great is that the infrastructure, the reimbursement model, the habit that retina doctors have of administering anti-VEGF products is, of course, kind of a perfect point of entry for us, right? The fact that we're talking about capacity rather than capability is a great point for us to start from because all of these physicians, these retinal docs are used to managing inventory, the buy and bill model that is typical for these products.

And we are slowly entering into a phase where with anti-VEGF injections, everything goes towards fewer anti-VEGF injections for less frequent dosing. Will hopefully become possible.

So in many ways, there is a scenario here where the introduction of our product should, if and when it occurs, would help us kind of fill what would otherwise be a void that gets created by less frequent dose antibiotics. But Adam, I'm going to hand it to you to talk more about that as well as the comment on the J codes, please..

Yes. Cedric, Laura. Yes, Cedric, you said it very well. I mean, we did some capacity research last year on our products. And one thing we found consistently, as Cedric said, is that retinal physicians know how to make sure that they can get their patients in and treated with the wet AMD as a great analog.

But they also consistently told us that they knew what it would take to allow them to improve that capacity, be it a new bed or a new set or a new technician to help onboard patients. So they already have started to think of plans should capacity be an issue.

So I think if capacity is going to be an issue, which I don't expect it will be, earlier on in the launch phase when there was people are getting -- the products approved, potentially, then people are starting to identify patients and bring them in. So I think in the initial phase of the launch window, that's when we would see any headwinds there.

But we have plans on how we could help do that, and we have a pretty good piece of robust research that helps us do it. So also tied to your second part of your question around J code.

So obviously, a little bit of a refresher for people, all new physician-administered drugs like this one, they're built through miscellaneous J codes, right? So we expect a much that we would have that type of miscellaneous J code. And then we'll work with CMS, and permanent J codes are awarded, as probably most people know, on a quarterly basis.

January, April, July and October off top of my head. And we understand the impact of that, right? So we understand that providers are going to be relatively sensitive around the certainty of reimbursement for these type of drugs.

And so therefore, I think they're going to take that into account as they look in the early stage of the launch until a permanent J code becomes effective for them.

We're looking also -- based on the capacity question, we're looking at various ways that we can help support, that provider confidence in prescribing our product as quickly as is possible. And we'll obviously apply and obtain a permanent J code to help take all of the claims processing and payment.

And I expect that to be within, hopefully, 6 to 9 months of approval. So that's where we stand on all things J code..

Thank you. I'll now turn the call back over to CEO, Cedric Francois, for any closing remarks..

Thank you very much. And in closing, thank you all for joining us today. We look forward to keeping you updated on our progress in the months ahead. We are around later today and tomorrow. If you have any additional questions, feel free, of course, to reach out to Meredith, and have a wonderful rest of the week..

Ladies and gentlemen, this concludes today's conference call. Thank you for participating, and you may now disconnect..