Good day and thank you for standing by. Welcome to Apellis Fourth Quarter and Full Year 2021 Financial Results Conference Call. At this time, all participants are in a listen-only mode. After the speakers presentation there will be a question and answer session. . Please be advice that today's conference is being recorded. .

I would now like to hand the conference over to Meredith Kaya, Senior Vice President of Investor Relations and Strategic Finance.. Please go ahead..

Good afternoon, and thank you for joining us to discuss Apellis’ fourth quarter and year end 2021 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 will turn the call over to Cedric..

Thank you all for joining today. 2021 was a remarkable year for Apellis.

We received our first FDA approval for EMPAVELI delivers an exceptional initial launch, reported top-line results from our DERBY and OAKS studies positioning us to potentially receive our second FDA approval and advanced our broader pipeline, or simply said, we strengthen our position as a global leader in complement. Let me start with EMPAVELI.

In May of last year, EMPAVELI was approved by the FDA for the treatment of adults with Paroxysmal Nocturnal Hemoglobinuria or PNH.

This approval marked the transition from us being an R&D focused company with a passion to develop transformative therapies to now also being a commercial stage company delivering the first ever target C3 therapy to patients.

EMPAVELI is well-positioned to elevate the standard of care and I am excited by the progress we are making so far with the launch. Physician feedback is strong. Patients are reporting significant improvements, compliance is high, and we are seeing continued positive recognition by payers.

Globally, we and our partner, Sobi were also thrilled to see additional approvals over these past few months including in the European Union. In ophthalmology, the Phase 3 results from DERBY and OAKS and Geographic Atrophy or GA were a critical step in our efforts to bring the first ever treatment for GA to patients.

Since reporting top-line results last September, the team has been engaging closely with the Retinal community through medical meetings, one-on-one discussions and through many other forums. We received positive FDA feedback last fall and recently completed the pre-NDA meeting. The final step in the run-up to our submission.

More than ever, we believe pegcetacoplan represents a potential breakthrough for the 5 million patients globally who are living with GA, a relentless disease that is a leading cause of blindness worldwide.

We also made progress in advancing our broader pipeline, including our late-stage programs with systemic pegcetacoplan and our three pre-clinical programs. Let me now spend a moment on our key priorities for 2022.

First, as I mentioned, First, as I mentioned, we are focused on bringing pegcetacoplan to the market as the first ever therapy for patients with GA. GA can best be described as a forced fire raging through your retina, which is a continuous process with irreversible retinal cell death.

Once these cells are gone you start going blind and there are currently no approved treatments. We believe that with pegcetacoplan, we have an opportunity to slow this process and preserve patients vision for longer. We are actively preparing our NDA and are on-track to submit it to the FDA in the second quarter.

We will include 18 months safety and efficacy data from DERBY and OAKS in our NDA and plan to share these data publicly in March. In parallel, we are beginning the pre-submission discussions with the European regulators. Our initial market research has been quite encouraging.

And as we approach a potential approval we will continue our efforts to educate the physician and patient communities/ Secondly, we aim to elevate the standard of care in PNH and further establish EMPAVELI as a first-line treatment.

We want to ensure that all patients with PNH regardless of their baseline hemoglobin levels have the potential to benefit from EMPAVELI. Beyond PNH, we are seeking to advance EMPAVELI as a transformative therapy for rare complement driven diseases. Together with Sobi, we plan to have four late-stage programs underway this year.

Collectively, these opportunities could address the needs of as many as 35,000 patients per year, significantly expanding the opportunity for EMPAVELI.

Third, we want to advance systemic pegcetacoplan as a novel approach to enabling adeno-associated viruses or AAVS for gene therapies by controlling the many issues that are associated with these therapies.

By targeting C3, we believe that we may be able to see benefits such as increasing safety and tolerability, decreasing the dose needed and allowing for dosing in patients with pre-existing antibodies. In collaboration with our research partners, we look forward to sharing pre-clinical data in the first half of this year.

And finally, we are continuing to advance our pipeline and plan to expand our clinical portfolio with the submission of an IND for APL-1030, our first-in-class Brain-Active C3 inhibitor in the second half of this year.

We also are continuing to progress additional programs including APL-2006 and our siRNA plus EMPAVELI program towards the clinic over the next 18 months. We look forward to reporting on our progress across these four strategic priorities over the course of 2022.

By the end of this year, we could have two commercial products, a robust pipeline encompassing multiple late-stage rare disease programs and additional pre-clinical programs heading into the clinic further cementing our position as a global leader in complement.

I am amazed by the extraordinary science that has been pioneered by the team here at Apellis. 2021 was an incredible year. And we look forward to building on our momentum in 2022. And let me now turn the call over to Adam for a commercial update.

Adam?.

Thank you Cedric. As Cedric mentioned, EMPAVELI commercial results in PNH continued to be strong since our launch last May. As a reminder in the U.S. approximately 1,500 PNH patients are currently treated with C5 inhibitors and another 150 are newly diagnosed each year.

As expected demand was initially generated by patients on C5 inhibitors who are highly transfusion dependent. However, we are also seeing patients with hemoglobin levels near normal that have also experienced the benefits of EMPAVELI.

Patients from this latter group can still suffer from symptoms such as jaundice and fatigue, which result in prolonged morbidity and the feedback from those on EMPAVELI has been very positive.

With a clinical profile demonstrating superiority in raising hemoglobin levels as compared to C5 inhibition and in line with our key priorities for 2022, we aim to further establish EMPAVELI as a first-line treatment for patients.

Since our launch in May through the end of December, we saw continued positive momentum across several key metrics, including over 125 start forms in total received since launch. We continue to see the vast majority of EMPAVELI patient starts coming from C5 inhibitor patient switches with over 75% of these switches coming from Ultomiris.

We also hit our 2021 goal of having 90% of our top payers place EMPAVELI in a positive formulary position. As we've described, we initially focused on the Top 20 payers covering approximately 85% of all U.S. PNH prescriptions. Several large payers have placed EMPAVELI as exclusive for all treatment naive patients or as a preferred agent for PNH.

As we continue to secure broader payer coverage over time, we expect gross to net levels to net out in the low to mid-teens percentage range consistent with other rare disease drugs.

And lastly, we are seeing high patient compliance rates, which is a testament to the benefits of EMPAVELI and how much better patients feel when their disease is well controlled. We do anticipate that this will come down slightly over time, but these initial compliance levels are very encouraging.

We are optimistic about the continued momentum in 2022 and beyond. We are still very much in the early stages of the launch as we continue to educate physicians, secure additional payer coverage and hopefully benefit more and more patients.

Like many other pharma companies in-person engagement slowed in January due to the spread of the Omicron variant, we continue to utilize a variety of digital technologies to continue to reach HCPs virtually. But there is a strong correlation between in-person interaction and uptake.

We expect this impact will be brief and that we will maintain our strong growth trajectory over the course of this year/ Turning to our global efforts, EU launch activities are also progressing with our partners Sobi. As a reminder. EU approval was received in December 2021 under the brand name Aspaveli and Sobi's initial commercial launch in ex-U.S.

markets is expected this quarter. We were also pleased to see additional approvals in Australia and Saudi Arabia, key milestones in our collective goal of bringing EMPAVELI to patients around the world.

The 2022 is also going to be a pivotal year for pegcetacoplan in GA and a potential game changer for many of the 5 million patients suffering from GA globally. With the NDA submission on-track, our commercial team is preparing to launch what would be the first ever therapy for GA.

Near-term initiatives prior to approval will focus on disease state education as well as KOL and payer engagement activities. Market research and general feedback from retina specialists continue to reinforce our belief in pegcetacoplan's blockbuster potential.

This feedback supports the huge unmet need in GA and the paradigm shift that pegcetacoplan could drive for patients. We look forward to providing more detail on our commercial plans as we prepare for a potential launch. I will now turn the call over to Fede to review our clinical developments.

Fede?.

Thank you, Adam. A top priority for Apellis is our NDA submission for GA and we are on pace to submit the NDA in the second quarter. We believe we have a robust data package with data from 1500 patients across three trials. DERBY, OAKS and FILLY.

We were pleased to receive feedback from the FDA last fall, stating that they do not make distinction between phases, provided the clinical trial is adequate and won't control. And that all three trials appear to be adequate and well controlled. The totality of the data package underscores the potential of pegcetacoplan in this indication.

We think about the approval process in three important components; biological activity, treatment effect and safety. First biological activity. In all three trials, pegcetacoplan slowed the retinal cell death that typically occurs in GA. This was shown by the rate of reduction in GA lesion growth that was observed in the primary input.

This effect was then confirmed in the fellow analysis, assessing the rate of reduction in patients who have bilateral GA. Second, treatment effect. The magnitude of effect was further evaluated in a post-hoc analysis adjusting for baseline imbalances known to be associated with lesion growth.

There is a wide range of variability in the characteristics of GA across the patient population. This analysis helps to minimize the variability and again, in all three trials show a clinically meaningful treatment effect. And lastly, safety.

DERBY and OAKS demonstrated a favorable safety profile building on the safety profile that was observed in FILLY. That seemed to be some confusion around how accusations were reported in our studies. And we want to take this opportunity to clear this up. The same criteria for reporting exudations were used across FILLY, DERBY and OAKS.

As Cedric mentioned, the NDA will also include 18-month data from DERBY and OAKS, including the rate of reduction in GA lesion growth extended out into year two and the overall safety profile. Given the need in this indication, we plan to request priority review, which it granted would allow for a six-month review cycle.

This could set the stage for a potential approval by the end of this year. We look forward to working with the FDA to hopefully bring this drug to as many patients possible as quickly as possible. Before I move to EMPAVELI, I would like to briefly comment on our efforts in intermediate AMD. We had a productive discussion with the FDA.

Based on the feedback on expected endpoints we believe that pivotal studies in intermediate AMD should be sizable and lengthy, which would require significant investments. As a result, we have de-prioritized development of this program for now and will re-evaluate over time.

This does not minimize our view of the unmet need in this disease or the benefit of pegcetacoplan as a potential treatment. Another key objective for 2022 is delivering in the broad platform potential of EMPAVELI to advance our world disease franchise.

To that end our development strategy includes four late-stage studies in multiple complement-driven diseases. For our ongoing ALS study, we continue to expect to complete involvement in the first half of 2022.

Additionally our partner, Sobi commented in the recent earnings report that they dosed the first patient in the phase 2 study in hematopoietic stem cell transplantation-associated thrombotic microangiopathy or HSCT-TMA, and that they expect to initiate the Phase 3 study in cold agglutinin disease or CAD in the first half of this year.

We're also actively screening patients in anticipation of dosing our first patient in the Phase 3 study in Immune complex membranoproliferative glomerulonephritis or IC-MPGN and C3 glomerulopathy or C3G. We look forward to sharing our progress across these 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 full year 2021. Total revenue for 2021 was $66.6 million, which consisted of $15.1 million in EMPAVELI net product revenue in the U.S., a strong start for the franchise.

We also recorded a $50 million milestone payment from Sobi, in connection with the first regulatory approval and reimbursement approval in Europe. With EU approval granted last December, we view the likelihood of achieving the milestone as high and therefore recorded the revenue in the fourth quarter in accordance with U.S. GAAP.

We continue to expect to achieve this milestone and receive the cash in the first half of 2022. R&D expenses were $426 million, which included the $50 million upfront payment associated with the beam collaboration.

We also accrued an additional $25 million on our P&L in 2021 associated with the payment due on the one year anniversary of the beam collaboration that we view as likely to occur in the coming months. G&A expenses were $177 million and we reported the net loss of $746 million for the year.

As of December 31, 2021 Apellis had approximately $700 million in cash, cash equivalents and short-term marketable securities. This reflects net proceeds of $380 million from our recent offering in November, which we believe will provide us with the resources to execute our strategy into the second quarter of 2023.

Looking ahead to 2022 with an approved product in EMPAVELI, a robust pipeline and the potential upcoming blockbuster in GA, we are confident in Apellis' financial future. I will now turn the call back over to Cedric for closing remarks.

Cedric?.

Thank you, Tim. We have made excellent progress and look forward to an exciting 2022. Let me close with a brief recap of our upcoming milestones. In the first quarter, we are starting our pre-submission discussions with European regulators for GA. And for Aspaveli, we expect the initial ex-U.S. PNH launches by our partner, Sobi.

In the second quarter, we plan to submit our NDN and geographic atrophy to the U.S. FDA and publish our preclinical data on AAVs administered with C3 inhibition.

Over the course of the first half, we expect to complete the enrollment in our Phase 2 study in ALS, initiate the Phase 3 study in IC-MPGN and C3G and Sobi plans to initiate the Phase 3 study in CAD. In the third quarter, we plan to report the 24 months DERBY and OAKS update.

And in the fourth quarter, should we receive priority review, we expect to have an approval decision for GA in the U.S. In the second half of this year, we also expect the MAA submission in the European Union for GA and to submit our IND for APL-1030. We look forward to updating you on these efforts. Let us now open the call for questions.

Operator?.

Thank you. Our first question comes from Madhu Kumar with Goldman Sachs. Your line is open..

Yes. Thanks for taking our questions everybody. So let's start with CAD.

So I guess kind of how are you thinking about pivotal trial design with your collaborators Sob, given the recent approval of the Sanofi drug, sutimlimab in the condition?.

Thank you so much, Madhu, for that question. So, Sobi has been working hard in collaboration with us to prepare for this trial in cold agglutinin disease. Sutimlimab as you know, is a drug that is given intravenously every two weeks. So there's an important I think advantage to treating to self administering the drug at home twice per week.

As we have always said from an efficacy perspective, we will have to see if there is really a benefit to be gained, but it is really the convenience of adcom dosing. That trial is going to start in the very near future.

And right now, it is a trial that will kind of follow the conventional registration endpoints in cold agglutinin disease and we're not yet guiding on when it will read out..

Okay. Moving over to GA. So, you guys have announced you guys are going to have 18-month data in March and you're going to use that as part of the filing package.

How much of that data is kind of already in hand and like what are the kind of considerations people should have when thinking about that data relative to the results put out in September of last year?.

Yes. Thank you, Madhu. So in September when we -- after the primary endpoint readout and when we engaged in our discussions with the regulators, we proposed to include the data beyond 12 months on the lesion size growth to really get a full sense of what the effect has of the drug would be over time.

And we agreed to include, since it would not affect our timelines for submission, we agreed to include all of the data available up to 18 months both on efficacy as well as unsafe. And with efficacy in this case, of course, indicative of lesion growth and whatever we have available beyond 18 months as well..

Okay. And one last question on the EMPAVELI launch. I want to kind of come back something Adam said about patients who are coming onto EMPAVELI despite having normal hemoglobin.

How should we think about the kind of distribution of those patients? And where you think there's a longer term opportunity for those patients who don't have, say, low hemoglobin levels, but as you mentioned, could have other kind of complications of PNH that would switch over onto EMPAVELI as compared to the existing therapies?.

Yes. So patients with normal hemoglobin levels, on average represent approximately a third of the patients who are on treatment with C5 inhibitors.

But I think the really important point about what we aim to achieve in PNH is to elevate the standard of care not for patients who are transfusion dependent or who have poor hemoglobin levels, but in all patients with PNH.

Patients with normal hemoglobin levels and PNH get to those normal hemoglobin levels because they have very good bone marrow and produce typically very large amount of red blood cells. But these red blood cells also in an unusual way die in this process of exovascular hemolysis. That can lead to jaundice where patients have an ash in appearance.

It leads to reticulocytosis where a maximum amount of red blood cells have to be made in the bone marrow. And in short, this disease is not well controlled more broadly when extravascular hemolysis is not addressed.

Adam, I don't know if you want to add something to that?.

Yes. Well said, Cedric. So yes, we're seeing a much wider use of EMPAVELI. As we expected we're getting through the stages of the launch, right? So, we expected to have the hardest to treat patients first, those who are heavily dependent on transfusions. Now we're seeing those with high hemoglobin levels.

Hemoglobin levels around 10 for example, and we're seeing really and hearing really positive results of those patients. We're also hearing treatment naive patients that are starting on EMPAVELI too. So, where we should be in this phase of the launch, right? The hardest to treat patients.

Physicians have got experience and now they're broadening their experience to a wider population. So, the team is working incredibly hard to remind people that this is a first-line product and we believe we can truly elevate the standard of care and we're seeing that transition within the market..

Okay, great. Thanks very much..

Thank you, Madhu..

Thank you. Our next question comes from Jon Miller with Evercore ISI. Your line is now open..

Thanks for taking my question guys.

I guess, while we're on the subject of longer term data for GA, what functional data should we expect to be included in the NDA? And has the agency made any specific requests on that front? Or is any specific guidance on that? I think we all expect the imaging data to be front and center, it was the primary endpoint.

But what's the role of functional data from a doc perspective in your market research and outreach versus imaging alone when they talk about drivers of prescribing?.

Thank you so much, Jon. So the formal analysis on the functional endpoints will happen at 24 months, the way it has always been planned.

And then the way physicians look at it, I think most retina docs understand very well that a reduction in the growth rate of geographic atrophy as measured by autofluorescence is reflective of a loss of photoreceptor cells. So if you lose for receptor cells, you lose vision.

So that is also the -- that's clear connection right between living self and being able to see is also the really key reason why the FDA found this endpoint to be acceptable as the primary endpoint of course..

Great. Makes sense. I guess, on some of the rare disease trials that we're expecting to get started, it seems like these have been a little bit slower to get off the ground than you were suggesting last year? Obviously, we haven't seen some of those Phase 3 studies start already. I think we were expecting some of them in Q4.

So how should we think about timelines for the -- well, really the bulk of the Phase 3 studies that haven't started yet.

How long is it likely to take to get those up and running? And what are your expectations for readouts there?.

Yes. Thank you, Jon for the question. Yes. So, I think reflective of the broader industry getting studies started these days can take a little bit longer than expected we also of course had to coordinate with our partner Sobi. We were very happy with the designs that came together and with the regulatory feedback that led to those designs.

And you should generally expect all three of these new trials to start in the first half of this year, many of them now in the very near future..

Okay. Thanks very much. And as we think about PNH launch, I guess last one. I know you guys told us that you expect gross net to even out to the low to mid-teens sort of standard levels there. But at this point given that your commercial patient mix has been reasonably good in the launch.

What's your expectation for the remainder of the trend there? How much longer until we hit equilibrium on gross to net? And what's the -- what are we waiting for on the rest of your commercial transition?.

Thank you, Jon. I will hand that over to Adam Townsend..

Yes. Thanks Jon for the question. Yes. So, we still have some work to do with some payers. We had a great start to our launch last year and hit all of our targets with players. So now, we have some more targets with players that we're executing in this phase of the launch.

So, as we start to continue to try and get as good access as is possible with all of the payers that cover PNH phase, that that will have potentially an impact on growth today..

Okay. Thanks..

Thank you. Our next question comes from Anupam Rama. Your line is now open with JPMorgan..

Hey guys. Thanks so much for taking the question. Just a quick question on the 24-month data. I don't think this is the case, but just to confirm that there are no plans to submit the 24-month data to the FDA or rather you might do it as a supplement at a later point? Thanks so much..

Thank you so much, Anupam. Yes. We do not have plans to create an amendment to include the 24-month data. It will of course be available to us around that period in time, but we believe that we have everything available and we have the agrees to do our submission in the second quarter estimate. .

Thanks so much..

You're welcome..

Thank you. Our next question comes from Layla Yosuf with Cowen. Your line is now open..

Hi. This is Lyla on for Phil. Thank you for taking the question. Maybe on the potential commercial prep in GA. Can maybe talk a little bit about the progress with hiring a potential sales force? And in terms of your near term initiatives, have you already gone through and identified maybe key positions you plan to target? Thank you..

Thank you, Layla. I will hand that one over to Adam as well..

Yep. Thank you Layla. So yes, I'm very happy with the progress for hiring towards the GA launch. So we've hired all of the leadership positions in medical affairs, sales, marketing and market access within the U.S. and also the leadership positions outside of the U.S. in our EU office in Zurich and Switzerland.

We've also set up affiliates in Germany and Australia as well. So we're progressing really well. We've identified the size and the scale of the sales force. A good benchmark for everyone is the way FD products. So, we've used them regularly to make sure that we've got the right level of approach for when we potentially come to the market.

And we're probably going to target in the U.S. about 3,000 retina physicians, a much smaller subset of those do the majority of the FD Administration. So -- but you can see, right, it's not a huge build. It's well within the Apellis' capabilities. So, we are ready to go and we'll be very thoughtful as we start to expand and hire the sales force.

We're very excited to progress towards that..

Very helpful..

Thank you. Our next question comes from Steven Seedhouse with Raymond James. Your line is open..

Hi. Thanks for taking the question. Cedric, you mentioned just in response to an earlier question about including whatever data is available beyond 18 months as well.

I just hoping if you could clarify what you meant there if you were just speaking about lesion growth data or something else?.

Yes. Thank you Steven. Just to clarify, I'm talking about lesion growth data, correct..

Okay.

And is the FDA in your dialogue with them about this 18-month analysis interested in the slope of the data or just a point estimate at 18 months?.

The FDA is interested in the totality of the data. So we've had discussions with them around the mRNA transform data around slopes, around fellow eye analysis. I mean, all of these things, we believe are relevant, and I think this is a division that takes all of the data into account and its evaluation..

Okay. And maybe two just real quick last ones or I guess the second one might not be so quick. But your current view in your dialogue with the FDA of an ad com.

I know initial previously you said, you do not expect one, but I'm just curious about your updated view? And then the fellow eye analysis you just mentioned there's plenty of debate in the investment community about this analysis.

So it seems like you've had dialogue with the FDA about a fellow eye comparison and why it -- and may be valid supportive efficacy assessment. Could you just expand on that? Thanks so much..

Yes. Thank you so much Steve. So, the outcome of course is not our decision, right? We will be ready to have one. And we will see what FDA decides to do. On the fellow eye analysis, as I mentioned, it is something that is we believe very important and confirmatory of the biological activity for the drug.

There's something that we have discussed with the FDA. And I would say that, what stands out probably the most in FILLY, DERBY and OAKS are the sham control groups, where you clearly see how and this was well described in the past by investigators like Janssen where the study eye and the untreated fellow eye progress at virtually identical rates.

With if anything a little bit of a faster progression typically in the study eye, which is the worst seeing eye. So I think it's a really impressive control and in all three studies we see a consistent dose response effect compared to the fellow eye as opposed to the same control..

Thanks for taking the questions..

You're welcome..

Thank you. Our next question comes from Colleen Kusy with Baird. Your line is open..

Hi. Good afternoon. Thanks so much for taking our questions.

So, have you gotten any feedback from regulators or do you have any thoughts on how regulators may evaluate the every other month versus the monthly dosing arms?.

So, our plan to submit, Colleen, is the complete data package for monthly as well as for every other month. So, that has been discussed and that is what will be part of the package..

Okay, great. Thank you. And then so following up on PNH. Quite impressive that you've been able to get even exclusive reimbursement for EMPAVELI versus C5 inhibitors.

I guess, do you see that continuing to grow still? Or how do you think about the favorable reimbursement that you've been able to get in PNH?.

Yes. Thank you for that question.

Adam, would you like to comment?.

Yes, sure. Thanks Colleen. So yes, I'm actually very proud of the team. Done some great work with all of the payers. It does help that we have some great data that we can talk to the parents about particularly around transfusions and hemoglobin et cetera.

So, we've managed to have some really robust scientific conversations that have got us to have very positive positions with many, many payers. We want to continue to have those discussions over the next couple of months. And make sure that every patient that wants to get access to EMPAVELI can get access to Aspaveli.

And so that's our plan as we continue. So, yes, team's done a great job. We're not over yet. We want to continue to keep pushing..

Great. Thank you so much for taking our questions..

Thank you. Our next question comes from Alethia Young with Cantor Fitzgerald. Your line is open..

Hi. Good afternoon and thank you for taking our questions. This is Anon for Alithea. Maybe two from us. For GA, we know that this is ahead in clinical development.

But how are you guys seeing the competitive landscape shaping up if GA -- in GA if some of the competitors have positive data? And the second, just if you could share if there's been any ongoing COVID impacts across the business? Thanks..

Thank you so much Alithea. And just for the COVID question was that related to geographic atrophy..

Just across the business over across..

Well, so first of all with the -- as it relates to geographic atrophy, of course, we will have to see what happens with the data this summer. Just a quick reminder across that backdrop. How we plan to submit our data package, because we believe that every single component of that submission is important.

First of all, of course, there is the safety, which was better than I think most people expected. Number two, there is the biological activity with two studies having shown a positive primary endpoint out of the three. And the fellow eye analysis to confirm that that biological activity. The third piece is then what is the real effect size.

Because across these three studies at least that one year we see between 12% and 29%. And the reason why these results can be divergent is because the baseline characteristics of these patients can be very different and cannot be controlled for in these studies because there are too many.

So what you can do is afterwards do an analysis where you model these baseline differences between active and chime groups, and where you a clear reflect that is north of 20%. And then the last piece will be, again, what will that effect look like beyond 12 months? Is that is this a durable effect in patients.

What does this mean in the long term for these patients. Also very important, of course, in our submission is the every other month dosing on which we had a statistically significant result both in FILLY as well as into OAKS as when something that we believe is a really important advantage for physicians and for patients.

Especially in patients that are early on in the disease and to those patients that typically present for the first time with extrafoveal lesions being able to dose every two months instead of monthly is a very important advantage. So that's as it relates to geographic atrophy as it relates to COVID.

The impact on the trials has been limited in geographic atrophy. We used to speak about that a lot right, but we believe that the impact on the studies has been minimal. As it relates to the additional registration studies that we have ongoing, the only one of course in this case that is really important is the ALS study.

And there we have not really seen an impact either.

So Federico, I don't know if you would like to add something to that for the COVID impacts on clinical trials?.

No. Certainly, I think you're going to write most of the impacts that we have seen as across the board in pharma is on the initiations of new studies, that Omicron played a bit of a role in there. But other than that, no major effect of COVID I would say..

Thank you..

Thank you..

Thank you. Our next question comes from Tazeen Ahmad with Bank of America. Your line is open..

Hi. Good afternoon. Thanks for taking my question. And I'm sorry, I did join this call a few minutes late. So, if you've already answered this, I'm sorry for asking it a second time.

But just in terms of your expectations for the time to review, is it possible that you could get a regular review period not an accelerated path just because it does seem that in our experiences monitoring other companies during COVID at least, it seems like FDA is taking a little bit longer. They are issuing more PDUFA extensions, for example.

So based on your most recent discussion with the agency have they provided any color on your review period what that would be? And if you do expect an adcom, do you think that one could happen if you got a more, a shorter review period, a priority review? Thanks..

Thank you so much, Tazeen. So, we have not received any indication so far that we would have a longer review time than usual. So our discussions with regulators have all been positive. We of course cannot predict whether we will have priority review.

We are hopeful that we will based on precedent and based on the unmet need that exists in this disease of course. And as it relates to the adcom kind of really goes back to the first question as well where we will have to see what comes out of the acceptance.

But we are optimistic that we will receive priority review and that should there be an adcom that the feedback from physicians will be positive..

Okay. Thank you..

You're welcome..

Thank you. Our next question comes from Yigal Nochomovitz with Citigroup. Your line is open..

All right. Great. Thanks. Thanks for the questions. Cedric, regarding the 18-month look for DERBY and OAKS. So, obviously you've seen a very appreciable and steadily increasing separation of lesion growth curves through 12 months, almost like a wedge growing between pegcetacoplan and the sham.

So my question is, do you believe you need to see a continuing separation of the lesion growth curves between pegcetacoplan and sham at the 18-month point to support approval? Or as long as the curve stays separated and don't converge at the later time points that will be sufficient for a favorable efficacy claim?.

Thank you guys. So we have not received specific feedback on that particular expectation that you're talking about. But we are looking for a continued defect over time. Should there be a separation? Of course, that would be an extraordinary outcome..

Okay, great. And then just one follow-up regarding the pre-NDA meeting. I'm just wondering if the FDA weighed in at all regarding some of the changes in formulation that have occurred with pegcetacoplan over the years, i.e. from the lyophilized form in FILLY to the pre-filled bile in DERBY and OAKS where you had a slight recipient change.

And then finally, I believe after approval and launch you will introduce a pre-filled syringe?.

Correct. So just to be clear. What we did in the Phase 3 clinical trial was a pre-filled bile. And we will also launch with the pre-filled bile in the future. We will in all likelihoods introduce a pre-filled syringe, but that takes several years of development. But the key thing here is you got this was not the pre-NDA meeting.

But immediately after we had the data in September we thought it was important to understand the regulatory view on the FILLY trial. And what we did is we sent to the FDA the three trials in parallel explaining what the similarities and the differences were. What the quality of the studies was.

How they were run et cetera, with the specific question what the regulatory view was on the trials. And the answer that we received from the FDA was described in the second paragraph of the press release that we released early on in November at the time of the American Academy of Ophthalmology..

Okay. Thank you..

You're welcome..

Thank you. Our next question comes from Ellie Merle with UBS. Your line is open..

Hey guys. Thanks so much for the question. Just a logistical clarification questions. Just in terms of the stats around the 18 month analysis, could you just remind us of those.

And I guess in the discussions with the FDA, any discussion around any additional analyses at 18 months or any kind of things that made learning from say the fellow eye data, say, in terms of this 18 month analysis? And then just also, just a clarification question, I guess is that NDA filing contingent on the data scene at 18 months or is this sort of just additional color and data that could potentially get on the label? Thanks..

Thank you. So the formal analysis will happen at the 24-month time point. So we will of course run stats at 18 months, but they will be descriptive in nature. The contingent piece is we went to the FDA and we proposed to include that.

Because we realized that we had an opportunity to do that with the timing that we had in mind and included in our complete NDA submission without a significant delay. So that was something that we saw as an important opportunity to provide a more complete data package and all possible data as it relates to the lesion size growth.

So as it relates to the type of data that we will include it is the lesion size growth and the safety..

Got it. That's helpful. Thanks..

You're welcome..

Thank you. Our next question comes from Joseph Stringer with Needham and Company. Your line is open..

Hi, everyone. Thanks so much for taking our questions. Just giving your going to be starting a Phase 3 trial and I see MPGN and C3G. Just can you remind us of the market opportunity and this indication? And what you'd be looking for in terms of a competitive profile for pegcetacoplan in this indication? Thank you..

Thank you Joe. So we've used C3G and IC-MPGN as very important next indications for EMPAVELI and Aspaveli .We had a robust and very impressive proof-of-concept study that was run in C3G as you may recall.

In terms of the market opportunity, the market opportunity for each of C3G and IC-MPGN should probably be viewed in the range of what PNH represented. This is of course an unmet need for which there are currently no approved therapies. And we're based on our data, we believe that we have the possibility of having a best-in-class profile..

Great. Thanks for taking our question..

You're welcome..

Thank you. And I'm currently showing no further questions at this time. I'd like to hand the conference back to Mr. Cedric Francois for final remarks..

Thank you so much. 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. And if you have any additional questions feel free to reach out to Meredith. Thank you again for joining us today and have a wonderful rest of the week..

Ladies and gentlemen, this concludes today's conference call. You may now disconnect..