Earnings Call Transcript - APLS Q4 2021

Operator, Operator

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 advised 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.

Meredith Kaya, Senior Vice President of Investor Relations and Strategic Finance

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.

Cedric Francois, CEO

Thank you all for joining today. 2021 was a remarkable year for Apellis. We received our first FDA approval for EMPAVELI, which delivered 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. Simply said, we strengthened 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 being an R&D-focused company with a passion for developing transformative therapies to now being a commercial stage company delivering the first-ever targeted C3 therapy to patients. EMPAVELI is well-positioned to elevate the standard of care, and I am excited about 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 for 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 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, 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 forest fire raging through your retina, 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 of 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. 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. 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. Let me now turn the call over to Adam for a commercial update. Adam?

Adam Townsend, Chief Commercial Officer

Thank you, Cedric. As Cedric mentioned, EMPAVELI's 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 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. 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. However, we continue to utilize a variety of digital technologies 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 throughout 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 pleased to see additional approvals in Australia and Saudi Arabia, key milestones in our collective goal of bringing EMPAVELI to patients around the world. 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?

Federico Grossi, Chief Medical Officer

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 distinctions between phases, provided the clinical trial is 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 inputs. This effect was then confirmed in the fellow eye 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. Lastly, safety. DERBY and OAKS demonstrated a favorable safety profile building on the safety profile that was observed in FILLY. There seemed to be some confusion around how exudations 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 if 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 as 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 deprioritized the 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 on the broad platform potential of EMPAVELI to advance our rare 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 enrollment 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 they expect to initiate the Phase 3 study in cold agglutinin disease or CAD in the first half of this year. We are 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?

Tim Sullivan, Chief Financial Officer

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 a 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?

Cedric Francois, CEO

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 NDA for 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 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-month 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?

Operator, Operator

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

Madhu Kumar, Analyst

Yes. Thanks for taking our questions, everybody. So let's start with CAD. So, I guess, how are you thinking about pivotal trial design with your collaborators Sobi, given the recent approval of the Sanofi drug, sutimlimab in this condition?

Cedric Francois, CEO

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, which provides an important advantage over 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 at-home dosing. That trial is going to start in the very near future, and right now, it is a trial that will follow the conventional registration endpoints in cold agglutinin disease, and we are not yet guiding on when it will read out.

Madhu Kumar, Analyst

Okay. Moving over to GA. So, you have announced you would 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 currently in hand and what considerations should be made regarding that data relative to the results published in September of last year?

Cedric Francois, CEO

Yes. Thank you, Madhu. In September, after the primary endpoint readout, 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 drug's effect would be over time. We agreed to include all of the data available up to 18 months, both on efficacy as well as safety. In efficacy, this means, of course, indicative of lesion growth and whatever we have available beyond 18 months as well.

Madhu Kumar, Analyst

Okay. And one last question on the EMPAVELI launch. I want to revisit what Adam said about patients coming onto EMPAVELI despite having normal hemoglobin. How should we think about the distribution of those patients? And where do you see the longer-term opportunity for patients who don't have low hemoglobin levels but, as you mentioned, could have other complications of PNH that would switch over onto EMPAVELI compared to existing therapies?

Cedric Francois, CEO

Yes. Patients with normal hemoglobin levels, on average, represent approximately a third of the patients who are on treatment with C5 inhibitors. The key point about what we aim to achieve in PNH is elevating the standard of care for all patients with PNH, not only those who are transfusion-dependent or have poor hemoglobin levels. Patients with normal hemoglobin levels have good bone marrow and produce typically large amounts of red blood cells, but these red blood cells can die in the process of extravascular hemolysis. That can lead to jaundice, where patients have an ashen appearance. It leads to reticulocytosis, where a maximum number of red blood cells have to be made in the bone marrow. 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?

Adam Townsend, Chief Commercial Officer

Yes. Well stated, Cedric. So yes, we're seeing a much wider use of EMPAVELI. As we expected, we're progressing through the stages of the launch. Initially, we had the hardest to treat patients, those who are heavily dependent on transfusions. Now we're seeing those with high hemoglobin levels, around 10 for example, and we're hearing really positive results from those patients. We're also seeing treatment-naive patients starting on EMPAVELI as well. So, in this phase of the launch, we are expanding our reach. The team is working incredibly hard to remind everyone that this is a first-line product, and we believe we can elevate the standard of care.

Madhu Kumar, Analyst

Okay, great. Thanks very much.

Cedric Francois, CEO

Thank you, Madhu.

Operator, Operator

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

Jon Miller, Analyst

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 there any specific guidance on that? I think we all expect the imaging data to be front and center, as it was the primary endpoint. But what's the role of functional data from the physician's perspective in your market research and outreach versus imaging alone when talking about drivers of prescribing?

Cedric Francois, CEO

Thank you so much, Jon. The formal analysis on the functional endpoints will happen at 24 months as it has always been planned. Most retina doctors understand that a reduction in the growth rate of geographic atrophy, as measured by autofluorescence, is reflective of a loss of photoreceptor cells. If you lose photoreceptor cells, you lose vision. That is also the clear connection between losing cells and being able to see. This is also why the FDA accepted this endpoint as the primary endpoint.

Jon Miller, Analyst

Great. Makes sense. I guess on some of the rare disease trials 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 yet. How should we think about timelines for 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?

Cedric Francois, CEO

Yes. Thank you, Jon, for the question. Yes, reflective of the broader industry, getting studies started these days can take longer than expected. We also, of course, had to coordinate with our partner Sobi. We are very happy with the designs that came together, and with the regulatory feedback that led to those designs. You should generally expect all three of these new trials to start in the first half of this year, many of them in the very near future.

Jon Miller, Analyst

Okay. Thanks very much. And as we think about the PNH launch, I guess my last question. I know you told us that you expect gross-to-net to even out in the low to mid-teens sort of standard levels there. But 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 are we waiting for on the rest of your commercial transition?

Cedric Francois, CEO

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

Adam Townsend, Chief Commercial Officer

Yes. Thanks, Jon, for the question. 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 payers. Now, we have some more targets with payers that we're executing in this phase of the launch. As we continue to try and get as good access as possible with all the payers covering PNH, that will potentially have an impact on growth today.

Operator, Operator

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

Anupam Rama, Analyst

Hey, guys. Thanks so much for taking the question. Just a quick question on the 24-month data. I just want to confirm that there are no plans to submit the 24-month data to the FDA, and rather, that you might do it as a supplement at a later point? Thanks so much.

Cedric Francois, CEO

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

Operator, Operator

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

Layla Yosuf, Analyst

Hi. This is Layla on for Phil. Thank you for taking the question. Maybe on the potential commercial prep in GA, could you talk a little bit about the progress with hiring a potential sales force? Have you identified key positions you plan to target?

Cedric Francois, CEO

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

Adam Townsend, Chief Commercial Officer

Yes, thank you, Layla. So yes, I'm very happy with the progress on hiring toward the GA launch. We have hired all of the leadership positions in medical affairs, sales, marketing, and market access within the U.S., as well as leadership positions outside the U.S. in our EU office in Zurich and in Switzerland. We've also set up affiliates in Germany and Australia as well. We're progressing really well. We've identified the size and scale of the sales force. A good benchmark for everyone is the way FDA products are used regularly to ensure that we have the right level of approach when we potentially come to the market. We are likely to target about 3,000 retina physicians in the U.S., though not all do a majority of the administration of FDA products. So it’s not a huge build, and it's well within Apellis' capabilities. We are ready to go and will be very thoughtful as we start to expand and hire the sales force. We're excited to progress toward that.

Operator, Operator

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

Steven Seedhouse, Analyst

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. Could you clarify what you meant there? Were you speaking about lesion growth data or something else?

Cedric Francois, CEO

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

Steven Seedhouse, Analyst

Okay. And could you clarify your current view in your dialogue with the FDA on an advisory committee? Initially, you mentioned you do not expect one, but I am curious about your updated view?

Cedric Francois, CEO

Yes. The outcome, of course, is not our decision. We will be ready to have one if it occurs, but we will see what the FDA decides to do. On the fellow-eye analysis, we believe it’s very important and confirmatory of the biological activity for the drug. It's something we have discussed with the FDA, and I would say that, what stands out in FILLY, DERBY, and OAKS are the sham control groups, where it is clear how the study eye and the untreated fellow eye progress at virtually identical rates. We see a consistent dose response effect compared to the fellow eye across all three studies.

Steven Seedhouse, Analyst

Thanks for taking the questions.

Cedric Francois, CEO

You're welcome.

Operator, Operator

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

Colleen Kusy, Analyst

Hi. Good afternoon. Thanks so much for taking our questions. Have you gotten any feedback from regulators or do you have any thoughts on how they may evaluate the every other month versus the monthly dosing arms?

Cedric Francois, CEO

Our plan to submit, Colleen, is the complete data package for both monthly as well as for every other month. This has been discussed and will be part of the package.

Colleen Kusy, Analyst

Okay, great. Thank you. Following up on PNH, it's impressive that you've been able to secure exclusive reimbursement for EMPAVELI versus C5 inhibitors. Do you see that continuing to grow, or how do you think about the favorable reimbursement you've achieved in PNH?

Cedric Francois, CEO

Thank you for that question. Adam, would you like to comment?

Adam Townsend, Chief Commercial Officer

Yes, sure. Thanks, Colleen. Yes, I’m proud of the team. We've done great work with the payers. Our excellent data allows us to have robust scientific discussions. We've been able to secure very positive positions with many payers, and we want to continue those discussions. We want to ensure that every patient wanting access to EMPAVELI can get access to Aspaveli. So yes, the team's done great work; we're not done yet, and we will keep pushing.

Operator, Operator

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

Alethia Young, Analyst

Hi. Good afternoon and thank you for taking our questions. This is Anupam for Alethia. Maybe two from us. For GA, we know that this is ahead in clinical development, but how are you seeing the competitive landscape shaping up if competitors have positive data? And the second question, if you could share any ongoing COVID impacts across the business?

Cedric Francois, CEO

Thank you so much, Alethia. Just to clarify, was your COVID question related specifically to geographic atrophy?

Alethia Young, Analyst

Just across the business.

Cedric Francois, CEO

As it relates to geographic atrophy, we will have to see what happens with the data this summer. Our strategy for the submission package includes every component, including safety, biological activity with two studies showing a positive primary endpoint, fellow eye analysis to confirm that biological activity, and the real effect size. It’s crucial that we assess the durability of the effect in patients over the long term. Also, of importance is the every other month dosing, which has shown statistically significant results in FILLY and OAKS with important advantages for physicians and patients alike. Regarding COVID, we believe the impact on trials has been limited in geographic atrophy. We used to talk about COVID's impact often, but it has been minimal regarding our studies. Specifically for the ALS study, we did not see any notable effects whatsoever.

Federico Grossi, Chief Medical Officer

No. Certainly, I think the majority of the impacts we’ve seen across the board in pharma relate to the initiation of new studies, and while Omicron played a role, there have been no major effects.

Alethia Young, Analyst

Thank you.

Cedric Francois, CEO

Thank you.

Operator, Operator

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

Tazeen Ahmad, Analyst

Hi. Good afternoon. Thanks for taking my question. I'm sorry, I joined this call a few minutes late. If you've answered this already, my apologies for asking again. Regarding your expectations for the time to review, is it possible that you could get a regular review period instead of an accelerated path? It seems that, in our experience monitoring other companies during COVID, the FDA has been taking longer, issuing more PDUFA extensions. Based on your recent discussions with the agency, have they provided any color on your review period?

Cedric Francois, CEO

Thank you so much, Tazeen. We have not received any indication so far that we would have a longer review time than usual. Our discussions with regulators have been positive. We cannot predict whether we will have priority review. However, we remain hopeful based on precedent and the unmet need that exists in this disease. Should there be an advisory committee, we believe feedback from physicians will be positive.

Operator, Operator

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

Yigal Nochomovitz, Analyst

Great. Thanks. Thanks for the questions. Cedric, regarding the 18-month look for DERBY and OAKS, obviously you've seen a steadily increasing separation of lesion growth curves through 12 months. Do you believe you need to see a continued separation of the lesion growth curves between pegcetacoplan and sham at the 18-month point to support approval? Or will it be sufficient for the curves to remain separated without converging at later time points?

Cedric Francois, CEO

Thank you, guys. We have not received specific feedback on that particular expectation. However, we are looking for a sustained effect over time. A continued separation would be an extraordinary outcome.

Yigal Nochomovitz, Analyst

Okay, great. Regarding the pre-NDA meeting, did the FDA mention anything about the changes in formulation that have occurred from the lyophilized form in FILLY to the pre-filled vial in DERBY and OAKS? After approval and launch, do you plan to introduce a pre-filled syringe?

Cedric Francois, CEO

Correct. The Phase 3 clinical trial used a pre-filled vial, and we will launch with that. We will likely introduce a pre-filled syringe, but that takes years of development. However, after receiving the data in September, we believed it was important to understand the regulatory view on the FILLY trial. We sent the FDA information on the three trials concurrently, explaining the similarities and differences, quality, and execution of the studies. The FDA responded clearly.

Yigal Nochomovitz, Analyst

Okay, thank you.

Cedric Francois, CEO

You're welcome.

Operator, Operator

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

Ellie Merle, Analyst

Hey, guys. Thanks so much for the question. Just a logistical clarification about the stats around the 18-month analysis. Could you remind us of those? And in discussions with the FDA, were there any additional analyses mentioned or insights derived from the fellow eye data in relation to this 18-month analysis? Is the NDA filing contingent on the data at 18 months or will it be supplementary?

Cedric Francois, CEO

Thank you. The formal analysis will occur at the 24-month time point. We will run statistics at 18 months, but they will be descriptive. We proposed to include that data to the FDA, realizing it co-aligns with our timelines and allows us to present a more complete package ultimately. This includes safety and lesion size growth.

Operator, Operator

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

Joseph Stringer, Analyst

Hi everyone, thanks for taking our questions. Could you remind us of the market opportunity with the Phase 3 trial in IC-MPGN and C3G? What do you anticipate for the competitive profile of pegcetacoplan in these indications?

Cedric Francois, CEO

Thank you, Joe. We view C3G and IC-MPGN as very important next indications for both EMPAVELI and Aspaveli. We had a robust proof-of-concept study in C3G. The market opportunity for both should likely be viewed similarly to that of PNH, which we know is unmet with currently no approved therapies. Based on our data, we believe we can achieve a best-in-class profile.

Joseph Stringer, Analyst

Great. Thanks for taking our question.

Cedric Francois, CEO

You're welcome.

Operator, Operator

Thank you. 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.

Cedric Francois, CEO

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 available later today and tomorrow. 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.

Operator, Operator

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