Q4 2021 Apellis Pharmaceuticals Inc Earnings Call

Good day, and thank you for standing by welcome to <unk> fourth quarter and full year 2021 financial results Conference call. At this time, all participants are in a listen only mode.

Operator: Good day, and thank you for standing by. Welcome to the Apellis Force Quarter and Folier 2021 Financial Results Conference call. At this time, all participants are not in listening only mode. As for the speaker's presentation, there will be a question and answer session. To ask a question during the session, you'll need to press star one on your telephone.

The speaker's presentation there'll be a question and answer session to ask a question during the stress and you'll need to press star one on your telephone. Please be advised that today's conference is being recorded if you would.

Operator: Please be advised that the day's conference is being recorded. If you require any further assistance, please press star zero. I would now like to hand the conference over to Meredith Kaya, Senior Vice President of Investor Relations, Institute of Finance. Please go ahead.

Require any further assistance. Please press star zero 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 the palace's fourth quarter and year end 2021 financial results.

Meredith Kaya: Good afternoon, and thank you for joining us to discuss Apellis's 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'd 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.

With me on the call our co founder and Chief Executive Officer, Dr. Cedric Francois Chief Commercial Officer, Adam Johnson, Chief Medical Officer, Dr. Federico Christie, and Chief Financial Officer, Jim Sullivan.

Before we begin I'd 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.

Encourage you to consult the risk factors discussed in our SEC filings for additional detail now I'll turn the call over to Patrick.

Thank you all for joining us today.

Cedric Francois: 2021 was a remarkable year for Apellis. We received our first MDA approval for Empaveli, delivered an exceptional initial launch, and reported its top-line results from our Derby and Oakes studies, positioning us to potentially receive our second FDA approval and advance our broader pipeline. Simply said, we strengthened our position as a global leader in complement. Let me start with M-PAVE.

2021 was a remarkable year for applebee's.

We received our first FDA approval for it and by that he did.

A diverse and exceptional initial launch reported topline results from our Derby and Oaks studies positioning us to potentially receive our second FDA approval and advance our broader pipeline.

Simply said, we strengthened our position as a global leader in complement.

Let me start with empathy.

Cedric Francois: In May of last year, Annabel was approved by the FDA for the treatment of adults with paroxysmal nocturnal hemoglobinuria, or PNA. In May of last year, Annabel was approved by the FDA for the treatment of adults with paroxysmal nocturnal hemoglobinuria, or PNA. 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 targeted C3 therapy to patients.

In may of last year, but then he was approved by the FDA for the treatment of adults with paroxysmal nocturnal hemoglobinuria or <unk>.

This approval marks the transition from 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 targeted Q3 therapy to patients.

Cedric Francois: And Paveri 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 partners, Soby, were also thrilled to see additional approvals over these past few months, including in the European Union. In ophthalmology, the phase three results from derby and oaks in geographic atrophy, or GA, were a critical step in our efforts to bring the first ever treatment for GA to patients.

And then he is well positioned to elevate the standard of care and I am excited by the progress we are making so far with the launch.

<unk> feedback is strong.

Patients are reporting significant improvements compliance is high and we are seeing continued positive recognition by payers.

Globally, we and our partners Sobey, we're also thrilled to see additional approvals over these past few months, including in the European Union.

In ophthalmology, the phase III results from Derby and Oaks in geographic atrophy or G. We're a critical step in our efforts to bring the first ever treatment for <unk> patients.

Unknown Executive: [inaudible] Since reporting top-line results last September, our 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 Pexi-Taco Plan represents a potential breakthrough for the five million patients globally who are living with GA, a relentless disease that is a leading cause of blindness worldwide.

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.

Final step in the run up to our submission.

More than ever we believe <unk> will plan represents a potential breakthrough for the 5 million patients globally, who are living with G. A 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 fixes that group them and our three preclinical programs.

Unknown Executive: We also made progress in advancing our broader pipeline, including our late-stage programs with systemic maxillofan and our three preclinical programs. Let me now spend a moment on our key priorities for 2022. First, as I mentioned, we are focused on bringing effects that go down to the market as the first ever therapy for patients with GA. can best be described as a forest fire raging through your retina, which is a continuous process with irreversible retinal cell death.

Let me now spend a moment on our key priorities for 2022.

Sure as I mentioned.

We are focused on bringing sexy back open to the market as the first ever therapy for patients with <unk>.

Gee can best be described as a forest fire raging through your retina, which.

Which is a continuous process with irreversible retinal cell death.

Once the cells are gone you start growing blades and there are currently no approved treatments.

Cedric Francois: Once these cells are gone, you start going blind, and there are currently no approved treatments. We believe that with Pexvita CoolPlan we have an opportunity to slow this process and preserve patients' vision for longer. We are actively preparing our NDA and our own 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 pre-submission discussions with European regulators.

We believe that with Brexit that coupon, 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 European regulators.

Cedric Francois: 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 empavedy 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. Additionally, beyond PNH, we are seeking to advance empyveli as a transformative therapy for rare, complement-driven diseases.

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 <unk> and further establish <unk> as a first line treatment.

Want to ensure that all patients with <unk>, regardless of their baseline hemoglobin levels has the potential to benefit from <unk>.

Beyond <unk>, we are seeking to advance <unk> as a transformative therapy for rare complements driven diseases.

Cedric Francois: Together with Suvi, we plan to have four late-stage programs underway this year. We plan to have four late-stage programs underway. Collectively, these opportunities could address the needs of as many as 35,000 patients per year, significantly expanding the opportunity for EmpaVeri. [inaudible] Third, we want to advance systemic fixed data co-plan as a novel approach to enabling adino-associated viruses or AAVs for gene therapy 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.

Together with <unk>, we plan to have four late stage programs underway this year.

Collectively these opportunities could address the needs of as many as 35000 patients per year significantly expanding the opportunity for <unk>.

Third we want to advance systemic fixes that group plan as a novel approach to enabling <unk> associated viruses or aav's for gene therapies by controlling the many issues that are associated with these therapies.

By targeting <unk> three 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 and.

Cedric Francois: In collaboration with our research partners, we look forward to sharing preclinical 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 APL1030, our first-in-class brain-active C3 inhibitor, in the second half of this year. We are also continuing to progress additional programs, including APL 2006 and our siRNA plus empavedi 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.

In collaboration with our research partners, we look forward to sharing preclinical data and the first health 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 and <unk>. Our first in class brain active <unk> inhibitor in the second half of this year.

We also are continuing to progress additional programs, including APL 206, and our SA RNA plus and poverty 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.

Could have two commercial products, a robust pipeline encompassing multiple late stage rare disease programs and additional preclinical programs heading into the clinic further cementing our position as a global leader in complement.

Cedric Francois: 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 complementarity. I am amazed by the extraordinary signs that have been pioneered by the team here at Edda. I am amazed by the extraordinary signs that have been pioneered by the team here at Edda. 2021 was an incredible year, and we look forward to building on our momentum in 2022. And now, I will now turn the call over to Adam for a commercial update. Adam. Thank you, Cedric.

I am amazed by the extraordinary science that has been pioneered by the team here at.

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 and per valleys commercial results in Pn H continued to be strong since our launch last may.

Adam Townsend: As Cedric mentioned, Empa Valley's commercial results in P&H continue to be strong since our launch last year. As a reminder, in the U.S., approximately 1,500 PNH patients are currently being treated with C5 inhibitors. And another 150 new cases are diagnosed each year. As expected, demand was initially generated by patients on C5 inhibitors who were highly transfusion dependent. However, we are also seeing patients with hemoglobin levels near normal that have also experienced the benefits of empevem. However, patients from this latter group can still suffer from symptoms such as jaundice and fatigue, which result in prolonged morbidity.

As a reminder, in the U S. Approximately 1500 <unk> patients are currently treated with <unk> inhibitors.

And another 150 are newly diagnosed each year.

As expected demand with initially generated by patients on <unk> inhibitors, who are highly transfusion dependent however.

However, we are also seeing patients with hemoglobin levels near normal.

<unk> also experienced the benefits of that in preventing.

Patients from this latter group can still suffer from symptoms, such as jaundice, and fatigue, which result in prolonged morbidity.

Adam Townsend: And the feedback from those on Empire Valley 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, 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 chemists, including over 125 start forms in total received since launch. We continue to see the vast majority of EMPA Valley patients come from C5 inhibitor patient switches, with over 75% of these switches coming from Altamira.

And the feedback from those on the MPA Valley has been very positive.

With a clinical profile demonstrating superiority in raising hemoglobin levels as compared to <unk> inhibition and in line with our key priorities for 2022, we aim to further establish <unk> 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 thoughtful in total received since launch.

We continue to see the vast majority of <unk> patients start coming from C. Five inhibitor patient switches.

With over 75% of the switches coming from Altamira.

We also hit our 2021 goal of having 90% of our top partners placed <unk> in a positive formulary position.

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

As we've described we initially focused on the top 20 payers covering approximately 85% of all U S <unk> prescriptions.

Several large payers have placed Emperor valley has exclusive for all treatment naive patients or as the preferred agent for <unk> as we continue to secure broader payer coverage overtime, we expect gross to net levels to net out in the low to mid teen percentage range consists.

Adam Townsend: As we continue to secure broader payer coverage over time, we expect growth-to-net levels to net out in the low-to-mid teens percent range, consistent with other rare disease drugs. And lastly, we are seeing high patient compliance rates, which is a testament to the benefits of empovaline 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.

With other rare disease drugs.

And lastly, we are seeing high patient compliance rate.

Which is a testament to the benefits of them per value and how much better patient steel when that disease is well controlled.

We do anticipate that this will come down slightly over time with these initial compliance levels are very encouraging.

We are optimistic about the continued momentum in 2022 and beyond.

Adam Townsend: 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 are still very much in the early stages of the launch as we continue to educate physicians.

Additional payer coverage and hopefully benefit more and more patients.

Like many other pharma companies in passenger engagement slowed in January due to the spread of the omicron variance.

Adam Townsend: We continue to utilize a variety of digital technologies to continue to reach HCPs virtually. 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 being up-to-date.

We continue to utilize a variety of digital technology to continue to reach Hcp's virtually.

But there is a strong correlation between in person interactions and uptake we.

Adam Townsend: We expect this impact to be brief and that we will maintain our strong growth trajectory over the course of this year. Canning to our global U-Launch activities are also progressing with our partners, so. As a reminder, EU approval was received in December 2021 under the brand name Asperger, and Sobey's initial commercial launch in ex-U.S. markets is expected this quarter.

We expect this impact will be brief and then 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 partner <unk>. As a reminder, new approval was received in December 2021 under the brand name hospitality and so these initial commercial launch in ex U S markets is expected this.

Water.

Adam Townsend: We were also pleased to see additional approvals in Australia and Saudi Arabia, key milestones in our collective goal of bringing Empire Valley to patients around the world. 2022 is also going to be a pivotal year for Pexeta-Coplin 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. Market research and general feedback from retina specialists continue to reinforce our belief in Pegstetter-Coplan's blockbuster potential.

We were also pleased to see additional approvals in Australia, and Saudi Arabia key.

Key milestones in our collective goal of bringing in totality to patients around the world.

2022 is also going to be a pivotal year for <unk>.

And a potential game changer for many of the 5 million patients suffering from Gi globally.

With the NDA submission on track our commercial team is preparing to launch what would be the first ever therapy for <unk>.

Near term initiatives prior to approval, we'll focus on disease state education, as well as Kols and payer engagement activities.

Market research and general feedback from retina specialists continue to reinforce our belief in <unk> blockbuster potential.

Federico Grossi: This feedback supports the huge unmet need in GA and the paradigm shift that Pegstetter-Coughlin could drive. 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?

This feedback supports the huge unmet need in Gi and the paradigm shift that <unk> could drive for patients.

We look forward to providing more detail on our commercial plan as we prepare for a potential launch.

I will now turn the call over to <unk> to review our clinical development.

Bye bye.

Thank you Adam.

Federico Grossi: Thank you, Adam. Our 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 1,500 patients across three trials. Derby, Oaks, and Phil.

A top priority for our police is our NDA submission for <unk> and we are on pace to submit the NDA in the second quarter.

We believe we have a robust data package with data from 2500 patients across three trials Darby Oaks and feeling well.

Federico Grossi: We were pleased to receive feedback from the FDA last fall stating that they do not make distinctions between faiths, provided the clinical trial is adequate and well-controlled and that all three trials appear to be adequate and well-controlled. The totality of the data package underscores the potential effects of the couplant in this indication. We think about the approval process in terms of three important components: biological activity, treatment effect, and safety. First, biological act. In all three trials, the couple slows the retinal cell death that typically occurs in GA. In all three trials, the couple slows the retinal cell death that typically occurs in GA. This was shown by the rate of reduction in J lesion growth that was observed in the primary end.

We were pleased to receive feedback from the FDA last fall, stating that they do not make distinction between faces provided a clinical trial is adequate and one control.

And that all three trials appear to be adequate and well control.

The totality of the data package and the scores the potential effects of the compound in this indication.

We think about the approval process in three important components.

Logical activity treatment effect and safety.

First biological activity.

In all three trials et cetera, Copeland slowed the retinal cell death that typically of course in <unk>.

These was shown by the rate of reduction in J lithium growth that was observed in the primary endpoint.

Federico Grossi: This effect was then confirmed in the fellow analysis, assessing the rate of reduction in patients who have bilateral GA. Second, she's a man. The magnitude of the 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, shows a clinically meaningful treatment effect. And lastly, safety. Derby & Oaks demonstrated a favorable safety profile.

This effect was confirmed in the fellow eye analysis assessing the rate of reduction in patients who have bilateral.

Second treat them in 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 <unk> across the patient population.

This analysis helps to minimize the variability and again in all three trials showing a clinically meaningful treatment effect.

Lastly safety.

Derby and Oaks demonstrated a favorable safety profile.

Federico Grossi: Building on the safety profile that was observed, there does seem to be some confusion around how accusations were reported in our studies, and we want to take the opportunity to clear this up. The same criteria for reporting exudations were used across Philly, Derby, and Knox.

Building on the safety profile that was observed to increase.

Does that seem to be some confusion around how activations were reported in our studies and we want to take this opportunity to clear this up the.

At the same criteria for reporting explanations were used at clubs freely Derby unlocks.

As <unk> mentioned the NDA will also include 18 months data from Derby unlocks, including the rate of rate action NGA lesion growth extended out into <unk>.

Federico Grossi: As Cedric mentioned, the NDA will also include 18-month data from Derby and Oakes, 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 is granted without allowance for a six-month review cycle. This could set the stage for a potential approval by the end of this year.

And the overall safety profile.

Given the need in this indication we plan to request priority review would you granted will allow for a six month review cycle.

This will 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.

Federico Grossi: 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 Empawele, I would like to briefly comment on our efforts in Intermediate M. We had a productive discussion with the FDA. Based on their feedback on expected endpoints, we believe that pivotal studies in intermediate MD should be sizable and lengthy, which would require significant investment. As a result, we have deprioritized the development of this program for now and will reevaluate it over time.

Quickly as possible.

Before I move to end poverty I would like to briefly comment on our efforts in intermediate AMD.

We had a productive discussion with FDA.

Based on the feedback unexpected endpoints, we believe that pivotal studies in intermediate AMD to be sizeable.

Thanks.

Which would require significant investments.

As a result, we have de prioritized the development of this program for now and we'll reevaluate overtime.

Federico Grossi: This does not minimize our view of the unmet need in this disease or the benefits of Bexetacoplam as a potential treatment. Another key objective for 2022 is delivering on the broad platform potential of Empaveli to advance our word that this is fine. To that end, our development strategy includes four late-stage studies in multiple complement-driven diseases. For our ongoing LS study, we continue to expect to complete involvement in the first half of 2020.

This does not minimize our view of the unmet need in decent fees or the beneficial effects of the compound as a potential treatments.

Another key objective for 2022 is delivering in the broad platform potential of bubbly to advance or where do you see sponges.

And our development strategy includes four late stage studies in multiple complement driven diseases.

For our ongoing <unk> study, we continue to expect to complete enrollment in the first half of 'twenty two.

Federico Grossi: Additionally, our partner, Savi, commented in the recent earnings report that they dosed the first patient in the Phase 2 study of hematopoietic stem cell transplantation associated thrombotic microangiopathy, or HSCTDMA, and that they expect to initiate the Phase III study of cholaglutinin 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 of immune-complex membranoproliferative glomerulonephritis, or ICMPGN, and C3 glomerulopathy, or C3GP. We look forward to sharing our progress on this program. Let me now turn the call over to Tim for a review of the financials. Tim?

Additionally, our partner <unk> commented in the recent earnings report that they dosed the first patient in the phase III study.

Nobody stem cell transplantation associated thrombotic, microangiopathy or Hs CET DMA.

And that they expect to initiate the phase III study in cold agglutinin disease or in.

In the first half of this year.

We're also actively screening patients in anticipation of boasting our first patient in the phase III study in immune complex Mcdonough project for glomerulonephritis, or IC, and PGM and see particular neuropathy or CPG.

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 theme.

Thank you for that.

Tim Sullivan: 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 Empa Valley net product revenue in the U.S., a strong start for the franchise.

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 and <unk> net product revenue in the U S. A strong start for the franchise.

Tim Sullivan: We also recorded a $50 million milestone payment from SOVI in connection with the first regulatory approval and reimbursement approval in Europe. [inaudible] 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 Beam Collaborate.

We also recorded a $50 million milestone payment from stoping 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 is 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 received 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 collaborations that we view as likely to occur in the coming months.

Tim Sullivan: 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... GNA 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.

G&A expenses were $177 million and we reported a net loss of $746 million for the year.

As of December 31, 2021, appellate had approximately 700 million in cash cash equivalents and short term marketable securities.

Tim Sullivan: 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 Impevelli, a robust pipeline, and a 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.

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 and <unk>, a robust pipeline and the potential upcoming blockbuster in Georgia, we are confident in the palaces financial future.

I will now turn the call back over to Cedric for closing remarks Cedric.

Thank you Tim.

Cedric Francois: 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 mouse.

We have made excellent progress and look forward to an exciting 2022.

Let me close with a brief recap of our upcoming milestones.

Cedric Francois: In the first quarter, we plan to start our pre-submission discussions with European regulators for GA. And for Aspa Vetti, we expect the initial XUSPNH launches by our partners, Sophie. [inaudible] In the second quarter, we plan to submit our MDN geographic atrophy application 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.

In the first quarter, we are starting our pre submission discussions with European regulators for GE.

And for <unk>, we expect the initial X USP niche launches by our partners Shogun.

In the second quarter, we plan to submit our NDA in geographic atrophy to the U S FDA and.

And to publish our preclinical data on AAV administered with <unk> inhibition.

Over the course of the first health, we expect to complete the enrollment in our phase II study in AOS.

Cedric Francois: Initiate the Phase 3 Study in ICMPGN and C3G, and SOVI plans to initiate the Phase 3 Study in CAD. The Phase 3 Study in ICMPGN and C3G, In the third quarter, we plan to report the 24-month Derby and Oaks update, and in the fourth quarter, should we receive prior to review, we expect to have an approval decision for G.A. and the U.S.

Initiate the phase III study and ICM PGN <unk> <unk> and.

And so the plan is to initiate the phase III study in CAD.

In the third quarter, we plan to report 24 months there'll be an update.

In the fourth quarter should we receive priority review, we expect to have an approval decision for <unk> in the U S.

Cedric Francois: 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. Operator.

In the second half of this year, we also expect.

Submission in the European Union for <unk> and submit our AMD Aplp's 10 30.

We look forward to updating you on these efforts that is now open the call for questions operator.

Operator: Thank you. As a reminder, to ask a question, you'll need to press star 1 on your telephone. To withdraw your question, please press the pound key.

Thank you as a reminder to ask a question you will need to press star one on your telephone to withdraw your question. Please press the pound key.

Operator: Please stand by while we compile the Q&A roster. Our first question comes from Nadu Kumar with Goldman Sachs. Your line is open.

These standby, while we compile the Q&A roster.

First question comes from Madhu Kumar.

Kumar with Goldman Sachs. Your line is open.

Yes, thanks for taking our questions everybody. So let's start with CA. So I guess kind of how are you thinking about.

Cedric Francois: Yeah, thanks for taking our questions, everybody. So let's start with CAD. So I guess kind of what you are thinking about a pivotal trial design with your collaborators, given the recent approval of the Sanity Drugs at Timor Mab in the game. Thank you so much, Madhu, for that question. So SOBE has been working hard in collaboration with us to prepare for this trial in cold agglutinin disease. Shetimdimab, as you know, is a drug that is given intravenously every two weeks.

Pivotal trial design with your collaborators sobey given the recent approval of the S&P drugs to Timolol mab into condition.

Thank you so much for that question, so <unk> been working hard in collaboration with us.

To predict prepared for this round in cold agglutinin disease.

Jimmy them up as you know is a drug that is given intravenously every two weeks. So there is an important I think advantage to treating to self administering the drug at home twice per week.

Cedric Francois: So there's an important 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's 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, you know, right now, it is a trial that will kind of follow the conventional registration endpoints in cold agglutinin disease, and we're not yet sure when it will read out. Okay, I'm moving over to GA.

We have always said from an efficacy perspective, we will have to see if there should be the benefits to be gained but it is really the convenience of at home dosing.

That trial is going to start in the very near future.

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

Okay.

Cedric Francois: So you guys have announced that you're going to have 18 months of 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? Yeah, thank you, Madhu. So in September, when we, after the primary endpoint readout, when we engaged in our discussions with the regulators, proposed to include data beyond 12 months on the lesion size growth, you know, to really get a full sense of what the effect size of the drug would be over time.

It'll really GAA. So you guys have announced you guys are going to have 18 month data in March and Youre going to use that as part of the filing package how much of that data because you kind of.

Already in hand, and like what are they kind of considerations people should have when thinking about that data relative to the results put out in September of last year.

Yeah. Thank you Matt So in September when we 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 success of the drug would be overtime.

Cedric Francois: 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 on safety, 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 empathy belly launch. So when I kind of come back to Adam's side about patients who are coming on to empathy belly 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 are you mentioned to have other kind of complications at PNH, so it would switch over on that the belly is compared to the acoustic therapy.

And we agreed to include since it would not affect our timeline for submission. We agreed to include all of the data available up to 18 months, both on efficacy as well as on safety and 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 MPA Valley launch when I kind of come back to Adams at about patients who are coming on Dan to valley. Despite having normal hemoglobin, how should we think about the kind of distribution of those patients and where you think there is a longer term opportunity for those patients who don't have sales.

Low hemoglobin levels that you mentioned could have other kind of complications of PMA that would switch over on that the valley as compared to the existing therapies.

Cedric Francois: So patients with normal hemoglobin levels represent, on average, 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 for 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, a very large amount of red blood cells, but these red blood cells also, you know, in an unusual way, die in this process of extravascular hemorrhage.

Yes, so patients with normal hemoglobin levels.

On average represent approximately a third of the patients who are on treatment with <unk> inhibitors, but I think the really important point about what we what.

What we aim to achieve in PNM 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 ph patients with normal hemoglobin levels <unk> gets to those normal hemoglobin levels, because they have very good bone marrow and produce.

Typically very large amounts of red blood cells, but these red blood cells also in an unusual way die in this process of extravascular hemolysis.

Cedric Francois: That can lead to John Biss, where patients, you know, you know, have an ashy appearance. It leads to reticulocyte forces where a maximum amount of blood cells have to be made in the bone marrow. And in short, this disease is not well controlled more broadly when exofascler hemosis is not addressed. Adam, I don't know if he wants to add something to that. Yeah, well said,

That can lead to John this revisions.

You don't have an ash in appearance.

It leads to reticulocyte to assist where maximum on the red blood cell has to be made in the bone marrow and to ensure this disease is not well controlled some more broadly.

When extra vascular hemolysis is not addressed.

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

Yes, <unk>, so yes, we're seeing a much wider.

Adam Townsend: So, yeah, we're seeing a much wider use of EmpaVeli than we expected as we get 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 positive results in those patients. We're also hearing from treatment-naive patients that are starting on EmpaVeli too.

As we expected.

We're getting through the stages of double a trial. So we expect it to have the hardest to treat patients who are heavily dependent on transfusions now we're seeing those with higher hemoglobin levels hemoglobin levels around 10 for example, and we're seeing really I'm hearing really positive results. If those patients were also hearing treatment naive patients.

Starting on empathy too so.

Adam Townsend: So it's 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's 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.

We should be in this phase of the whole drive the hardest to treat patients physicians are quite experienced that now they are broadening broadening their experience to a wider population. So the team's working incredibly hard to remind people that this is.

<unk> products and we believe we can truly elevate the standards of care and we're seeing that transition within the market.

Okay, great. Thank you very much.

Thank you Madam thank you.

Operator: Our next question comes from John 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 MBA, and has the agency made any specific request on that front or any specific guidance on that?

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

Federico Grossi: I think we all expect the imaging data to be front and center as the primary endpoint, but what's the role of functional data from a doctor's perspective in your market research and outreach versus imaging alone when they talk about drivers of description? Yeah, I think so. Thank you so much, John. 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. And if you lose photoreceptor cells, you lose vision.

Thanks for taking my question guys.

I guess, while we're on the subject of longer term data for G E.

Functional data should we expect you included the NDA and has the agency made any specific request.

That front or is there any specific guidance on that I think we all expect the imaging data to be front and center was the primary endpoint, but what's the role of functional data from a doctor perspective in your market research and outreach versus imaging alone when.

They talk about drivers of prescribing.

Thank you so much John so the formal analysis on the functional endpoints will happened at 24 months the way it has always been planned.

And then the way physicians look at it I think most retina docs understands very well that's a reduction in the growth rate of geographic atrophy as measured by ultra fluorescence is.

Reflective of a loss of photoreceptor cells Redstone, if you lose photoreceptor cells you lose vision. So that is also the clear connection read between living cells and being able to see is also the really key reason why the FDA.

Federico Grossi: So that is also that clear connection between living cells 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 three studies start yet. I think we were expecting some of them in Q4.

Found this endpoint to be acceptable as the primary endpoint of course.

Federico Grossi: So how should we think about timelines for the, well, really the bulk of the phase three 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? Yeah, thank you so much for the question. Yeah, so, I think, reflective of the broader industry, getting studies started these days can take a little bit longer than expected.

Those up and running and what are your expectations for read that Sir.

Yeah. Thank you so I'm sure that a question yeah. So it's you know I think reflect this also can be brought her industry get it getting studies started these days I can take a little bit longer than expected. We also of course have to coordinate with our partner sobey, but we're very happy with the designs that came together and with the regulatory feedback that led to those design.

Federico Grossi: We also, of course, have to coordinate with our partners, so 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 an environment in the very near future.

And you should generally expect all three of these new trials to start in the first half of this year many of them now <unk> and is there in your future.

Okay. Thank you very much and as we think about P. N H one should I guess the last one I know you guys told us that you expect <unk> to even out to the low to mid teens sort of standard levels, there, but but at this point given that your commercial patient mix has been read.

Federico Grossi: Okay, thanks very much. And as we think about the PNH launch, I guess, last one. I know you guys told us what you expected before the rest of your commercial transition. Thank you, John. I will hand that over to Adam and Tim. Yes, John, for the question. Yeah, so we still have some work to do with some payers.

Gonna be good and launch what's the your explanation for the remainder of the trend there how much longer until we hit equilibrium on gross to night and what's the what are we waiting for on the rest of your commercial transition.

Thank you John I will send that over to Adam <unk>.

Yeah. Thanks child to the question yet so we we still have some what to do with some pay as we had.

Adam Townsend: We had a great start to our launch last year and hit all of our targets with payers. So now we have some more targets with payers that we're executing in this phase of the launch. So as we start to continue to try and get as good an access as is possible with all of the payers that cover PNH lives, that will potentially have an impact on growth. Okay, thanks. Thank you. The next question comes from Anupam Rama. Your line is now open with J.P. Morgan. Hey guys,

<unk> to to a launch last year and he had one of our pockets with past. So now we have some more targets with past that we're executing in this phase of the launch so as we stopped to continue to try and get as good a access as as possible with all of the past cover P. Initialize that will have potentially an impact sound great Tonight.

Oh, okay. Thanks.

Thank you. Our next question comes from on a Palm Ramos. Your line is now open with J P. Morgan.

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

Operator: 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.

Thank you so much and yes, we do not have planned to create an amendment to include the 24 months data. It will of course be available to us around that period in time, but do you believe that we have everything available and you have the agrees to do our submission in the second quarter restaurant.

Thanks, so much.

Federico Grossi: Thanks so much. Thank you so much, Anupam. Yes, we do not have plans to create an amendment to include the 24-month data.

You're welcome.

Federico Grossi: It will, of course, be available to us around that period in time, but we believe that we have everything available, and the FDA agrees to make our submission in the second quarter as well. Thanks so much. Thank you. Our next question comes from Lila Youssef with Cowen. Your line is now open. Hi, this is Milo on behalf of Phil.

Thank you and next question comes from Lila You said with Cowen. Your line is now open.

Hi, This is Tyler okay, well. Thank you for taking my question maybe mm mm mm.

Adam Townsend: Thank you for taking the question. This may be on specific targets for potential commercial prep in GA – 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, Laila. So yeah, I'm very happy with the progress on hiring towards the GA launch.

<unk> commercial Pat <unk> tomato talk a little bit about the pockets of the call I'll go punch that sounds forced Montana junior Kevin and sugar Alrighty counselling, how can I keep assistance at the time you can't attacking thank you.

Thank you that I will and then went over to Adam as well.

Adam Townsend: So we've hired all of the leadership positions in medical affairs, sales, marketing, and market access within the US and also leadership positions outside of the US in our EU office in Zuckerberg. We've also set up affiliates in Germany and Australia as well.

Yep. Thank you I that so yeah, I'm very happy with the progress for hiring uhm towards the G. Eight or so we've had ordered 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 and he was in Switzerland with also.

Set up uhm affiliates in Germany, and Australia as well. So we are progressing really well we've identified the size of the scale of the sales force you know a good benchmark for everyone is the way M. D products. So we've used them regularly to make sure that we've got the right level of approach for when we potential.

Adam Townsend: So we're progressing really well. We've identified the size and the scale of the sales force. You know, a good benchmark for everyone is the WETMD products.

Adam Townsend: 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 wet AMD administration, but you can see, right, it's not a huge build.

She comes to the market and we're probably going to target in the U S. About 3000 read the physicians are much smaller subset of that is due the majority of the white a empty administration. So but you can see right. It's not a huge build it's well within the palaces capabilities. So we are ready to go and will be very thoughtful as we stopped.

Adam Townsend: It's well within Apellis' capability, 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.

To expand and hire the sales force, we're very excited to progressed with that.

Alright, well thank you.

<unk>.

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

Our next question comes from Stephen Seedhouse with Raymond James Your line is open.

Hi, Thanks for taking the question. Sir can you mentioned just in response to an earlier question about including whatever data is available beyond 18 months as well as just hoping you could clarify what you meant there. If you were just speaking about we can grow theater or something else.

Cedric Francois: Hi, thanks for taking the question. Cedric, you mentioned in response to an earlier question about including whatever data is available beyond 18 months as well. I was just hoping 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 it I'm talking about <unk> vision grew up data correct.

Cedric Francois: Okay, and if the FDA, in your dialogue with them about this 18-month analysis, is interested in the slope of the data or just a point estimate at 18 months. [inaudible] The FDA is interested in the totality of the data, right? So we've had discussions with them around the MRM 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 in its evaluation.

Okay and is the F D. A in your your dialogue with them about this 18 month analysis interested in the slope of the data or just a point estimate at 18 months.

Do you have to be as interested in the totality of the day that right. So we set discussions with them around the M. A R. I'm transferring data around slopes around fellow I analysis, I mean, all of these things we'd leave a relative but I think this is a division that takes all of the data into account and its evaluation.

Oh, Okay, and and maybe two just real quick last ones are I guess, the second one might not be so quick but your current view in your dialogue with the F. D. A of an AD com Ah no <unk> previously you'd said he did not expect one but I'm just curious about your updated Ya and then the fellow I analysis or you just mentioned, there's there's plenty of debate.

Cedric Francois: 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 about an ADCOM, I know previously you had said you did 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 the fellow eye comparison and why it may be valid. Supportive efficacy assessment. Could you just expand on that? Thanks so much. Yeah, thanks so much, Steve. So the outcome, of course, is not our decision, right?

In the investment community about this analysis. So it seems like you've had dialogue with the F. D. A about a fellow I comparison in N Y. It may be valid supportive efficacy assessment could you just expand on that thanks, so much.

Cedric Francois: We will be ready to have one, and we will see what the 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 Philly, Derby, and Oakes are the sham control groups, right, where you clearly see how, and this was well described in the past by investigators like Janet Sennons, 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.

Yeah. Thank you so much do so you have come of course. This is not our decision right. We will be ready to have one and you know we will see what the what the F. D. A decides to do on the fell away analysis as I mentioned that is something that is we believe very important and confirmatory of the biological activity for the drink.

There's something that we have discussed with the F. D. A and you know I would say that's what stands probably the most in Philly Derby and <unk> are the same control groups right, where you can only see how and this was well described in the past by investigators like tended centers for the study I entreated fell away progress and virtually I.

Identical <unk> with if anything a little bit of a faster progression typically in the study I, which is the worst seeing that so I think it's it's a really impressive control and and all three studies, we see a consistent dose response effect you know.

Cedric Francois: So I think it's a really impressive control, and in all three studies, we see a consistent dose response effect, you know, compared to the fellow eye, as opposed to December. Thanks for taking the questions. Thank you. Our next question comes from Colleen Kusy with Naird. 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 arm?

Compared to the satellite.

As opposed to dish out control.

Thanks for taking the questions.

You're welcome thank you.

Our next question comes from calling Cussing with Ne'er do Y'all 97.

Hi, good afternoon. Thanks, Thanks for taking my questions.

So <unk> have you gotten any feedback from regulators or do you have any thoughts on how regulators may evaluate the every other month for our system on pregnancy arms.

So our our plan to submit a clean as the the complete did that package for Muncie as well as for every couple months. So you know that has been discussed and that is what will be part of the package.

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

Okay, great. Thank you and then the following up on T N H.

Federico Grossi: And then, so, following up on PNH, you're quite impressive that you've been able to get even exclusive reimbursement for ampivelli 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? Thank you for that question. Adam, would you like to comment?

<unk> quite impressed that you've been able to get you an exclusive reimbursement for at the valley versus the five inhibitors iced tea do you see that continuing to grow still or how do you think about the the favorable reimbursement that you've been able to get in P. N H.

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

Adam Townsend: Yeah, sure. Thanks, Colleen. So, yeah, I'm actually very proud of the team.

Sure. Thanks, Colleen so yeah, I'm actually very proud of the team. Some some some great work with all of the pay is it does help that we have some great day. So that you know we can talk to the pass about particularly around transfusions and hemoglobin etcetera.

We've we've managed to have some radio a robust scientific conversation.

To a very positive positions with with many many past we want to continue to have those discussions in the next couple of months with and make sure that you know every patient that wants to get access to anybody can get access to it.

Adam Townsend: We've done some great work with all of the payers. It does help that we have some great data that, you know, we can talk to the payers about, particularly around transfusions and hemoglobin, et cetera, so we've managed to have some really robust scientific conversations that have got us into a very positive position with many, many payers. We want to continue to have those discussions over the next couple of months and make sure that, you know, every patient that wants to get access to EmpaVeli can get access to it. And so that's our plan as we go on. So, yeah, the team's done a great job. We're not over yet.

And so that's our plan as we continue so yeah. He's done a great job with no. We get we wanted to continue said to keep pushing.

Great. Thank you so much for anything else I think.

Adam Townsend: We want to continue to keep pushing. Great. Thank you so much for taking the time. Thank you. Thank you. Our next question comes from Alicia Young with Canter Fitzgerald. Your line is open. Hi, good afternoon, and thank you for taking our questions. This is Nenon for Aletheia. Maybe two from us.

Thank you and next question comes from Unleashing again with Cantor Fitzgerald Your 97.

Hi, good afternoon, and thank you for taking your questions. This is Jean on Friday, Yeah, maybe two from us.

Operator: For GA, we know that PEG is ahead in clinical development, but how are you guys seeing the competitive landscape shaping up in GA if some of the competitors have positive data? And second, just if you could share if there's been any ongoing COVID impacts across the business. Thank you so much, Adithya. And so just for the COVID question, was that related to geography... just across the business overall? Well, first of all, as it relates to geographic atrophy, of course, we will have to see what happens with the data this summer.

Oh for G. A vanilla that tech is ahead in clinical development, but how are you guys seen the complaint and landscape keeping us S. A G. A N G a estimate the competitiveness.

Pasadena and the second chest that you could share if there's been any I'm going to call the impacts coffee business. Thanks.

Thank you so much <unk> just for the code with question was that related to geographic ketchup.

Just across the business across it okay.

Well, so first of all with the as it relates to geographic ketchup fee of course, we will have to see what happens with data. This summer just a quick reminder, across the bedroom, 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.

Operator: Just a quick reminder, against that backdrop, of 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.

The safety, which was better than I think most people expected.

Cedric Francois: Number two, there is the biological activity, with two studies having shown positive primary endpoints of the three, and fellow eye analysis to confirm that biological activity. The third piece is, then, what is the real effect size? Because across these three studies, at least at one year, we see between 12% and 29%. The reason why these results can be divergent is that the baseline characteristics of these patients can be very different and cannot be controlled for in these studies because there are too many.

Number two there is a biological activity with two studies, having shown that's almost as primary endpoints under the tree.

And the fellow I analysis to confirm that's that's biological activity.

The third piece is then what is the real effects because across the street studies at least that one year receive between 12 and 29%.

And the reason why these results can be divergent is because of the baseline characteristics of these stations can be very different and cannot be controls for any studies course neighborhood too many.

So what you can just ask for it to do an analysis, where you model. These baseline differences between active in church groups and where do you see P. Respect that is north of 20 per cent and then the last piece will be you know again, what will that effect looked like beyond 12 months is that this is your busy effect impatience what does this mean <unk>.

Cedric Francois: So what you can do is afterwards do an analysis where you model these baseline differences between active and sham groups and where you see a clear effect that is north of 20%. And then the last piece will be, you know, again, what will that effect look like beyond 12 months? You know, is this a durability effect in patients?

Cedric Francois: 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 Philly as well as in Oakes, 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 those patients that typically present for the first time with extra foveal lesions. Being able to dose every two months instead of monthly is a very important advantage.

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 results both in Philly as well as into <unk> has been something that we believe is a really important advantage for physicians and for patients, especially ambitions that.

Early on in the disease and to those patients that typically present for the first time with extra 40 allegiance being able to dose every two months instead of monkey isn't very important advantage. So that says it relates to geographic atrophy as it relates to cool fifth.

Cedric Francois: So that's as it relates to geographic atrophy, as it relates to COVID. So, you know, the impact of the trials has been limited in geographic accuracy. 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 of studies that we have ongoing, the only one, of course, in this case, that is really important is the ALS study.

You know the impact of <unk> on the trial has been limited and geographic atrophied, we <unk>, we used to speak about that a lot tried but we believe that the impact on the studies has been minimal as it relates to the additional Registrational studies that we have ongoing you only one of course in this case that is really important is the air This study and there.

Cedric Francois: 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 about COVID's impact on clinical trials. No, I think you got it right. Most of the impacts that we have seen as, you know, across the board in pharma are on the initiations of new studies that Omicron plays a bit of a role in there. But other than that, you know; no major effects of COVID, I would say.

We have not really seen an impact either so fit that equal I don't know if she would like to add something to that for the Covid in fact I'm clinical trials.

And also I think you're gonna write most of the input that we have seen.

Of course, the board and pharma.

The initiations of new studies, and <unk>, sorry, a bit of a room.

<unk> in there, but other than that you know no major in fact of course, you know what I'm, saying.

Thank you.

Thank you Sir thank you.

Federico Grossi: Thank you. Thank you so much. Thank you. Our next question comes from Tazeen Ahmad with Bank of America. Your line is open. Hi. Good afternoon.

And next question comes from <unk> on mine with Bank of America, Your line or something.

Hi, good afternoon. Thanks for taking my question and I'm, sorry, I didn't join this call a few minutes late so you've already answered this I'm sorry for asking it a second time, but just in terms of your expectations for the time Kerry yeah.

Operator: 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, and is it possible that you could get a regular review period, not an accelerated path, just because it does seem, in our experiences monitoring other companies during COVID, at least, it seems like FDA is taking a little bit longer. They are issuing more, you know, PDUFA extensions, for example.

Is it possible that you could get a regular review period, not an accelerated path just because it does seem that on our experiences monitoring other companies during cold that at least it seems like F. D. A uhm is taking a little bit longer they are issuing more Pat in L. M could you pay attention for example.

<unk> help you know based on your most recent discussion with the agency have they provided any color on your review period, what that would be and uhm. If you do expect an AD Tom do you think that one could happen.

Cedric Francois: So, you know, 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 ad comm, do you think that one could happen, you know, if you got a more, a shorter review period, a priority review? Thanks. Thank you so much, Tazeen. So far, we have not received any indication so far that, you know, we would have a longer review time than usual. And our discussions with regulators have all been positive. We, of course, cannot predict whether we will have a priority review.

If you you know got a more shorter with your period of priority right yeah. Thanks.

Thank you so much doesn't even so we have not received any indications. So far that you know we would have a longer review time than usual so our discussions with the regular theater steps have all been positive you of course cannot predict whether we will have play right to review you know we have we are hopeful that we.

Cedric Francois: You know, we are hopeful that we will, based on precedent and on the unmet need that exists in this disease, of course. And then as it relates to the outcome, it kind of really goes back to the first question as well, where we will have to see what comes out of the acceptance. But, you know, we are optimistic that, you know, we will receive priority review and that, should there be an outcome, the feedback from positions will be positive.

Will based on precedent and based on the unmet needs that exist and this disease of course, and then as it relates to the <unk> you know, it's kind of really goes back to the first question is well aware, we will have to see what what comes out of the the acceptance, but you know we are optimistic that you know.

Cedric Francois: We will receive priority review and, should there be an outcome, the feedback from positions will be positive. Okay, thank you. You're welcome. Thank you. Our next question comes from Yigal Nochomovitz with Citibank. Your line is open.

We will receive priority review and that should there be an <unk>. That's a feedback from physicians will be positive.

Okay. Thank you.

You're welcome thank you.

Our next question comes from <unk> not to move six with city.

Your line is open.

Operator: Great. Thanks. Thanks for the questions. Cedric, regarding the 18-month look for Derby and Oaks, obviously, you've seen a very appreciable and steadily increasing separation of the lesion growth curves through 12 months, almost like a wedge growing between Pegceta, Copeland, and the sham.

Alright, great. Thanks, Thanks for the questions Uhm Cedric regarding the 18 months 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 Texas at a coke My name's Sham. So my question is do you believe you need to see.

Cedric Francois: So my question is, do you believe you need to see a continuing separation of the lesion growth curves between Pegceta, Copeland, and sham at the 18-month point to support approval, or as long as the curves stay separated and don't converge at the later time points, that will be sufficient for a favorable efficacy claim? Thank you, Yigal. 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.

A a continuing separation of the lesion growth curves between fix it is put Copeland Sam at the 18 months point to support approval or as long as the curve stay separated and don't converge at the later time points that will be sufficient for a favorable efficacy Clinton.

Thank you you go so we have not received specific feedback on that particular expectation that you're talking about but we are looking for a continued effect 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 N D. A meeting I'm just wondering just the F. D. A weighed in at all regarding some of the changes in formulation that have occurred with fix it a co plant over the years are you from the white authorized form in Philly to the pre filled file Derby and helps where you had a slight excipient.

Cedric Francois: 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 Thixotocoplan over the years, i.e., from the lyophilized form in Philly to the prefilled vial in Derby and Oaks, where you had a slight excipient change, and then, finally, I believe after approval and launch, you will introduce a prefilled syringe. So just to be clear, what we did in the phase three clinical trial was a pre-filled vial, and we will also launch with a pre-filled vial in the future. We will, in all likelihood, introduce a pre-filled syringe, but that takes several years of development.

Change and then finally I believe after approval and launch you will introduce a prefilled syringe.

Correct, so just to be clear it it's what we did in the phase three clinical trial was it a prefilled style and we will also launch with a pre filled style in the future. You know we will in all likelihood introduce a prefilled syringe, but that takes several years with the government, but you.

Cedric Francois: But you know, the key thing here is, Yigal, this was not a pre-NDA meeting, but immediately after we had the data in September, we thought it was important to understand the regulatory view on the Philly trial. And what we did was we sent the three trials in parallel to the FDA, explaining what the similarities and the differences were, what the quality of the studies was, how they were run, et cetera, with a specific question: what the regulatory view was on the trials.

You know the the key thing here. If you go this was not the pre N D. A meeting that's immediately after we had the data in September we thought it was important to understand the regulatory review on the city trial.

Cedric Francois: And the answer that we received from the FDA was described in the second paragraph of the press release that we released early in November at the American Academy of Ophthalmology meeting. Thank you. You're welcome. Thank you. Our next question comes from Ellie Merle with UBS. Your line is open.

And what we did is we sent to the F D. A.

The three trials in parallel extending what's the similarities and the differences were what the quality of the studies was how they were run etc. With a specific question what the regulatory few us on the trials and.

And the answer that we received from the F. D. A once described in the second paragraph of the press release that re released early on in November at the time of the American Academy of Ophthalmology.

Okay.

Thank you.

You're welcome thank you.

The next question comes from early marrow with E. B S online is Hanson.

Operator: Hey, guys, thanks so much for the question. Just a logistical clarification question, 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, you know, things that may be learning from, say, the fellow eye data, say, in terms of this 18-month analysis? And then also, just a clarification question, I guess: is the NDA filing contingent on the data seen at 18 months, or is this sort of just, you know, additional color and data that could potentially get on the label?

[noise] Hey, guys. Thanks, so much for the question just kind of like logistical clarification question just in terms of the stops around the 18 month analysis could you just remind us at the end I got in the discussions like the F. T. A any discussion around any additional analyses at 18 months or any kind of you know things that may be learning from say the.

Yeah.

Hello, I data same concept, that's 18 months in office and then just also I just a clarification question I guess is that N D. A filing contingent on the date is seen at 18 months or as I started I've. Just you know additional color and data that could potentially getting <unk> all thanks.

Federico Grossi: So the formal analysis will happen at the 24-month time point.

Thank you so the foreman analysis will happen at the 24 months standpoint. So we will of course runs that at 18 months, but they will be descriptive and <unk> and and nature Uhm. The contingent pieces. We went to the <unk>. Yeah. We proposed to include that because we realized that we had an opportunity to do that.

Federico Grossi: So we will, of course, run stats at 18 months, but they will be descriptive in nature. The contingent piece is that 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 include it 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. As it relates to the type of data that we will include, it is the lesion size growth and the size of the lesion.

With the timing that we had in mind.

And included in our complete NDA submission without a significant delay. So that's that was something that we saw was an important opportunity to provide a more complete data package and all possible data as it relates to the decent size gross so as it relates to the type of data that we will include it as condition says gross and the safety.

Got it that's helpful. Thanks.

Federico Grossi: Got it. That's helpful. Thanks. Thank you. As a reminder, to ask a question, you'll need to press star 1 on your telephone. Our next question comes from Joseph Stringer with Needham & Company. Your line is up.

You're welcome.

Thank you as a reminder to ask a question you'll need to press start wondering your telephone.

Operator: Our next question comes from Joseph Stringer with Needham & Company. Our next question comes from Joseph Stringer with Needham & Company. Hi, everyone. Thanks so much for taking our questions. Just given you're going to be starting a phase three trial in ICMPGN and C3G, just can you remind us of the market opportunity for this indication and what you'd be looking for in terms of, you know, a competitive profile for pexitacopalin in this indication?

Our next question comes from gesture Stringer with Needham and company. Your line is open.

Hi, everyone. Thanks, so much for taking our questions. Just give me are going to be starting a phase three trial and I see M. P. G N C. Three D. Just.

Federico Grossi: Thank you. Thank you, Joey. So we view C3G and ICMPGN as very important next indications for NPAVELI and ASPAVELI. You know, 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 ICMPGN 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.

Can you remind us of the market opportunity and that's indication and what you'd be looking for in terms of you know a competitive profile for takes it a coke when in this indication. Thank you.

Thank you Joey So we view C. Three G and iced tea M. P. G. N S is very important in the next indications 14th of Indiana 70.

Uhm, you know, we had a robust and I'm very impressed with proof of concept study that was run and T. Three G. S. You may recall in terms of the the market opportunity <unk> the market opportunity for each of <unk> Icmp Jan should probably be viewed in the range of what to Pee in a trip reason.

This is of course, an unmet need for which there are currently no approved therapies and were based on our data. We believe that we have the possibility of having a best in class profile.

Great. Thanks for taking my question.

Federico Grossi: And based on our data, we believe that we have the possibility of having the best in class. Great. Thanks for taking our question. You're welcome. Thank you. And I'm currently showing no further questions at this time.

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 Mister Cedric since last her final remarks.

Operator: I'd like to hand the conference back to Mr. Cedric Francois for final remarks. Thank you so much, Naran. 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 so much and around 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.

Cedric Francois: Thank you for joining us today. 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. Everyone have a wonderful day!

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 everyone has a wonderful day.

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Alright.

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