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

Good morning. My name is Catherine, and I will be your conference operator today. At this time, I would like to welcome everyone to the Apellis Pharmaceuticals conference call. For those of you participating via conference call, a slide presentation has been made available via webcast and will be posted to the Investor page of the company's website, www.apellis.com, at the conclusion of the call today. [Operator Instructions] Please be advised that this call is being recorded at the company's request. I would now like to turn the call over to Ms. Tracy Vineis, Vice President of Communications. Please proceed.

Thank you for joining us today to discuss the FDA approval of Empaveli, also known as Pegcetacoplan. With me on the call are Co-Founder and Chief Executive Officer, Dr. Cedric Francois; Chief Medical Officer, Dr. Federico Grossi; Chief Commercial Officer, Adam Townsend; and Chief Financial Officer, Tim Sullivan, who will be joining us for Q&A. Before we begin, I would like to point out that we'll 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'm pleased to turn the call over to Cedric.

Thank you, Tracy, and thank you, everyone, for joining the call. This is a remarkable time for people living with paroxysmal nocturnal hemoglobinuria or PNH. The FDA approved EMPAVELI, or pegcetacoplan, for the treatment of adults with PNH. EMPAVELI is approved for use in patients with PNH who are naive to treatment, as well as patients switching from the C5 inhibitors Ultomiris or Soliris. The approval of EMPAVELI is a tremendous achievement for people living with PNH, many of whom continue to suffer from debilitating symptoms despite treatment with C5 inhibitors. We are thrilled that adults with PNH in the United States will now have access to EMPAVELI. This approval also represents a major scientific advancement in complement. Empaveli is the first and only targeted C3 therapy to receive FDA approval. It is also the first new class of complement medicine to be approved in almost 15 years. We believe that EMPAVELI has the potential to redefine treatment for the PNH community, and its broad label reflects the impressive clinical profile seen in our Phase III PEGASUS study. Our Commercial, Medical Affairs and Value & Access teams are in place and ready to ensure that adults with PNH have the opportunity to benefit from EMPAVELI. When we founded Apellis in 2009, our ambition was to become the first company to develop a targeted C3 therapy for serious diseases driven by complement. Controlling C3 was viewed as scientifically difficult, if not impossible, by many, but the significant unmet needs of patients living with complement-driven diseases inspires our efforts. As our first FDA-approved medicine, Empaveli is a testament to our world-class science and fearless determination to bring forward the first and only targeted C3 therapy for patients. And the approval in PNH is just the start. Apellis is singularly positioned to deliver on the broad platform potential of targeting C3 for patients with serious complement driven diseases. We continue to advance registrational programs of Empaveli across multiple rare diseases with high unmet need. We also look forward to announcing top line results from our Phase III studies in geographic atrophy in just a few months, and are progressing 3 new product candidates into clinical development by the end of next year. I would now like to take a moment to thank the many people who supported our efforts over the years and made this approval possible. We are especially grateful to the PNH patients who participated in our clinical trials, their families and caregivers, and the health care professionals who contributed to the studies. Thank you so much for your invaluable support. And I would also like to commend the FDA for their hard work and collaboration throughout the review of the EMPAVELI application. Furthermore, I would like to recognize our amazing team at Apellis. Thank you for your unwavering dedication to improve the lives of patients, and your constant pursuit of the highest level of scientific integrity. And finally, I'd like to thank our partners and the investors who have helped advance Apellis to this point. Together, thanks to all of you, we hope to transform the treatment of PNH. And I will now turn the call over to Dr. Federico Grossi, our Chief Medical Officer, to review the U.S. prescribing information, including data that supported the FDA approval. Fede?

Thank you, Cedric. First, I would like to reiterate how grateful we are to everyone who contributed to EMPAVELI's approval. I'm incredibly proud of what we have accomplished, advancing EMPAVELI from our initial IND submission in 2014 to FDA approval. And I'm excited that we can now deliver this important medicine to people with PNH. As many of you know, PNH is a rare, chronic blood disorder that is characterized by destruction of oxygen-carrying red blood cells through both extravascular and intravascular hemolysis caused by uncontrolled activation of complement. Soliris and Ultomiris inhibit the complement cascade downstream, controlling intravascular but not extravascular hemolysis. As a result, C5 inhibitors do not address many debilitating symptoms from which people with PNH suffer. Retrospective studies show that many treated patients require transfusions and experience severe fatigue. Only EMPAVELI targets complement centrally at C3, controlling both intra and extravascular hemolysis. The FDA's approval is based on positive results from the head-to-head Phase III PEGASUS study, which were published earlier this year in the New England Journal of Medicine. PEGASUS was a randomized controlled study in 80 adults with PNH who had been on Soliris for at least 1 year prior to enrollment, that had a hemoglobin level of less than 10.5 grams per deciliter. EMPAVELI met the study's primary endpoint for efficacy, demonstrated superiority to Soliris for the change from baseline and hemoglobin levels at week 16 with an adjusted mean increase of 3.84 grams per deciliter of hemoglobin. The p value was less than 0.0001. With those results, EMPAVELI became the first and only therapy to achieve statistically superior improvements in hemoglobin levels compared to Soliris. Additionally, EMPAVELI met non-inferiority compared to Soliris on the endpoint of transfusion avoidance. 85% of EMPAVELI treated patients were transfusion-free over 16 weeks compared to 15% in of Soliris-treated patients. EMPAVELI was generally well tolerated in the PEGASUS study. At week 16, the most common serious adverse reaction in patients treated with EMPAVELI was infections. The most common adverse reaction with EMPAVELI were injection site reactions, infections, diarrhea, abdominal pain, respiratory tract infections, viral infections and fatigue. No cases of meningitis and no deaths were reported in patients treated with EMPAVELI. Let me now turn to the EMPAVELI label. EMPAVELI has been approved by the FDA for the treatment of adults with PNH. Administered by subcutaneous infusion twice weekly, EMPAVELI is approved for use with treatment-naive patients as well as patients switching from C5 inhibitors. Importantly, the prescribing information includes instructions for transitioning patients from both Ultomiris and Soliris to EMPAVELI. The prescribing information for EMPAVELI contains a box warning. EMPAVELI may increase the risk of meningococcal and other serious infections caused by encapsulated bacteria. A risk evaluation and mitigation strategy of REMS has been approved by the FDA for EMPAVELI to inform health care professionals about the risk associated with treatment. As I mentioned on the prior slide, we did not see any cases of meningitis in the PEGASUS study. In December, we shared top line 48-week results, which demonstrated sustained improvements in hemoglobin and other key markers of the disease. The safety profile of EMPAVELI was consistent with previously reported data through the 48-week study. I will now turn the call over to Adam Townsend, our Chief Commercial Officer, to discuss our plans for the commercial launch of EMPAVELI in the U.S. Adam?

Thank you, Fede. The commercial organization has been eagerly awaiting and preparing for this approval for the last 2 years. We are thrilled to make EMPAVELI available to people with PNH, and our team is ready to hit the ground running. We have spent the last 2 years listening to and engaging with the PNH community. Learning from those conversations, our team has developed a very thoughtful and strategic approach to bringing EMPAVELI to patients. Our top priority is ensuring that people with PNH have access to this important new medicine. Within the United States, there are approximately 1,500 patients who are currently being treated with C5 inhibitors. And every year, another approximately 150 people are diagnosed with PNH who may benefit from treatment. As you can see on this slide, there remains a pressing unmet need in PNH, despite the availability of Soliris and ULTOMIRIS. Based on the efficacy results across multiple hematologic measures, and the safety data we saw in PEGASUS, we believe that PNH patients may benefit from treatment with EMPAVELI. Retrospective studies and our own research show that about 1/3 of patients on C5 inhibitors continue to require transfusions to address their falling hemoglobin levels. Another 1/3 of these patients remain severely anemic and experience other symptoms, like severe fatigue. The final third of patients have closer to normal hemoglobin levels, but only achieve that at the expense of maximum output of red blood cells from the bone marrow. When talking to physicians and patients, the most important factor that they look for when deciding on a therapy is efficacy. At launch, we will focus on patients who have suboptimal control of their disease, beginning first with the 1/3 of patients who have the highest unmet need and then expanding to the broader PNH community. We plan to make EMPAVELI commercially available through our specialty pharmacy partner within 2 weeks. And in the next couple of days, our trained field teams will immediately begin educating health care providers or HCPs, and patients about the potential of EMPAVELI. Our launch efforts are focused on the top 1,000 to 2,000 health care providers, including more than 90 key treatment centers. I'd now like to discuss the value proposition of EMPAVELI. When determining price for EMPAVELI, we prioritized several factors, including ensuring patient access and removing costs from the health care system. Keeping these priorities in mind, we performed a thorough analysis of the clinical value delivered by EMPAVELI within PNH. EMPAVELI demonstrated superior clinical efficacy in improving hemoglobin levels compared to Soliris, a C5 inhibitor, in a head-to-head study. Even with the superior effect on hemoglobin, and with the reduction in transfusion burden for patients, EMPAVELI will be set at parity to ULTOMIRIS and at a discount to Soliris. The average and annual wholesale acquisition cost, or WAC, for EMPAVELI will be $458,000. We are committed to ensuring that every eligible patient who wants EMPAVELI will have access, regardless of the ability to pay. To that end, we have established Apellis Assist, a program designed to provide a comprehensive support system for patients throughout their treatment journey, including a dedicated Apellis Care Educator team of individuals with a nursing background. The goal of Apellis Assist is to ensure a high-quality treatment experience and provide support with insurance questions, infusion training, ongoing education on PNH, and financial assistance if eligible. We expect that utilization of the Apellis Assist financial programs will be consistent with industry benchmarks. Given the current landscape, our team is closely monitoring regional COVID-19 restrictions to ensure compliance. Our initial commercial strategy has focused on digital and online education, and virtual engagements for both patients and health care providers. We plan to pivot to in-person engagement when and where appropriate. Over 2,000 patients, caregivers, advocates and other PNH community members have opted in to communicate with Apellis via our community outreach and patient marketing efforts. Patients and caregivers are also spending considerable time on our website, which tells us they are interested in our information, particularly around the existing unmet need. Starting quickly and over the next 2 to 3 quarters, our Value & Access team is expected to engage with high priority payers representing more than 80% of all U.S. PNH patients on coverage decisions of EMPAVELI. In our discussions to date, we have received positive payer feedback on the clinical profile of Empaveli. On average, we anticipate reimbursement decisions to be made approximately 3 to 6 months post launch. In terms of coverage breakdown, we anticipate that about 50% of patients will have commercial private insurance, and about 50% will be covered under government programs like Medicare and Medicaid. The Apellis team will be laser-focused on ensuring a successful EMPAVELI launch. And while we are not providing revenue guidance in the near term, we are evaluating the potential to provide certain launch metrics over the next few quarters as we ramp up post-launch. We look forward to keeping you updated on our progress as our team works to bring this transformative treatment to the PNH community. I will now turn the call back over to our CEO, Dr. Cedric François, for closing remarks.

Thank you so much, Adam. As the first and only targeted C3 therapy, EMPAVELI has the potential to redefine treatment for the PNH community. We are proud to bring EMPAVELI to patients in the U.S., and our partner, Sobi, is working to make this important medicine available for the global PNH community. A marketing authorization application, or MAA, is under review by the European Medicines Agency, or EMA, with the potential for a European Commission decision on the MAA in the second half of 2021. We are also on track to read out top line results from the Phase III PRINCE study in treatment-naive PNH patients in only a couple of weeks, which we expect will continue to reinforce the strong clinical profile of EMPAVELI. PNH is only the start of what is possible with a targeted C3 therapy, and we are focused on expanding our global leadership in complements. We look forward to advancing EMPAVELI in registrational programs across multiple rare diseases with high unmet need, and to seeing top line results from our Phase III study in geographic atrophy in the third quarter. Now before we open the call to questions, I would just like to, once again, offer my sincere thanks to everyone who helped Apellis get to this important moment. And special recognition goes to our original home, the Bluegrass State of Kentucky, the City of Louisville and the University of Louisville; notably Dr. Don Miller and Dr. John Barker, without whose support Apellis would not exist. And thank you also to all our families at Apellis, who endured countless days and nights with us and to our co-founder Paul Olsen and toxicologist Ray Stoll, who played such a critical role, that are no longer with us to enjoy this milestone. And finally, a very special thank you to our early investors who supported us through a decade of work. [ Bernard Polederti ], [ Frederik Whitemore ], Michael Gellert, Robert and Nathaniel de Rothschild, [ Pierre Vala ], Robert and Nathalie Scherer, [ Jack Now ], the Snyder family, Mark Kristoff and [ Allen Doctor ], David Darst, Senior, and last and most importantly, the extraordinary Gerald Chan and the Morningside Ventures, who have been our rock through all these years. Operator, please open the call to Q&A.

[Operator Instructions] Our first question comes from Anupam Rama with JPMorgan.

Congratulations on the approval here. Can you talk a little bit about the strategy you guys took to getting [ suggest about say ] in the naive [ market ] ?

I [ don't ] know if I'm up for that question. Well, first of all, as we said last year, we believe that the data that we generated in PEGASUS supported a broad label, including in naive patients, based on the fact that we had not just the randomized period of 4 months, but also the whole extension period beyond that, in which both the active and the control group went on pegcetacoplan monotherapy. So it was really the data that supported this. In the context of the preparation for the launch, a couple of things stood out, which came out in the label. First of all, in the PEGASUS study, we focused very heavily on establishing the role that extravascular hemolysis plays in PNH, and how that generates the unmet need in that disease. And that is something that came out very clearly in the label as well. Secondly, we were, of course, very interested not just in Soliris, but also ULTOMIRIS, as a baseline treatment, to see if we could elevate the standard of care. And last but not least, the fact that we showed superiority on hemoglobin levels in the PEGASUS study contributed to the label that we generated. Now as it relates to the preparation for commercialization, Adam, I don't know if you want to add a few comments to that.

Yes. Thanks, Anupam. Thanks, Cedric. So yes, Anupam, you're spot on. There are 1,500 PNH patients in the U.S. currently being treated with C5 inhibitors and for the treatment-naive patients that you asked, every year, we think there's another approximately 150 people who are diagnosed with PNH who may benefit from EMPAVELI. Now obviously, with our label, we're pretty well positioned to provide a treatment option for all PNH patients who would require a complement inhibitor. So we still see the immediate opportunity in the U.S., which will be our focus, is on the patients who are seeing suboptimal control of their disease on current C5s. And at launch, we'll be focusing on the first 1/3 of those 1,500, who have the highest unmet need, which is a low hemoglobin level and frequent need for transfusions. We will be having a conversation about treatment-naive patients. Obviously, we strongly believe in the efficacy of our product, and we think treatment-naive patients would benefit. So whilst we're focused on the highest and most pressing unmet need, we will still be discussing the opportunity of onboarding patients to EMPAVELI who are treatment-naive.

Congrats again on the approval.

Our next question comes from Jonathan Miller with Evercore ISI.

I'll echo Anupam's congratulations on the broad label. You mentioned providing several launch metrics in the next couple of months as we wait for reimbursement discussions to reach fulfillment. What do you view as the most important number to track in early days? And how would you provide that to us? And then relatedly, how will you communicate updates on payer discussions and reimbursement negotiations?

Thank you very much, John. I'm going to hand that question over to Adam.

Thanks, Jon. So we don't expect to guide on product revenues for the foreseeable future, as our focus is, we want to ensure that every patient who wants to go on EMPAVELI can get on it. So we're going to be laser-focused on a successful launch. We hope to provide progressive updates with metrics on our commercial launch over the next few quarters as we ramp up post launch. Now obviously, as we've discussed before, our Value & Access team is out talking to U.S.-based payers. And on average, we expect the majority of payer coverage to take place within 3 to 6 months. As we start to work through that payer coverage and make sure that we can get patients onto EMPAVELI as quickly as possible, we'll continue to look at how we update and communicate around those terms as we progress into the later phases of the launch.

I think Adam -- did that answer your question, John?

Well, not really, but I'll wait and see what you guys provide. Thank you.

Our next question comes from Madhu Kumar with Goldman Sachs.

As Anupam and Jon said, congratulations, it's a really proud day for you all and for the PNH community. Kind of following from Anupam's question, how do you think about this kind of incident population opportunity, mostly in terms of how you balance kind of how much the Prince trial data will influence treatment-naive patients getting EMPAVELI versus clinicians' real-world experience using EMPAVELI in the commercial setting? Then I have a follow-up after that.

Yes. Thank you so much, Madhu for that question. So the incident population is fortunately not very large, of course, but does contribute to the overall population, of course, and I'll hand it over to Adam to talk more about what that means. But I think what's important here is, again, that the treatment-naive data that we generated, some of which was included in the label with the [ PADDOCK ] data, more of that, of course, coming with the PRINCE study as well, kind of all contributes to what we have clearly observed through all of the data, and that is that there is a clear opportunity to elevate the standard of care in PNH by addressing not just intra but also extravascular hemolysis, and protecting all of the red blood cells. And Adam, I don't know if you want to add something as it relates to the commercial opportunity around the incident population.

Yes. Thanks for the question, Madhu and Cedric. So yes, as said before, so we believe there are approximately 150 people who are diagnosed with PNH who we truly believe could benefit from the treatment with EMPAVELI. So one thing that we believe also is that once physicians start to put a patient on EMPAVELI and they start, we truly think that the impact of a hemoglobin increase, the potential for reductions in transfusions and other effects they'll truly see the benefits of being treated with EMPAVELI. And that noise that we get from the switch population will also have a big impact on the treatment-naive population, as physicians and patients will get comfortable with switching and starting on EMPAVELI. And we truly then believe the efficacy of our product will have an impact on a treatment naive patient, or a switch patient. So we think the word-of-mouth from physicians and patients will have a big impact to help us move patients who are in the treatment-naive category onto EMPAVELI.

Okay. And then kind of very practically, thinking about switching patients off C5 onto EMPAVELI, is [ basically ] the approach going to very much track the way you all ran the PEGASUS trial? I know the label talks about this kind of, like, going on both drugs for 4 weeks. Is that [ track you couldn't declare ] run it the way you did the PEGASUS trial, where there's an overlapping dose period and then you kind of switch on to monotherapy? Is that kind of the long-term kind of commercial switch plan? And how does that -- is that kind of similar to how you intend to do it for ULTOMIRIS patients as well?

Yes. Thank you, Madhu. I think the -- more than a commercial question, it's really a medical question. PNH is a lethal disease, as you know, and it is very important to control complement in an exquisite fashion without kind of a breakdown of that control. So that was one of the leading motivations why we have that overlap period in treatment. So in the label are instructions both for Soliris as well as for ULTOMIRIS, on how that switchover needs to happen. And we expect physicians to follow those instructions.

Okay. And then kind of last question, thinking about other indications for pegcetacoplan in kind of systemic setting. To what extent does this approval kind of move things forward? Is it just kind of like things are what they are and so like things like CAD, bone marrow, TMA, they'll just kind of kind of get started, hopefully, second half of this year?

Yes. Thank you, Madhu. So one of the very important elements, of course, of this approval as well is the safety database that we are generating with this systemic pegcetacoplan with EMPAVELI to control C3. That builds a foundation for the many other indications, including the ones that are in registrational trials right now, to see if we can add benefits to patients with ALS, cold agglutinin disease, hematopoietic stem cell-associated thrombotic microangiopathy, and then C3 glomerulopathy, with IC-MPGN included in that. So that's something that we are really looking forward to. It is -- it has been a decade in the making. We are getting around 300 patient years of dosing now. That is, of course, going to ramp up quite meaningfully in the months and the years to come. It is worth mentioning again, as Federico mentioned, that we have not yet seen a case of meningococcal infection, something that you would expect on control with C5, for example, every 100 to 200 patient years. So we are tracking that closely. But safety database, in combination with the very special way in which C3 activation is controlled with EMPAVELI, is what we seek to explore further.

Our next question comes from Yigal Nochomovitz with Citigroup.

Ceric and team. Allow me to extend my congratulations as well on the Empaveli approval. I had a few questions. First of all, do you expect to update the label with the PRINCE data once you report that trial? Or is everything you need to treat naive patients effectively already contained in the label? And second, does the label stipulate that hemoglobin needs to be below a certain threshold before switching from Soliris or ULTOMIRIS to pegcetacoplan, or is that based upon physician discretion? And third, if you could speak a bit about the manufacturing capacity for the launch, how much of the market can you currently supply? And do you have a second source supplier?

Thank you so much, Yigal, for those questions. So as it relates to the -- I'm going to start at the back. So for the manufacturing, we are absolutely ready to supply patients with PNH. It is something that we made large investments in early on. And again, the launch is fully on track with what we had anticipated. And you should hear more about that in the days and weeks to come. Then as it relates to the label, so the hemoglobin levels, physicians will have the liberty to prescribe this regardless of the hemoglobin levels that the patients have. So this is a label for all adult patients with PNH. I don't know, Federico, if you would like to add something to that?

Thank you, Cedric, thank you Yigal. Now as Cedric was saying, the hemoglobin levels do not have to be at a certain level for treatment. And when it comes to the label itself, the label is broad and includes all PNH patients. We are [ actually ] happy with the label. It recognizes the role of extravascular hemolysis and includes already transition from [ automize ancillaries ] and includes naive patients as well. We see PRINCE as further adding information to the label and reinforcing the use of EMPAVELI for PNH treatments, including safety data, but just to provide additional information for physicians.

And then the first question was just are you planning to update the PRINCE label -- I'm sorry, update the EMPAVELI label with the PRINCE data once you get that data?

Yes. So it's -- yes, we're not ready to comment on that. We haven't seen the data yet. But right now, we have a broad label that covers the entire patient population that we want to be able to treat.

Our next question comes from Phil Nadeau with Cowen & Company.

Let me add my congratulations on the approval. A few questions from us. First, the label mentions a REMS program. Can you discuss that program? How -- what's required of the physicians and the patients to comply with it?

Thank you, Phil. Federico would you like to answer that?

Yes. Thank you. Well EMPAVELI was approved, as you point out, with the REMS program. It's to ensure the prescribers and patients are informed of the risk of serious infections by encapsulated bacteria. This -- all the physicians in the PNH community are used to the REMS programs and our REMS program is very similar to what you have for eculizumab and ULTOMIRIS. And we don't expect the REMS programs really to be a limitation. So it's really easy for physicians to get certified and for pharmacies to be certified. So prescribers get certified in the program, and then that allows them to prescribe. And we're collecting information on the vaccinations, making sure the patients have vaccination before they receive pegcetacoplan or EMPAVELI.

And the label mentions monitoring for those infections, but it doesn't really say a frequency or a method of monitoring. How is it done practically?

Well, it's done in a way so that the patients or the physicians as they get certified, they get educated on how to educate the patients to look for signs and symptoms of these infections and all the patients get a safety card. And if they see any of those signs and symptoms, they need to report to the physician. Very similar, again, to the problems that Alexion has for the 2 products.

Perfect. That's very helpful. And then second, on the device itself, is training going to be necessary for the patients before they start? And how is Apellis going to train the patients?

Thank you, Phil. I'm going to hand that one over to Adam.

Thanks, Phil. So yes, we're proud to talk about Apellis Assist, which is our really support -- full patient support service. And so if a patient would like training, either virtually or face-to-face, we'll offer that through our Apellis Care Educators, who are a compassionate care partner, have a nursing background. And they'll help with all aspects of self infusion training if requested or wanted by a patient. And that said, look, following all COVID guidelines, we will do that face-to-face, if it's compliant, and we'll also be able to offer it virtually, and have tested and trained all of those virtual interactions and got very positive feedback on that. So through Apellis Assist, we'll be able to support all patients who want to onboard and be trained at their request on doing the subcu infusion.

Perfect. And then last question from us. As you mentioned, there are some patients with PNH today who are transfusion-dependent. Is there a mechanism, a compassionate use program or whatnot to get those patients on therapy today, as we wait for the insurance companies to make their reimbursement decisions?

Adam?

Yes, Phil, it's Adam again. So we obviously want every patient that wants to come onto EMPAVELI to be able to come onto EMPAVELI. And as we said, we're targeting the patients with the highest unmet need. So as we work through the market access time lines to make sure that patients can get access, we will also be working with those patients to come on board, and we'll help them transition onto EMPAVELI as we work through those market access time lines. So yes, we expect to be able to allow patients to start on EMPAVELI as soon as possible, particularly all PNH patients, but initially, those we expect have high transfusion burdens.

Our next question comes from Tazeen Ahmad with Bank of America.

My congratulations to you as well on your first approval. Just wanted to follow-up on the comment that you had made in your prepared remarks about focusing on the 1/3 of patients who have the highest need based on hemoglobin and transfusion needs. Do you have those patients actually identified, or will your sales force have to go and seek them out? That's my first question. And then secondly, as it relates to the next 3 to 6 months on getting the drug onto formulary. Can you talk us through what kind of process a physician would need to undertake in order to get the drug reimbursed while we're waiting for final formulary coverage? And then I have one more follow-up.

Thank you, Tazeen. I will hand that one over -- or both of those actually, over to Adam as well.

Thanks, Tazeen. So yes, we -- so we've been working over the last 2 years, speaking to health care providers and PNH patients. We have been targeting over 1,000 to 2,000 key HCPs, 90-plus treatment centers. We know where PNH patients are. We believe we understand the pressing unmet need of those patients and where they physically exist and sit, and which physicians they speak to. So we have a very strong targeting plan, which we will be executing as of today. So -- and please remind me of the second part of your question.

For the next 3 to 6 months as you wait to get the drug formally added to the formulary, what is the process that physicians would need to undertake to get reimbursement?

Yes. It's a great question. So yes, so obviously, as a quick reminder, right? The payer mix is approximately 50% Commercial, 25% Medicare, 21% Medicaid, approximately, and 5% other plans. Now we expect, if you look at the commercial plans, the majority of decisions to be implemented 4 months post launch, some may take up to 6. And the Medicare plans and the Medicaid plans take about 6 months. Now we'll work through Apellis Assist with physicians and patients to make sure that all of the on-boarding for treatment with EMPAVELI is as smooth as it possibly can be. So if a patient speaks to a physician or a physician contacts a patient, we hope they'll enroll in Apellis Assist. And then we'll start to help the physician make sure that all of the paperwork is done to transition patients smoothly onto EMPAVELI. Apellis Assist will be a strong help for us to allow us to do that. So we hope the burden for patients and physicians is as light as possible so that they can get access to this truly efficacious product.

Okay. And maybe my last question would be on how important is it for the actual reopening for patients to be on-boarded to drug? So some of the other companies we cover have stated that certain therapeutic areas have been more impacted by patients not seeing their physicians in person. For PNH, can you give us a sense of how important a face-to-face interaction will be between doctor and patient, not virtual, but in the office, as a gating factor for getting a doctor comfortable for writing that first script?

So obviously, our Commercial and Medical Affairs teams have really been monitoring the COVID-19 restrictions. Our near-term commercial strategy is on digital education and virtual engagements for both patients and HCPs. Where we can have in-person engagements, I think we would love to, and we will. We have field teams meeting HCPs in their offices, and we're obviously diligent following all of the guidelines. Once it's safe to gather, we plan to resume in-person engagements with both patients and HCPs. I -- my gut tells me we'll start to transition more to in-person as the U.S. and the states start to unlock. But we've had really, really positive responses to our virtual interactions. So Apellis Assist is going to help virtually. And then obviously, we'll have our sales teams and our market access teams, medical affairs teams and our care partners working hopefully, face-to-face with patients. But we truly believe that we can onboard patients virtually as well as face-to-face as we transition to the later part of the year.

Tazeen. And maybe just one little element there because I think that's really important: What came out in the label and what came out in these studies. Because, of course, we want -- we have that 1/3 of patients that we want to help as quickly as possible. But it's the fact that extravascular hemolysis plays such an important role in this disease. That's not just for that 1/3 of patients. This is something that affects all patients, just to different extents. And I think the -- what really matters in elevating the standard of care in PNH is that by controlling all forms of hemolysis, we're hoping to make the lives of patients better.

Our next question comes from Steve Seedhouse with Raymond James.

Can you just talk about to what extent patients enrolled in a long-term extension study would be converted or could be converted to commercial patients? When you might expect that to happen? And I think, according to clintrials.gov at least, that could be up to 160 patients. Maybe you could just also clarify precisely how many EMPAVELI patients are in clinical trials right now for PNH?

Yes. Thank you so much, Steve, for that question. So we're not going to comment on exactly how many patients are currently on dosing, but based on the number of patient years that we mentioned, of course, it's a large number. And we have plans to make that transition smoothly. I'm going to hand it over to Adam again to briefly comment on how we plan to do that.

Yes. Thanks, Cedric. So obviously, any patient who wants to transition to EMPAVELI, we will help and we do expect PEGASUS patients and also other patients, be they new commercial patients to transition. I think Fede can perhaps comment on the long-term extension studies in a little bit more detail.

Thank you, Adam. Yes, the long-term extension studies, as we've made everybody aware, capture all the patients from all our PNH studies. And 97% of the patients from the PEGASUS study transition into -- into the extension study. Just as a reminder, PEGASUS was a global study. So many of those patients are actually based outside of the U.S. I don't know, Cedric, if you want to add anything, but I think this will cover.

And if I could just ask one more, Cedric, if it's okay. Just what are you expecting for gross to net? And is this going to be reimbursed through medical or pharmacy benefit?

Thank you so much for that question. Tim, can you take that?

Yes, sure. So we anticipate the gross to net to incorporate all the typical fees and expenses of a product like EMPAVELI. And we've been actively engaged in the payer discussions and have received strong feedback. And I think probably for that piece of it, I'll turn it over to Adam.

Yes. So I agree with Tim on the gross to net. And obviously, the second part of your question, based on our discussions with payers, we think they're going to manage EMPAVELI on the pharmacy benefit due to its self-administration.

Our next question comes from Alethia Young with Cantor.

Congrats on the approval. It's a great day for you guys, and patients on Friday. I guess a lot of the U.S. questions have been asked, but maybe just one on just -- when you think about pricing, I totally get what it might be at parity to ULTOMIRIS, but I guess I just wanted to get a little bit more flavor from your payer conversations as to your confidence in setting it at parity, versus maybe a slight discount to try [ even ] get an edge there. And then in Europe, I just wanted to talk a little bit, again, if you can remind us of like roughly the numbers there, that would be the opportunity and how the regulatory conversation is going there as well.

Yes. Thank you so much, Alethia, for that question. So as it relates to the price, Adam and his team have done an enormous amount of work in preparation for the commercialization, which included numerous payer discussions. And I think what really came out of that, again, was the strength of the data that was generated and the benefits that we believe we'll be able to convey to patients. Also very important in those discussions and from our perspective is, of course, Apellis Assist, which again is meant to ensure that no patients with PNH who could benefit from our drug would have to live without it. Adam, I don't know if you want to add something to that, and then I'll briefly talk about Europe.

Yes. Just a quick addition on top of that. So based on our payer discussions, and our payer discussions are ongoing as we speak now, as well. We believe that payers are going to be willing to cover EMPAVELI to label without additional restrictions, given the clinical merits of the product. So yes, I think we expect approval to label based on the superior hemoglobin result we saw in the PEGASUS study, but also the true value of reducing transfusions for patients. So we'll continue now to negotiate with the payers. And we expect to have really, really strong value discussions.

Thank you, Adam. And as it relates to Europe. So of course, our partner Sobi is responsible for that. In the second half of this year, we expect to have approval from the European authorities for EMPAVELI. And at that point in time, we'll talk more about that.

Just like another just follow-up. With your Apellis Assist, can you just talk a little bit about what support you think is needed, more than what maybe Alexion or AstraZeneca is giving? And is it -- is there something in particular in the chain of patients being under care that's kind of lacking or missing? And that would be helpful.

Yes. Thanks, Alethia. Look, we didn't -- Apellis Assist was not built with our competitors in mind. It was built with the patients in mind. And we did a deliberate effort to really -- as we did in our clinical trials, by the way -- to really try to understand what it is like to live with PNH and how we can best be there for patients. I think that in short kind of answers what we are doing there. We also have created kind of a welcome package for patients to really understand all the aspects related to the disease, to treatment with EMPAVELI, and how we can be there for them. Adam, I don't know if you want to add something to that?

Yes. Just on top of that, as Cedric said, that we spent a lot of time talking to PNH patients and understanding their needs around the disease, around the emotion that comes with the disease, around their current treatment, and we also benchmarked against a lot of rare disease similar programs. So obviously, while the support that we'll offer will include help with insurance questions, financial assistance, if eligible, self administration, infusion training and education, and the ongoing education of treatment around PNH, but we also believe that there's something special in our Apellis Assist program based on the time we spent with PNH patients. So we truly, truly believe this -- the Apellis Assist will be by the sides of PNH patients throughout their journey. We're very, very proud of this program.

Our next question comes from Justin Kim with Oppenheimer & Company.

Congratulations on this remarkable achievement and exciting news for patients. Just maybe one from me. With respect to the dose adjustment guidelines related to LDH levels in the label, how has the clinical experience in PEGASUS and prior studies informed this protocol? And do you anticipate that flexibility in the real-world setting will allow for better patient management than for the more rigid clinical trial allowed for with respect to hemolysis event?

Thank you so much, Justin. I'm going to hand that one over to Federico to answer.

Thank you, Cedric. That's a great question. Yes, as you point out, the clinical sites are more strict, but we saw the dose adjustments being implemented in the study. And that help. And we see in the real world, also physicians using the dose adjustments if needed, and having more flexibility on that so that those adjustments are allowed.

Our next question comes from Matthew Luchini with BMO Capital.

Congrats on the accomplishment So two for me. First, it sounds like, in the initial part of the launch especially, you're prioritizing high unmet need switch patients. But on naive, what does your market research say about what's really going to drive the treatment decision? Is it docs getting first-hand experience with the drug in their switch patients? Is it -- do they have in their mind some specific type of patient that -- as a naive might be particularly well suited to EMPAVELI? Just a little bit more on that. I think it's been discussed earlier a little bit, I would just like to understand more. And then secondly, recognizing that you're not providing revenue guidance, but on this question of metrics, do you plan to provide perhaps patient numbers, number of patients that are on drug during this transition toward a period where reimbursement is coming online?

Yes. Thank you so much, Matt. So before I hand it over to Adam to answer those questions, again, as I reiterated earlier, we are focused initially on those high unmet need patients, of course, but extravascular hemolysis is something that affects all patients with PNH, just to different extents. So we believe that in the coming years, that will elevate the standard of care for that broad population. And then how that translates into numbers, I'm going to hand that over to Adam.

Thanks, Matt, for your question. So yes, we truly believe that all PNH patients or adult PNH patients can benefit from EMPAVELI. And your first part of your question about what do physicians need to see based on our research, right? So we've been talking about PNH treatment-naive patients in our market research for a long time. And we found that this is still an efficacy-driven market. So we expect physicians to have a conversation with the 150 treatment-naive patients around what efficacy could mean to them. So what does a superior hemoglobin increase compared to Soliris mean to them? What's transfusion reduction burden mean to them? We do believe, based on our research, that some treatment-naive patients are going through transfusions. And we think we can have an impact to that. So we truly believe that EMPAVELI is a drug for all adult PNH patients, be those on switches from C5s or treatment-naive. And we expect word-of-mouth to accelerate from a physician perspective as well as a patient perspective as patients start their journey onto EMPAVELI. Now in terms of the metrics, et cetera. Yes, and this comes back to John's question earlier, right? We want to get into the launch phase. We want to make sure that we're focused on our plans, that we can help get access for patients as quickly as possible. We can be there for physicians and patients and deliver everything. And then we're going to work out what the best metrics are for us to be sharing with the markets as we progress through the early phases of the launch. So at the moment, it's a little up in the air, but we'll be much more solid with what we want to share as we start to progress patients onto EMPAVELI.

Our next question comes from Joseph Stringer with Needham & Company.

Congratulations again on the approval. Most of our questions have been answered. But just digging a little bit deeper into the treatment-naive population here. You mentioned the initial focus and most of the discussion on the highest patients with highest unmet need with transfusion dependence. But just wondering, just in terms of timing -- the timing of the focus, I guess, in terms of shifting or at least focusing on those treatment-naive patients. Maybe you could help us with the timing of that sort of focus kind of going forward post-launch here?

Thank you, Joe. Adam, would you like to give some color to that?

Yes. Thanks, Joey. So now we have an approved product for the treatment of adult PNH patients. We'll be talking about elevating the standard of care for all adult PNH patients today moving forward. And whilst we believe in the -- how we're going to see adoption of our product, we believe those with the highest unmet need will be the ones to raise their hands first and talk about switching to EMPAVELI, but we truly also believe that the treatment-naive, the 150 patients that exist out there, we have a great value story for them. And with the efficacy of our product, we can transition them. I do expect them to transition later on within the launch window, but we'll be having conversations as of today. It's a very typical rare disease drug, in which the patients with the highest unmet need will be the ones we would expect to see first, but due to the efficacy of the product, we'll be having conversations and helping all adult PNH patients.

Our next question comes from Colleen Kusy with Baird.

Congratulations on the approval. Of the key 90 centers that you're targeting, how many have clinical experience with EMPAVELI? Do you have a sense of how concentrated PNH patients are across those 90 centers?

Thank you so much, Colleen. It's a great question. Adam?

Thanks, Colleen. So how we got -- let me just talk a little bit about how we got to our approach for speaking to health care providers. So we looked at various pieces of data within the U.S. market. So we looked at claims data. We also looked at all aspects of PNH experience. So we have a pretty impressive map of where the key subscribers -- prescribers, excuse me, are, and also where patients are, and we have an idea of the transfusion burden that some of these patients are going through. So of the key 90 to a 100 centers, we believe that, that encompasses a large proportion of the patients that we want to transition in the initial phases of our launch. We expect the majority of those patients to be new to EMPAVELI; i.e., C5 switch patients or treatment-naive patients. Hopefully, Colleen, that helps answer your question.

Yes. And on the pricing at parity with ULTOMIRIS, on top of that, can you quantify a little bit of the saving -- expected savings to the health care system you might expect with EMPAVELI?

Yes. Absolutely. So we've been discussing with all the U.S.-based payers our PEGASUS data and the value of EMPAVELI. [Audio Gap] I do truly believe that the increase in hemoglobin and the impact that, that can have on patients and the ability that, that allows patients to control their disease has a value impact, and that's been recognized in our payer discussions. The other aspect is the release of transfusion burden and the impact that, that has, not just to the payers, but also to the hospitals and the patients themselves. So the total efficacy, be that hemoglobin increase and transfusion reduction, plus all of the other parameters we saw in the PEGASUS study, is what's resonating incredibly well and believe that, that's helping us put value back into their world if these patients were to switch to EMPAVELI.

Our next question comes from Laura Chico with Wedbush Securities.

Congratulations on the approval. I guess, I just had one that I wanted to follow up on with respect to the pricing. And I'm just wondering if you could walk through a few more of your assumptions to get to that $458,000 price tag per year. And you gave great color on the payer mix in terms of commercial versus government. I guess I'm more interested in terms of dosing per week, how many people you think may need to updose to 3x? And then also, any color around projections for compliance and persistence?

Thank you, Laura. Adam?

Yes. Thanks, Laura. So obviously, when we were going through all of our work to look at how we could discuss the value and what pricing we should do. We went back to our PEGASUS study, where EMPAVELI demonstrated superior clinical efficacy improving hemoglobin levels versus Soliris in the head-to-head trials. We chose to set at parity to ULTOMIRIS and at a discount to Soliris, due to that superior effect on hemoglobin and also the reduced transfusion burdens of patients. We spent a lot of time looking at what it would -- what that looks like for patients and how they onboard to the drug. But also to make sure that we were offering that superior efficacy and we could allow that patients could have access. So that was the driving force behind how we picked the price. Now we will obviously expect patients to follow the guidance in the label. And in our assumptions, we looked at various aspects of what that would look like through standard dosing, which we expect consistent with the label and anything to do with escalating dosing. So we mapped all of that into our assumptions when we came to choosing our WAC price, but also believe in the efficacy of this drug and the value it can create.

Adam, maybe one quick follow-up. Just a point of clarification. Just in terms of cost coverage during the combination therapy period, does the patient assistance program specifically provide a bridge, I guess, for lack of a better word, during that 1 month interval in which patients are going to be on both EMPAVELI and a C5 therapy?

Yes. Thanks, Laura. So yes, we hope that all patients opt-in -- all eligible patients opt into Apellis Assist, and we truly believe that Apellis Assist is going to help transition patients who will switch from C5, be that Soliris and/or ULTOMIRIS to EMPAVELI. And Apellis Assist will help with all of those switch discussions, as well as the transition in terms of timing and -- from timing from the switch from Soliris or ULTOMIRIS. So Apellis Assist is the place that we hope people will go to.

Thank you, Laura, and thank you, everyone, for joining us on our EMPAVELI FDA approval conference call. We look forward to executing on our launch in PNH and are excited for the transformational year ahead for Apellis as we continue to build our global leadership in complement. So have a great rest of your day, and thank you so much for joining.

This concludes today's conference call. Thank you for participating. You may now disconnect.