Apellis Pharmaceuticals, Inc. (APLS) CEO Cedric Francois on Q3 2021 Results - Earnings Call Transcript

Nov. 08, 2021 11:38 PM ETApellis Pharmaceuticals, Inc. (APLS)
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Apellis Pharmaceuticals, Inc. (NASDAQ:APLS) Q3 2021 Earnings Conference Call November 8, 2021 4:30 PM ET

Company Participants

Meredith Kaya - Vice President, Investor Relations

Cedric Francois - Co-Founder and Chief Executive Officer

Adam Townsend - Chief Commercial Officer

Federico Grossi - Chief Medical Officer

Tim Sullivan - Chief Financial Officer

Conference Call Participants

Umer Raffat - Evercore

Anupam Rama - JPM

Phil Nadeau - Cowen & Company

Steven Seedhouse - Raymond James

Madhu Kumar - Goldman Sachs

Justin Kim - Oppenheimer & Company

Tazeen Ahmad - Bank of America

Colleen Kusy - Baird

Alethia Young - Cantor

Ellie Merle - UBS

Matthew Luchini - BMO

Joseph Stringer - Needham & Company

Laura Chico - Wedbush Securities

Operator

Good day and thank you for standing by. Welcome to the Third Quarter 2021 Apellis Pharmaceuticals, Inc. Earnings Conference Call. [Operator Instructions] I would now like to hand the conference over to your host today, Meredith Kaya, Vice President of Investor Relations. Please go ahead.

Meredith Kaya

Good afternoon and thank you for joining us to discuss Apellis’ third quarter 2021 financial results. With me on the call are Co-Founder and Chief Executive Officer, Dr. Cedric Francois; Chief Commercial Officer, Adam Townsend; Chief Medical Officer, Dr. Federico Grossi; and Chief Financial Officer, Tim Sullivan.

Before we begin, I would like to point out that we will be making forward-looking statements that are based on our current expectations and beliefs. These statements are subject to certain risks and uncertainties, and our actual results may differ materially. I encourage you to consult the risk factors discussed in our SEC filings for additional detail.

Now, I will turn the call over to Cedric.

Cedric Francois

Thank you, Meredith, and good afternoon to everyone joining us today for our conference call. The third quarter was another exceptional period for updates, highlighted by strong U.S. commercial execution for EMPAVELI and PNH, our Phase 3 DERBY and OAKS data, which we believe position pegcetacoplan to become the first treatment for GA and the continued advancement of our pipeline. Our achievements this past quarter underscore the broad potential of our unique approach of targeting C3 and further reinforce our leadership position in complement.

I will start with the most significant event of the quarter, which are the top line results from DERBY and OAKS. In these studies, pegcetacoplan showed a clinically meaningful reduction in GA lesion growth and a favorable safety profile with both monthly and every other month dosing. Importantly, pegcetacoplan showed an even greater effect in patients with extrafoveal lesions, supporting treatment earlier in disease progression. Fede will review these results shortly.

With these data, we believe pegcetacoplan is a breakthrough for the millions of people living with GA, a relentless disease that is a leading cause of blindness worldwide. We are thrilled with these results, but we understand that there remains uncertainty within the investment community right now, both in regards to our path forward in GA and then how we intend to capitalize the company. Gaining clarity on both is a high priority for us in the near term. On the regulatory side, we will be meeting with the FDA to discuss our submission strategy and plan to share feedback with you before the end of the year. Regarding funding needs, as Tim will detail later, we are taking a thoughtful approach as we evaluate various financing strategies so that we are well positioned for the future.

Turning to EMPAVELI, the first and only targeted C3 therapy approved for the treatment of PNH. In our first full quarter since launch, EMPAVELI delivered $5.3 million in net product revenue, exceeding our expectations and showed strong momentum across each of our launch metrics. Additionally, pegcetacoplan, which will be known as Aspaveli in the EU and marketed by Sobi received a positive CHMP opinion last month. We expect a decision regarding approval from the European Commission by the end of this year, further advancing our goal to elevate the standard of care for PNH patients around the world. If approved, Aspaveli will become the first new therapeutic approach for PNH in the European Union since 2007.

Our efforts in PNH are just the first steps in building our rare disease franchise. Together with Sobi, we are continuing to advance a robust portfolio across multiple indications. We have a steady cadence of milestones over the next 12 to 18 months, including the start of 3 late-stage trials designed to support registration in 4 separate indications. We are also continuing to enroll patients in our potentially registrational Phase 2 ALS study. Ultimately, our ambition is to become the global leader in complement. Pegcetacoplan represents the foundation for this goal, and this is our most immediate opportunity. However, behind these programs, we have a growing portfolio of candidates across several modalities that will allow us to address a broad range of complement-driven diseases. We look forward to providing more details on all of these efforts as the programs advance.

And let me now turn the call over to Adam for a discussion on our commercial efforts. Adam?

Adam Townsend

Thank you, Cedric. As Cedric mentioned, our EMPAVELI commercial launch is off to a very strong start. We are making great progress across each of our top launch priorities, which is designed to ensure that every eligible PNH patient who want EMPAVELI has access to this important new medicine. As we said previously, within the U.S., there are approximately 1,500 patients who are currently being treated with C5 inhibitors and another 150 people diagnosed with PNH each year. Our initial focus is on those PNH patients who have suboptimal control of their disease, beginning with a third of patients on C5 inhibitors with the highest unmet need, those who require transfusions to address their falling hemoglobin levels. We plan to expand to the broader PNH community, many of whom are also suffering from signs and symptoms like anemia and severe fatigue.

At the end of October, over 115 physicians have signed up for our REMS program since launch within the U.S. an impressive figure, indicating the significant number of physicians who have identified EMPAVELI as a potential treatment option for their patients. Additionally, we received more than 50 start forms in the third quarter alone and over 100 start forms since launched through October. Consistent with last quarter, we are finding that C5 inhibitor switch patients are the vast majority of new EMPAVELI starts with about 70% of switches coming from Ultomiris.

On the payer front, our value and access team continues to engage with high-priority payers, including the top 20 payer who cover approximately 85% of all U.S. PNH prescriptions. To date, 14 of these 20 have agreed to place EMPAVELI in a positive formulary position. We remain on track to be on formulary with approximately 90% of plans by the end of the year. In parallel with the execution of the EMPAVELI launch, our commercial team is preparing for a potential approval of pegcetacoplan in GA and the opportunity to finally bring a treatment to patients. Based on early market research, the initial feedback from surveyed retina specialists on derby and OAKS has been highly encouraging and reinforces our belief in the blockbuster potential of this product. They believe there is a clear need for a treatment that the data support treating their patients’ earlier in disease progression and that as a result, they plan to prescribe pegcetacoplan, if approved.

As you can see on this slide, some of the feedback from retina specialists include comments like this is huge. We don’t have anything to treat GA and this would be a complete shift in the paradigm of how we approach and treat GA. 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 Fede to review our clinical development. Fede?

Federico Grossi

Thank you, Adam. I am going to spend the next few minutes providing a high level review of the DERBY and OAKS data. These were presented for the first time at the Retina Society Meeting in September. We look forward to presenting data again at the American Academy of Ophthalmology meeting later this month.

In the OAKS study, monthly and every other month treatment with pegcetacoplan met the primary endpoint, providing a clinically meaningful and highly statistically significant reduction in GA lesion growth compared to pooled sham at 12 months. In a prespecified analysis, pegcetacoplan showed an even greater reduction in patients with extrafoveal lesions, by as much as 35% in the monthly arm. As a reminder, GA typically begins with extrafoveal lesions and later progress into the fovea. With research suggesting that as many as 85% of patients start the lesion outside of the fovea, Pegcetacoplan, [indiscernible] statistical significance in DERBY, very with a p-value of 0.0528 in the monthly treatment arm. However, pegcetacoplan again show a greater reduction in lesion growth in extrafoveal lesions, as you can see in this slide. A quick question is why DERBY? In [indiscernible] analysis we offset an expected imbalances in base and characteristics known to be associated with rapid disease progression. In DERBY, these imbalances reflected the presence of faster progress in patients enrolling in the pegcetacoplan use as compared to the sham groups, which may have contributed to the mix.

Turning to the follow analysis, further confirming the treatment effect, pegcetacoplan is the first investigational therapy to demonstrate consistent and clinically meaningful reductions in GA lesion growth when looking at the treated eye versus the untreated fellow eye. In patients with bilateral GA, lesions are well known to grow at similar rates in both eyes. Therefore, this analysis serves as an important validation of the treatment effect. This slide shows the study eye versus the fellow lesion growth across the sham groups for both DERBY and OAKS. Overall, as expected, we do not see a big difference in the rate of lesion growth in the study eye versus fellow eye in the sham-treatment patients, which confirms the relevance of this analysis. Then when you look at the every other month groups, you start to see separation of the cords between the pegcetacoplan treated eye and the untreated fellow eye. And finally, when you look at the monthly groups both DERBY and OAKS show an even more robust separation between pegcetacoplan treated eye versus the untreated fellow eye.

In terms of safety, pegcetacoplan demonstrated favorable safety profile across both studies, the pull rate of new [indiscernible] exudations with 6% of patients in the monthly treatment group, 4.1% in the every other month treatment group and 2.4% in the sham group. And data from endophthalmitis and intraocular inflammation were generally in line with those reported in studies of other intravitreal therapies. Between DERBY, OAKS and our Phase 2 FILLY study, we now have results across more than 1,500 patients from 3 randomized well-controlled study, providing our robust statistic, which we believe demonstrates pegcetacoplan’s efficacy and safety and supports approval. We remain on track to submit our NDA in the first half of 2022.

I will now turn the call to Tim for a review of the financial results. Tim?

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 from the third quarter of 2021. In the third quarter of 2021, total revenue was $5.7 million, which primarily consisted of $5.3 million of EMPAVELI net product revenue, a strong start for the launch and additional revenue associated with our collaboration with Sobi. R&D expenses were $88 million, G&A expenses were $46 million, and we reported a net loss of $196 million. As of September 30, 2021, Apellis had $430 million in cash and cash equivalents, which are expected to fund our operations into the third quarter of 2022. A reminder that the $50 million payment associated with our beam collaboration was paid in cash during the third quarter.

We acknowledge that we will need to raise additional capital as we advance our leading C3 platform and that we will do so in a thoughtful manner as we have always done. We are evaluating multiple financing strategies, ranging from traditional equity or debt approaches to royalty, partnerships or other more strategic paths as we simultaneously work to advance our regulatory path in geographic atrophy.

Importantly, we are also tightening expenses, which includes dating spend tied to certain derisking milestones and managing hiring across the organization during this interim period. With an approved product in EMPAVELI, a potential blockbuster in GA and a robust pipeline, we are confident in our ability to access capital in a way that we believe will help us deliver long-term value for our shareholders.

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

Cedric Francois

Thank you, Tim. The first 9 months of 2021 represented a transformative period for Apellis as we launched our first commercial product, and EMPAVELI in PNH and showed a clinically meaningful reduction of GA lesion growth with a favorable safety profile in the Phase 3 DERBY and OAKS studies. We are committed to building on this momentum to further support growth and advance our leadership position in complement. Over the next 12 to 18 months, we expect a number of key milestones across our portfolio. Beginning with the remainder of 2021, we expect Sobi to receive EU approval for pegcetacoplan in PNH to have regulatory feedback from the FDA in GA and to initiate a Phase 3 study in immune complex membranoproliferative glomerulonephritis or IC-MPGN and C3 glomerulopathy or C3G.

Additionally, our partner, Sobi reiterated in their recent earnings report that they remain on track to initiate a Phase 3 study in cold agglutinin disease, or CAD, and their program in hematopoietic stem cell transplantation-associated thrombotic microangiopathy or HSCT-TMA in 2021. Enrollment in our ALS study is ongoing, but we now expect that we will complete enrollment in the first half of 2022. This slight delay is partially due to COVID as well as completing enrollments of other ongoing trials recruiting in ALS. 2022 is also set to be a milestone-rich year.

In the first half of 2022, we expect to submit our new drug application in GA to the FDA and to begin pre-submission discussions with the European regulators about plans for our EU submission and for Sobi to begin launching Aspaveli in EU countries following EMEA approval. We also expect new preclinical data to be published early next year with a C3 inhibitor designed for the prevention of complement immune system activation coincidence with AAV vector administration for gene therapies and other indications.

In the second half of 2022, we expect to initiate a Phase 3 study in intermediate AMD pending regulatory feedback to submit an IND for APL-1030, our first-in-class brain active C3 inhibitor for neurodegenerative diseases to report the 24-month results from DERBY and OAKS and to receive a potential U.S. approval decision for GA. We have made excellent progress, and we look forward to providing updates as we advance our efforts.

And now operator, please open the call for questions.

Question-and-Answer Session

Operator

[Operator Instructions] Our first question comes from Umer Raffat with Evercore. Your line is open.

Umer Raffat

Thanks so much for taking my questions. I would want to get any initial feedback from the FDA on Phase 3? And if you could remind us of any bottlenecks going to the end of next year, that will also be great? And then particularly beyond GA [indiscernible] on the pipeline indications and you expect it to continue to [indiscernible]. Could you maybe talk about opportunity around some of those quantifications especially it seems like a bit of a substantial on near-term. Potentially, I understand there is some news of [indiscernible] complemented fast or currently? And what the penetration is the understanding of [indiscernible] practice in that indication?

Cedric Francois

Yes. Thank you so much. So as it relates to the Phase 3, so as we have outlined earlier, we have submitted a request to the FDA for a meeting regarding the DERBY and OAKS studies. Before Christmas, we plan to provide an update to street as to what’s regulatory landscape looks like. Specifically, there are two important elements that we need to – we are hoping to get clarity on. One is whether the FDA would expect us to wait for the 24-month data before actually doing the submission. The second one is whether at this point in time, the FDA believes that another trial may be needed or not. We believe that neither of those are going to be requested and demanded, but getting clarity on that would be important. Then as it relates to EMPAVELI and the pipeline, so we have, as we mentioned in the call four additional registrational programs going on in these four additional indications. And indeed, C3 glomerulopathy is one of the very exciting ones that we are working on. This is indeed an indication for which Soliris and Ultomiris are sometimes used off label. We are running a Phase 3 clinical trial, and our objective is to identify whether EMPAVELI can be a treatment for that indication. But both based on the mechanism, based on the Phase 2 data that we generated, we believe that this is a very important indication where we have an opportunity to be a best-in-class product for these patients potentially. And we are also, importantly – I’d like to point out that the IC-MPGN component, which is essentially the other half of the patients that will be enrolled in this study, are a form similar to C3G, but one that is more driven or I say, represented by the presence of antibodies in the kidney and therefore, the classical pathway as well.

Umer Raffat

Okay, thank you so much. Just one more. I appreciate your [Technical Difficulty] remarks that you are exploring all options for financing and for [Technical Difficulty] sending a little bit. I understand there is a lot of concern about financing right now. Are you open to less traditional perhaps beyond that? And could you a little bit about what your preferred solution would be? And you’re looking first and foremost at the combination also covering to our performance.

Cedric Francois

Thank you so much. I will hand that one over to Tim.

Tim Sullivan

Sure. And I’ll do my best to also feedback the question. I think you were asking, generally speaking, are we open to other less traditional forms of financing in the context of our acknowledged capital raising needs. And look, we’re certainly aware of the – is that correct, Umer, first of all?

Umer Raffat

Yes, so.

Tim Sullivan

Okay. Yes. So we’re aware of the current conditions that could impact our ability to raise capital, and we’re exploring all of those options. Those raise range from traditional equity, debt, royalty, partnerships or some more strategic paths. So really, we’re looking at the entire range of things. And we’re basically also simultaneously, as we mentioned, looking at our expenses to extend our runway while our cost of capital is where it is. But at this point, we’re taking our time to do the right thing for shareholders, as we said, and we will look at all options.

Umer Raffat

Well, thanks so much.

Cedric Francois

Thank you, Umer.

Operator

Our next question comes from Anupam Rama with JPM. Your line is open.

Anupam Rama

Hey, guys. Thanks so much for taking the question. Can you hear me, alright?

Cedric Francois

Yes. We can hear you, well, Anupam.

Anupam Rama

Alright. Cool. Just a quick one on the PNH launch, on the start forms, I know it’s early, but any data points on the time from start form to getting a patient on therapy. And is there any synergies we can think about over time? Thanks so much.

Cedric Francois

Thank you, Anupam. I’m going to hand that one over to Adam.

Adam Townsend

Thanks, Anupam. Hopefully, you can hear me too. So yes, we’re very, very pleased with the progress of the EMPAVELI launch in PNH. What we’re finding, Anupam, is that the transition of start forms to commercial patients, it takes between 2 and 3 weeks, which is pretty normal for a rare disease drug launch, we get hugely positive feedback on the process from – not only from physicians, but also patients, but once we go through all of the REMS and we go through all of the paperwork that’s required, it takes on average between 2 to 3 weeks to transition a patient across. Hopefully, that answers your question.

Anupam Rama

Thanks so much for taking the question.

Cedric Francois

Thank you, Anupam.

Operator

Our next question comes from Phil Nadeau with Cowen & Company. Your line is open.

Phil Nadeau

Good afternoon. Congrats on the quarter and thanks for taking our questions. A couple on GA for us and then one on EMPAVELI. On GA, in terms of the regulatory strategy, we’ve had some KOLs suggest that the 18-month data could strengthen the package. Is that something you’re considering? And we’ve also had KOL suggest that the consistency in the every other month dosing arm specifically in the extrafoveal lesions would appeal to the FDA. Is it possible to apply for approval just for every other dosing in extrafoveal lesions? Is that something you’d be satisfied with?

Cedric Francois

Thank you so much, Phil. So well, let me first take those two questions. With the 18 months, that is not – we had – there was a KOL call that specifically you had that whether that was given us feedback. We have never guided that or mentioned that. So that has been a misunderstanding that I think came out of one of the conferences. As it relates to the every other month extrafoveal data, we are, of course, very, very happy with the data that we have there because every other month for early patients is especially attractive, but we run trials that we believe represents a breakthrough geographic atrophy for all patients, the way we studied it in these studies.

There are three pieces to the application. One is the safety, which I think met or exceeded our expectations. Second is does the drug work? And in that context, the data is very telling. We also have the fellow eye analysis, which further confirms a clear effect from the drug. And the third one is what is the effect size. And in the effect size. That is why we did this post hoc analysis, where you can essentially make the three trials that we ran FILLY, DERBY and OAKS, kind of more equal to each other by making the baseline lesions more by lesion. And there, we’ve seen effects that we believe is in the range of 20% to 25% for the broader population and then with the benefit that we believe may be north of 25% in these patients with extrafoveal lesions. All of that and whether the FDA wants to take up sort of that, of course, is going to be up to them, but we will submit all these data as one package.

Phil Nadeau

That’s very helpful. And then in terms of FDA interactions, you mentioned a disclosure by the end of the year post your FDA meeting. Are you going to wait for the meeting minutes before making the disclosure? Or will you be in a position to do it, do you think right after meeting. And then similarly on the review timelines, I think you suggested an approval in the second half of the year 2022. Just to clarify, does that assume a 6-month review because this is a label expansion?

Cedric Francois

Yes. Thank you so much, Phil. So we do not comment on FDA interactions until we have minutes so we can make a proper and well-qualified representation. So that will be something that we’d like to have in our hands. As it relates to the approval, we set the second half of next year, and that is indeed premised on a priority region. So all drugs in the retina in the last 20 years, as far as we know, have received priority review, and we believe that our product growth in that category as well.

Phil Nadeau

Perfect. And then last question from us is just on EMPAVELI launch. Congratulations on the solid number for the quarter. You mentioned that most patients are switched. Are those, in fact, patients who require transfusions well on Ultomiris, the population that you’re targeting? Or are you getting a broader swath of patients switching to EMPAVELI in the early days?

Cedric Francois

Thank you so much, Phil. I’m going to hand that one over to Adam, but we are very excited that we are breaking into this segment of patients that have more normal hemoglobin levels and may not necessarily be transfusion-dependent happen. Adam?

Adam Townsend

Yes. Thanks, Phil, and thanks for the summary, Cedric. Yes, so of the 1,500 C5 treated patients, we are getting patients from across all of the segments as Cedric described, including the treatment naive segments, which is great. I think that tells us that physicians and patients can see the benefit of elevating the standard of care with PNH, with EMPAVELI. A bonus of those patients, particularly the majority of the Ultomiris switches do have low hemoglobin and require transfusions as we would have expected, they are the ones with the highest unmet need. So as Cedric said, as the team is executing, we’re getting patients from across all of those unmet need segments as well as treatment naive. So progress is looking good.

Phil Nadeau

Perfect. Thank for taking my questions.

Cedric Francois

Thank you, Phil.

Operator

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

Steven Seedhouse

Yes. Thank you and good afternoon. Congrats on the quarter, you not only beat consensus, but I think you beat all six seeking analyst estimates, so kudos to that. My question is actually about GA commercial because you mentioned in your slide that you’re preparing for a potential launch in GA. And I just want to drill down on that and ask, does that mean you’re hiring a field force. What does that look like? And is this an indication that you anticipate Apellis would be able to independently launch in the U.S. without a commercial partner? Thanks.

Cedric Francois

Thank you so much, Steve. Thank you for the kind words. I’m going to hand that one over to Adam.

Adam Townsend

Thanks, Steve. Yes, absolutely, you’re right. We are behind the scenes. We’ve already started to build out our global ophthalmology commercial team in advance of what we see as a blockbuster opportunity. So we’ve hired the marketing and sales leadership within the U.S. affiliate, and we’ve also built out our European team and our affiliates in Germany and Australia. So we truly believe that we can launch this breakthrough product in GA, and we’re preparing thoughtfully behind the scenes to get ready to do so.

Steven Seedhouse

Thanks. Actually, maybe I’ll ask one more again commercial, but back to PNH. The Enable device – just maybe could you update us on the progress there, do you think it’s still necessary, just given the strength of the launch and when might that be coming to market? Thanks again.

Adam Townsend

Yes. Thanks, Steve. Yes, we’re big fans of the Enable device. We’re also thrilled with how our patient support services are helping train new PNH patients. I think there is a great opportunity for us to continue to elevate the standard of care with the launch of the Enable device. So we’re still planning on launching our device. We wanted to get through the first initial phases of the launch. And we also wanted to make sure that all of our systems and processes are working as well as possible. So as we get through the launch period into next year, we will start to look at the best way of us launching the Enable device. We think we will have a big benefit for patients on top of already the benefits they are seeing if they switch to EMPAVELI.

Steven Seedhouse

Thank you.

Cedric Francois

Thank you, Steve.

Operator

Our next question comes from Madhu Kumar with Goldman Sachs. Your line is open.

Madhu Kumar

Hey, everyone. Thanks for taking our question. So kind of a follow-up on Phil’s question about the timing for PEG approval in GA. So even with priority view to have a second half approval would imply relatively early in the first half ‘22 filings. So kind of is it reasonable to assume that preparations to be made for an NDA to get a turnaround in relatively quick time after the FDA interactions by year-end?

Cedric Francois

Thank you, Madhu, and great to hear you. We have – we started working on the preparations for the NDA when we got the top line data. So yes.

Madhu Kumar

Okay. And then on the other kind of expansion indications for EMPAVELI with the caveat that similar being run by Sobi, so you buy throw back as you go out Sobi, about them. How should we think about the design of some of these trials, particularly when we think about like CAD versus the sutimlimab trial or bone marrow TMA versus some of the other kind of registrational trials as indication. Are we going to largely be in line with the kind of scale and scope of what’s been seen previously. And with C3G, similarly, is there kind of a scale and scope we should think about for how big these trials will be practically when they start.

Cedric Francois

Yes. Thank you, Madhu. So there too, when we design these trials, we look at, obviously, at what our competitors and others before us have done. But we evidently have our own interactions with the FDA. We make sure that we have alignment on the endpoints and the design of the studies. And that was applied for all four of the registration studies that we have. And that’s not to mention the fact that we try to harmonize the regulatory feedback from the various geographies as well. Fede, I don’t know if you want to add something to that?

Federico Grossi

No, Cedric. I think you hit on the spot. We try – These are global development programs so not incorporating the FDA feedback, but also the European regulatory bodies are very important, but they do not generally deviate from what you see out there.

Madhu Kumar

Okay, great. Thanks you very much, everyone.

Cedric Francois

Thank you, Madhu.

Operator

Our next question comes from Justin Kim with Oppenheimer & Company. Your line is open.

Justin Kim

Hi, good afternoon. Thanks for taking the questions. Just two, one on commercial and one C3G. With the sort of start forms, can you talk a little bit about how the pace of those forms might have been influenced by the early access programs that are concluding? And then what impact, if any, COVID-19 and the Delta variant had for the third quarter?

Cedric Francois

Thank you, Justin. Adam?

Adam Townsend

Thanks, Justin. Yes. So we – the demand that we’re seeing from a start form and a precision REMS enrollment is agnostic to our transition of the early access program – patients. They are all transitioning across to commercial product, but the demand is out there and it’s real. And we’re really happy with how we’re seeing that progress. So that’s the first part of your question. The second part is – Justin, you asked me if I wanted to launch a rare disease drug in the time of the global pandemic. My answer would always be no. But I’m thrilled with how the team is managing those situations, so about 40% of all of our interactions are in person at the moment. And we’re making the most of those in-person calls. But we’re also – we pivoted very quickly to virtual interactions. So our pallet care educators who help train patients on how to administer the product, etcetera, at the request of physicians. They are interacting virtually and we’re getting hugely positive feedback on that as well. So we pivoted pretty well to virtual interactions as and when needed. We’re also monitoring all of the situations. So we will follow all of the COVID protocols and as and when physicians change their process and allow face-to-face interactions, we will make sure that we’re very compliant with that. But we’re using everything within our arsenal to interact with PNH physicians and PNH patients, and it’s going well launched to date. So we’re happy with what the team is doing.

Justin Kim

Great. Great. And maybe just on C3G. With some of the posters presented at ASN and also you’re taking a look at clinical trials. Just wondering how the company thinks about the IC-MPGN and C3G population post transplant. And so you kind of alluded to maybe the fact that antibody-mediated disease could sort of be an opportunity potentially for pegcetacoplan. So just wondering is this an enriched population and sort of the motivations for having a Phase 3 program as well there.

Cedric Francois

Yes. Thank you, Justin. So we did not specifically study IC-MPGN in a Phase 2 setting, but we believe that the biology is shared between the two diseases. And for those on the call not familiar with that, the real difference between C3G and IC-MPGN is the presence of antibodies in the deposits of C3 that are present in the kidney. So that’s implies the classical pathway and all likelihood involved and an alternative pathway inhibitor such as the anti-factor B or D molecules can be expected to be less efficacious on that. Also hand in hand with that is, of course, the post-transplant setting, where we believe the best-in-class profile will be very important. And we’ve always thought about the C3G or IC-MPGN patients in three buckets, very early patients, typically adolescents often that have been newly diagnosed that may have 10 years or more until they get to a final renal disease and where we believe there is a special place for these oral products that are in development, including our own.

The second category we are starting patients that are getting closer to end-stage renal disease and potentially the need for transplantation or hemodialysis, of course, there, the advantage of having a best-in-class product will outweigh kind of the benefits that may come with these oral products. And then last but not least, in the post-transplant setting where convenience will always come second to having maximum efficacy. So that’s how we think about the world and our trials are designed to be lockstep with that strategy.

Justin Kim

Understood. Thanks and congrats on the progress.

Cedric Francois

Thank you, Justin.

Operator

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

Tazeen Ahmad

Hi, one question for me. So Tim, as it relates to the preferences that you listed about the types of financing that the company is looking into? Is there one, whether it be a royalty agreement or a partnership, some combination of debt that you think is your preferred option right now. And then how important is it to actually have the application filed and accepted by FDA in order to increase your chances of getting the type of deal that you are looking for? Thank you.

Tim Sullivan

Thank you, Tazeen. So look, as we have always done, we will be very thoughtful about how we access capital and that includes taking into consideration timing and feedback of our engagements with FDA, of course, and for certain members of the community that provides capital, that’s going to be important. So, of course, that is a consideration from a timing perspective. Overall, I would say we acknowledge that we need to raise capital in a way that is thoughtful and done as we always have. So, I can’t probably comment any more on what the preferred options are. But one thing we do want is to have all of those options sort of laid out on the table. So, from the timing perspective, we will update you in due course. Thanks for the question.

Operator

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

Colleen Kusy

Great. Thanks for taking our questions and congrats on the quarter. One question for us, I know you have presented the top line DERBY and OAKS data at a number of medical meetings since the results were initially announced. Have you had an opportunity to speak to any European KOLs and how they might view the top line data differently from U.S. position?

Cedric Francois

Thank you, Colleen. That’s an excellent question. And the simple answer to that question is no. So, we have done a lot of outreach work already in Europe, in the U.S. and other regions as well. And Adam, you have been in charge of that work, maybe you can give a quick update on the results from that.

Adam Townsend

Yes. Thanks, Cedric, and thanks, Colleen. So yes, we have – no surprise, right. So, we presented some great data at ASRS and the Retina Society. And we have been interacting through various forms of market research with retina physicians all over the world, including Europe. And we are hearing that consistently, the U.S. or Europe or international that there is a real need for a treatment and the data supports treating patients. And no surprise, very similar to what we are hearing in the U.S. that physicians are impressed with the safety and they are also impressed with the ability of having some flexibility on dosing, monthly and every other month and the ability to treat patients earlier. We get the same consistent feedback in our market research run in Europe as the U.S. there. So hopefully, that answers your question, Colleen.

Colleen Kusy

Yes. That’s helpful. Thank you for taking the question.

Cedric Francois

Thank you.

Operator

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

Alethia Young

Hey guys. Thanks for taking my questions and congrats on the early launch progress. I guess two for me. One, when you are thinking of – I know the majority of our switches, but maybe talk about some of the data that we might see especially in the higher hemoglobin levels and how you think about that might help evolve physicians to think about maybe treating more of their naïve patients or maybe it’s just a matter of time before kind of experience and the switches before they go to the naïve. That’s my first question. And my second question is just do you plan on having any other like data with geographic attribute before you plan on filing the data that you would present in a public or either via a press release? Thanks.

Cedric Francois

Thank you so much, Alethia. I will send the first question Adam’s way.

Adam Townsend

Thanks, Alethia. Yes. So, we are actually seeing EMPAVELI starts across all of the paradigm of the patient mix as I have described. So, the 1,500 C5 treated patients, we are seeing usage – the majority of usage at the moment within that lower falling hemoglobins requirement for transfusions. But we are also getting usage in higher hemoglobin levels and also through patients who have the signs and symptoms of PNH basically. We are also getting EMPAVELI starts in the naïve population, which is great. I think it’s supported by the label and people understand the superiority data within the label. And I think the ASH abstracts helped us get more data out there to have those discussions. One thing we do consistently hear is it’s a small prescriber base with a small patient population. Physicians keep telling us they want to try EMPAVELI in their hardest to treat patients, those that have the highest unmet need, and then they start to broaden out to a wider population. So, typically we have read these drug launches, I think we will start to see as we close the year and enter next year that we will be able to broaden that base of patients as physicians have got through their first second or third patients, for example. So, we expect to see that happen as we go into the stages as the launch next year. And I will hand you back to Cedric for the second part of your question.

Cedric Francois

Yes. Thank you, Alethia. So, that’s an easy answer. So, we made a deliberate effort, as you know, in September, to have kind of very complete presentations at the Retina Society and ASRS and AAO is going to be a recap and kind of concentrating again on kind of the data that we believe will make a difference in the lives of these patients.

Alethia Young

Great. Thank you.

Cedric Francois

Thank you.

Operator

Our next question comes from Yigal Nochomovitz with Citi. Your line is open.

Unidentified Analyst

Hi, this is Carly on for Yigal. Thanks for taking our questions. We have two on GA. First, we were wondering what the regulatory precedent looks like in ophthalmology when one Phase 3 works and one misses the primary endpoint. Is there anything that you can lean on based on previous situations like this that the FDA had faced. And then just a follow-up on the dosing regimen, is the current plan to pursue approval of both the monthly and the every other month regimen, or will you just focus on one? Thanks so much.

Cedric Francois

Thank you so much. So, I look with regulatory precedence, yes, there are regulatory presence. But I think it’s important to point out here what we have outlined before as well, which is just from the FDA’s perspective, the fact that the p-value kind of was on the border of 0.05 needs to be contextualized with the extraordinary p-value that we had in OAKS, right. I mean, statistically, the trial like OAKS and a trial like DERBY in combination are statistically more powerful than, for example, the p-value of 0.04 on two trials. The way I think the FDA will look at this is the way we are going to present it and the way we have talked about it, which is we had an explicit safety profile. We have a drug that we believe clearly works, where the fellow analysis again kind of clearly put that stake in the ground. And then thirdly, and that’s really the key question, what is the effect size when you have three trials between FILLY, DERBY and OAKS, which in effect says that ranges from 12% to 29%, where exactly does it sit. And again, with that analysis, where you are correct for the baseline imbalances in the groups, you get quite a consistent picture; again, indicating that this is going to be great with treatment for these patients. Then as it relates to every other month and monthly, as we indicated earlier as well, we plan to submit all of the data to the FDA as a full package every other month, monthly, all patients with GA and then also the extra foveal data. So, all of that will be presented and then the label discussion will be something that will come at the end of that process.

Unidentified Analyst

Okay. Thanks very much.

Cedric Francois

Thank you.

Operator

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

Ellie Merle

Thank you, guys. Thanks for taking my questions. Just a couple from us, I guess just first on commercial and PNH, just trying to get a sense of kind of the average number of scripts per site. And then maybe like the proportion of REM site sign-up the prescribed patients or kind of submitted the new start forms? I know you kind of alluded to the fact that initially physicians might want to start one or two patients, see how it goes before prescribing more, but curious kind of maybe the breakdown if there have been some sites that have submitted a lot of start forms versus last on some. And then just in terms of geographic atrophy, just curious if you could give us any more color on when we can expect to get the BCVA data or any more info on kind of what happened with the ex-U.S. sites in DERBY. I know that some of the ex-U.S. work has been ongoing, but just curious kind of how that analysis is going? And I guess if we can expect more and more at AAF. Thanks.

Cedric Francois

Thank you, Ellie. Adam, do you want to take the first part?

Adam Townsend

Absolutely. Thanks, Ellie. So yes, we are thrilled with the demand that we are seeing over 115 physicians signed up for REMs over 100 start forms. And not getting into too many details, but we are seeing a nice geographical spread across the U.S. So, it’s a very healthy mix as patients with unmet need are showing up geographically across the U.S. We do have multiple sites and centers that have submitted more than one start forms. So, we are getting follow-on patients, as you would expect, but I am thrilled that the demand seems to be widespread, and that means that, as I said before, that physicians and patients want to start and try and see the benefits of switching to EMPAVELI and then I think the physicians will start to broaden that prescription as we get into the late stages of this year’s launch and into next year’s launch. So, very happy with how we are seeing the start forms pop-up around the U.S. And I will hand you back to Cedric for the second part.

Cedric Francois

Thank you, Adam. Alright. And there were really two parts to your question there as well. I will lead the first one as it relates to the BCVA data, so the best corrected visual acuity, that is one of the functional endpoints that will be assessed at 24 months. So, that’s something that we will have to wait for. As it relates to the investigation into what happened ex-U.S., etcetera, that is still ongoing, but as became quite clear from the analysis that we did, again, with the coherent, that brings the data much closer to each other between the various studies. And that’s something that, again, we will focus on and elaborate on at the American Academy of Ophthalmology, the safety profile, the fact that the drug works with the fellow eye analysis as a clear anchor in that and the three trials, of course. And then the third piece, assessing what the real two effect sizes of the drug where that coherent analysis puts us in the ranges that we discussed before.

Ellie Merle

Great. Thanks so much.

Cedric Francois

Thanks Ellie.

Operator

Our next question comes from Matthew Luchini with BMO. Your line is open.

Matthew Luchini

Hi. Thanks so much for taking the questions and congrats on the quarter. So, first on PNH, in the past, you have talked about sort of 12 days average from prescription to first dose. And I was just wondering as the patient population has diversified a little bit, perhaps since last quarter, if there has been any shift in that number or the inclusion of perhaps a little bit less of your patients, they are taking longer to get through the approval process. And then secondarily, just I was curious, there was no mention of it. If there is anything from an inventory perspective that we need to be mindful of this quarter as it relates to the PNH results. Thank you.

Cedric Francois

Thank you, Matt. Adam?

Adam Townsend

Yes. Thank you, Matt. So, just on the inventory perspective, I will start there. So, basically, our specialty pharmacy holds a very low level of inventory. So, it’s not an issue for us moving forward. But as part of the progress also your first part of the question was how long is it taking to transition patients. So, at the moment, it’s taking on average two weeks to three weeks. And there is some real different reasons why some of that time period is there. And I have not – we are not worried about that time period. So, not a surprise, patients have to follow-up with their physician and follow-up appointments are required. So, sometimes that delays the transition of the stock for commercial EMPAVELI prescription. Also, we want to make sure that we have signed everybody up who is winning and opts into our patient services and that also happens and when we would schedule the visits to help support and train patients at their request. So, that activity is happening. A few things around Q4 to think forward looking, right, I actually think there will be some seasonality in that, right. When moving into Q4, there are some holidays, which have an impact of when patients want to transition from a start form to a prescription to a commercial product, we have Thanksgiving coming up. We also have the December holidays. So, there will be some seasonality within that time period. So, that’s something to think about. But two weeks to three weeks at the moment, the feedback that we get once we are holding the patient’s hands through that transition period and once we train them, they are on the drug, is very positive for our patient support programs. So, I do hope as we transition to the broader population, we will be able to shrink that time from start form to commercial drug. But it’s – as I would expect it to be where we are in the launch. Matt, hopefully, that answers your questions on patients and inventories.

Matthew Luchini

Yes. Thank you.

Cedric Francois

Thank you, Matt.

Operator

Our next question comes from [indiscernible] with Jefferies.

Unidentified Analyst

Hi team. This is [indiscernible] on for Chris. What lessons learned and best practices from the entire GA study experience, would you potentially apply to your intermediate AMD study? Anything you would do differently directly because of that experience. Thank you very much.

Cedric Francois

Thank you so much. So, we are – we are figuring out still how these intermediate AMD studies need to be run. That is something that will take a little bit of time. What we have learned is that in the GA studies, when you look at the zone outside of the dead retina, right. It’s not like the retina all of sudden goes from dead to alive and well. There is a zone outside, which is probably very similar to what we see in intermediate AMD. That is something that we studied and presented last year and what we call this iRORA to cRORA conversion. It’s a very interesting way of measuring not pure geographic atrophy, but the earlier reasons. There is going to be a question how the FDA looks at that.

Unidentified Analyst

Thank you very much.

Cedric Francois

Thank you.

Operator

Our next question comes from Joseph Stringer with Needham & Company. Your line is open.

Joseph Stringer

Hi everyone. Congrats on the quarter and thanks for taking my questions. Just a quick one on the pipeline on ALS, I want to get your thoughts on, given the competitive landscape and enrollment. Where your thoughts are around the sort of a threshold or a clinically meaningful readout from that study, whether it would be on the CAFS score or other genomic biomarkers? Thank you.

Cedric Francois

Thank you so much, Joe. So, I am going to hand that question over to Federico to answer.

Federico Grossi

Sorry. So, the question was what threshold do we expect or…?

Cedric Francois

What would – considering the competitive landscape setting, what do you expect from the clinical studies in terms of the endpoint?

Federico Grossi

Yes. So, we are looking at the combined mortality and efficacy. And we are expecting on function to have a change of around one unit per month and mortality to have a difference of 20% versus placebo. That’s what we have powered the studies for. Does that answer your question?

Joseph Stringer

Yes. Thank you very much.

Cedric Francois

Thank you, Joe.

Operator

Our next question comes from Laura Chico with Wedbush Securities. Your line is open.

Laura Chico

Good afternoon guys. Thanks very much for taking my question. I have got two on GA. So first, I think earlier, you commented Cedric, clearly, BCVA is probably not the best endpoint to use to gauge visual acuity in GA patients. But I guess what I am trying to understand is if you could kind of contextualize how do you see overall visual acuity actually fitting into the review process for pegcetacoplan?

Cedric Francois

Yes. Thank you, Laura. So BCVA with the FDA was specifically indicated as not relevant in the efficacy analysis. So, that was a whole process that NIH went through with the FDA a couple of years ago and where Wiley Chambers in the end same as you said, I think we can all agree that a dying retina is a bad thing. And the reason why BCVA is a poor measure for GA, as you know, is that it’s really a reflection only of what happens in the fovea and not for what goes on in the periphery of the macula.

Laura Chico

Okay. That’s helpful. And then kind of one more related to GA and then, I guess, one financial question for Tim. In GA, is there a precedent for any recent drug approvals in the ophthalmology space where you get approval on one study and perhaps a subset analysis on the second one. And then the financing question for Tim or probably also Cedric, are there scenarios in which you would push back the GA submission further out than in the first half of ‘22, perhaps to just engage with partners in a little bit more detail. Thanks very much. I appreciate it.

Cedric Francois

You’re welcome. So, on the precedence, I think an interesting precedence on what AMD would be visiting. But I think one of the features of this division at the FDA that are very pragmatic. And I mean we have three trials FILLY, DERBY and OAKS, two of them with high statistical significance for monthly and every other month. The third one will be directionally positive. The FDA is going to look at the totality of the data and making assessments as to where they think it lies. And again, as mentioned earlier, they will look at safety, they will look at whether the drug is biologically active, and they will find out whether the effect size is clinically relevant. So, those are kind of the steps we have to go through. And we believe that this will become a breakthrough and the first therapy for these patients. And then on the GA submission, so it’s very much our plan to submit in the first half of next year. I don’t know, Tim, if you want to add something to that.

Tim Sullivan

Yes. I would just say that I don’t think we are going to change anything operationally around financing. Our view from the GA perspective is that we are going to plow ahead with our filing. We have a very high degree of confidence in the probability of approval. So, the financing will still cater to that.

Laura Chico

Thanks very much.

Cedric Francois

Thank you, Laura.

Operator

There are no further questions. I would like to turn the call back over to Cedric Francois for any closing remarks.

Cedric Francois

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

Operator

This does conclude the program. Thank you for participating. You may now disconnect.

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