Apellis Pharmaceuticals - Earnings Call - Q3 2021

Transcript

Speaker 0

Good day and thank you for standing by. Welcome to the Third Quarter twenty twenty one Apillis Pharmaceuticals Inc. Earnings Conference Call. At this time, all participants are in a listen only mode. After the speakers' presentation, there will be a question and answer session.

Please be advised that today's conference may be recorded. I would now like to hand the conference over to your host today, Meredith Kaya, Vice President of Investor Relations. Please go ahead.

Speaker 1

Good afternoon, and thank you for joining us to discuss Apellis' third quarter twenty twenty one financial results. With me on the call are Co Founder and Chief Executive Officer, Doctor. Cedric Francois Chief Commercial Officer, Adam Townsend Chief Medical Officer, Doctor. 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'll turn the call over to Cedric.

Speaker 2

Thank you, Meredith, and good afternoon to everyone joining us today for our conference call. The third quarter was another exceptional period for Atenis, highlighted by strong U. S. Commercial execution for Empavedi in PNH, our Phase III DURBI and OAX data, which we believe position bexetacoplan 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 was the top line results from Derby and OAX. In these studies, texitacoplan showed a clinically meaningful reduction in GA lesion growth and a favorable safety profile with both monthly and every other month dosing. Importantly, pexitacoplan showed an even greater effect in patients with extra foveal lesions, supporting treatment earlier in disease progression. Ferre will review these results shortly. With these data, we believe pexitacoplan 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 path, 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 Empavelli, the first and only targeted C3 therapy approved for the treatment of PNH.

In our first full quarter since launch, Empavelli delivered $5,300,000 in net product revenue, exceeding our expectations and showed strong momentum across each of our launch metrics. Additionally, Pexeta Coplan, which will be known as Aspavelli in The EU and marketed by Sovi, 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, Asclavelli will become the first new therapeutic approach for PNH in the European Union since 02/2007. Our efforts in PNH are just the first steps in building our rare disease franchise.

Together with Sovi, we are continuing to advance a robust portfolio across multiple indications. We have a steady cadence of milestones over the next twelve to eighteen months, including the start of three late stage trials designed to support registration in four separate indications. We are also continuing to enroll patients in our potentially registrational Phase two ALS study. Ultimately, our ambition is to become the global leader in complement. Bexsutacoplan represents the foundation for this goal and 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 complements 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?

Speaker 3

Thank you, Cedric. As Cedric mentioned, our Empivalli 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 wants Empiveli has access to this important new medicine. As we said previously, within The U. S, there are approximately fifteen hundred patients who are currently being treated with C5 inhibitors and another one hundred and fifty 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 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 Empiveli 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 launch through October.

Consistent with last quarter, we are finding that C5 inhibitor switch patients are the vast majority of new Empivalli starts with about seventy percent 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 payers who cover approximately 85% of all U. S. PNH prescriptions. To date, 14 of these 20 have agreed to place Empiveli in a positive formulary position.

We remain on track to be on formulary with approximately 90% of plans by the end of the year.

Speaker 4

In parallel with the execution of the Empivalli launch, our commercial team is preparing for a potential approval of

Speaker 3

pegzetacoplan 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 pegzetacoplin if approved. As

Speaker 2

you can

Speaker 3

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 Ferre to review our clinical developments.

Ferre?

Speaker 4

Thank you, Adam. I'm going to spend the next few minutes providing a high level review of the derbionox 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 OCH study, monthly and every other mass treatment with bexetacoplin met the primary endpoint providing a clinically meaningful and highly statistically significant reduction in GA lesion growth compared to pool sham at twelve months.

In a pre specified analysis, pexetacoplan showed an even greater reduction in patients with extra folio lesions by as much as thirty five percent in the monthly arm. As a reminder, GA typically begins with extra folio lesions that later progress into the fovea, with research suggesting that as many as eighty five percent of patients start the lesion outside of the fovea. Hexatecoplan narrowly misses statistical significance in Derby with a p value of 0.0528 in the monthly treatment arm. However, exotacoplan again showed a greater reduction in lesion growth in extra further lesions as you can see in this slide. A quick question is why there'll be missed.

In the past hoc analysis, we observed unexpected imbalances in baseline characteristics known to be associated with rapid disease progression. In Derby, this imbalances reflected the presence of faster progress in patients enrolling in the bexetacoplin use as compared to the sham groups, which may have contributed to the mix. Turning to the fellow analysis further confirming the treatment effect, pixatacotlin 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 eye 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 everyotumab groups, you start to see separation of the curves between the pixetacopan treated eyes and the untreated fellow eyes. And finally, when you look at the monthly groups, both Derby and Oates show an even more robust separation between exotacoplin treated eyes versus the untreated fellow eyes. In terms of safety, exotacoplin demonstrated a favorable safety profile across both studies.

The full rate of neonatal excretions was six percent of patients in the monthly treatment group, four point one percent in the every other month treatment group and two point four percent in the sham group. And rate of endophthalmitis and intraocular inflammation were generally in line with those reported in studies of other intravitreal therapies. Between DERBY, OCHs and our Phase II Phealy study, we now have results across more than 1,500 patients from three randomized, well controlled studies providing a robust set of steps, which we believe demonstrate berceptacoplan's efficacy and safety and supports approval. We remain on track to submit our NDA in the first half of twenty twenty two. I will now turn the call to Tim for a review of the financial results.

Tim?

Speaker 5

Thank you, Ferre. Since we issued a press release earlier today with the full financial results, I will just focus on the highlights for the third quarter of twenty twenty one. In the third quarter of twenty twenty one, total revenue was $5,700,000 which primarily consisted of $5,300,000 of Empiveli net product revenue, a strong start for the launch and additional revenue associated with our collaboration with Sovi. R and D expenses were $88,000,000 G and A expenses were $46,000,000 and we reported a net loss of $196,000,000 As of 09/30/2021, Apellis had $430,000,000 in cash and cash equivalents, which are expected to fund our operations into the third quarter of twenty twenty two. A reminder that the $50,000,000 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 gating spend tied to certain de risking milestones and managing hiring across the organization during this interim period. With an approved product in Empivalli, 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?

Speaker 2

Thank you, Tim. The first nine months of 2021 represented a transformative period for Apellis as we launched our first commercial product Empavedi in PNH and showed a clinically meaningful reduction of GA lesion growth with a favorable safety profile in the Phase III DURBI and OAX studies. We are committed to building on this momentum to further support growth and advance our leadership position in complement. Over the next twelve to eighteen months, we expect a number of key milestones across our portfolio. Beginning with the remainder of 2021, we expect Sovi to receive EU approval for bexetacoplan in PNH, to have regulatory feedback from the FDA in GA and to initiate a Phase III study in immune complex membranoproliferative glomerulonephritis or iCMPGN and C3 glomerulopathy or C3G.

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

Speaker 6

the

Speaker 2

first half of twenty twenty two, we expect to submit our new drug application in GA to the FDA to begin pre submission discussions with the European regulators about plans for our EU submission and for Sobe to begin launching Astaviri 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 coincident with AAV vector administration for gene therapies and other indications. In the second half of twenty twenty two, we expect to initiate a Phase III study in intermediate AMD pending regulatory feedback to submit an IND for APL-ten thirty, our first in class brain active C3 inhibitor for neurodegenerative diseases to report the twenty four month results from Derby and OX 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.

Speaker 7

Our first question comes from Umer Raffat with Evercore. Your line is open.

Speaker 8

Thanks so much for taking my question. I would love to get any initial feedback from the FDA on Phase 3s? And if you could remind us of any bottlenecks going into the end of next year that would also be great. And then speaking to maybe beyond GA, which I'm sure will get a ton of attention on I'm the pipeline indications and downstream to continue to diverse batch set. Could you maybe look into the opportunity around some of those modifications, maybe especially C3G, which seems like a substantial one near term.

Especially, I understand Zuliris has some use of label C3G.

Speaker 3

Do you have any sense for

Speaker 8

what proportion of patients that try to complement the past or are currently and what the penetration is? I'm really understanding the utility of complementing practice in that indication.

Speaker 2

Thank you so much. I don't know if it was my line or not, but I had a very hard time hearing the questions. I'm going to quickly repeat them to make sure I got them right. So, you wanted to know the insights, or what the FDA process would look like, then about what we have going on beyond GA with Empaventi pipeline and specifically C3G. Is that correct?

Speaker 8

So far the bottlenecks are going in India next year? And then specifically on T3G, you just look at an opportunity for us there and maybe tell us a little bit more about how much is currently being used in the indication?

Speaker 2

Yeah. Thank you so much. So, as it relates to the Phase III, so as we have outlined earlier, we have submitted a request to the FDA for a meeting regarding the DURBI and OX studies. And before Christmas, we plan to provide an update to The Street as to what the regulatory landscape looks like. Specifically, are two important elements that we need to or are hoping to get clarity on.

One is whether the FDA would expect us to wait for the twenty four 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 Empivari 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 III clinical trial, and our objective is to identify whether Empiviri can be a treatment for that indication. But both based on the mechanism, based on the Phase II 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 iCMPGN components, 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.

Speaker 8

Okay. So I guess one more. I appreciate that you mentioned in your prepared remarks that you are exploring all options for financing and for getting your rental a little bit. I understand there's a lot of concern on financing right now. Are you open to maybe some of the less traditional reps beyond that?

Could you maybe tell us a little bit about what your preferred solution would be and whether you're looking first and foremost at these non traditional or alternative routes or first and foremost?

Speaker 2

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

Speaker 5

Sure. And I'll do my best to also feedback the question. I think you were asking, you know, 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 those is that correct, Sean, first of all?

Speaker 8

Yes, sure.

Speaker 9

Okay. Yes. So we're aware of

Speaker 5

the current conditions that could impact our ability to raise capital and we're exploring all of those options. Those 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'll look at all options.

Speaker 8

Thanks so much.

Speaker 2

Thank you so much.

Speaker 7

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

Speaker 10

Hey guys. Thanks so much for taking the question. Can you hear me all right?

Speaker 2

Yes, we can hear you well Anupam.

Speaker 10

All right, 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.

Speaker 2

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

Speaker 11

Thanks, Anupam. Hopefully, you can hear me too. So yes, we're very, very pleased with the progress of Empivalli launch in PNH. What we're finding, Anapam, is that the transition of start forms to commercial patients, it takes between two and three weeks, which is pretty normal for rare disease drug launch. We get hugely positive feedback on the process from not only from physicians, but also from 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 two to three weeks to transition a patient across. Hopefully that answers your question.

Speaker 10

Thanks so much for taking our question.

Speaker 2

Thank you.

Speaker 7

Next question comes from Phil Nadeau with Cowen and Company. Your line is open.

Speaker 6

Good afternoon. Congrats on the quarter and thanks for taking our questions. A couple on GA for us and then one on Empivalli. On GA, in terms of the regulatory strategy, we've had some KOLs suggest that the eighteen month data could strengthen the package. Is that something you're considering?

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 month dosing in extrafoveal lesions? And is that something you'd be satisfied with?

Speaker 2

All right. Thank you so much, Phil. So, well, let me first take those two questions. With the eighteen months that is not we had there was a KOL call that specifically you had was given as 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 extrafovial 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 ran trials that, we believe represents a breakthrough in 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 Fili, Derby and Toux kind of more equal to each other by making the baseline lesions more bypassed.

And there we see an effect size that we believe is in the range of twenty percent to twenty five percent for the broader population and then with the benefit that we believe may be north of twenty five percent in these patients with extra 40. All of that and whether the FDA wants to take cuts out of that of course is going to be up to them. But we will submit all these data as one package.

Speaker 6

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 think right after the meeting? And then similarly on the review timelines, think you suggested an approval in the second half of the year 2022.

Just to clarify, does that assume a six month review because this is a label expansion?

Speaker 2

Yes. Thank you so much, Phil. So we do not comment on FDA interactions until we have minutes and we can make a proper and well qualified representation. So that will indeed be something that we would 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 review. So all drugs in the retina in the last twenty years as far as we know have received priority review and we believe that our products will fall in that category as well.

Speaker 6

Perfect. And then last question from us just on Empivalli's launch. Congratulations on the solid number for the quarter. You mentioned that most patients are switched. Are those in fact patients who require transfusions while on ULTOMIRIS, the population that you're targeting?

Or are you getting a broader swath of patients switching to Empivalli in the early days?

Speaker 2

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. Adam?

Speaker 11

Yes. Thanks, Phil. And thanks for the summary, Cedric. Yes, so of the fifteen hundred C5 treated patients, we are getting patients from across all of the segments, as Cedric describes, including the treatment naive segments, which is great. I think that tells us that physicians and patients can see the benefit of elevating their standard of care with PNH with Empiveli.

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're the ones with the highest unmet need. So as Cedric said, and 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.

Speaker 6

Perfect. Thanks for taking my questions.

Speaker 2

Thank you, Phil.

Speaker 7

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

Speaker 12

Great. Thank you. Good afternoon. Congrats on the quarter. You not only beat consensus, but I think you beat all 16 analyst estimates.

So kudos to that. My question is actually about GA commercial because you mentioned in your slide that you're preparing for 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 Appellis would be able to independently launch in The U.

S. Without a commercial partner? Thanks.

Speaker 2

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

Speaker 11

Thanks, Steve. Yes, absolutely, you're right. We are behind the scenes. We have already started to build out our global ophthalmology commercial team in advance of what we see as a blockbuster opportunity. 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.

Speaker 12

Thanks. Actually, maybe I'll ask one more again commercial, but back to PNH, the enabled 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? Yes.

Speaker 11

Thanks, Steve. Yes, we're big fans of the enabled device. We're also thrilled with how our patient support services are helping train our new PNH patients. I think there's a great opportunity for us to continue to elevate the standard of care with the launch of the enabled device. So we're still planning on launching that 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 were working as well as possible. So as we get through the launch period into next year, we'll start to look at the best way of us launching enabled device. We think it will have a big benefit for patients on top of already the benefits they're seeing if they switch to pempiveli.

Speaker 7

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

Speaker 13

Hey everyone. Thanks for taking our questions. So kind of 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 a relatively early in the first half twenty twenty two filing. So kind of is it reasonable to assume that preparation to be made for an NDA to get a turnaround in relatively quick time after the FDA interactions by year end?

Speaker 2

Thank you, Madame. Great to hear you. We have we started working on the preparations for the NDA when we got the top line data. So yes.

Speaker 13

Okay. And then on the other expansion indications for Empivalli, with the caveat that some of them are being run by Sobe, so you might throw back to me as you go ask Sobe about them. How should we think about the design of some of these trials, particularly when we think about like CAD versus the sotimlimab trial or bone marrow TMA versus some of the other kind of registrational trials as indication? Like are they 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?

Speaker 2

Yes. Thank you, Madhu. So there 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 registrational 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. Ferri, I don't know if you want to add something to that.

Speaker 4

No, Fieri, 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.

Speaker 13

Okay, great. Thanks very much, everyone.

Speaker 2

Thank you, Madhu.

Speaker 7

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

Speaker 10

Hi, good afternoon. Thanks for taking the questions. Just two, one on commercial and one on C3G. With the sort of start forms,

Speaker 8

can you talk a little

Speaker 10

bit about how, the pace of those forms might have been influenced by the early access programs that are concluding? And what impact if any COVID-nineteen and the Delta variant had for the third quarter?

Speaker 2

Thank you, Justin. Adam?

Speaker 11

Thanks, Justin. Yeah, so we the demand that we're seeing from a start form and the physician REMS enrollment is agnostic to our transition of early access program patients. They're 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, if 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 Appellate Care educators who help train patients on how to administer the product, etcetera, at the request of physicians. They're 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'll follow all of the COVID protocols and as and when physicians change their process and allow face to face interactions, we'll 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.

Speaker 10

Great, great. And maybe just on C3G, with some of the posters presented at ASN and also sort of taking a look at clin trials, just wondering how the company thinks about the iCMPGN and C3G population And Cedric, you kind of alluded to maybe the fact that antibody mediated, disease could sort of be an opportunity potentially for pixitaclopin. So just wondering, is this an enriched population sort of the motivations for having a Phase II program as well there?

Speaker 2

Yes. Thank you, Justin. So we did not specifically study iCMPGN in a Phase II setting. But we believe that the biology is shared between the two diseases. And for those of the on the call not familiar with that, the real difference between C3G and iCMPGin is the presence of antibodies in the deposits of C3 that are present in the kidney.

So that implies that the classical pathway is in 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 iCMPGIN patients in three buckets: very early patients, typically adolescents often that have been newly diagnosed that may have ten years or more until they get to final renal disease and where we believe there's a special base for these oral products that are in development, including our own the second category, which are 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 the benefits that may come with these oral products.

And then last but not least, in a 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 in lockstep with that strategy.

Speaker 10

Understood. Thanks and congrats on the progress.

Speaker 2

Thank you, Justin.

Speaker 7

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

Speaker 14

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're looking for? Thank you.

Speaker 5

Thank you, Tazeen. So look, as we've 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 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 anymore 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 a timing perspective, we'll update you in due course. Thanks for the question.

Speaker 7

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

Speaker 15

Great. Thanks so much for taking our questions and congrats on the quarter. One question for us. I know you presented the top line DERVOY HOCH data at a number of medical meetings since the results were initially announced. Guess have you had any opportunity to speak to any European KOLs and how they might view the top line data differently from U.

S.-based Physicians?

Speaker 2

Thank you, Colleen. That's an excellent question. And the simple answer to that question is no. So we've done a lot of outreach work already, in Europe, in The U. S.

And other regions as well. And Adam, you've been in charge of that work. Maybe you can give a quick update on the results from that.

Speaker 11

Yes. Thanks, Cedric. And thanks, Colleen. So yes, we've no surprise, right? So we presented some great data at ASRS and the Retina Society, and we've been interacting through various forms of market research with retina physicians all over the world, including Europe.

And we're hearing that consistently, U. S, 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're hearing in The U. S. That physicians are impressed with safety and they're 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.

Speaker 15

Yes, that's helpful. Thank you for taking the question.

Speaker 2

Thank you.

Speaker 7

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

Speaker 16

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

Thanks.

Speaker 2

Thank you so much, Alethia. I'll send the first question Adam's way.

Speaker 11

Thanks, Alethia. Yes, so we are actually seeing Empivalli starts across all of the paradigm of the patient mix as I've described. So the 1,500 C5 treated patients, we're seeing usage, the majority of usage at the moment within that low falling hemoglobin's requirement for transfusions. But we're also getting usage in higher hemoglobin levels and also through patients who have the signs and symptoms of PNH basically. We are also getting Empivalli starts in the naive 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 only help us get more data out there to have those discussions. One thing we do consistently here is, it's a small prescriber base with a small patient population. Physicians keep telling us they want to try Empivalli in their hardest to treat patients, those that have the highest unmet need, and then they'll start to broaden out to a wider population. So typical with rare disease drug launches, I think we'll start to see as we close the year and enter next year that we'll 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 of the launch next year. And I'll hand you back to Cedric for the second part of your question.

Speaker 2

Yes. Thank you, Alicia. 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 the SRS. And the AAO is going to be a recap and kind of concentrating again on kind of the data that we believe will make a huge difference in the lives of these patients.

Speaker 16

Great. Thank you.

Speaker 2

Thank you.

Speaker 7

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

Speaker 1

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 three works and one misses the primary endpoint. Is there anything that you can lean on based on previous situations like this that the FDA has faced?

And then just to follow-up on the dosing regimen, is the current plan to pursue approval of both the monthly and the every other month regimens? Or will you just focus on one? Thanks so much.

Speaker 2

Thank you so much. So look, with regulatory precedent, yes, there are regulatory precedents. But I think it's important to point out here, what we've 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 OX, right? I mean statistically, a trial like OX and a trial like DURBI in combination are statistically more powerful than for example, the Vivo, the 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've talked about it, which is we had an exquisite safety profile.

We have a drug that we believe clearly works, where the fellow eye analysis again kind of clearly puts 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 Philly, Derby and OAX with an effect size that ranges from twelve percent to twenty nine percent, where exactly does it fit? And again with that analysis where you correct for the baseline imbalances in the groups, you get quite a consistent picture. Again, indicating that this is going to be breakthrough treatment for these patients.

Then as it relates to every other month and month, 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.

Speaker 1

Okay. Thanks very much.

Speaker 2

Thank you.

Speaker 7

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

Speaker 17

Hey guys, thanks for taking the 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 REMS site sign up that have prescribed patients or, you know, kind of submitted the new starts 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 less 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 to learn more at AAS? Thanks.

Speaker 2

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

Speaker 11

Absolutely. Thanks, Ellie. So yes, we're thrilled with the demand that we're seeing over 115 physicians signed up for REMS, over 100 start forms. And not to get into too many details, but we're 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 form. So we're getting follow on patients as you would expect. But I'm thrilled that the demand seems to be widespread.

And that means that, as I've said before, that physicians and patients want to start and try and see the benefits of switching to Empivalli. And then I think the physicians will start to broaden that prescription as we get into the later stages of this year's launch and into next year's launch. So very happy with how we're seeing the start force pop up around The U. S. And I'll hand you back to Cedric for the second part.

Speaker 2

Thank you, Adam. All right. And there were really two parts to your question there as well, Eli. 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 twenty four months. So that's something that we will have to wait for.

As it relates to the investigation into what happened ex U. S, U. S, etcetera, that is still ongoing. But, as became quite clear from the analysis that we did, again with the covariance, 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 true effect size is of the drug where that coherent analysis puts us in the ranges that we discussed before.

Speaker 0

Great. Thanks so much.

Speaker 8

Thanks, Jenny.

Speaker 7

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

Speaker 9

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

Speaker 2

Thank you, Matt. Adam?

Speaker 11

Yes. Thank you, Matt. So just on the inventory perspective, I'll 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 to three weeks. And there's some real different reasons why some of that time period is there. And I'm not remotely 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 a start form to a commercial Empivalli prescription. Also, we want to make sure that we've signed everybody up is willing and opts in to our patient services, and that also happens. And then 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'll be some seasonality in that, right? We're moving into Q4. There's some holidays, which have an impact of when patients want to transition from a start form to a prescription and to a commercial product that we have Thanksgiving coming up. We also have the December holidays. So there'll be some seasonality within that time period.

So that's something to think about. But two to three weeks at the moment, the feedback that we get once we're holding a patient's hands through that transition period and once we train them up and they're on the drug is very positive for our patient support programs. So I do hope as we transition to the broader population, we'll 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 inventory.

Speaker 5

Thank you.

Speaker 8

Thank you, Matt.

Speaker 7

Our next question comes from Kambe Ziazzi with Jefferies. Your line is open.

Speaker 10

Hi, team. This is Kambe 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.

Speaker 2

Thank you so much. So 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've 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, what we call this iRORA to cRORA conversion. It's a very interesting way of measuring not pure geographic atrophy, but the earlier lesions. And there's going to be a question how the FDA looks at that.

Speaker 10

Thank you very much. Thank you.

Speaker 7

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

Speaker 6

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

Speaker 2

Thank you so much, Joey. So I'm going to hand that question over to Federico to answer.

Speaker 6

Hello?

Speaker 2

Yes. We can hear Yes,

Speaker 4

couldn't unmute. So the question was, what threshold do we expect or

Speaker 2

would considering competitive landscape fit in, what you expect from the clinical studies in terms of the endpoint?

Speaker 4

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 twenty percent versus placebo. That's what we have powered the studies for. Does that answer your question?

Speaker 6

Yes. Thank you very much. All

Speaker 8

right. Thank you.

Speaker 2

Thank you, Joey.

Speaker 7

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

Speaker 18

Good afternoon, guys. Thanks very much for taking the question. I've 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'm trying to understand is if you could kind of contextualize how do you see overall visual acuity actually fitting into the review process for pegcitacaplan?

Speaker 2

Yes. Thank you, Laura. So BCVA with the FDA was specifically indicated as not relevant in the efficacy analysis. So it was a whole process that the NIH went through with the FDA a couple of years ago and where, Wiley Chambers in the end famously 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.

Speaker 18

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 approval in the ophthalmology space where you get approval on one study and perhaps a subset analysis on a 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 the first half of 'twenty two perhaps to just engage with partners in a little bit more detail? Thanks very much.

Appreciate it.

Speaker 2

You're welcome. So on the precedent, I think an interesting precedent in wet AMD would be Visuddin. But I think one of the features of this division at the FDA is that they're very pragmatic, right? I mean we have three trials, Philly, Derby, OX, two of them with high statistical significance for Monctane every other month. The third one directionally positive.

The FDA is going to look at the totality of the data and make an assessment 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 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.

Speaker 5

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

Speaker 18

Thanks very much guys.

Speaker 2

Thank you, Laura.

Speaker 7

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

Speaker 2

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.

Speaker 7

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