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Operator
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 Appellus' 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'll 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 Atedes, highlighted by strong U.S. commercial execution for Empa-Veti in P&H, our phase three Derby and Oaks data, which we believe position back 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 Oaks. In these studies, pexetacoplans showed a clinically meaningful reduction in GA lesion growth and a favorable safety profile with both monthly and every other month dosing. Importantly, pexetacoplans showed an even greater effect in patients with extra fovea lesions, supporting treatment earlier in disease progression. Fede will review these results shortly. With these data, We believe Pexita Copeland 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 in 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 Empavel, 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, Texeta Copeland, 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, Asklaveli 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 Shobi, 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 three late-stage trials designed to support registration in four separate indications. We are also continuing to enroll patients in our potentially registrational Phase II ALS study. Ultimately, our ambition is to become the global leader in complement. Bexita Copeland 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 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.
Meredith
Thank you, Cedric. As Cedric mentioned, our Emper Valley 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 Emper Valley 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 level. 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 Empavelli 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 Empaveli starts, with about 70% of switches coming from Altamiris. 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 percent of all US P&H prescriptions. To date, 14 of these 20 have agreed to place Emper Valley in a positive formulary position. We remain on track to be on formulary with approximately 90 percent of plans by the end of the year. In parallel with the execution of the Emper Valley launch, our commercial team is preparing for a potential approval of Pexetacotlin 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 pegceticoplin 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 war. I will now turn the call over to Fede to review our clinical development.
Cedric
Fede? Thank you, Adam. I'm going to spend the next few minutes providing a high-level review of the Derby and OX 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 OX study, Monthly and every other mass treatment with Bexeta-Copeland met the primary endpoint, providing a clinically meaningful and highly statistically significant reduction in GA lesion growth compared to poor sham at 12 months. In a pre-specified analysis, Bexeta-Copeland showed an even greater reduction in patients with extra forward lesions by as much as 35% in the monthly arm. As a reminder, GA typically begins with extra fovea lesions that later progress into the fovea, with research suggesting that as many as 85% of patients start with lesions outside of the fovea. Breast at the Copeland narrowly misses statistical significance in Derby, with a p-value of 0.0528 in the monthly treatment arm. However, pexetacoplin again showed a greater reduction in lesion growth in extra-further lesions, as you can see in this slide. A key question is why DERBY missed. In a post hoc analysis, we observed unexpected imbalances in baseline characteristics known to be associated with rapid disease progression. In DERBY, these imbalances reflected the presence of faster-progressive patients enrolling in the pexetacoplin use as compared to the sham groups, which may have contributed to the miss. Turning to the fellow analysis, further confirming the treatment effect, Bexetacoplin is the first investigation on 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 DERVI and OPS. Overall, as expected, we do not see a big difference in the rate of lesion growth in the study eye versus fellow eyes in the sham treatment patients, which confirms the relevance of this analysis. When you look at the every-month groups, you start to see separation of the courts between the pexetocoplan-treated eyes and the untreated fellow eyes. And finally, when you look at the monthly groups, both Derby and OGS show an even more robust separation between pexetocoplan-treated eyes versus the untreated fellow eyes. In terms of safety, pexetocoplan demonstrated a favorable safety profile across both studies. The pool rate of new on-site excavations was 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 rate of endophthalmitis and intraocular inflammation were generally in line with those reported in studies of other intravitreal therapies. Between Derby, Oaks, and our Phase II Philly study, We now have results across more than 1,500 patients from three randomized world-controlled studies providing a robust data set which we believe demonstrates Percetacoplin'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?
Fede
Thank you, Fede. Since we issued a press release earlier today with the full financial results, I will just focus on the highlights for the third quarter of 2021. In the third quarter of 2021, total revenue was $5.7 million, which primarily consisted of $5.3 million of EMPA Valley net product revenue, a strong start for the launch, and additional revenue associated with our collaboration with SOBE. 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, Appellus 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 gating spend tied to certain de-risking milestones and managing hiring across the organization during this interim period. With an approved product in EMPA Valley, 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 nine months of 2021 represented a transformative period for Avedis 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 3 Derby and Oaks studies. We are committed to building on this momentum to further support growth and advance our leadership position in complements. 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 Shobi to receive EU approval for pexetacoplan and PNH, to have regulatory feedback from the FDA and GA, and to initiate a phase 3 study in immune complex membranocolliferative glomerulonephritis, or ICMPGN, and C3 glomerulopathy. or C3G. Additionally, our partners should be 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 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, to begin pre-submission discussions with the European regulators about plans for our EU submission, and for SOBI to begin launching AspaVedi 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 2022, we expect to initiate a Phase III study in intermediate AMD pending regulatory feedback, to submit an IND for APL1030, 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.
Tim
To ask a question, please press star then 1. If your question has been answered and you'd like to remove yourself in the queue, press the pound key. Our first question comes from Uma Rafat with Evercore. Your line is open.
C3 glomerulopathy
Thanks so much for taking my question, Dan. Thanks for taking my question, Chris. I would love to get any initial feedback that you've had 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 speaking to me beyond GA, which I'm sure will get a ton of attention, Michael, It could be progress on the pipeline indications and downstream to continue to a diverse batch set. Could you maybe look into the opportunity around some of those modifications, maybe especially C3G, which it seems like we know is a substantial one in near term? Essentially, I understand Solera's got some use off-label with C3G. Do you have any sense for what proportion of patients have tried? compliments have passed or are currently and what the penetration is. What are your understanding of utility and compliments? Is it your practice in that engagement?
Cedric Francois
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 M580, the pipeline, and specifically C3G. Is that correct?
C3 glomerulopathy
No. I'm so sorry, but based on that, what does the agency say so far about the bottlenecks of our company and the next year, and then specifically on C3G, if you just look at an opportunity for us there, and maybe tell us a little bit more about how it's currently being used in the occasion.
Cedric Francois
Yeah, thank you so much. So as it relates to the phase three, so as we have outlined earlier, we have submitted a request to the FDA for a meeting regarding the Derby and Oaks studies. And before Christmas, we plan to provide an update to the street as to what the regulatory landscape looks like. Specifically, there 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 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 Ultramiris are sometimes used off-label. We are running a phase three clinical trial, and our objective is to identify whether Empaveri 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. Okay.
C3 glomerulopathy
Thank you so much. I guess one more. I appreciate that you mentioned in your remarks that you are exploring options for financing and for spending 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 routes beyond that? And could you tell us a little bit about what your preferred solution would be and, you know, whether you're looking first and foremost at these non-traditional or alternative routes or first and foremost
Cedric Francois
Thank you so much. I will hand that one over to Tim.
Fede
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, you know, our acknowledged capital raising needs? And, look, we're certainly aware of those. Is that correct, Sean, first of all?
C3 glomerulopathy
Yeah, sure. Okay. Okay.
Fede
Yeah, so we're aware of the current conditions that could impact our ability to raise capital, and we're exploring, you know, all of those options. Those range from traditional equity, you know, debt, royalty, partnerships, or some more strategic paths. So, you know, really we're looking at the entire range of things, and, you know, we're, you know, basically also simultaneously, as we mentioned, you know, looking at our expenses to extend our runway while our cost of capital is where it is. You know, 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.
Cedric Francois
All right. Thanks so much. Thank you so much.
Tim
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 all right?
Cedric Francois
Yes, we can hear you well enough now.
Anupam Rama
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.
Cedric Francois
Thank you, Anupam. I'm going to hand that one over to Adam.
Meredith
Thanks, Anupam. Hopefully you can hear me, too. So, yeah, we're very, very pleased with the progress of the Empaveli launch in PNH. What we're finding, Anipam, is that the transition of start forms to commercial patients, it takes between two and three weeks, which is pretty normal for a rare disease drug launch. We get hugely positive feedback on the process, not only from physicians but also from patients. But once we go through all of the RAMs 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.
Anupam Rama
Thanks so much for taking our question.
Cedric Francois
Thank you.
Tim
Our next question comes from Phil Nido with Cohen & Company. Your line is open.
Phil Nido
Good afternoon. Congrats on the quarter, and thanks for taking our questions. A couple on GA from us and then one on Empatheli. 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 KOLs suggest that the consistency in the every other month dosing arm, specifically in the extra foveal lesions, would appeal to the FDA. Is it possible to apply for approval just for every other month of seeing an extra foveal lesions, and is that something you'd be satisfied with?
Cedric Francois
All right. Thank you so much, Phil. So, well, let me first take those two questions. With the 18 months, there was a KOL call that specifically you had where that 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 extra foveal 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 represent 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, you know, 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, Philly, Derby, and Oaks, kind of more equal to each other by making the baseline lesions more pari passu, And there we see an effect size 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 extra phobia lesions. 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.
Phil Nido
That's very helpful. And then in terms of FDA interactions, you mentioned disclosure by the end of the year, post your FDA meeting. Are you going to wait for the meeting minutes to... before making the disclosure, or will you be in a position to do it, do you think, right after the 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 six-month review because this is a labeling convention?
Cedric Francois
Yeah, 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... 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 review. 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 will fall in that category as well.
Phil Nido
Perfect. And then last question from us just on Empa Valley's launch. Congratulations on the solid number for the quarter. You mentioned that most patients are switch. Are those, in fact, patients who are require transfusions while on Ultramaris, 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. Adam?
Meredith
Yes, thanks, Phil, and thanks for the summary, Cedric. Yes, so, you know, of the 1,500 C5-treated patients, we are getting patients from across all of the segments that 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 M-Pavelli. A bolus of those patients, particularly the majority of the ultramarine 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.
Phil Nido
Perfect. Thanks for taking my questions.
Cedric Francois
Thank you, Phil.
Tim
Our next question comes from Steven Seahouse with Raymond James. Your line is open.
Steven Seahouse
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 slides 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 Appellus 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.
Meredith
Thanks, Steve. Yeah, 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 Seahouse
Thanks. Actually, maybe I'll ask one more, again, commercial, but back to P&H. 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? Thanks again.
Meredith
Yes, thanks, Steve. We're big fans of the Enable device. We're also thrilled with how our patient support services are helping train our new P&H patients. I think there's 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 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 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 the 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 Empaveli.
Cedric Francois
Thank you. Thank you, Steve.
Tim
Our next question comes from Madhu Kumar with Goldman Sachs. Your line is open.
Kumar
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 22 filing. So kind of, is it reasonable to assume that preparations are being made for an NDA to kind of turn around in relatively quick time after the FDA interactions by year end?
Cedric Francois
Thank you, Madan. Great to hear you. We started working on the preparations for the MDA when we got the top-line data, so yes.
Kumar
Okay. And then on the other kind of expansion indications for Empivelli, with the caveat that some of them are being run by SOBI, so you might throw back to me as you go ask SOBI about them, how should we think about the design of some of these trials? Particularly, we think about like CAD versus the cetimolamab trial or bone marrow TMA versus some of the other kind of registrational trials as an 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?
Cedric Francois
Yeah, thank you, Madhu. So there, too, you know, 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.
Cedric
Not that I think you hit on the spot. You know, we try these global development programs, so not incorporating the FDI feedback, but also, you know, the European regulatory bodies are very important. But they do not, you know, generally deviate from what you see out there.
Kumar
Okay, great. Thanks very much, everyone.
Cedric Francois
Thank you, Madhu.
Tim
Our next question comes from Justin Kim with Oppenheimer and Company. Your line is open.
Justin Kim
Hi, good afternoon. Thanks for taking the questions. Just two, one on commercial and one on 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?
Meredith
Thanks, Justin. You know, the demand that we're seeing from a start form and a physician REMS enrollment is agnostic to our transition of early access 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, you know... Just 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, you know, we're making the most of those in-person calls. But we're also, we pivoted very quickly to virtual interactions. So our palace care educators who help train patients on how to administer the product, et cetera, the requested physicians, they're interacting virtually and we're getting hugely positive feedback on that as well. So we've 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 P&H physicians and P&H patients, and it's going well, launched to date. So we're happy with what the team's doing.
Justin Kim
Great, great. And maybe just on C3G, with some of the posters presented, at ASN and also sort of taking a look at ClinTrials, just wondering how the company thinks about the ICMPGN and C3G population post-transplant. And, you know, Cedric, you kind of alluded to maybe the fact that antibody-mediated disease could sort of be an opportunity, potentially, for Pexacocin. So just wondering, is this an enriched population and sort of the motivations for having a Phase II program as well there?
Cedric Francois
Yeah, 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 on the call not familiar with that, the real difference between C3G and ICMPGN 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, you know, 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, you know, will be very important. And we've always thought about the C3G or ICMPGN 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 final renal disease and where, you know, we believe there's a special place 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, you know, 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 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.
Cedric
Understood. Thanks, and congrats on the progress.
Cedric Francois
Thank you, Justin.
Tim
Our next question comes from Tazin Ahmad of Bank of America. Your line is open.
Tazin 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 that, 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.
Fede
Thank you, Suzanne. 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 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, you know, thoughtful and, you know, 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 a timing perspective, you know, we'll update you in due course. Thanks for the question.
Tim
Our next question comes from Colleen Cousy with Baird. Your line is open.
Colleen Cousy
Colleen Cousy Great. Thanks so much for taking our questions and congrats on the quarter. One question for us, I know you presented the top line DERVIOG data at a number of medical meetings since the results were initially announced. Have you had any opportunity to speak to any European KOLs? and how they might view the top line data differently from US-based positions.
Cedric Francois
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 US, 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.
Meredith
Yes, thanks, Cedric, and thanks, Colleen. So yes, 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 that data supports treating patients. And no surprise, very similar to what we're hearing in the U.S., that physicians are impressed with the 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.
Colleen Cousy
Yeah, that's helpful. Thank you for taking our question.
Cedric Francois
Thank you.
Tim
Our next question comes from Alethea Young with Cantor. Your line is open.
Alethea Young
Hey, guys. Thanks for taking my questions, and congrats on the early launch progress. I guess two for me. One, you know, 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, you know, kind of they just be experienced in 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 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, Alicia. I'll send the first question Adam's way.
Meredith
Thanks, Alicia. Yeah, so we are actually seeing – Emper Valley starts across all of the paradigm of the patient mixes I've described. So of the 1,500 C5-treated patients, we're seeing 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 Mpavelli 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, you know, it's a small prescriber base with a small patient population. Physicians keep telling us they want to try Emper Valley 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.
Cedric Francois
Yeah, 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.
Alethea Young
Great. Thank you.
Cedric Francois
Thank you.
Tim
Our next question comes from Yagal Nakumovitz with Citi. Your line is open.
spk15
Hi, this is Carly on for Yagal. 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.
Cedric Francois
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 Oaks, right? I mean, statistically, a 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've talked about it, which is, We had an explicit 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 Oaks, with an effect size that ranges from 12% to 29%, 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 a breakthrough 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.
spk15
Okay, thanks very much.
Cedric Francois
Thank you.
Tim
Our next question comes from Ellie Merle with UBS. Your line is open.
Ellie Merle
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 REM site sign-ups that have prescribed patients or you know, 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, you know, submitted a lot of start forms versus less on some. And then just in terms of geographic atrophy, I'm 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 XUS sites and Derby. I know that some of the XUS work had been ongoing, but just curious kind of how that analysis is going, and I guess if we can expect to learn more at AAF. Thanks.
Cedric Francois
Thank you, Ellie. Adam, do you want to take this first part?
Meredith
Absolutely. Thanks, Ellie. Yet we're, you know, 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 Empavelian. 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. I'm very happy with how we're seeing the Starforce pop up around the US. And I'll hand you back to Cedric for the second part.
Cedric Francois
Thank you, Adam. All right, and there were really two parts to your question there as well, Ali. The first one is related 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-US, US, et cetera, that is still ongoing, but as became quite clear from the analysis that we did, again, with the covariates, 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 is of the drug, where that coherent analysis puts us in the ranges that we discussed before.
Tazin Ahmad
Great. Thanks so much.
C3 glomerulopathy
Thank you.
Tim
Our next question comes from Matthew Buccini with BMO. Your line is open.
Matthew Buccini
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 12 days average from prescription to first dose and 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 P&H results. Thank you.
Cedric Francois
Thank you, Matt. Adam?
Meredith
Yes, thank you, Matt. So just on the inventory perspective, I'll start there. So, you know, basically our specialty pharmacy holds a very low level of inventory. So it's, it's not an issue, uh, for us moving forward. But as part of, um, part of the progress, also your first part of the question was, you know, 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, um, different reasons why some of that, that time period is there. And I'm not remotely worried about that time period. So, um, Not a surprise, you know, 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 MPHA fairly prescription. Also, we want to make sure that we've signed everybody up who 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, to a commercial product. 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 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.
Matthew Buccini
Yes, thank you.
C3 glomerulopathy
Thank you, Matt.
Tim
Our next question comes from , with Jeffrey. Your line is open.
Jeffrey
Hi, team. This is 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 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, it's not like the retina all of a 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 C-RORA conversion. It's a very interesting way of measuring, not pure geographic atrophy, but the earlier lesions. There's going to be a question how the FDA looks at that.
Jeffrey
Thank you very much.
Cedric Francois
Thank you.
Tim
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 our questions. Just a quick one on the pipeline on ALS. I want to get your thoughts on, you know, given the competitive landscape and enrollment, what 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 relevant biomarkers. Thank you.
Cedric Francois
Thank you so much, Joey. So I'm going to hand that question over to Federico to answer.
Cedric
Hello?
C3 glomerulopathy
Yes. We can hear you.
Cedric
Sorry. I couldn't. So the question was, what threshold do we expect or what what would considering competitive landscape fitting you know what you expect from the clinical studies in terms of the endpoint yeah 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
All right, thank you.
Cedric Francois
Thank you, Joey.
Tim
Our next question comes from Laura Chico with Wedbush Securities. Your line is open.
Laura Chico
Good afternoon, guys. Thanks very much for taking the question. I've got two on GA. So first, you know, I think earlier you commented, Cedric, clearly BCVA is probably not the best standpoint 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 Yeah, thank you, Laura.
Cedric Francois
So BCVA with the FDA was specifically indicated as not relevant in the efficacy analysis. So that 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.
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 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 2022 perhaps to just engage with partners in a little bit more detail? Thanks very much. Appreciate it.
Cedric Francois
You're welcome. So on the precedent, I think, you know, an interesting precedent in what AMD would be visiting but I think, you know, 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, Oaks, two of them with high statistical significance for monthly and 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 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 GH 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.
Fede
Yeah, I would just say that I don't think we're going to change anything operationally around financing. You know, 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, you know, cater to that.
Laura Chico
Thanks very much, guys.
Cedric Francois
Thank you, Laura.
Tim
There are no further questions. I'd 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.
Tim
This does conclude the program. Thank you for participating. You may now disconnect.
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