Good morning ladies and gentlemen. Thank you for standing by and welcome to the Apellis Pharmaceuticals Third Quarter 2023 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.

[Operator Instructions] Please note that today’s conference is being recorded. I will now hand the conference over to your speaker host, Meredith Kaya, Senior Vice President of Investor Relations and Strategic Finance. Please go ahead..

Good morning and thank you for joining us to discuss Apellis' third quarter 2023 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. Caroline Baumal; and Chief Financial Officer, Tim Sullivan.

Before we begin, let me 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..

Thank you, Meredith, and thank you all for joining us this morning. It has been a busy few months here at Apellis and the period is not without its share of ups and downs. That said, I am thrilled with where our company is today and then more confident than ever in the opportunities that we have in front of us.

Importantly we are delivering on our goals of bringing EMPAVELI and SYFOVRE to patients with nearly $100 million in total of the U.S. net product revenue generated in the third quarter and continuing to be [indiscernible] potentially transformative new treatments. I'll begin with SYFOVRE. We reported $75 million in SYFOVRE U.S.

net product revenue in the third quarter, up about 12% quarter-over-quarter resulting in more than $160 million in U.S. net product revenue generated in the first seven months since launch.

A few key highlights include more than 100,000 vials of SYFOVRE have been distributed since launch through our last update on October 5th which we believe underscores the positive impact it is having on the lives of thousands of patients across the U.S.

The permanent J-code effective on October 1st, driving even stronger demand to date with some of our largest weeks ever in October. The long-term data emerging from our GALE extension study continues to show increasing effects over time.

[Indiscernible] feature of SYFOVRE's efficacy profile and additional analyses have been presented this fall demonstrating the visual function benefits of SYFOVRE in GA patients. And finally, the estimated rate of retinal vasculitis with SYFOVRE continues to be rare at 0.01%.

Visual outcomes in these cases are really important and the rate of events that that resulted in this year irreversible vision loss is substantially less than 0.01%. Given the continuous stability in the rates, we plan to continue provide the estimated rate of events which we will no longer discuss in the visual cases.

The success of SYFOVRE reinforces the unmet need in GA and the strength of our product profile. We faced unexpected challenges with the rare events of vasculitis emerging this summer, but we have worked hard to build trust with the retina community through continued transparency and sharing the learnings from our investigation.

In doing so, we have provided retina specialists with the information they need to make the right treatment decisions for their patients. I had the privilege of spending time with some of our key opinion leaders this fall at both EURETINA and Retina Society.

It was encouraging to hear the discussions shifting back to what this product can do for patients. After a challenging few months, we have turned the corner and believe we are now back to the demand growth trajectory that we were on in July.

Globally, we are looking forward to the decision on our MAA submission for the European Medicines Agency, which is on track for early 2024. At EURETINA, I was impressed with the incredible amount of work our European team has been doing to prepare for the launch.

There was also a lot of enthusiasm from the European physicians about the possibility of finally having a treatment for their GA patients. Turning to EMPAVELI, we generated $24 million in third quarter U.S. net product revenue and $67 million year-to-date.

With EMPAVELI we now have over 1300 patient years and compliance rates at 97% and still not a single case of meningococcal infection. One of the key highlights for EMPAVELI during the quarter was receiving FDA approval for the EMPAVELI Injector, an innovative and first of its kind high tech volume injector.

With this approval, we are further enhancing the patient's experience by offering greater mobility and simplifying administration. We also announced top line data from our Phase 2 NOBLE study with systemic pegcetacoplan and IC-MPGN and C3G, which will be presented this Saturday at the American Society of Nephrology.

The strength of this data is driven by the speed and magnitude of effect, especially that pegcetacoplan had in the kidney which is unprecedented in these diseases.

We believe that we have an opportunity to significantly expand the number of patients who are benefiting from pegcetacoplan and IC-MPGN and C3G affect more than three times the treated PNH population. We look forward to the top line results from our Phase 3 Valium study expected in the third quarter of 2024.

Before I turn it over to Adam, I would like to comment on our recent corporate restructuring. In late August, we took actions to streamline our organization, prioritizing the growth of SYFOVRE and EMPAVELI and positioning the company for continued long-term success.

This was a difficult decision and we are grateful for the commitment and contributions of all of our colleagues.

As a reminder, key elements of our reprioritization includes maximizing SYFOVRE's global leadership in GA, streamlining the EMPAVELI business, focused on the commercialization and PNH and development in IC-MPGN and C3G, prioritizing certain CNS and retina research initiatives and continuing our collaboration with Beam and finally improving operational efficiencies.

We anticipate total cost savings of up to $300 million through 2024 as a result of this restructuring. And as Tim will speak to later, we expect our cash runway to now extend into at least the second quarter of 2025.

As a more focused organization, we believe we are in a stronger position to create value for shareholders and deliver on our mission for patients now and in the future. With that, I will now turn it over to Adam to discuss our commercial activities..

Thank you, Cedric. It was a strong quarter commercially for both SYFOVRE and EMPAVELI. Starting with SYFOVRE, in the third quarter we delivered 37,000 commercial vials and 10,000 samples to physician practices generating $75 million in U.S. net product revenue. We are encouraged by this performance.

In particular, the quarter-over-quarter growth compared to Q2 and the return of weekly demand growth beginning in August. We believe this was driven by physicians and patients having a better understanding of the real world safety profile of SYFOVRE and the long-term data including increasing treatment effects seen in our GALE extension study.

On October, the first, the permanent J-code for to SYFOVRE became effective simplifying the billing and reimbursement process. This is a significant milestone that will help ensure efficient reimbursement of SYFOVRE, building on our goal of bringing this important treatment to all GA patients in need.

As a result of our commercial execution, excellent payer coverage with more than 95% of Medicare payers now covering SYFOVRE and the addition of the permanent J-code demand is higher than where we were in July and growing.

We continue to see weekly orders coming from both new and existing sites of care, with a double digit number of new sites of care ordering SYFOVRE every week since launch.

Additionally, we are seeing the vast majority of physicians treating patients with SYFOVRE every six to eight weeks, reinforcing how important dosing flexibility is for this patient population. Our commercial strategy going forward is to remain laser focused on engaging our key stakeholders; patients, physicians and payers.

We plan to leverage this current momentum by building breadth, depth and retention among retina specialists. We are also preparing to bring SYFOVRE to patients globally.

We are thoughtfully building out the European commercial infrastructure and subject to approval, plan to launch initially in Germany where we can sell products immediately while we work simultaneously to obtain reimbursement in other EU countries.

Europe represents a significant opportunity for us as there are more than 2.5 million people living with GA and no treatment available. We recently submitted our dossier to the National Institute for Health and Care Excellence, or NICE, for reimbursement in the United Kingdom.

We expect a decision by the local regulatory authorities in the UK as well as Canada, Australia and Switzerland in the first half of 2024. Turning to EMPAVELI, in the third quarter, we continued to see positive trends across the key leading indicators for this patient population, including more than 250 patients on therapy.

Over 75% of C5 inhibitor patient switches coming from Ultomiris since launch, patient compliance rates remaining high at 97% and continued strong access among the top 20 players. We are also seeing continued growth coming from the treatment naive population given the inclusion of the print data in the label and more experience with EMPAVELI.

This progress resulted in $24 million in U.S. net product revenue for the third quarter. PNH is market driven by both efficacy and safety, which is reflected in these continued strong results. As Cedric mentioned, we are excited about the approval of the EMPAVELI Injector.

The field teams are now working to transition existing patients onto the injector. Initial feedback has been positive and we look forward to bringing the injector to more and more patients over the coming months.

We are also focused on bringing EMPAVELI to new patients who may benefit from this treatment and reinforcing the long-term safety and efficacy data and real world experience. Now, I will turn the call over to Caroline..

Thanks, Adam, and good morning everyone. We have had a significant presence these past few months at multiple medical meetings including the ASRS Annual Meeting, EURETINA and the Retina Society meeting.

The reactions and feedback we are hearing from the medical community, especially in these last several weeks, support the solid performance of SYFOVRE and its continued growth.

As shown on Slide 8, at ASRS we presented for the first time the 30-month results of our GALE extension study, deepening our understanding of the long-term efficacy of SYFOVRE. These data continue to demonstrate increasing effects with SYFOVRE out to 30 months and a safety profile consistent with previously reported clinical data.

In GALE SYFOVRE reduced GA lesion growth with both monthly and every other month treatment compared to the projected sham arm with an even more pronounced effect in patients with nonsubfoveal lesions, the greatest effect shown by any GA therapy to date.

Additionally, we continue to build on the functional data supporting the efficacy profile of SYFOVRE. We recently presented our third functional analysis showing a visual function benefit.

In this post-hoc microperimetry analysis data showed that SYFOVRE extended foveal light sensitivity in the Phase 3 OAKS study, which is critical for prolonging visual function. We also presented an updated covariate adjusted analysis of visual acuity data at the Retina Society from our GALE long-term extension study.

As we saw with the 24-month data at ARVO, we continue to see favorable trends on best corrected visual acuity in patients in the continuous cycle retreatment arms as compared to patients on sham for two years who then crossed over to active treatment in GALE. Both of these analyses add to the overall efficacy profile pegcetacoplan.

We are looking forward to presenting at the upcoming American Academy of Ophthalmology meeting this weekend in San Francisco. At this meeting we will share 36-month data from our GALE extension study further demonstrating SYFOVRE's long-term efficacy and increased effects over time and a consistent safety profile out to three years.

As seen on Slide 9, we are also presenting new data this weekend at Kidney Week from the Phase 2 NOBLE study investigating pegcetacoplan for the treatment of post-transplant recurrence of IC-MPGN and C3G.

IC-MPGN and C3G are rare, debilitating kidney diseases that are estimated to affect 5000 people in the United States and up to 8000 in Europe with no approved treatments available.

What is particularly striking in these data, as shared in our recent press release, is how quickly pegcetacoplan showed the potential for a treatment effect in transplanted kidneys that had disease recurrence.

In just 12 weeks, 80% of patients treated with pegcetacoplan showed a reduction in C3c staining by at least one order of magnitude of intensity from baseline.

50% showed a reduction in C3c staining by two or more orders of magnitude, which was the primary endpoint of the study, and 40% showed 0 staining intensity, indicating that C3c deposits were cleared. The image on this slide is an example of one patient.

You can see the disease activity or C3c staining at baseline on the left with the immunofluorescence or bright green areas lit up. At week 12, you can see in the second image that it's gone. This magnitude of C3c clearing in the kidney has never been shown before.

Additionally, treatment with pegcetacoplan showed improvements across key clinical measures including proteinuria and stable kidney function.

While this was a small study, these data indicate that pegcetacoplan is targeting the underlying cause of the disease, strengthening our confidence in pegcetacoplan as a potential treatment for both native and post-transplant forms of these rare and serious diseases.

We are currently enrolling patients in our Phase 3 VALIANT study evaluating pegcetacoplan in adolescent and adult patients with native and post-transplant recurrent IC-MPGN and C3G. Investigators in this study have been enthusiastic about bringing in new patients.

We anticipate completing enrollment by the end of this year with top line results expected in the third quarter of 2024. Now I will turn the call over to Tim for a review of the financials.

Tim?.

Thank you, Caroline. Total revenue for the third quarter was $110 million, which consisted of $24 million in EMPAVELI U.S. net product revenue, $75 million in SYFOVRE U.S. net product revenue and $11 million in collaboration revenue from Sobi.

As a reminder, revenue is recognized as shipments to the distributor and therefore includes any product in inventory at the distributor as well as product shipped to the physician by the distributor.

We continue to estimate approximately two to three weeks of inventory on hand at the distributor and expect these inventory levels to be consistent going forward based on anticipated demand. Turning to the rest of the P&L, R&D expenses were $79 million and G&A expenses were $146 million and we reported a net loss of $140 million.

I'd like to point out a few items in our financial statements that will help in evaluating our business. First, cost of goods sold was $22.4 million for the third quarter, higher than in previous periods due to milestone payments to Penn and purchase price variances, combined totaling approximately$ 8.6 million.

Second, we recorded accounts receivable of $169.3 million, which is also higher than previous quarters and is primarily associated with payment terms that we provide to the SYFOVRE distributors. The accounts receivable line item has increased as SYFOVRE sales have increased and is in line with those payment terms.

Third, we are now categorizing a majority of medical affairs and certain other costs in G&A instead of in R&D. This represents an approximately $19 million shift from R&D to G&A in the current quarter. No reclassifications were necessary for prior periods; however, it is important to note when reviewing trends in our operating expenses.

And finally, our operating expenses do not yet reflect the ongoing efficiencies we expect from our restructuring due to severance and winding down of certain projects. We expect to realize these efficiencies beginning in 2024. As of September 30, 2023, we had $452 million in cash and cash equivalents.

September and October demand provided us with a better view of the demand and sales trajectory going forward. Based on this and cost savings from our recent restructuring, we now expect our cash balance to fund our operations into at least the second quarter of 2025. I will now turn the call back over to Cedric for closing remarks.

Cedric?.

Thanks Tim. This quarter was not without challenges, but we are now seeing a clear rebound in the growth and progress we accomplished earlier this year. We are on the cusp of expanding SYFOVRE's reach in global markets alongside steady growth in the PNH market with EMPAVELI.

We remain dedicated to delivering on our strategic priorities and creating long-term shareholder value. Let us now open the call for questions.

Operator?.

Hi, guys. This is Jon Miller on.

Maybe now that you've had some more commercial experience through all of this speculative stuff, can you maybe update our assumptions on the difference between vials shipped and doses given and what proportion of doses are sitting in fridges at various places in your estimation? And then secondly, maybe on the etiology of vasculitis, do you have any early signs out of the needle switch at this point? Is that really making an impact in rate or are there any suggestions of a patient risk profile that might identify patients ahead of time? Has there been any motion on that front?.

Hey, Jon, great to hear you. I'm going to hand the first question over to Adam and then I'll take the second one..

Hey, Jon. So first things first, I think we're extremely confident and pleased with the commercial execution and let me give you a few numbers. So obviously, 37,000 commercial vials in the third quarter and about 10,000 samples.

All of these vials were shipped to physicians and we assume, based in our math, an average of about 1 to 1.5 weeks of demand vials sitting in a refrigerator. So we think we have over 100,000 injections since launch, about 50,000 patients being treated with SYFOVRE. I think it's a really strong commercial execution.

So hopefully that answers your question and I'll hand back to Cedric for the second part..

Thank you, Adam. And then talking about etiology, so it is still too early, right? I mean we're going to need probably another quarter or two to really understand whether the needle had an impact or not. That's the most important metric here is that the rate of vasculitis is very low and stable, right.

That's something that's over the past couple of months we've been able to track and of course it provides confidence to the physicians. So with more than 100,000 injections done in the real world, we are at a rate and continues to be at a rate of 0.01%.

But it's of course also important to look into which patients have significance and severe vision loss and there the rates are meaningfully lower than 0.01% on a per injection basis. And using that metric with 50,000 patients treated, you're also still at a rate of 0.01%.

So something that of course we hope to understand better in the future, but most importantly, stable and being followed over time..

Thanks guys..

Thank you, Jon..

Thank you. And our next question coming from the line of Tazeen Ahmad with Bank of America. Your line is open..

Hi, thank you. Good morning guys. I just wanted to ask you a question about the competitive landscape if I could and how you think it's evolving. It looks like Dallas has reported $8 million for its first month on the market and they are projecting about $72 million for their full calendar year, which I believe ends in March.

So can you just talk about what feedback you're getting from field force about competition? Whether it's increasing and where if anywhere you might be seeing patients switching? Thank you..

Thank you, Tazeen, great to hear you. Adam will take that question..

Yes, thanks Tazeen. So it's interesting we hear firstly from analysts and investors a lot of surveys done with physicians where the sentiment that's given back to us is that these physicians are bullish on iSURVEY. It's different to what we hear in the field. It's been relatively quiet in the fields.

We're not hearing a lot of noise, we're really, really not hearing very much from the field. And I think if you look at our first three quarters which is in line with their fiscal year reporting, we were $160 million in the first three quarters of launch. So that's a hugely successful launch.

I think we are going to be laser focused on executing our plan, which is to continue to talk about increasing effects over time, the strong clinical profile, long-term efficacy, dosing flexibility and just to say the vast majority of physicians are using SYFOVRE every six to eight weeks. We have strong payer coverage. Our J-code in October.

I'm very confident that we will continue to show positive growth with SYFOVRE. So we're going to be focused on our plan. We execute our plan. I think we'll do incredibly well..

Okay and thanks Adam. And maybe as a follow up, Apellis is going to be showing in 24 months I believe at the AAO Conference this week, this weekend.

And as it relates to every other month, what are physicians telling you about what they want to see on curve separation for every other month's dosing?.

Thank you, Tazeen.

Caroline would you like to answer that?.

Thank you. Physicians would like to see increasing effects overtime, I think that's very important for them.

And at the American Academy of Ophthalmology this weekend we will be presenting our GALE data, the first year of the extension study where our patients have received, some of the patients have received three years of continuous pegcetacoplan therapy.

I think physicians will be impressed by our data and they also are impressed by the science that's behind pegcetacoplan. They like the flexibility with dosing with monthly and every other month dosing being meaningful and three years of data.

And actually the first patient will be -- patients will be rolling out of GALE this December, that's five years in the clinical study with continuous pegcetacoplan treatment. So we're really proud of that data..

Okay thank you..

Thank you, Tazeen..

Thank you. And our next question coming from the line of Anupam Rama with JPMorgan Your line is open..

Hey, guys. Thanks so much for taking the question.

So in terms of use of SYFOVRE, back in the summer you talked about this one third, one third, one third breakdown when it comes to utilization, what is that breakdown now and what are you seeing from those that were maybe previously in that one third bucket that was on the sidelines or you're waiting for more information? Thanks so much..

Thank you, Anupam.

Adam?.

Yes, thanks Anupam. So obviously the last update to our market research was in August and that showed similar results as to the research that we shared in on the Q2 call. Now I think we're super encouraged to see continued enthusiasm for SYFOVRE from physicians.

We've started to see new physicians start SYFOVRE start new patients and one metric I absolutely love and I think it's been a really powerful metric for us is since launch we have had double digit numbers of new accounts signed for SYFOVRE for the first time every week and that's continued since launch.

That shows you a little bit of the sentiment of physicians that we're being transparent, we're sharing with them, we're being open and I think it's driving the continued growth that you're seeing from our results. We have seen totally honestly we've seen some physicians become a bit more conservative.

For example, many physicians are now starting the worst eye first and also they're not doing bilateral injections as their first injections. We do still see bilateral injections being done, but they're being a bit more thoughtful in how they approach it.

But the segments from the market research we're making in grounds in each of those one third segments, I think we're really, really driving demand and I think you're seeing the results of that in the number of patients that are choosing to use SYFOVRE..

Thanks so much for taking our question..

Thank you, Anupam..

Thank you. And our next question is coming from the line of Colleen Kusy with Baird. Your line is open..

Colleen, I don't think we can hear you..

Please check your mute button..

I don't think we can hear you, Colleen..

Okay. I'll go on to the next question. Our next question coming from the line of Yigal Nochomovitz with Citigroup. Your line is open..

Hi, Cedric and team. Thank you for taking the question. I had one on IC-MPGN and C3G.

So for that the standing you showed in the slide, was that an IC-MPGN patient or C3G patient? And then more broadly, would you expect pegcetacoplan to behave similarly in each indication? And then as regards VALIANT, could you talk about what level of proteinuria reduction would be considered clinically meaningful and will there be any interim analysis of that trial before the three 3Q 2024 top line? Thank you..

Thank you so much, Yigal and thank you for that question.

So that was a C3G patient that you saw that image from and I cannot overemphasize how meaningful that histopath is, right? So just as a reminder for those that are not familiar with this, in C3G and IC-MPGN you get a deposition of C3 covalently bound, so irreversibly attached to the cells in the glomerulus.

For these, for those deposits to go away you need to have healthy cells that can actually internalize that C3 product and process it properly. So for us to see these improvements over the course of three months is actually really unbelievable. And this isn't a post-transplant situation.

So these are actually patients that were transplanted and that had recurrence of the disease. So needless to say, really, really meaningful to this population. We see these effects both in C3G and in IC-MPGN and again as mentioned this is a very important segment as well in the post-transplant setting.

As it relates to VALIANT, there's no interim readout. There's going to be six-month readout and we will consider 50% reduction in proteinuria to be clinically meaningful..

Great. Thank you, Cedric..

Thank you, Yigal..

Thank you. And our next question is coming from the line of Steven Seedhouse with Raymond James. Your line is open..

Good morning. Thanks so much. I had three questions on SYFOVRE.

First is just on if you expect a label amendment at some point and if so, would that include just retinovasculitis update or would you also look to add some GALE data or some of the visual function data that you noted? Second question is Astellas actually provided peak sales guidance as well, I think about U.S.$1.3 billion to U.S.$2.6 billion.

Curious if you're modeling less similar or more for SYFOVRE? And then lastly, the 50,000 patients treated that you mentioned, I'm curious if you know or have a sense of how many are currently on treatment and can estimate basically therefore, how many discontinuations you had amid the RV disclosures, patients that you might be able to bring back to SYFOVRE? Thank you..

Thank you so much, Steve. I will take the first question and then hand the other two over to Adam. As it relates to the label, so I think we should expect that there will be a label change and an update at some point.

I think it's noteworthy, right that it hasn't happened, which is again a reflection of the fact that we have a stable situation with a very rare event that I think the FDA along with us is tracking before we get to a label change. So that's, something to be followed as far as it relates to what that will be, that of course we don't know yet.

Adam, can you take the next two?.

Yes, thanks, Steve. So obviously, we don't guide, but we -- with 5 million GA patients worldwide, we think it is a very sizable market. It's probably the best way of me answering that question. And then the third part of your question, of the 50,000 patients currently on SYFOVRE, we think discontinuations is very low at the moment.

We obviously did see some discontinuations during the retinal vasculitis phase, but we think it's very low because it's early in launch. And I think if you look now as a metric in October demand trajectory was back to July levels.

So I think again I think we expect to see all of the new patients that are starting and all the continued patients to start to benefit from this treatment and try and stay on it. Patients are incredibly motivated. But short answer is discons we believe are quite low during this time period especially now we're back to the growth trajectory..

Thanks, Adam.

Just to clarify, so I think I misheard, so 50K is the current patients on SYFOVRE estimate?.

All right. Thanks so much..

Thank you..

Thank you. One moment for our next question. And our next question is coming from the line of Phil Nadeau with TD Cowen. Your line is open..

Good morning. Thanks for taking our questions.

A question is on the rate of vasculitis, do you expect to present any updated rate or number of cases at the AAO meeting this weekend? Do you expect ASRS to make a presentation on their evaluation of vasculitis this weekend? And then going forward when could we expect future updates? Is there a cadence that you'd be willing to guide to like once a quarter or just that significant medical meetings or something like that? Thanks..

Thank you, Phil. So I think it's, you know what's really important here is that this rate is constant, is under control and has remained unchanged. I think that is really something. So we're going to stop talking about individual cases because frankly that's not an effort that we think is fruitful.

To put this in perspective, the last case of a patient with geographic atrophy that was reported to us with vasculitis is already from September first, right. So we had that case. With a non-GA patient on September 22nd, but that's been it. So again, we keep tracking all of this.

We will report on this if there are changes, but we are not going to do this on a case by case basis. Then as it relates to ASRS, Caroline can briefly speak to this because we've been collaborating very closely with them..

Thank you, Cedric. We are in close communication with the ASRS Rest Committee and with regards to cases. And as far as we are aware, there will be no update at the American Academy.

But we did provide an update at the Retina Society and at the Academy this weekend in addition to the GALE data, we'll be presenting some very meaningful microperimetry data as well as having a presentation on artificial intelligence imaging and photoreceptor preservation from our studies..

And going forward should we expect an update on the rate like once a quarter or any sense of when you'll provide update?.

Well we continue to remain transparent with physicians and everything that we receive is reported to the FDA as per regulations and if that rate changes, we will update the community..

Great. Thanks for taking our questions..

Thank you, Phil..

Thank you. One moment for our next question and our next question is coming from the line of Derek Archila with Wells Fargo. Your line is open..

Hey, good morning and thanks for taking the questions. May be just one on Europe. I guess, have your recent interactions with the EMA been on the application? And just in terms of the market opportunity, maybe this one's for Adam, and do you think the overall adoption in the EU will be any different than the U.S.? Thanks..

Thank you so much, Derek. So EMEA is on track and has continued to be on track.

As we've mentioned a couple of times in the past, this has really has been a labor of love over many, many years of preparing the physician community as well as the regulators as well as the payers in Europe and we're very excited about being able to offer this product we believe next year, right.

So Adam, do you want to maybe briefly talk about the adoption?.

Yes, thanks, Derek. Thanks for the question. Yes, we are ready to go in terms of commercial and medical affairs infrastructure. So we're ready in Germany, right. So we are good to go once we get feedback. 5 million GA patients worldwide, Derek, obviously about 1 to 1.5 in the U.S. so the rest is all ex-U.S., so it's a very sizeable opportunity.

As a nice little analogue, about 45% of sales of anti-VEGF drugs are ex-U.S., right? So it's a sizeable opportunity for us. A few things to think about, obviously it's a payer market and a health technology assessment market and highly likely that brand, for example again, branded anti-VEGF prices are about 40% to 70% discount to the U.S.

anti-VEGF prices. Even with that metric, this is a sizeable opportunity and the teams really invested the time to get to know the key opinion leaders and we believe that being transparent as we were in the U.S., we've been with key opinion leaders and doctors, ex-U.S.

We think that they have all of the information that they need and should we get approval, I think the doctors will be ready to go very quickly..

Thank you. One moment for our next question. Our next question is coming from the line of Eliana Merle with UBS. Your line is open..

Hey, guys. Thanks so much for taking the question. Just another on Europe.

Can you just talk a little bit about how the review is going and the latest on your confidence on approval there? And then in terms of the feedback you've gotten from physicians in Europe relative to the U.S., maybe on safety and their perspective? And then any commentary on what we should expect in terms of the contribution to revenues next year from Europe.

Thanks..

Okay, thank you, Ellie. Well, I'll take the first one, then I will have Caroline speak about the doctors on safety in Europe and then Adam or Tim can talk about revenue. But again, European discussions have gone very well. As you all know, kind of correlation to functionality is very important in Europe.

And as the data kind of comes together over time now also with GALE, that is something that we feel very good about.

Caroline, on the doctors in Europe?.

Thank you. The KOLs in Europe are very well connected with the U.S. KOLS. It's really a global community. Many of them were involved in the clinical study and have high confidence in our product and are familiar with its use. Also they are really data-driven and we have this visual function microperimetry data. We have key leaders in the U.S.

but also in Europe on microperimetry who are impressed by this data and are looking forward to use of SYFOVRE..

Thanks, Ellie. And then in terms of revenue, ex-U.S. is a very large proportion of potential future revenues. So with the anti-VEGFs we expect that we estimate that's around 45% of total revenue. It's actually more patients but less revenue per patient.

In terms of next year however, while we expect approval in the first quarter, really that rollout becomes a sort of a country type by country basis, the first one being Germany. So we don't expect a huge amount of contribution next year, but we do expect we will be able to recognize revenue right after approval, which we expect in the first quarter..

Great. Thanks so much..

Thank you, Ellie..

Thank you. One moment for our next question. And our next question is coming from the line of Akash Tewari with Jefferies. Your line is open..

Good morning. This is Ivy on for Akash. We have two questions. First, as you said in the prepared remarks on accounts receivables, which is found at $170 [ph] million this quarter compared to $7 million at year end.

Could you maybe give us more visibility there? What's the current inventory level at the distributors level? And the second is, I think someone already asked this, but today I think competitors also announced their fixed sales estimate of around $1.3 million to $2.6 billion, which seems quite conservative compared to numbers laid out in their proxy, which implies fixed sales of around like $4 billion in just the U.S.

We're just curious what do you think may have led to the changes in part for them on the GA market potential and has your view changed at all? Thanks..

Thank you so much for that question. I will hand it over to Tim and then Adam..

Sure. The big change in accounts receivables relates to the fact that we have fairly extended but also market typical payment terms. So that receivable is primarily the distributors in particular the largest portion is for SYFOVRE. It's typical for a launch in this space and we don't expect any issues in terms of collections.

So it's just fairly typical and I think you'll see that number increase slightly over time as sales increase. And then with respect to EMPAVELI, I think it's hard for us to speculate why they've had that change.

We obviously think this is a gigantic market and anything that they do, I mean if you look at their prepared remarks from what we saw based on their, they're early in their launch and they're still evaluating based on not only what they're seeing personally, but also what they're seeing from us and I expect you will see that number evolve over time..

Yes. And just to add to Tim's, Ivy, it's Adam. Yes, we truly believe it's a large market, but it's also a market which is driven by certain aspects of a good product profile, so flexible dosing, increasing effects over time. So within a large market, we truly believe we have a very competitive product.

It's an exciting opportunity to prevent and help patients vision over time worldwide. So we're excited to go and get after that..

Thank you..

Thank you. One moment for our next question, and our next question is coming from the line of Annabel Samimy with Stifel. Your line is open..

Hi, thanks for taking my question. I had a couple. So I guess with the greater experience that physicians are having and more understanding of this rare event, do you notice a change in the way physicians are selecting their patients? I know that you had identified some low hanging fruit initially.

Have they become more selective in their use since those events or is the comfort level now increasing and they're becoming a little bit more liberal with their use and maybe moving to less severe patients? So just to add a little bit of color around the type of patient selection physicians have? And then secondly, was wondering if there is any moment where you'd be comfortable giving guidance on SYFOVRE sales going forward? Thanks..

Thank you so much, Annabel, and Caroline..

Thank you. I think physicians are very enthusiastic about SYFOVRE and they understand whenever we present about the large robust data set that we have and the clinical findings, they understand the science and that's and that's really what drives them.

What we have seen is that physicians may be a little more conservative than they were in the beginning.

For example, not treating both eyes first visit or starting with the worst eye first which is not uncommon from intravisual injections, but they are very comfortable now with the technique of drop of the product which is slightly thicker and they have continued their use with enthusiasm.

Adam, do you have anything to add to that?.

Yes. Thanks for the question, Annabel.

Just to add to Caroline's comments, right, I think, you the graph in the presentation in October we're seeing demand trajectory eclipse and back to the July levels, right? And one thing I love about this is that we're seeing new patients come on to SYFOVRE every week and that to me is a really solid signal of confidence.

I gave this metric earlier, I'll give it again because it excites me. It's every week since launch we've had double digit new accounts start and order SYFOVRE for the first time. And I think that's a very positive, positive thing. And now with the J-code, I expect us to continue to drive that.

But as Caroline said, it was a little bit of a pause in terms of how people use the drug and I think we're starting to make inroads, that confidence is coming back into the community..

Sure. And I'll just jump in on guidance. I don't know when we plan to give any guidance. What I will say is that if you'd asked me where we were three months ago and where we are today, I'm really excited and I think the more we can get the next couple of quarters under our feet, we'll have a really good sense of where we are.

I don't know when we'll actually give guidance. It's something we haven't committed to, but we'll let you know when we have a decision on that..

Okay, great. Thank you..

Thank you..

Thank you. [Operator Instructions] Our next question is coming from the line of Douglas Tsao with H.C. Wainwright. Your line is open..

Good morning. Sorry about that. Good morning and thanks for taking the question. I guess, Adam, I wanted to touch on something that you commented and we talked about it before in terms of patient interest and demand.

I'm just curious how are you trying to overcome perhaps, physician, I don't want to say resistance, but sort of hesitation to start treatment for any number of reasons, safety or some docs aren't necessarily fully convinced on the efficacy in the face of sort of trying to get patients to get treated, because it seems like sometimes I've been talking to doctors, they speak about patient enthusiasm and they say that they're sort of trying to pump the brakes on their patients.

And how are you trying to sort of get docs to ease up on that? Or is it a matter of trying to just redirect patients to doctors who are more readily treating with SYFOVRE? Thank you..

Yes. Thanks Doug for the question. So yes, interestingly pre-launch of SYFOVRE did a lot of, we spent a lot of time with GA patients and they were super enthusiastic about our potential treatment.

They used to give us anecdotes like, I want to spend time with my grandkids and be able to read to them and all of those type of activities, that has not changed since launch. This is a very driven patient population.

We are obviously doing some commercial activities to help patients flag that they may have vision impairment and they should go and see a retina physician or an ophthalmologist or an optometrist through our TV and radio campaign with Henry Winkler. I think that's had a very positive impact in the market. That has driven patients into physicians.

We've also started to see that physicians can now have a benefit risk discussion with these patients and the patient motivation has an impact on that prescribing physician. So we'll continue to do more activities to drive patients.

We have found that if some physicians are for whatever reasons, not injecting SYFOVRE that these patients will seek other physicians that are. So that's happening within the market. But this is a highly, highly motivated patient population and it meets in an incredibly good discussion of highly motivated physician conversation..

Great. And if I can ask one follow up, I know there's been a lot of focus on the third, third, third sort of market research that you had talked about from the summer.

I'm just curious to your sense of the third who had sort of stopped using or weren't using, do you think some of those were just physicians or how many of them were just doctors or just for whatever reason, we're never going to be big users and so that you're sort of right now sort of really sort of hitting a good part of the sort of truly receptive market? Thank you..

Yes, thanks Doug. So again if I jump back to pre-SYFOVRE relaunch, we always had a segment of physicians who said, I'm not going to use your drug until the permanent J-code.

So there was an assumption in our third, a third, a third that that segment that said we're not going to use your drug, basically also included those physicians who were waiting for the J-code. So I think we potentially will see an impact within that segment and have seen an impact within that segment in the last quarter.

I think the more transparent we can be, the more transparent we can be, the more open we can be, but also now we're pushing our efficacy message with physicians, I think it unlocks all of those segments and we started to see those segments unlocked with the strong demand levels that we've had since for this quarter and moving forward.

So I think it's going to be a very positive next couple of quarters..

Okay, great. Thanks and congrats on the progress..

Thank you..

Thank you. One moment for our next question. And our next question is coming from the line of Joseph Stringer with Needham. Your line is open..

Hi, thanks for taking our question.

Just following up on the last two questions for the physicians who are not currently injecting SYFOVRE for safety reasons, is it your sense to say that rate of vasculitis is the sticking point or is it more physicians are comfortable with the rate and it's more a matter of, they want to see the total number of patients or the total number of injections a lot higher before they would start injecting? And is there a threshold number of patients or injections if that they would need to see to get more comfortable if that is the case before injecting?.

Yes. I think, Joey, thank you so much for that question.

It's important to bear in mind that this rate in itself was never an issue, right? I mean, the problem that we had is that a couple of years ago, there was another drug that started with this rate and ended up with a rate that was orders of magnitude worse, because there was a sensitization against the drug. This is absolutely not the case here.

So this is an extremely rare event sporadically over time. And as I mentioned, we're going to keep tracking that, but it is a very straightforward conversation now between the physician and the patient. Adam, can maybe comment briefly on the commercial impact of that..

Yes, thanks. Hey, Joey. So no surprise, take out vasculitis from the conversation for a second. Every launch has a subset of physician population that I would deem as laggards. Those that it's a technical term. They wait to see what happens with the drug once it launches. They follow key opinion leaders, they follow that experience.

It doesn't matter if you're launching a drug in the retina or launching a drug in another space, that subset of physician population exists. It's the same within this launch, right? So we had physicians who said I would wait for the permanent J-code.

We've had physicians who said I want to see that Professor X or Doctor Y is using and has good experience before I start. So as we get through the launch trajectory, we expect to unlock all of those segments.

As those physicians who are waiting will get the check in the box that they need to say, I've seen enough, I understand this now, my colleagues are using, I'm going to start to use it. So it's a future opportunity. I think we'll continue to make inroads within that segment..

Great. Thank you for taking our question..

Thank you, Joey..

Thank you. And I see no further questions in the Q&A queue at this time. I will now turn the call back over to Dr. Cedric Francois for any closing remarks..

Thank you so much. Well, in closing, thank you all for joining us today. We are around later today and tomorrow. If you have any additional questions, feel free to reach out to Meredith. Thank you again and have a wonderful day..

Ladies and gentlemen, that does conclude our conference for today. Thank you for your participation. You may now disconnect..