Q3 2021 Apellis Pharmaceuticals Inc Earnings Call

Good day and thank you for standing by welcome to the third quarter 2021 tell US Pharmaceuticals, Inc. Earnings Conference call. At this time, all participants are in a listen only mode. After the speech.

Operator: Thank you for standing by. Welcome to the third quarter 2021 Apellis Pharmaceuticals, Inc. Earnings Conference Call. At this time, all participants are in a listen-only mode.

Unknown Speaker: Transcripts provided by Transcription Outsourcing, LLC.

<unk> presentation, there will be a question and answer session to ask a question. During the session you will need to press star one on your telephone. Please be advised today's conference may be recorded if you require any further assistance. Please press Star then zero I would now like to hand, the conference over to your host today Meredith Kaya Vice President of Investor Relations. Please go ahead.

Operator: The advice given in today's conference may be recorded. If you require any further assistance, please press star then zero. I would now like to hand the conference over to your host today, Meredith.

Meredith Kaya: My host today is Meredith Kaya, Vice President of Investor Relations. Please go ahead. Good afternoon, and thank you for joining us to discuss Apellis's third quarter 2021 financial year.

Good afternoon, and thank you for joining us to discuss the pallets in third quarter 2021 financial results with you.

Meredith Kaya: 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 consider the following.

On the call our co founder and Chief Executive Officer, Dr. Cedric Francois.

<unk> commercial officer, Adam Townsend.

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 Anchorage, you to consult the risk factors discussed in our SEC.

Meredith Kaya: risk factors discussed in our SEC filings for additional detail. Now, I'll turn the call over to Cedric.

Filings for additional detail now I'll turn the call over to Cedric.

Thank you.

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 Ateneo, highlighted by strong U.S. commercial execution for EmpaBedi and PNH. Our Phase III Derby and Oaks data, which we believe positioned Baxeta Coplan 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 to targeting C3, and further reinforce our leadership position in Continental. I will start with the most significant event of the quarter, which was the top line results from Derby and Oaks.

And good afternoon to everyone joining us today for our conference call.

The third quarter was another exceptional period for updates.

Highlighted by strong U S commercial execution for <unk>.

Our phase III Derby, and Oaks data, which we believe positions <unk> to become the first treatment for GE.

And the continued advancement of our pipeline.

Our achievements this past quarter underscore the broad potential of our unique approach of targeting CET.

Further reinforce our leadership position and confident.

I will start with the most significant events of the quarter, which was the topline results from Derby and Oaks.

Cedric Francois: In these studies, Bexita-Copland showed a clinically meaningful reduction in GA lesion growth and a favorable safety profile with both monthly and every other month doses. Importantly, sexy tackle plans show that even greater resect in patients with extra foveal lesions. Supporting Treatment Earlier in Disease Progression. FEDA will review these results shortly. With this data, we believe Plexi-TacO-Plan is a breakthrough for the millions of people living with GA, a relentless disease that is a leading cause of blindness worldwide.

In these studies makes it that group and showed a clinically meaningful reduction in GDP growth and a favorable safety profile with both monthly and every other month dosing.

Unfortunately.

Makes it a copeland showed that even greater <unk> in patients with extra phobia lesions.

Porting treatment earlier in disease progression.

Peter will review these results shortly.

With these data we believe fixed at that group is a breakthrough for the millions of people living with.

A relentless disease that is a leading cause of blindness worldwide.

Cedric Francois: 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.

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 <unk> and then how we intend to capitalize the company.

Gaining clarity on both the high priority for us in the near term.

Cedric Francois: 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 K3 therapy approved for the treatment of DNA. 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.

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 the.

First and only targeted therapy approved for the treatment of UNH.

In our first full quarter since launch and partly delivered $5 3 million in.

Net product revenue exceeding our expectations and showed strong momentum across each of our launch metrics.

Cedric Francois: Additionally, TxETA Co-Plan, which will be known as Aspa Valley in the EU and marketed by Sobe, 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 P&H patients around the world. If approved, Aspavedi will become the first new therapeutic approach for PNH in the European Union since 2007. Our efforts in P&H are just the first steps in building our rare disease franchise.

Additionally, six at that growth plan, which will be known as <unk> in the EU and marketed by still be received a positive <unk> 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 <unk> patients around the world.

If approved <unk> will become the first new therapeutic approach for <unk> in the European Union since 2007.

Our efforts and <unk> are just the first steps in building our rare disease franchise.

Together with <unk>, we are continuing to advance a robust portfolio of across multiple indications.

Cedric Francois: Together with Sovi, 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 a global leader in complement. The Exeter Co-Plan represents the foundation for this goal and is our most immediate opportunity.

We have a steady cadence of milestones over the next 12 to 18 months.

The start of three late stage trial designed to support registration in four separate indications.

We are also continuing to enroll patients and are potentially registrational phase II study.

Ultimately our ambition is to become the global leader in complement.

The exit that coupon represents the foundation for physical and is our most immediate opportunity.

Cedric Francois: However, behind this, we have a growing portfolio of candidates across several modalities that will allow us to address a broad range of complements-driven diseases. We look forward to providing more details on all of these efforts as the programs advance. And now, I will now turn the call over to Adam for a discussion on our commercial efforts. Adam.

However, behind this.

We have a growing portfolio of candidates across several modalities that will allow us to address a broad range of compliments 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.

Thank you Cedric as Cedric mentioned ample valley commercial launch is off to a very strong start we are making great progress across each of our top launch priorities, which are designed to ensure that every eligible PSNH patient who want something valley has access to this important new medicine.

Adam J. Townsend: Thank you, Cedric. As Cedric mentioned, our Amper 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 Empaveli has access to this important new medication. 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.

As we said previously.

Within the U S. There are approximately 1500 patients who are currently being treated with <unk> inhibitors.

And another 150 people diagnosed with <unk>.

Our initial focus is on those <unk> patients, who have suboptimal control of their disease.

Adam J. Townsend: Our initial focus is on those PNH patients who have suboptimal control of their disease, beginning with a third of patients on C5 inhibitors with the highest unmet need, those who require transfusions to address their falling hemoglobin levels.

Beginning with the third patient from <unk> inhibitors, with the highest unmet need those who require transfusions to address their falling hemoglobin levels.

Adam J. Townsend: We plan to expand to the broader P&H 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 its launch within the U.S., an impressive figure indicating the significant number of physicians who have identified Empaveli as a potential treatment option for their patients. Additionally, we received more than 50 start forms in the third quarter alone and over 100 start forms since launch through October.

We plan to expand to the broader <unk> community. Many of whom are also suffering from signs and symptoms like anemia and to be a fatigue.

At the end of October of a 115 physicians have signed up for our Rems program since launch within the U S and impressive CAGR, indicating the significant number of physicians, who have identified <unk> as a potential treatment option for their patients.

Additionally, we received more than 50 start forms in the third quarter alone.

Of the 100 start forms since launch through October.

Adam J. Townsend: 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 Altamira. On the payer front, our value and access team continues to engage with high priority payers, including the top 20 payers who cover approximately 85% of all US P&H prescriptions. To date, 14 of these 20 have agreed to place Empabelli in a positive formulary position. We remain on track to be on formulary with approximately 90% of plans by the end of the year.

With last quarter, we are finding that <unk> inhibitor switch patient or the vast majority of new MTV stopped.

With about 70% of switches coming from <unk>.

On the payer front.

<unk> and access team continues to engage with high priority payers.

The top 20.

Who cover approximately 85% of all U S <unk> prescriptions.

To date <unk>.

Of these 20 have agreed to place empathy and a positive formulary position.

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

In parallel with the execution of the <unk> launch our commercial team is preparing for a potential approval of <unk>.

Federico Grossi: In parallel with the execution of the EmpaVali launch, our commercial team is preparing for a potential approval of Pexeter-Cotlan in GA and the opportunity to finally bring a treatment to patients. Based on early market research, the initial feedback from surveyed retina specialists in Derby and Oakes has been highly encouraging and reinforces our belief in the blockbuster potential of this product. They believe there is a clear need for the treatment, that the data support treating their patients earlier in disease progression, and that, as a result, they plan to prescribe Pegsteticopline if it is approved.

And the opportunity to finally bring a treatment to patients.

Based on early market research the initial feedback from retina specialists on therapy.

Has been highly encouraging and reinforces our belief in the blockbuster potential of this product.

They believe there was a clear need for a treatment that the data support treating their patients earlier in disease progression and as a result, they plan to prescribe pegs Tetra Copeland if approved.

Federico Grossi: As you can see on this slide, some of the feedback from retina specialists included comments like, "this is huge, we don't have anything to treat GA, and this would be a complete shift in the paradigm of how we approach and treat GA." We look forward to providing more detail on our commercial plan as we prepare for a potential launch. I will now turn the call over to Fede to review our clinical development.

As you can see on this slide some of the feedback from retina specialists, including comments like this is huge we don't have anything to treat <unk>.

And this would be a complete shift in the paradigm of how we approach and treat geordie.

We look forward to providing more detail on our commercial plan as we prepare for a potential launch.

I will now turn the call over to Fred to review our clinical development.

Federico Grossi: Thank you, Adam. I'm going to spend the next few minutes providing a high-level review.

Hey.

Thank you Adam I'm going to spend the next few minutes, providing a high level review of the Derby and Oaks data.

Federico Grossi: A review of the Derby and OUCH data.

These four percentage towards the first time at the Retina Society meeting in September.

Federico Grossi: These were presented for the first time at the Retina Society meeting.

Federico Grossi: We look forward to presenting data again at the American Academy of Ophthalmology meeting later this month. In the OCKSS study, monthly and every other mass treatment with Buxeta-Coupland met the primary endpoint, providing a clinically meaningful and highly statistically significant reduction in GA lesion growth compared to post-sham at 12 months.

We look forward to presenting data again at the American Academy of Ophthalmology meeting later this month.

In depth study monthly and every other month Kidman with Brexit the Compton.

Mary endpoint.

Abiding, a clinically meaningful and highly statistically significant reduction in Gi industry growth.

First you both sham at 12 months.

Federico Grossi: In a pre-specified analysis, Pexeta-Coupland shows an even distribution.

In a pre specified analyses.

Copeland showed an even greater reduction in patients with extra for the emissions.

Federico Grossi: and an even greater reduction in patients with extra-fold elision, by as much as 35% in the month of June.

As much as 35% in the monthly arm.

Federico Grossi: As a reminder, GA typically begins with extra follicle lesions that later progress into the follicles, with research suggesting that as many as 85% of patients start with lesions.

As a reminder, J typically begins with extra for the emissions that later progress into the quality.

With research, suggesting that as many as 85% of patients stagnation outside of the forecast.

Unknown Speaker: 2012 University of Georgia College of Agricultural and Environmental Sciences U.S. Department of

The Copeland narrowly missed statistical significance in Derby with a P value of 0.0528 in the monthly treatment arm.

However, the Coppola again show a greater reduction in lesion growth in extra flood ambitions as you can see in this slide.

Unknown Speaker: Thanks for watching!

Unknown Speaker: Value of 0.0528 in the Motley Treatment R. However, except a couple again show a greater reduction in lesion growth in extra-fossil lesions.

A quick question is why there'd be mist.

Soccer analogy.

Unexpected imbalances and based on characteristics known to be associated with disease progression in.

Unknown Speaker: As you can see in this slide, a quick question is why there have been so many, you know. I've spoken.

In Derby this imbalances reflected the persons faster progressing patients enrolling in the fix at the proppant use.

Unknown Speaker: We observe unexpected imbalances in baseline characteristics known to be associated with rapid disease progression. In Derby, these imbalances reflected the presence of...

As compared to the Sham groups, which may have contributed to the Miss.

Turning to the Fuller analysis further confirming the treatment effect.

Gordon is the first investigational therapy to demonstrate consistent and clinically meaningful reductions in <unk> from growth when looking at the treated eye versus down treated Shanghai.

Unknown Speaker: Thank you very much.

Unknown Speaker: As compared to the shangu, which may have contributed to the Turning to the follow-up analysis, further confirming the treatment effect, Lexetha Copeland is the first investigational therapy to demonstrate consistent and clinically-meaning...

In patients with bilateral GA lesions are well known to grow at similar rates in both eyes.

Therefore, this analysis says that's an important validation of the treatment effect.

Unknown Speaker: at the Treated Eye versus the Untreated Cellular Eye.

This slide shows the steady items versus the fellow eye lesion growth caused a sham groups for both Derby and Oaks.

Unknown Speaker: In patients with bilateral GA, lesions are well known to grow at similar rates in both eyes.

Unknown Speaker: Therefore, this analysis serves as an important validation of the treatment effect.

Overall as expected, we do not see a big difference in the rate of lesion growth in the study eye.

Unknown Speaker: This slide shows the study aims of the fellow ILEGION groups across the SHAM groups for both Derby and OPS.

Versus realized in the sham treatment patients, which confirms the relevance of this analysis.

Unknown Speaker: 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 patient, which confirms the relevance of this analysis. Then, when you look at the area of the math groups, we...

Then when you look at the every other month groups you start to see separation of the courts between except the concentrated high.

The untreated fellow eyes.

And finally, when you look at the monthly groups both Derby, our notes show, an even more robust separation between the coker treated eyes versus down could it go lives.

Unknown Speaker: Thank you.

Unknown Speaker: And finally, when you look at the monthly groups, both Derby and Noll,

In terms of safety exit the Coke and demonstrated a favorable safety profile across both studies.

Unknown Speaker: In terms of safety, Exeter Copeland demonstrated a favorable safety profile across both studies. The pull rate of new on-site excavations was 6% of patients in the monthly treatment group.

The full weight of New York.

<unk> was 6% of patients in the monthly treatment group.

Unknown Speaker: 4.1% in the Every Other Mass Treatment group and 2.4% in the SHAM group.

1% in the every other month treatment group and two 4% in the Sham group.

Unknown Speaker: 2012 University of Georgia College of Agricultural and Environmental Sciences UGA Extension Office of Communications and Creative Services

And data from dose by Microsoft and a drop in inflammation were generally in line with those reported in studies of other HIV til therapies.

Between Derby folks in our phase II filly study.

Now help results across more than 1500 patients from three randomized well controlled studies.

Unknown Speaker: Thank you.

Unknown Speaker: [inaudible]

Timothy E. Sullivan: We now have results across more than 1,500 patients from three randomized, well-controlled studies, providing a robust data set that we believe demonstrates Percepta Copeland's efficacy and safety and supports approval. We remain on track to submit our NDA in the first half of 2020. I will now turn the call to Tim for a review of the financial results.

Adding a robust credit book, which we believe demonstrate specific 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 your team for a review of the financial results David.

Thank you Kelly.

Since we issued a press release earlier today with the full financial results I'll 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 <unk> net product revenue for <unk>.

Timothy E. Sullivan: Thank you. Thank you. Thank you.

Timothy E. Sullivan: 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 Empaveli Net Product Revenue, a strong start for the launch, and additional revenue associated with our collaboration with Sobeys. R&D expenses were $88 million, G&A expenses were $46 million, and we reported a net loss of $196 million.

Wrong start for the launch and additional revenue associated with our collaboration with Servier.

R&D expenses were $88 million G&A expenses were $46 million and we reported a net loss of 196 million.

As of September 32021, hotels 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 collaborations was paid in cash during the third quarter.

We acknowledge that we will need to raise additional capital as we advance our leading <unk> 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 for other more strategic path as we simultaneously work to advance our regulatory path and geographic atrophy.

Timothy E. Sullivan: As of September 30, 2021, Apellis had $430 million in cash and cash equivalents, which are expected to fund our operations into the third quarter of 2022. A reminder that the $50 million payment associated with our BEAM collaboration was paid in cash during the third quarter. We acknowledge that we will need to raise additional capital as we advance our leading C3 platform and that we will do so in a thoughtful manner, as we have always done.

<unk>. We are also tightening expenses, which includes gaming spend tied to certain derisking milestones and managing hiring across the organization. During this interim period.

With an approved product and <unk> a potential blockbuster in GE 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.

Timothy E. Sullivan: 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 Empaveli, a potential blockbuster in GA, and a robust pipeline, we are confident in our ability to access capital in a way that we believe will help us deliver long-term value for our shareholders. I will now turn the call back over to Cedric for closing remarks. Cedric?

Yes.

Thank you Tim.

The first nine months of 2021 represented a transformative period for <unk> as.

As we launched our first commercial product <unk> and showed a clinically meaningful reduction of G. A decent growth with a favorable safety profile the phase III Derby and Oaks studies.

We are committed to building on this momentum to further support growth and advance our leadership position in confidence.

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 <unk> to receive EU approval for <unk> and <unk>.

To have regulatory feedback from the FDA in G H.

And to initiate a phase three study in immune complex, Ben Brownlow, proliferative, glomerulonephritis, or icmp gin and C III Columbia rollover three or <unk>.

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 in GA lesion growth with a favorable safety profile in the Phase III, Derby, and Oaks studies. We are committed to building on this momentum to further support growth and advance our leadership position with confidence. Over the next 12 to 18 months, we expect a number of key milestones across our portfolio.

Additionally, our partner so the reiterated in their recent earnings reports that they remain on track to initiate a phase III study in cold agglutinin disease or CAD and.

And there are programmed hematopoietic stem cell transplantation associated thrombotic microangiopathy or <unk> TMA in 2021.

Enrollment in our <unk> study is ongoing but we now expect that we will complete enrollment in this first half of 2022.

Cedric Francois: Beginning with the remainder of 2021, we expect Sobe to receive EU approval for PlexiTacoplan and PNH, to have regulatory feedback from the FDA and GA, and to initiate a phase 3 study in immune complex membranoproliferative glomerulonephritis, or ICMPGN, and C3 glomerulopathy, or C3G. Additionally, our partners SOBE reiterated in their recent earnings report that they remain on track to initiate a phase 3 study in cold agglutinin disease, or CADD, and their program in hematopoietic stem cell transplantation associated with thrombotic microangiopathy, or HSCT, TMA, in 2021.

Slight delay is partially due to COVID-19 as well as competing enrollment of other ongoing trials recruiting in AOS.

2022 is also set to be a milestone rich year.

In the first half of 2022, we expect to submit our new drug application and <unk> to the FDA.

To begin pre submission discussions with the European regulators about plans for our EU submission.

And for <unk> to begin launching especially in EU countries following EMEA approval.

We also expect new preclinical data to be published early next year with a <unk> inhibitor designed for the prevention of consonants 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.

Cedric Francois: 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 competing enrollments of other ongoing trials recruiting in ALS. 2022 is also set to be a milestone-rich year.

<unk> and <unk> four EPS 30 are first in class <unk> active <unk> three inhibitor for neuro degenerative diseases.

To report the 24 month results from Derby and Oaks.

And to receive a potential U S approval decision for GE.

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.

To ask a question. Please press Star then one did.

Cedric Francois: In the first half of 2022, we expect to submit our new drug application in GA to the FDA, and to begin pre-submission discussions with the European regulators about plans for our EU submission, and for Sobe to begin launching Aspartame 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 therapy 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.

If your question has been answered and you'd like to remove yourself from the queue press the pound key.

Our first question comes from Omar Saad with Evercore. Your line is open.

Yeah.

Thanks, So much taking my question guys.

Thanks for taking my question.

Any initial feedback.

From the.

On the phase three and if you could remind us of any.

That's filling the NDA next year that would be great.

Okay.

Yeah.

Okay.

Paul.

Progress on the pipeline indications in downstream.

To continue.

The research.

Could you maybe.

Youre ransom.

No.

Modification.

Especially.

It seems like.

Central line near term.

Especially.

So there is some used off label.

Any tangible.

Operator: 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 to questions. To ask a question, please press star and then 1. If your question has been answered and you'd like to remove yourself from the queue, press the pound key. Our first question comes from Umer Raffat of Evercore. Your line

Complement as fast or currently in.

I appreciate it.

The name of utility in a couple of months.

In practice and then.

Thank you so much I don't I don't know if it was my line or not that is a very hard time hearing your questions I'm going to quickly repeat them to make sure I got them right. So you wanted to know the insights or whats. The FDA process would look like then about what we have going on beyond G with empathy, both diamond specifically.

<unk> is that correct.

Okay.

Got it.

Got it.

Operator: Our first question comes from Umer Raffat of Evercore. Your line is open.

So far the bottleneck.

Thank you the next year and then specifically on <unk>.

Umer Raffat: I would love to get any initial feedback that you have received from the FDA on phase 3s, and if you could remind us of any problems that are going to be in the next year, that would also be great. And then, secondly, to move beyond GA, which I'm sure we'll get a ton of attention on. It could be progress on the pipeline indications and downstream efficiency to continue to do a diverse batch test. Could you maybe bookend the opportunity around some of those two qualifications, and maybe especially CPPT, which seems like there's a potential one near term?

An opportunity for us there and maybe even more.

Pardon me.

Okay.

Yeah. Thank you so much so as it relates to.

The phase III, so as we have.

As outlined earlier, we have submitted a request to the FDA for a meeting regarding the Derby and Oaks studies in before Christmas We plan to provide an update to the street as to what's the regulatory landscape looks like specifically there are two important elements that we need to we're hoping to get clarity on one is.

Umer Raffat: Actually, I understand the lyrics get some use off-label with A3G. Do you have any chance for a portion of the paper that compliments it past or currently, and what is the penetration?

Is weather.

You would expect us to wait for the 24 month data before actually doing the submission in the second one is whether at this point in time.

Yea believes that a another trial may be needed or not we believe that neither of those are going to be.

Cedric Francois: 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 MPAP-80 and specifically C3G. Is that correct? I'm so sorry, David.

<unk> requested and demanded.

Any clarity on that would be important.

Then as it relates to <unk> and the pipeline. So we have as we mentioned in the call for additional Registrational programs going on in these four additional indications and indeed see three kilometer Liberty is one of the very exciting ones that we are working on.

Cedric Francois: What is the agency saying so far? The bottlenecks are going to be next year, and then specifically on 3G. Just look at an opportunity for us there, and maybe tell us a little bit more about it. Yeah, thank you so much. As relates to phase three, as we have outline earlier, we have submitted a request to the FDA for a meeting regarding the Derby and Oakes studies, and before Christmas, we plan to provide an update to the suite as to what the regulatory landscape looks like.

This is indeed, an indication for which <unk> and <unk>.

These are sometimes used.

Bill.

We are running a phase III clinical trial and our objective is to identify whether in fact that he can be a treatments or that indication, but they're both based on the mechanism based on the phase two data that we generate this we believe that this is a very important.

The occasions, where we have an opportunity to.

To be a best in class products, where these patients potentially.

Cedric Francois: Specifically, there are two important elements that we need to or are hoping to get clarity on. One is whether, you know, 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.

And we are also importantly, I'd like to point out that the icmp, Jim components, which is essentially the other half of the patients that will be enrolled in this study.

Our a form similar to <unk>, but one that is more driven or actually represented by the presence of anti bodies in the kidney and therefore, the classical pathway as well.

Okay.

Yes, one more.

I appreciate it.

In the prepared remarks.

Our exposure.

Or.

Cedric Francois: Then as it relates to MPAVERI 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 Solures and ultramuris are sometimes used off-label.

Financing and for anyone with a little bit.

Okay, I understand there's a lot of financing right now.

Are you open to.

Less traditional.

Beyond that.

Could you repeat the whole thing.

Your preferred solution.

Would be in.

Yeah.

Cedric Francois: We are running a phase three clinical trial, and our objective is to identify whether MPAVERI can be a treatment for that indication. But both based on the mechanism and on the phase two 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. And 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.

So youre looking first and foremost.

These non traditional or alternative routes.

Yes.

Thank you so much I'll hand that one over to attend.

Sure.

My best too.

Also feedback the question I think you're asking.

Generally speaking are we open to other less traditional forms of financing in the context of.

Our acknowledged.

Capital raising needs.

And look we're certainly aware of is that correct Sean.

First of all.

Yeah.

Okay. Yeah. So we are aware of the current conditions that could impact our ability to raise capital and we're exploring all of those options those raised range from traditional equity debt Royal.

Royalty partnerships or some more strategic path so.

Really we're looking at the entire range of things and.

Cedric Francois: Thank you so much. I guess one more. I appreciate it. Thank you. All right.

We are.

Okay.

Timothy E. Sullivan: I mentioned in your previous remarks that you are exploring options for financing and for spending a little bit. I understand there's a lot of concern about financing right now. Are you open to using a less traditional solution, perhaps beyond equity? And could you speak to us a little bit about what your preferred solution would be? We're looking, first and foremost, at the non-judicial and all-sector groups that are first and foremost. Thank you so much.

Basically also simultaneously as we mentioned.

Looking at our expenses to extend our runway while our cost of capital is where it is but.

At this point we're.

Taking our time to do the right thing for shareholders. As we said, we'll look at all options.

Yeah.

Alright, thanks, so much.

Thank you so much.

Our next question comes from Omnicom Rama with JMP J P. M. Your line is open.

Hey, guys. Thanks, so much for taking the question can you hear me all right.

Yes, we can hear you well and have them.

Alright cool.

Just a quick one on the <unk> 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.

Timothy E. Sullivan: I will hand that one over to Tim. Douglas Goldstein, CFP®, is the director of Profile Investment Services and the host. And look, we're certainly aware of the, is that correct, Sean? Yeah, sure.

There any synergies we can think about over time. Thanks, so much.

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

Thanks Pam.

You can hear me too. So yes, we're we're very very pleased with the progress of the empathetic launched <unk>.

Timothy E. Sullivan: We're aware of the current conditions that could impact our ability to raise capital, and we're exploring all of those options. Those range from traditional equity, debt, royalty, partnerships, or some more strategic paths. Really, we're looking at the entire range of things and, as we mentioned, we're also simultaneously, as we mentioned, looking at our expenses to extend our runway while our cost of capital is low.

What we're finding out 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 sushi positive feedback on the process from not only from physicians, but also from patients.

Once we go through the Rems and we go through the paperwork that's required it takes on average between two to three weeks to transition a patient across.

Anupam Rama: Our next question comes from Anupam Rama with J&P. JPM, your line is open.

Hopefully that answers your question.

Thanks, so much for taking our question.

Anupam Rama: Hey guys, thanks so much for taking the question. Can you hear me all right?

Thank goodness that Scott.

Our next question comes from Phil Nadeau with Cowen and company. Your line is open.

Good afternoon, congrats on the quarter and thanks for taking my questions a.

Adam J. Townsend: 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 the start form to getting a patient on therapy, and are there any synergies we can think about over time?

A couple on GE from US and then one on <unk>.

G. A in terms of the regulatory strategy.

We've had some care where else suggests that the 18 month data could strengthen the package is that something you are considering and we've also had kols suggests that the consistency in the every other month dosing arm specifically the extra fulvio lesions.

Adam J. Townsend: Thanks so much. Thank you, Anupam. I'm going to hand that one over to Adam.

Would appeal to the FDA.

Is it possible to compete.

Adam J. Townsend: Thanks Anupam. Hopefully, you can hear me too. So yeah, we're very, very pleased with the progress of the M Povelli launch in P&H.

Hi for approval just for every other month dosing and extra foveate lesions and is that something you'd be you'd be satisfied with.

Alright, thank you so much Phil so.

Let me first take those two questions with the 18 months that is not.

Adam J. Townsend: We're very, very pleased with the progress of the Empaveli launch in PNH. What we're finding, Anupam, is that the transition of initial forms to commercial patients takes between two and three weeks, which is pretty normal for a rare disease drug launch. We get hugely positive feedback on the process from not only physicians but also from patients, but once we go through all of the REMS, and we go through all of the paperwork that's required, it takes, on average, between two to three weeks to transition a patient. Hopefully, that answers your question.

There was a cable to cool that specific that you have.

That.

Where did that was giving us feedback we have never guided that.

You mentioned that so that has been a misunderstanding.

He came out of it.

One of the conferences.

As it relates to the every other month extra mobile data. We are of course very very happy with the data that we have there because every other months for early patients is especially attractive but we've been trials that we believe represents a breakthrough in geographic atrophy for all patients. The way we studied it in these studies.

There are three pieces to the application one is the safety, which I think.

Philip M. Nadeau: Our next question comes from Phil Nadeau with Cohen & Company. Your line is open. Good afternoon, congratulations on the quarter.

I met or exceeded our expectations second is does the drug works in that context. The data is very telling we also have the fellow eye analysis, which further confirms that can you expect from the drip.

Philip M. Nadeau: A couple of them on GA from us and then one on Ampivelli.

Philip M. Nadeau: We've had some care whales suggest that the 18-month data could strengthen the package.

And the third one is what is the size and you said that is why we did this post hoc analysis, where you can essentially make the T trials that we ran city Derby and Oaks kind of more equal to each other by making the based on regions.

Philip M. Nadeau: 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

Philip M. Nadeau: I would appeal to the FDA; is it possible to apply for approval just for every other month dosing in extra foveal lesions, and is that something you'd be satisfied with? All right, thank you so much, Phil.

More berry vessel and there we've seen the success that we believe is in the range of 20% to 25%.

The broader population and then with the benefit that we believe may be north of 25% in these patients with extra four divisions all of that and whether the FDA wants to take us out of that of course is going to be up to them, but we will submit all these data as one package.

Cedric Francois: So, well, let me first take those two questions. With the 18 months, that is not, there was a KOL call that you specifically 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 extrafovial data, we are, of course, very, very happy with the data that we have there because every other month for early patients is especially attractive, but we ran trials that we believe 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 safety, which I think met or exceeded our expectations.

That's very helpful. And then in terms of FDA interactions you've mentioned.

The disclosure by the end of the year pushed your FDA meeting you're going to wait for the meeting minutes before making that disclosure or will you be in a position to do what you think right. After the meeting.

And then similarly on the review time lines I think you suggested an approval in the second half of the year trying to mine too just to clarify does that assume a six month review because this is a label expansion.

Yeah. Thank you so much Phil so we do not comment on it.

The interactions until we have minutes. So we can make.

Appropriate and well publicized representation, so that will 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.

Cedric Francois: Second, is whether the drug works? And in that context, the data is very telling. We also have cell-by-eye analysis, which further confirms a clear effect from the drug. And the third question is, what is the effect size? And for effect size, that is why we did this post-hoc analysis where you can essentially make the three trials that we ran, CILI, DERBY, and TOCS, kind of more equal to each other by making the baseline lesions more pari passu.

That is indeed premised on a priority review so all drugs in the retina and the last 20 years as far as we know have received priority review and we believe that our product will sell in that category as well.

And then last question from US just on temporary always launch.

Congratulations on the solid number for the quarter you mentioned that most patients are switch are those in fact patients who require transfusions, while on ultra mirrors. The population that you're targeting are you getting a broader swath of patients switching temporarily in the early days.

Cedric Francois: And there we've seen an effect size that we believe is in the range of 20 to 25% for the broader population, and then with a benefit that we believe may be north of 25% in these patients with extra fovea 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. That's very helpful. And then, in terms of FDA interactions, you mentioned a disclosure by the end of the year, following your FDA meeting.

Thank you so much.

I'm going to hand that one over to Adam, but we are very excited that we.

We are breaking into this segment of patients that have more normal hemoglobin levels.

May not necessarily be transfusion dependent Adam.

Yes, Thanks, Bill and thanks for the summer et cetera.

So.

The 1500 <unk> treated patients.

We are getting patients from across all of the segments as separate Cedric described including the treatment naive segments.

It's great I think that tells us that physicians and patients can see the benefit of elevating that standard of care with <unk>.

Philip M. Nadeau: And then, similarly, on the review timelines, I think you suggested approval in the second half of the year 2022. Just to clarify, does that assume a six-month review because this is an label expansion?

<unk>.

About us if those patients, particularly the majority of the ultimate switches do have low hemoglobin.

Quiet transfusions, as we would have expected that the ones with the highest unmet need so Patrick Ted.

Team is executing we're getting patients from from across all of those.

These segments as well as treatment naive so.

It's looking good.

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 would like to have in our hands. As for the approval, we set it for the second half of next year, and that is indeed premised on a priority review. So, all drugs in the retina for the last 20 years, as far as we know, have received priority review, and we believe that our product will fall in that category.

Perfect. Thanks for taking my questions.

Thank you Phil.

Our next question comes from Steven <unk> with Raymond James Your line is open.

Great. Thank you good afternoon congrats.

Congrats on the quarter you not only beat consensus, but I think you'd be all 16 analyst estimates so kudos to that my question is actually about.

G. A commercial because you mentioned in your slides you're preparing for potential launch in <unk> and I just wanted to drill down on that.

Does that mean, you're hiring the field force.

What does that look like.

And is this an indication that you anticipate appel us would be able to.

Philip M. Nadeau: Congratulations on the solid number for the quarter. You mentioned that most patients are switched. Are those, in fact, patients who require transfusions while on Altamiris, the population that you're targeting, or are you getting a broader swath?

Independently launch in the U S without a commercial partner.

Thank you so much Steve.

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

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

We've hired the marketing and sales leadership within the U S affiliate and we've also built out our European team in Australia, and Germany, and Australia. So we truly believe that we can launch this breakthrough product engine and we are preparing thoughtfully behind the scenes to get ready to do so.

Philip M. Nadeau: broader swath of patients switching to Ampivelli in the early 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.

Actually maybe I'll ask one more again commercial but back to <unk> enabled device.

Adam J. Townsend: 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, as Cedric describes, including the treatment-naive segment, 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 Empaveli.

Maybe could you update us on the progress there do you think its still necessary just given the strength of the launch and when might that be coming to market. Thanks again.

It looks like that yet.

Big fans of the enabled device, we're also thrilled with.

How a patient support services are helping train <unk> patients.

I think that's a great opportunity for us to.

We need to elevate the standard of care with the launch of the enabled device.

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.

Adam J. Townsend: http://www.nph.nih.gov.au Ebola says 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 numbers.

Some 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 saying if they switch to <unk>.

Thank you.

Thank you Steve.

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

Adam J. Townsend: And as the team is executing, we're getting patients from across all of those unmet need segments as well as treatment naive patients.

Hey, everyone. Thanks for taking our question so kind of a follow up on Phil's question about the timing for.

<unk> approval in <unk>, so even with priority view to have a second half approval would imply a relatively early in the first half 'twenty two filings so kind of is it reasonable to assume that.

Adam J. Townsend: So progress is looking good. Perfect. Thanks.

Philip M. Nadeau: Perfect. Thanks for taking my questions.

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

Preparations are being made for an anda to get a turnaround in relatively quick time after the FDA interactions by year end.

Steven Seedhouse: Thank you, good afternoon. Congratulations on the quarter. You not only beat consensus, but I think you beat all 16 analyst estimates, so kudos for 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? Uh, and is this an indication that you anticipate Apellis would be able to... independently launch in the U.S. without a commercial partner?

Thank you, Matt and good to hear you.

Have we started working on the preparations for the NDA.

When we go to the top line data so yes.

Okay, and then on the other expansion indications preemptive valley with the caveat that someone that were being run by <unk>. So you might throw back you'd be able to go out so it'll be about them. How should we think about that is I know some of these trials and particularly we think about <unk> versus the <unk> trial.

Bone marrow TMA versus some of the other kind of Registrational trials as indication like are they going to largely be in line with the kind of scale and scope of what's been seen previously.

Cedric Francois: Thanks. Thank you so much, Steve. Thank you for the kind words. I'm going to hand it to that one.

<unk>. Similarly is there kind of a scale and scope, we should think about or how big these trials will be practically when they start.

Adam J. Townsend: Thanks, Steve. Yeah, absolutely. You're right.

Yes, Thank you, Matt so there too.

Adam J. Townsend: 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 US 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

When we designed these trials, we look at obviously at what our competitors and others before us have done, but we evidenced <unk> have our own interactions with the FDA, we make sure that we have alignment on the endpoints and the design of the studies.

That was in place for all four of the Registrational studies that we have and that's not to mention the fact that we try to harmonize the regulatory feedback from the various geographies as well.

Steven Seedhouse: Thanks. Actually, maybe I'll ask one more, again, commercial, but back to PNH. The enabled device. Could you please 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?

Phil I don't know if you want to add something to that.

No.

Hey, Scott.

Good try.

These are global development program, so not incorporating the FDA feedback.

But also the European regulatory bodies are very important.

Steven Seedhouse: Thanks again.

Adam J. Townsend: Thanks Steve. We're big fans of the enabled device.

But they do not general deviate from from what you see out there.

Adam J. Townsend: 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 just wanted to get through the first initial phases of the launch.

Okay, great. Thank you very much everyone.

Thank you Madam.

Our next question comes from Justin Kim with Oppenheimer <unk> Company. Your line is open.

Hi, good afternoon, thanks for taking the questions just two one on commercial and one on <unk>.

With the sort of start forms can you talk a little bit about how.

Adam J. Townsend: And we also wanted to make sure that all of our systems and processes were working as well as possible. So as we get through the launch period into next year, we'll start to look at the best way of us launching the enabled device. We think it will have a big benefit for patients on top of the benefits they already see if they switch.

The pace of those forms might have been influenced by the early access programs are concluding and what impact if any COVID-19, and the Delta brand has had for the third quarter.

Thank you Justin Adam.

Adam J. Townsend: That's seeing if they switch to Pepper Belly.

Thanks, Justin so.

Madhu Sudhan Kumar: Our next question comes from Madhu Kumar with Goldman Sachs.

The demand that we're seeing from our Stockholm and that decision Rams and raw.

<unk> is agnostic to to our transition of early access program patients transitioning.

Madhu Sudhan 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 first half 22 filing. So is it reasonable to assume that preparations are being made for an NDA to get a turnaround in a relatively quick time after the FDA interactions by year end?

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.

Yes.

If you ask me if I wanted to launch a rare disease drug in the timing 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 paas and at the moment.

Madhu Sudhan Kumar: Thank you Madhu, and it's great to hear from you. We have. We started working on the preparations for the MDA when we got the top line data, so yes. Okay, and then on the other kind of expansion indications for Impaveli, with the caveat that some of them are being run by Sobe, so you might throw back to me as you go ask Sobe about them, how should we think about the design of some of these trials, and particularly how should we think about CAD versus the Satimlamab trial or bone marrow TMA versus some of the other kinds of registrational trials as Like, are they going to largely be in line with the kind of

And we're making the most of that impact in the calls, but we're also we pivoted very quickly to virtual interactions.

Ah.

Our appellate cat educators to help train patients on how to administer the product et cetera at the request of physicians, they're interacting virtually and we are getting positive feedback on that as well.

We pivoted pretty well to virtual interactions as and when needed. We're also monitoring all of the situations. So.

Hello, all of the Covid protocols, and as and when physicians changed their process and allow face to face interactions will make sure that we're very compliant with that.

But we are using everything within our arsenal to interact with <unk> physicians in teenage patients in and it's going well.

So we're happy with what the team's doing.

Great Great and maybe just on <unk> with some of the posters presented at ASN and also sort of taking a look at Quinn trials, just wondering how the company thinks about the ICM PGN <unk> <unk> population post transplant and.

Madhu Sudhan Kumar: C3G. Is there kind of a scale and scope we should think about for C3G?

Cedric Francois: Yes. Okay. Great.

Cedric Francois: about how big these trials will be practically when they start. Yeah, thank you, Madhu.

Cedric Francois: So there too, you know, when we design these trials, we look, obviously, at what our competitors and others before us have done, that we evidently have our own interactions with the FDA, and 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 regulatory feedback from the various geographies as well. Fedi, do you want to add something to that?

In fact, there can you kind of alluded to maybe the fact that antibody mediated.

Disease could sort of be an opportunity potentially for <unk>. So just wondering is this an enriched population and further motivation for having a phase III program as well there.

Yes. Thank you Justin So we did not specifically study icmp gin and a phase two setting.

But we believe that the biology is shared between the two diseases and for those on the call not familiar with that.

Federico Grossi: Dr. Adele, I think you hit the spot, you know, we try, these are 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.

The real difference between <unk> and the presence of anti bodies and the deposits. Obviously three that are present in the kidney so.

That's in place the classical pathways in all likelihood invoked and an alternative pathway inhibitor, such as the <unk> sector B or G molecules.

Federico Grossi: Okay, great. Thank you very much, everyone.

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

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.

It will be very important and we've always thought about the CTG or icmp Jin.

Justin Alexander Kim: Hi, good afternoon. Thanks for taking the questions. Just two, one on commercial and one on C3G. With the 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 what impact, if any, COVID-19 and the Delta variant had on the third quarter? Thank you, Justin and Adam.

<unk> in three buckets very early patients typically adolescence offices that have been newly diagnosed that may is 10 years or more until it gets to assign the renal disease and where we believe there is a special place where these oral products that are in development, including our own.

Got you worried we serve patients that are getting closer to end stage renal disease.

Well, thanks, Susan for transplantation or hemodialysis of course.

Adam J. Townsend: Thanks, Justin. Yep. So we, you know, the demand that we're seeing from a start form and a physician rems in enrollment is agnostic to

There the advantage of having a best in class products will outweigh the benefits that may come with these oral products and then last but not least in the post transplant setting where convenience will always come second to having maximum efficacy. So that's how we think about the world and our trials are designed to be in lock step with that strategy.

Adam J. Townsend: Welcome 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, Justin, if you asked me if I wanted to launch a rare disease drug in the time of a global pandemic, my answer would always be no, but I'm thrilled with how the team is handling those situations. So about 40% of all of our interactions are in person.

Understood, Thanks, and congrats on the progress.

Thank you Justin.

Our next question comes from <unk> <unk> of Bank of America. Your line is open.

Hi, one question for me.

And then it really is the preferences that you've listed about the types of financing.

That the company is looking into.

One whether it be a royalty agreement or a partnership.

Some combination of debt that you think is.

Your preferred option right now.

Unknown Speaker: Transcribed by https://otter.ai

And then how important is it.

So we have the application filed and accepted by FDA in order to increase your chances of getting the type of.

Adam J. Townsend: But we've also, we pivoted very quickly to virtual interactions, so our ApellisCare educators who help train patients on how to administer the product, etc., at the request of physicians, they're interacting virtually, and we're getting hugely positive feedback on that as well.

Of deal that you are looking for thank you.

Thank you Sir.

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 that's going to be important. So so of course, that's that is a consideration from a timing perspective.

Adam J. Townsend: We're monitoring all of the situations, so we'll follow all of the COVID protocols, and as and when physicians change their processes and allow face-to-face interactions, we'll make sure that we're very compliant with that.

Overall, I would say, we acknowledge that we need to raise.

Capital in a way that is.

<unk> and done as we always have so.

I can't probably comment any more on what the preferred options are but one thing. We do want is to have all of those options sort of laid out on the table. So from a timing perspective.

Adam J. Townsend: But we're using everything within our arsenal to interact with P&H physicians and P&H patients, and it's going well, launch to date, so we're happy with what the team's doing. Great, great.

We will update you in due course, but thanks for the question.

Our next question comes from Colin <unk> with Baird. Your line is open.

Yeah.

Great. Thanks for taking my question and congrats on the quarter one question for us.

Justin Alexander Kim: 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 for pegcetococin. So just wondering, is this an enriched population? And furthermore, what are some motivations for having a Phase II program as well there? Yeah, thank you, Justin.

You you presented the top line.

A number of medical meetings since that.

Results were initially announced.

I guess have you had any have you had any opportunities.

European Kols and how they might be the top line data differently.

Yeah.

Question.

Thank you Colin 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 and the U S.

And other regions as well and to Adam you've been in charge of that work.

If you can give a quick update on the results from that.

Yes, Thanks, Patrick Thanks, Colleen so yes, we've.

Cedric Francois: So, we did not specifically study ICMPGN in a phase 2 setting, but we believe that the biology is shared between the two diseases, and for those on the call not familiar with that, the real difference between C3G and 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 G molecules, can be expected to be less efficacious in treating that.

No surprise right. So we we presented some great data ASR at the Retina Society and.

We've been interacting through various forms of market research with retinal physicians all of the world, including Europe.

And.

We're hearing that consistently U S Europe or international that there is a real need for a treatment and the data supports treating patients.

And no surprise, it's 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.

We get the same consistent feedback in our market research run in Europe as.

As the U S that so hopefully that answers your question.

Cedric Francois: Also, hand-in-hand with that is, of course, the post-transplant setting, where we believe the best-in-class profile will be very important. And we've always thought about C3G or ICMPGN patients in three buckets. Very early patients, typically adolescents, 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.

Yeah. That's helpful. Thank you for taking my question.

Thank you.

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

Hey, guys. Thanks for taking my questions and congrats on the early launch progress I guess two for me one when Youre thinking about I know the majority of switches, but maybe talk about some of the data that we might see as especially in the higher hemoglobin levels and how you think about that might help us.

So think about maybe trading more of their naive patients or maybe it's just a matter of time.

Before.

Just the experience of 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 atrophy before you plan on filing the data that you presented at public are either via press release. Thanks.

Thank you so much that you can answer the first question Adam is wind.

Thankfully here, yes, so we are actually seeing.

And preventing starts across all of the paradigm of the patient mix as I've described.

1500, <unk> five treated patients, where we're seeing usage the majority of the usage at the moment within that lower falling hemoglobin requirement for transfusions.

Cedric Francois: The second category is 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 kind of outweigh the benefits that may come with these oral products. And 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.

We're also getting usage and higher hemoglobin levels and also through patients who have the signs and symptoms of <unk>.

<unk> basically.

Also getting and have any thoughts in the naive population, which is great. I think it's supported by the label and people understand the superiority data within the label I think the Ash abstracts, I mean help us get more data out there to have those discussions one thing we do consistently here as you know, it's a small prescriber base.

With a small patient population physicians keep telling us they want to try.

<unk> in the hardest to treat patients those that have the highest unmet need and then 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 into next year that we'll be able to broaden that base of patients that physicians have got through that first second or third patients for example.

Tazeen Ahmad: Understood. Thanks, and congrats on the sale. Our next question comes from Tazeen Ahmad of Bank of America. Your line is open.

Tazeen Ahmad: Hi, I have one question for you. 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, you know, 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?

We expect to see that happen as we go into the first stages of the launch next year.

And you're back to Cedric for the second part of your question.

Yeah, I think so that's an easy answer.

We made.

We made a deliberate effort as you know in September to has kind of very complete presentations at the retina Society, and the Srs and <unk> always going to be a recap and kind of concentrating again.

Yeah.

The data that we believe.

We'll make a huge difference in the lives of these patients.

Tazeen Ahmad: Thank you. Thank you, Tazeen.

Great. Thank you.

Thank you.

Timothy E. Sullivan: So look, as we've always done, we will be very thoughtful about how we access capital, and that includes taking into consideration the timing and feedback of our engagements with FDA, of course, and for certain members of the community that provides capital, that's, that's going to be important. So, so, of course, that's, that's a consideration from a timing perspective. Overall, I would say we acknowledge that we need to raise Dr. David Acheson, Cedric Francois, Joseph Stringer, Douglas Tsao, Eliana Merle, Madhu Kumar, Joseph Stringer, Derek Archila, Douglas Tsao, Eliana Merle, Siyue Wang, Philip Nadu, Joseph Stringer, Douglas Tsao, Eliana Merle

Okay.

Our next question comes from Yigal <unk> with Citi. Your line is open.

Hi, This is carly on for Yigal, Thanks for taking our question.

We have two <unk> first to be were wondering what the regulatory precedent looks like in ophthalmology, when one phase III wax and one message primary endpoint is there anything that you can lean on based on previous situations like this that the FDA had space.

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.

Thanks, so much.

Thank you so much so liquid regulatory precedents, yes, there are regulatory questions, but I think it's important to point out here.

Colleen Margaret Kusy: Our next question comes from Colleen Kusy with Aired. Your line is open.

Colleen Margaret Kusy: Great. Thanks so much for taking our questions, and congrats on the quarter. One question for us. I know you've presented the top-line Derby Health 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 U.S.-based physicians?

We've outlined before as well.

Is this from the Fda's perspective.

The P value chemicals on the border of going to face.

Needs to be contextualized with the extraordinary value that we had in books right I mean statistically.

The trial and the trial like Derby in combination are statistically more powerful than for example, the <unk>.

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 were in charge of that work. Maybe you could give a quick update on the results of that.

The value of point or four on two trials.

I think the FDA will look at this is the way.

We are going to present to them the way, we talked about it which is.

We had an exquisite safety profile, we have a drug that we believe clearly works.

Hello, and analysis again kind of clearly put that stake in the <unk>.

Adam J. Townsend: Yep, thanks, Cedric. And thanks, Colleen. So, no surprise, right? So we presented some great data at ASRF.

Round, and then third would be and that's really the key question. What does the six days when you have three trials between Philly Derby and Oaks within fixed says that ranges from 12 months to 29% where exactly does it and again with that analysis, where you correct for the baseline imbalances in the groups you get quite a consistent picture.

Adam J. Townsend: Thank you very much for joining us in the Retina Society. And we've been interacting through various forms of market research with retina physicians all over the world, including in Europe. And we're hearing consistently, U.S., Europe, or international, that there is a real need for treatment and that data supports treating patients.

Again, indicating that this is going to be breakthrough treatments for these patients.

Then as it relates to every other month and marquee wins.

We indicated earlier as well we plan to submit all of the data to the FDA.

Adam J. Townsend: And no surprise, very similar to what we're hearing in the U.S. from physicians.

Sure.

As a full package every other month monthly.

Tazeen Ahmad: Tazeen Ahmad, Annabel Samimy, Yigal Nochomovitz, Derek Archila, Douglas Tsao, Eliana Merle, Yeah, that's helpful. Thank you for that.

All patients with <unk> and then also the expense of your business. So all of that will be presented in the table discussion will be something that will come at the end of the process.

Tazeen Ahmad: Yep, that's helpful. Thank you for taking our questions.

Okay. Thanks very much.

Thank you.

Alethea Young: Our next question comes from Alethea Young with Canter. Your line is open.

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

Hey, guys. Thanks for taking the questions just a couple from US I guess just first.

Alethea Young: Hey guys, thanks for taking my questions and congrats on the early launch progress. I guess, two for me, one: when you're thinking of, 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 that might help evolve.

First on commercial and panic, just trying to get a sense of kind of the average number of script per site.

And then maybe like the proportion of bran sign up that are prescribed patients or.

You know kind of submitted the new starts and then you kind of alluded to the fact that initially possessions might want to start one or two patients and see how it goes before prescribing more but curious kind of maybe that that breakdown at their presence on site.

Unknown Speaker: Transcripts provided by Transcription Outsourcing, LLC.

Alethea Young: Before, you know, kind of, they just need experience with 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 data with geographic attributes before you plan on filing the data that you would present in a public or either via a press release?

Submitted a lot of start forms.

Last one.

And then just in terms of geographic atrophy I'm just curious if you could give us any more color I'm wondering can expose to that that the CBA data or any more info on kind of what happened with the axial assay for Derby I know that some of that gas where it had been ongoing but just curious.

Cedric Francois: Thank you so much, Alicia. I'll send the first question Adam's way.

Adam J. Townsend: Thanks, Alicia. Yeah, so

Adam J. Townsend: We are actually seeing. Empivelli starts across all of the paradigms of the patient mixes I've described. So of the 1,500 C5 treated patients, we're seeing usage, the majority of usage at the moment, within that low falling hemoglobin 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 Empivelli starts in the naive population, which is great.

And then how that analysis is going and I guess, if we can expect to learn more.

Thanks.

Thank you.

Adam do you want to take the first bench.

Absolutely. Thanks Ali so yes.

We're thrilled with the demand that we're seeing.

Over 115 physicians signed up for and is over 100 start forms and.

Not getting into too many details, but we're seeing a nice geographical spread.

Across the U S. So it's.

It's a very healthy mix as patients with unmet need are showing up geographically across the U S. We do have multiple sites incentives that have submitted more than one Stockholm. So we're getting follow on patient size you would add.

Adam J. Townsend: 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, but physicians keep telling us they want to try Empivelli.

As you would expect.

I am thrilled that the demand seems to be widespread and that means that as I've said before that physicians and patients.

And try and see.

The benefits of switching to Mpeg Valeant, and then I think that.

Cedric Francois: And I'll hand you back to Cedric for the second part of your question. Yeah, thank you, Alicia. So that's 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 AAO is going to be a recap and kind of concentrating again on the data that we believe will make a huge difference in the lives of these patients.

The physicians will start to broaden that prescription as we as we get into the late stages of this is launching into nexium launch so.

Are you happy with how we're seeing the stockholder pop up around the U S.

I'll hand, you back to Cedric for the second part.

Thank you Adam Alright, and there were really two parts to your question there as well.

The first one as it relates to the CCA 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 it.

Yigal Dov Nochomovitz: Our next question comes from Yigal Nochomovitz.

As it relates to the investigation into what happened ex U S. U S et cetera that is still ongoing but.

Yigal Dov Nochomovitz: From Yigal Nochomovitz with Citi: Your line is open.

Yigal Dov Nochomovitz: Hi, this is Carly Andreazal. Thanks for taking our questions. We have two on GA. First, we were wondering what the regulatory precedent looks like in ophthalmology when one phase 3 works and one misses the primary endpoint. Is there anything that you can lean on based on previous situations?

S became quite clear from the from the analysis that we did again with the covariance that brings the data much closer to each other between the various studies and that's something that will begin we will focus on an elaborate on at the American Academy of Ophthalmology, the safety profound affect us as drug works with the fellow eye analysis.

Cedric Francois: 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? Thank you so much.

There's a clear anchor in that.

The three trials of course.

The third piece assessing what the real true <unk> changes of the drug where does that coronary is analysis.

Cedric Francois: So a look at 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 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.

Puts us in the ranges that we discussed before.

Oh, great. Thanks, so much.

Thanks again.

Yeah.

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

Yeah.

Hi, Thanks, so much for taking the questions and congrats on the quarter.

So first on on P N H in the past you've talked about.

Sort of 12 days average from prescription a first out so I was just wondering as.

As the Ah patient.

Population is diversified a little bit perhaps since last quarter, if theres been any shift in that number or the inclusion of perhaps a little bit less severe patients.

Cedric Francois: 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 have an exquisite safety profile. We have a drug that we believe clearly works, where the fellow 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 the Oaks, with an effect size that ranges from 12 to 29%, where exactly does it go?

They're taking longer to get through.

The approval process.

And then secondarily.

Just was curious if 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 financial results. Thank you.

Thank you Adam.

Yes, Thank you Matt.

Just on the inventory perspective, I'll start that so.

No.

Basically our specialty pharmacy holds a very low level of inventory. So it's not an issue.

For us moving forward.

As part of our part of the progress also your first part of the question was how long has it taken to transition patients. So at the moment, it's taking on average two to three weeks and then some rail.

Cedric Francois: 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.

Different reasons why some of that at that time period is there I'm not remotely worried about at that time period.

Not a surprise.

Patients have to follow up with their physician.

And follow up appointments are required to sometimes that delayed the transition of his thoughtful too bad a commercial episodic prescription.

Also we want to make sure that we have signed everybody else, who is willing and ops into our patient services and that also happens and then we would schedule the patient visits to help support and training physician patients at their request so that activity is happening.

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

Eliana Rachel 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

A few things around Q4 to think forward looking right I actually think there'll be some.

Some seasonality in that right, we're moving into Q4.

Some holidays, which have an impact of when patients want to transition from a start form to a prescription.

Our commercial products that we have.

Given 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 the two to three weeks at the moment.

Eliana Rachel Merle: And I'm going to turn it over to you, Dr. Ameena, to talk about the new start forms. I know you kind of alluded to the fact that, initially, physicians might want to start one or two patients and see how it goes before prescribing more, but a curious kind of maybe the breakdown and...

The feedback that we get once we're holding a patient's hands through that transition period and once we can train them and they are on the drug is very positive for our patient support programs. So I do hope as we transition to the broader population will be able to shrink that time from start form to commercial truck, but it's.

Eliana Rachel Merle: And if there have been some sites that have, you know, submitted a lot of SART 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...

So I would expect it to be where we are in the launch.

Matt hopefully that answer your question is on patients in inventory.

Eliana Rachel Merle: at the BCVA data or any more info on kind of what happened with the Axios sites in Derby. I know that some of the Axios work had

Yes. Thank you.

Thank you Matt.

Our next question comes from Congress Yahtzee with Jefferies. Your line is open.

Eliana Rachel Merle: of the FTS work has been ongoing, but just curious kind of how that analysis is going and, I guess, if we can expect to learn more at AAS.

Hi team. This is a combi is on for Chris.

What lessons learned and best practices from the entire J study experience.

Or would you potentially apply to your intermediate AMD study anything you would do differently directly because of that experience. Thank you very much.

Adam J. Townsend: Thank you, Eddie. Adam, do you want to take this first part?

Adam J. Townsend: Absolutely. Thanks, Ellie. So yeah, we're, you know, we're thrilled with the demand that we're seeing.

Thank you so much. So we are you know.

Unknown Speaker: https://www.cdc.gov.au

And we are figuring out how these intermediate Mds studies need to be run.

Adam J. Townsend: Multiple sites and centers that have submitted more than one starter form. So we're getting follow-up patients, as you would expect. But I'm thrilled that the demand seems to be widespread. And that means, as I've said before, that, you know.

That is something that will take a little bit of time.

What we've learned is that in.

In the GH studies, when you look at the zoom outside of the dead rent it out right.

Cedric Francois: And I'll hand you back to Cedric for the second part. Thank you, Adam. All right. And there were really two parts to your question there as well, Ali.

It's not like the rest of the oldest building goes from did too alive and well there was a zoom outside which is probably very similar to what we've seen intermediate AMD.

Cedric Francois: 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 with XUS, US, et cetera, that is still ongoing, but, you know, as has become quite clear from the analysis that we did, again, with the covariance, that brings the data much closer to each other between the various studies, and that's something that, again, we will focus on and elaborate on at the American Academy of Ophthalmology.

That is something that we study them presented last year and what we call just I will run through SKU rack conversion.

It's a very interesting way of measuring north appears geographic atrophy earlier lesions is gonna be question, how the FDA looks at that.

Thank you very much.

Thank you.

Our next question comes from Joseph Stringer with Needham <unk> Company. Your line is open.

Hi, everyone. Congrats on the quarter and thanks for taking our questions just a quick one on the pipeline on.

I wanted to get your thoughts on given the competitive landscape in enrollment.

Cedric Francois: The safety profile, the fact that the drug works with the fallow eye analysis as a clear anchor in that, and the three trials, of course, and then the third piece, assessing what the real true effect size is of the drug, where that covariance analysis puts us in the ranges. Great, thanks.

What.

Your thoughts are around the sort of the.

Threshold or a clinically meaningful readout from.

That study whether it be on the.

<unk> score or other relevant biomarkers. Thank you.

Thank you so much Joey so I'm going to hand that question over to <unk> to answer.

Cedric Francois: Great, thanks so much.

Hello.

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

Yes.

We didn't hear sorry.

Sorry.

I couldn't have answered the question was.

What threshold.

Do we expect or.

Matthew Buccini: Hi, thanks so much for taking the questions and congrats on the quorum.

Considering the competitive landscape.

Matthew Buccini: So first on PNH, in the past, you've talked about sort of 12 days average from prescription of first dose, and I was just wondering, as the patient population has diversified a little bit, perhaps since last quarter, if there's been any shift in that number, or if you know, the inclusion of perhaps a little less severe patients, they're taking longer to get through.

What you expect from the clinical studies in terms of the endpoint.

Yeah. So we are looking at.

At the combined.

Mortality and efficacy.

We are.

Expecting on.

On function.

Do you have a change of around one unit per month.

On mortality.

Have a difference of 20% versus glossy what that's what we have powered the study for.

Does that answer your question.

Yes. Thank you very much alright. Thank you. Thank.

Thank you Jamie.

Matthew Buccini: The Approval Process. And then, secondarily,

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

Matthew Buccini: I 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 process?

Hi, Good afternoon, guys. Thanks, very much for taking our question I've got two on G. H. So first.

Matthew Buccini: Thank you.

Adam J. Townsend: Yes, thank you, Matt. So just on the inventory perspective, I'll start there. So, you know, basically, our specialty.

I think earlier you commented Saturday clearly PCB is probably not the best endpoint you use to gauge visual acuity and NGA patients, but I guess, what I'm trying to understand is if you could kind of contextualize, how do you see overall visual acuity actually fitting into the review process for Pegasus attack a plan.

Adam J. Townsend: Tazeen Ahmad, Annabel Samimy, Yigal Nochomovitz, Steven Seedhouse, Derek Archila, Douglas Tsao

Adam J. Townsend: And there are some real different reasons why some of that time period is there, and I'm not remotely worried about that time period. So, not a surprise, you know, patients have to follow up with their physicians and follow up and get

Yes, Thank you Laura so.

<unk> with the FDA was specifically indicated.

Adam J. Townsend: Appointments are required, so sometimes that delays the transition of a trial form to a commercial epithelial prescription.

Not relevant in the efficacy analysis.

So it was a whole process that the NIH went through with the vehicle of years ago, and we're one of the chambers and the same.

Adam J. Townsend: commercial epithelial 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 about forward looking, right? I actually think there'll be some.

Famous you said I think we can all agree that a dying retina is a bad thing and the reason why be CCA is a poor measure for GE. As you know is that it's really a reflection of what happens in the sugar in Knoxville, what goes on the periphery of the macula.

Okay. That's helpful and then kind of one more related to G&A and then I guess one final.

So a question for Tim.

Is there a precedent for any recent drug approval in the ophthalmology space, where you get approval on one study and perhaps a subset analysis on a second one and then the.

Adam J. Townsend: Some seasonality in that, right? We're moving into Q4. There are some holidays which have an impact on when patients want to transition from a starter 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 for two to three weeks at the moment,

Financing question for Tim or or probably also Cedric.

There are scenarios in which you would push back the Gi submission further out than the first half of 'twenty to perhaps to just engage with partners and a little bit more detail. Thanks very much appreciate it.

Adam J. Townsend: The fact that we get once we're holding a patient's hands through that transition period and once we train them up, and they're on the drug is very positive for our patient support programs. So I do hope as we transition to the broader population, we'll be able to shrink that time from start form to commercial drug, but it's as I would expect it to be where we are in the long term. Matt, hopefully that answers your questions on patients and infantry.

So on the precedent I think.

And interesting questions.

N D would be because you're doing.

But I think one of the features of this division at the FDA is that they are very pragmatic right. I mean, we have three trials surely there'll be oaks two of them with high statistical significance for a monthly and every other month.

Third one directionally positive.

It's going to look at the totality of the data and making assessments as to where they think.

Kambiz Yazi: Our next question comes from Kambiz Yazi, with Jeffrey. Your line is open.

And again as mentioned earlier, they will look at safety. They will look at whether the drug is biologically active and they will sign those whether it.

Kambiz Yazi: Hi team. This is Kambiz on for Chris.

Kambiz Yazi: 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. Thank you so much.

It's clinically relevant so those are kind of the steps we have to go through and we believe that this will become a breakthrough in the first therapy for these patients.

Cedric Francois: So we are, you know, in, we are still figuring out how these intermediate EMG studies need to be run. That is something that will take a little bit of time. What we've learned is that in the GA studies, when you look at the zone outside of the dead retina, right, it's not like the retina all of a sudden goes from dead to alive and well. There is a zone outside, which is probably very similar to what we've seen in intermediate EMG.

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 that that's something to that.

Yeah, I would just say that I don't think we're going to change anything operationally around around.

Ground financing.

Our view from an <unk> perspective is it wasn't a plow ahead with our filing.

We have a very high degree of confidence in the probability of approval.

Cedric Francois: That is something that we studied and presented last year, what we call this Irora-to-Cirora conversion. It's a very interesting way of measuring not pure geographic accuracy but earlier lesions. There's going to be a question about how the FDA looks at that.

So the financing will go.

Cater to that.

Thanks, very much guys.

Yeah.

Thank you Lauren.

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

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.

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

Joseph Stringer: Hi, everyone. Congratulations on the quarter and thanks for taking our questions. Just a quick one on the pipeline for ALS. I want to get your thoughts on, you know, given the competitive landscape and enrollment, what your thoughts are around the sort of a threshold or a clinically meaningful readout from that study, whether it be on the CAFS score or other relevant measures.

Thank you again for joining us today and have a wonderful rest of the week.

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

[music].

Cedric Francois: Thank you. Thank you so much, Joey. I'm going to hand that question over to Cedric to answer.

Cedric Francois: We can hear you. Sorry. I couldn't. I mean, the question was, what threshold do we expect or...

Cedric Francois: What would, considering the competitive landscape, fit in, you know, what you expect from clinical studies in terms of the end point?

Cedric Francois: Yeah, so we are looking at at the combined mortality and efficacy, and we are expecting on

Cedric Francois: Tazeen Ahmad, Annabel Samimy, Yigal Nochomovitz, Steven Seedhouse, Derek Archila, Douglas Tsao, Eliana Merle, Madhu Kumar, Joseph Stringer, Derek Archila, Douglas Tsao, Eliana Merle, Siyue Wang, Philip Nadau, John Miller, Akash Tewari, Siyue Wang, Jonathan Miller, Siyue Wang, Philip Na Editing and Production

Cedric Francois: around one unit per month and mortality to have a difference of 20% versus placebo. That's what we have part of the studies for. Does that answer your question?

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

Laura Kathryn Chico: Good afternoon, guys. Thanks very much for taking the questions. I've got two on GA. So first, you know, Cedric, clearly BCBA is probably not the best way to gauge visual acuity in GA patients. But I guess what I'm trying to understand is, if you can kind of contextualize, how do you see overall visual acuity actually fitting into the review process for PEG-CITS-ACCA plans?

Laura Kathryn Chico: Yeah, thank you, Laura. So, BCVA with the FDA was specifically indicated as not relevant in the efficacy analysis. So, it was a whole process that the NIH went through with the FDA a couple of years ago and where Wiley-Chambers, in the end, famously said, I think we can all agree that a dying retina is a bad thing. 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 of what goes on in the periphery of the macula.

[music].

Cedric Francois: Okay, that's helpful. And then, kind of, one more related to GA, and then, I guess, one financial question for Tim. In GA, is there a precedent for any recent drug approval in the ophthalmology space where you get approval for 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 22, perhaps to just engage with partners in a little bit more detail?

Laura Kathryn Chico: Thanks very much. I appreciate it. You're welcome.

Laura Kathryn Chico: You're welcome. So on the precedent, I think, you know, an interesting precedent in what AMD would be Visudyne. 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, Chile, Derby, and Oaks, two of them with high statistical significance for monthly and every other month.

Cedric Francois: The third one, directional 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 GA submission, so it's very much our plan to submit it in the first half of next year. I don't know, Tim, if you want to add something to that.

Timothy E. Sullivan: 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 Kathryn Chico: Thanks very much, guys. Thank you, Laura. There are no further questions. I'd like to turn the call back over to Cedric Francois for any closing remarks.

Cedric Francois: I'd like to call back over to Cedric Francois for any closing remarks.

Cedric Francois: And in closing, thank you all for joining us on our third quarter conference call. We look forward to keeping you updated on our progress in the months ahead. We are around later today and tomorrow if you have any additional questions, and feel free to reach out to Meredith. Thank you again for joining us today, and have a wonderful rest of the week.

Operator: This does conclude the program. Thank you for participating; you may now disconnect.

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Operator: Good day, and thank you for standing by. Welcome to the third quarter 2021 Apellis Pharmaceuticals, Inc. earnings conference call. At this time, all participants are in a listen-only mode.

Meredith Kaya: After the speaker's presentation, there will be a question-and-answer session. To ask a question during this session, you will need to press star 1 on your telephone. Please be advised that today's conference may be recorded. If you require any further assistance, please press star then 0. I would now like to hand the conference over to your host today, Meredith Kaya, Vice President of Investor Relations. Please go ahead.

Meredith Kaya: Good afternoon, and thank you for joining us to discuss Apellis's 3rd Quarter 2021 financial results.

Meredith Kaya: 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.

Meredith Kaya: Before we begin, I would like to point out that we will be making four of these.

Unknown Speaker: These are the four overriding 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 your doctor before making any decision. I hope that you have found this information helpful.

Unknown Speaker: https://www.census.gov

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 Ateneo.

Cedric Francois: Highlighted by strong U.S. commercial execution for Empa-Dedi and PNH, our Phase III Derby and Oaks data, which we believe positioned Bexita Coplan 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 to targeting C3, and further reinforce our leadership position on the continent. I will start with the most significant event of the quarter, which was the top line results from Derby and Oaks.

[music].

Cedric Francois: In these studies, Pexita-Copland showed a clinically meaningful reduction in GA lesion growth and a favorable safety profile with both monthly and every other month dosage. Importantly, Bexitacoplan showed an even greater effect in patients with extra foveal lesions. Supporting treatment earlier in disease progression. PAYDAY will review these results shortly. With this data, we believe Plexi-Tacl-Plan is a breakthrough for the millions of people living with GA, a relentless disease that is a leading cause of blindness worldwide.

Cedric Francois: 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.

Cedric Francois: 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 DNA. In our first full quarter since launch, Empaveli delivered $5.3 million in NEST product revenue, exceeding our expectations, and showed strong momentum across each of our launch metrics.

Cedric Francois: Additionally, Txeta Coplan, which will be known as Aspa Valley 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, Asclavedi will become the first new therapeutic approach for PNH in the European Union since 2007. Our efforts in P&H are just the first steps in building our rare disease franchise.

Cedric Francois: Together with Sovi, 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 Cotan represents the foundation for this goal, and this is our most immediate opportunity. However, behind this,

Good day and thank you for standing by welcome to the third quarter 2021 tell US Pharmaceuticals, Inc. Earnings Conference call. At this time, all participants are in a listen only mode.

After the speaker's presentation, there will be a question and answer session to ask a question. During the session you will need a press star one on your telephone. Please be advised that today's conference may be recorded if you require any further assistance. Please press Star then zero I would now like to hand, the conference over to your host today, Meredith Kaya Vice President of Investor Relations. Please.

Cedric Francois: We have a growing portfolio of candidates across several modalities that will allow us to address a broad range of confidence-driven diseases. We look forward to providing more details on all of these efforts as the programs advance. And now, I will now turn the call over to Adam for a discussion on our commercial efforts. Adam. Thank you, Cedric.

Go ahead.

Good afternoon, and thank you for joining us to discuss the palaces third quarter 2021 financial results.

To me on the call our co founder and Chief Executive Officer, Dr. Cedric Francois Chief Commercial Officer, Adam Townsend she.

Medical Officer, Dr. Federico Betsy and Chief Financial Officer, Tim Sullivan before we begin I'd like to point out that we'll be making forward looking statements that are based on our current expectations and beliefs. These statements are subject to certain risks and uncertainties and our actual results may differ materially I encourage you to consult the risk factors discussed in our SEC.

Adam J. Townsend: As Cedric mentioned, our Amper 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 Umpevele has access to this important new medication. 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.

Finally for additional detail now I'll turn the call over to Cedric.

Thank you Meredith and good afternoon to everyone joining us today for our conference call.

The third quarter was another exceptional period for applebee's.

Highlighted by strong U S commercial execution for G and H.

Adam J. Townsend: 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 haemoglobin levels. We plan to expand to the broader TNH 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 its launch within the US.

Our phase III there'd be an OS data, which we believe positions exited that group them to become the first treatment for G. H.

The continued advancement of our pipeline.

Our achievements this past quarter underscore the broad potential of our unique approach of targeting <unk>.

Further reinforce our leadership position and confident.

I will start with the most significant events of the quarter.

We chose the topline results from Derby and Oaks.

In these studies <unk> showed a clinically meaningful reduction in GDP growth and a favorable safety profile with both monthly.

Every other month dosing.

Adam J. Townsend: An impressive figure indicating the significant number of physicians who have identified Empaveli as a potential treatment option for their patients. Additionally, we received more than 50 start forms in the third quarter alone and over 100 start forms since launch through October.

Unfortunately.

That coupon showed an even greater reset inpatients with except for the lesions supporting treatment earlier in disease progression.

Peter will review these results shortly.

With these data we believe <unk> is a breakthrough for the millions of people living with <unk>.

Adam J. Townsend: Consistent with last quarter, we are finding that C5 inhibitor switch patients are the vast majority of new Empafeli starts, with about 70% of switches coming from Altamir. On the payer front, our value and access team continues to engage with high priority payers, including the top 20 payers who cover approximately 85% of all US P&H prescriptions. To date, 14 of these 20 have agreed to place Empaveli in a positive formulary position

And 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 <unk> and then how we intend to capitalize the company.

Gaining clarity on both the high priority for us in the near term.

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.

Adam J. Townsend: We remain on track to be on formulary with approximately 90% of plans by the end of the year. In parallel with the execution of the Empa Valley launch, our commercial team is preparing for a potential approval of Pexeta-Cotlin 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 Oakes has been highly encouraging and reinforces our belief in the blockbuster potential of this product.

Turning to.

The first and only target the Q3 therapy.

<unk> for the treatment of UNH.

In our first full quarter since launch and partly delivered $5 3 million and net revenue.

Exceeding our expectations and showed strong momentum across each of our launch metrics.

Additionally, exit that growth plan, which will be known as <unk> in the EU and marketed by <unk> received a positive <unk> opinion last month.

Adam J. Townsend: They believe there is a clear need for the treatment, that the data support treating their patients earlier in disease progression, and that, as a result, they plan to prescribe Pegsteticopline if it is approved. As you can see on this slide, some of the feedback from retina specialists included comments like, "this is huge, we don't have anything to treat GA, and this would be a complete shift in the paradigm of how we approach and treat GA." We look forward to providing more detail on our commercial plan as we prepare for a potential launch. I will now turn the call over to Fede to review our clinical development.

We expect a decision regarding approval from the European Commission by the end of this year.

They're advancing our goal to elevate the standard of care for <unk> patients around the world.

If approved as thought that you will become the first.

<unk> approach for <unk> in the European Union since 2007.

Our efforts and <unk> are just the first steps in building our rare disease franchise.

Together with <unk>, 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 trial designed to support registration and score separate indications.

Federico Grossi: Thank you, Adam. I'm going to spend the next few minutes providing a high-level review of the Dervian-Ox data.

We are also continuing to enroll patients and are potentially registrational phase II study.

Federico Grossi: These were presented for the first time at the Retina Society meeting in September.

Ultimately our ambition is to become the global either complement.

Federico Grossi: We look forward to presenting data again at the American Academy of Ophthalmology meeting later this year.

Thanks did that coupon represents the foundation for digital and is our most immediate opportunity.

Federico Grossi: In their study, monthly and every other mass treatment with Bexita Copeland met the primary end goal, providing a clinically meaningful and highly statistically significant reduction in GA lesion growth compared to post-sham at 12 months.

However, behind this.

Ron we have a growing portfolio of candidates across several modalities that will allow us to address a broad range of confidence driven diseases.

Federico Grossi: In a pre-specified analysis, Bexope-Coupland shows an even greater reduction in patients with extra-foggy lesions.

We look forward to providing more details on all of these efforts as the programs advance.

Federico Grossi: By as much as 35% in the monthly arm.

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

Federico Grossi: As a reminder, JATPK begins with exophobic lesions that later progress into the phobic, with research suggesting that as many as 85% of patients start with lesions outside.

Thank you Cedric and.

Cedric mentioned Emperor Valley commercial launch is off to a very strong start.

We are making great progress across each of our top launch priorities, which are designed to ensure that every eligible PSNH patient who want something valley has access to this important new medicine.

Federico Grossi: Missed statistical significance in Derby with a p-value of 0.05.

Federico Grossi: FQ8 in the Motley Treatment Park. However, it's a couple of, again, show a great.

As we said previously within the U S.

Federico Grossi: Thank you.

Federico Grossi: A key question is why they are being missed.

Federico Grossi: In a public analysis, we observe unexpected imbalances in baseline characteristics known to be associated with rapid disease progression. In Derby, these imbalances reflected the presence of faster-progressing patients.

<unk> 1500 patients who are currently being treated with <unk> inhibitors.

And then another 150 people diagnosed with <unk> yeah alright.

Our initial focus is on those <unk> patients, who have suboptimal control of their disease.

Beginning with the third patient from C. Five inhibitor with the highest unmet need those who require transfusions to address that falling hemoglobin levels.

Federico Grossi: As compared to the sham groups, which

Federico Grossi: which may have contributed to the Turning to the follow-up analysis, further confirming the treatment effect, Lexetha Copeland is the first investigational therapy to demonstrate consistent and clinically meaningful results.

We plan to expand to the broader <unk> community. Many of whom are also suffering from signs and symptoms like anemia and severe fatigue.

At the end of October of a 115 physicians have signed up for our Rems program since launch within the U S.

Federico Grossi: Productions in GA Leisure and Growth when looking at

Federico Grossi: and looking at the treated eye versus the untreated fellow eye.

An impressive figure, indicating that significant number of physicians, who have identified <unk> as a potential treatment option for that patient.

Federico Grossi: In patients with bilateral GA, lesions are well known to grow at similar rates.

Federico Grossi: at similar rates in both eyes.

Additionally, we received more than 50 start forms in the third quarter alone and over 100 start forms since launch through October.

Federico Grossi: Therefore, this analysis serves as an important validation of the treatment effects.

Consistent with last quarter, we are finding that <unk> inhibitor switch patient or the vast majority of new Mflb stop.

Federico Grossi: This slide shows study I, which is the fellow Eilish and Gross, across the Shatner.

Federico Grossi: Because the sham groups for both Derby and not.

With about 70% of switches coming from ultra nears.

Federico Grossi: Overall, as expected, we do not see a big difference in the rate of lesion growth in the study eye versus Philip.

On the pay upfront.

<unk> and access team continues to engage with high priority patients.

Federico Grossi: Relevance of this analysis. Then, when you look at the every-other-math groups, you start to see separation of the

Including the top 20 <unk>.

Approximately 85% of all U S <unk> prescriptions.

Federico Grossi: of the courts between the accepted, often treated eyes and the untreated fellow.

Good day 14 of these <unk> have agreed to place empathy and a positive formulary position.

Federico Grossi: And finally, when you look at the monthly groups, both Derby and November.

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

Federico Grossi: Thank you.

In parallel with the execution of the <unk> launch our commercial team is preparing for a potential approval of such a culture.

Federico Grossi: In terms of safety, Exeter Copeland demonstrated a favorable safety profile across both studies.

Federico Grossi: The full weight of news on...

And the opportunity to finally bring a treatment to patients.

Federico Grossi: Monthly Treatment Group. 4.1%

Based on early market research the initial feedback from retina specialists on therapy.

Federico Grossi: Thank you, and Great Appendectomy and Intraocular Inflammation were generally in line with those reported in studies of other intravitreal therapies.

Has been highly encouraging and reinforces our belief in the blockbuster potential of this product.

Federico Grossi: Between Derby, Oaks, and our Phase II Philly study, we now have results.

They believe there was a clear need for a treatment that the data support treating that patient earlier in disease progression and as a result, they plan to prescribe <unk> if approved.

Federico Grossi: We now have results across more than 1,500 patients from three randomized, well-controlled studies, providing a robust data set that we believe demonstrates Becerra Copeland's efficacy and safety and supports approval. We remain on track to submit our NDA in the first half of 2020.

As you can see on this slide some of the feedback from retina, especially include comments like this is huge we don't have anything to treat Gi.

And this would be a complete shift in the paradigm, how we approach and treat geordie.

We look forward to providing more detail on our commercial plan as we prepare for a potential launch.

Timothy E. Sullivan: 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 Empaveli Net Product Revenue, a strong start for the launch, and additional revenue associated with our collaboration with Sobeys. R&D expenses were $88 million, G&A expenses were $46 million, and we reported a net loss of $196 million.

I will now turn the call over to fed I used to review our clinical development.

Great.

Thank you Adam I'm going to spend the next few minutes, providing a high level review of the Derby and Oaks data.

These were presented for the first time at the Retina Society meeting in September.

We look forward to presenting data again at the American Academy of Ophthalmology meeting later this month.

In depth study monthly and every other month Kidman with Brexit the Compton.

Maryann point.

Riding a clinically meaningful and highly statistically significant reductions in G. A lesion growth.

Timothy E. Sullivan: As of September 30, 2021, Apellis had $430 million in cash and cash equivalents, which are expected to fund our operations into the third quarter of 2022. A reminder that the $50 million payment associated with our BEAM collaboration was paid in cash during the third quarter. We acknowledge that we will need to raise additional capital as we advance our leading C3 platform and that we will do so in a thoughtful manner, as we have always done.

I'm pretty bullish.

At 12 months.

In a pre specified analyses.

Copeland showed an even greater reduction in patients with extra for the emissions.

As much as 35% in the monthly arm.

As a reminder, J typically begins with extra farther missions that later progress into the fall here.

With research, suggesting that as many as 85% of patients stabilization outside of the program.

Thanks to the Copeland narrowly missed statistical significance in Derby with a P value of 0.0528 in the Montney treatment arm.

Timothy E. Sullivan: 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 Impavelli, 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?

However, except the copier again show a greater reduction in lesion growth in extra for the emissions as you can see in the slide.

I think question is why there'd be mist.

Ill talk analyses.

The offset unexpected imbalances and based on guard basics known to be associated with rapid disease progression.

Derby this imbalances reflected the persons faster progressing patients enrolling in the picks up a couple of years.

As compared to the Sham groups, which may have contributed to that mix.

Turning to the Sela analysis further confirming the treatment effect.

Gordon is the first investigational therapy to demonstrate consistent and clinically meaningful reductions in GE aviation growth when looking at the treated eye versus downgraded Shanghai.

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 in GA lesion growth with a favorable safety profile in the Phase III, Derby, and Oaks studies. We are committed to building on this momentum to further support growth and advance our leadership position with confidence. Over the next 12 to 18 months, we expect a number of key milestones across our portfolio.

In patients with bilateral G. A missions are well known to grow at similar rates in both eyes.

Therefore this analysis.

Potent validation of the treatment effect.

This slide shows the study items versus the fellow eye lesion growth caused the sham groups for both Derby and Oaks.

Overall as expected, we do not see a big difference in the rate of admission growth in the study eye.

This is Phil alive in the sham treatment patients, which confirms the relevance of based analysis.

Then when you look at the every other month groups you start to see separation of the courts between except the concentrated pie.

Cedric Francois: Beginning with the remainder of 2021, we expect Sobe to receive EU approval for Bexita Coplan and PNH, to have regulatory feedback from the FDA and GA, and to initiate a phase 3 study in immune complex membrane proliferative glomerulonephritis, or ICMPGN, and C3 glomerulopathy, or C3G. Additionally, our partners SOBE reiterated in their recent earnings report that they remain on track to initiate a phase 3 study in cold agglutinin disease, or CAD, and their program in hematopoietic stem cell transplantation associated with thrombotic microangiopathy, or HSTTMA, in 2021.

And then traded satellites.

And finally, when you look at the monthly groups both Derby, our notes show uneven mobile robots separation between exit the coker treated eyes versus downgraded their lives.

In terms of safety picks up a coke and demonstrated a favorable safety profile across both studies.

The full weight of new onset explanations with 6% of patients in the monthly trend in that group.

1% in the every other month treatment group and jumped from 4% in the sham good.

And greater spend might be and then dropping information were generally in line with those reported in studies of other HIV til therapies.

Cedric Francois: 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 competing enrollments of other ongoing trials recruiting in ALS. 2022 is also set to be a milestone-rich year.

Between Derby folks in our phase II filly study, we now have the results across more than 1500 patients from three randomized well controlled studies, providing a robust credit book, which we believe demonstrate specific efficacy and safety and supports approval.

We remain on track to submit our NDA in the first half of 2022.

Cedric Francois: In the first half of 2022, we expect to submit our new drug application in GA to the FDA, and to begin pre-submission discussions with European regulators about plans for our EU submission, and for Sobe to begin launching Aspaviri 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 therapy and other indications.

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

Thank you for that.

Since we issued a press release earlier today with the full financial results I'll 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 <unk> net product revenue the strong start for the launch and additional revenue associated with our collaboration with Servier.

Cedric Francois: In the second half of 2022, we expect to initiate a Phase III study in intermediate AMD, pending regulatory feedback, and to submit an IND for APL 1030, our first-in-class brain-active C3 inhibitor for neurodegenerative diseases. To report the 24-month results from Derby and Oaks and to receive a potential U.S. approval decision for GA. We have made excellent progress, and we look forward to providing updates as we advance our efforts. And now, operator, please open the call to questions.

R&D expenses were $88 million G&A expenses were $46 million and we reported a net loss of $196 million.

As of September 32021, appellate fell $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 collaborations was paid in cash during the third quarter.

We acknowledge that we will need to raise additional capital as we advance our leading <unk> platform and that we will do so in a thoughtful manner as we have always done.

To ask a question, please press...

We are evaluating multiple financing strategies, ranging from traditional equity or debt approaches to royalty partnerships for other more strategic path as we simultaneously work to advance our regulatory path and geographic atrophy.

If your question has been answered and you'd like to remove yourself from the queue, press

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

I would love to get any initial feedback from the SBA on Phase 3, and if you could remind us of any bottlenecks going into the end of next year, that would also be great. And it's going to be beyond GA, which is a little bit of time.

Currently we are also tightening expenses, which includes data spend tied to certain derisking milestones and managing hiring across the organization. During this interim period.

It could be progress on the pipeline indications and past trends that have been effective in continuing to a diverse patient set. Could you maybe bookend the opportunity around some of those modifications, maybe especially C3G, which it seems like we have a substantial one near term? Actually, I understand the lyrics that some use off-label with C3G. Do you have any sense for pushing the pace of that Trump compliment disaster currently and what the penetration is? I mean, what is the native utility of compliments?

With an approved product and <unk>, a potential blockbuster in Georgia, 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.

Okay.

Thank you Tim.

The first nine months of 2021 represented a transformative period for <unk> as we launched our first commercial product <unk> and showed a clinically meaningful reduction of G. A decent growth with a favorable safety profile the phase III Derby and Oaks studies.

Do you see a practice in that initiative? 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.

We are committed to building on this momentum to further support growth and advance our leadership position and complements.

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 the Empath Elite pipeline and specifically C3G. Is that correct?

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 <unk> to receive EU approval for <unk> and <unk>.

To have regulatory feedback from the FDA in G H.

And to initiate a phase three study in immune complex, Ben Brownlow, proliferative, glomerulonephritis, or icmp, gin and tier three colombia longer three or <unk>.

I'm so sorry, David, but what is the agency saying so far about bottlenecks in the next year and then specifically on 3G? If you could just look at an opportunity for us there and maybe tell us a little bit more about what is currently being used. Yeah, thank you so much. As relates to phase three, as we have outline 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 suite as to what the regulatory landscape looks like.

Additionally, our partner so the reiterated in their recent earnings reports that they remain on track to initiate a phase III study in cold agglutinin disease or CAD and.

And their program and hematopoietic stem cell transplantation associated thrombotic microangiopathy or <unk> in 2021.

Enrollment in our <unk> study is ongoing but we now expect that we will complete enrollment in this first half of 2022.

Slight delay is partially due to COVID-19 as well as competing enrollment of other ongoing trials recruiting and Alice.

Specifically, there are two important elements that we need to or are hoping to get clarity on. One is whether, you know, 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.

2022 is also set to be a milestone rich year.

In the first half of 2022, we expect to submit our new drug application and <unk> to the FDA.

To begin pre submission discussions with the European regulators about plans for our EU submission.

And for <unk> to begin launching especially in EU countries following EMEA approval.

We also expect new preclinical data to be published early next year with a <unk> inhibitor designed for the prevention of compromised immune system activation coincident with AAV vector administration for gene therapies and other indications.

Then as it relates to MPAVERI and the pipeline, so we have, as we mentioned in the call, four additional registrational programs going on and 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 Solures and ultramuris are sometimes used off-label.

In the second half of 2022.

We expect to initiate a phase III study in intermediate AMD pending regulatory feedback.

And <unk> four EPS 10, 30 are first in class <unk> three inhibitor for neuro degenerative diseases.

We are running a phase three clinical trial, and our objective is to identify whether MPAVERI can be a treatment for that indication. But both based on the mechanism and on the phase two 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 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.

To report the 24 month results from Derby, and Oaks and to receive a potential U S approval decision for GE.

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.

To ask a question. Please press Star then one if your question has been answered and you'd like to remove yourself from the queue press the pound key.

Our first question comes from Omar Saad with Evercore. Your line is open.

Thanks, so much taking my questions today.

Thanks for taking my question.

Any initial feedback.

Thank you so much. I guess one more. I appreciate it. Thank you. All right. Mr. Chairman, with the remarks that you are exploring options for financing and for spending a little bit, I understand there's a lot of concern about financing right now, are you open to using a less traditional, perhaps beyond academia, and could you speak to us a little bit about what your preferred solution would be? And, you know, We're here looking, first and foremost, at the non-conditional and also at the green tariff rates Thank you so much.

From the.

On the phase three and if you could.

Remind us of any bottlenecks billing getting next year that would be great.

And then.

Ges, which I've spoken at times.

Uh huh.

Progress on the pipeline indications in Boston.

To continue.

Numerous fashion.

Could you maybe.

You run some of those.

Uh huh.

All indications may be assessed.

Please.

Tim.

Potential near term.

I will hand that one over to Tim. Douglas Goldstein, CFP®, is the director of Profile Investment Services and the host. And, but we're certainly aware of the, is that correct, Sean? Yeah, sure. Okay, 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 raised range from traditional equity, you know, debt. Royalty partnerships and other more strategic paths

Shelly.

So there is some.

Use off label dosing regime.

Any tangible portion of it.

<unk> faster that's currently in test.

<unk> penetration.

And they're gonna be familiar.

Practice and then.

Thank you so much I don't I don't know if it was my line or another.

Really 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 <unk> with empathy, both diamond specifically <unk> is that correct.

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, looking at our expenses to extend our runway while our cost of capital is where it is. But, 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.

No.

Got it.

Okay.

Okay.

So far the bottleneck.

Thank you your next year and then specifically on <unk>.

An opportunity for us there and maybe talk a little bit more.

Our next question comes from Anupam Rama with JMP. JPM, your line is open. Hey guys, thanks so much for taking the question. Can you hear me all right?

Okay.

The occasion.

Yeah. Thank you so much so as it relates to.

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 the start form to getting a patient on therapy, and are there any synergies we can think about over time?

The phase III, so as we have.

As outlined earlier, we have submitted the request to the FDA for a meeting regarding the Derby and Oaks studies in before Christmas We plan to provide an update to the street as to what's the regulatory landscape looks like specifically there are two important elements that we need to we're hoping to get clarity on one is.

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

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, Anupam, is that the transition of initial forms to commercial patients 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 REMS, and we go through all of the paperwork that's required, it takes, on average, between two to three weeks to transition a patient.

Is weather.

You would expect us to wait for the 24 month data before actually doing the submission in the second one is whether at this point in time.

He believes that a another trial may be needed or not we believe that neither of those are going to be.

<unk> requested and demanded.

Any clarity on that would be important.

And then as it relates to <unk> and the pipeline. So we have as we mentioned in the call for additional Registrational programs going on in these four additional indications and indeed see Colombia loyalty is one of the very exciting ones that we are working on.

Hopefully, that answers your question. Thank you so much for taking our questions. Thank you. Our next question.

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

This is indeed, an indication for which <unk> and <unk>.

Phil Nadeau, Cedric Francois, Joseph Stringer, Derek Archila, Douglas Tsao, Eliana Merle

These are sometimes used.

Bill.

We are running a phase III clinical trial and our objective is to identify whether in fact that he can be a treatments for that indication, but they're both based on the mechanism based on the phase two data that we generate this we believe that this is a very important.

Douglas Goldstein, CFP®, is the director of Profile Investment Services and the host. 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-four-month dosing arm,

Vacation, where we have an opportunity to.

To be a best in class products, where these patients potentially.

Extrafovial lesions would appeal to the FDA. Is it possible to apply for approval just for every other month they're seeing in extrafovial lesions?

And we are also importantly, I'd like to point out that the icmp, Jim components, which is essentially the other half of the patients that will be enrolled in this study.

Is that something you'd be satisfied with?

Our a form similar to Q3 EBIT, one that is more driven or I say represented by the presence of anti bodies in the kidney and therefore, the classical pathway as well.

All right, thank you so much, Phil. So, well, let me first ask those two questions. With the 18 months, that is not, we had, there was a KOL call that specifically you had, 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 extrafovial data, we are, of course, very, very happy with the data that we have there because every other month for early patients is especially attractive, but we ran trials that we believe 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 safety, which, you know, I think met or exceeded our own expectations.

Okay.

Yes, one more.

I appreciate it.

Uh huh.

In your prepared remarks that you are exploring.

Or.

Financing and for anyone.

That little bit.

Okay, I understand there's a lot of them in China by anything right now.

Are you open to.

Okay.

Translational.

Beyond that.

Plus the whole thing.

Give or take.

It would be in.

You know.

What are you looking for some form of debt.

In addition, we're also figure into that first and foremost.

Thank you so much I'll hand that one over to attend.

Second, is whether the drug works? And in that context, the data is very telling. We also have cell-by-eye analysis, which further confirms a clear effect from the drug. And the third question is, what is the effect size? And for effect size, that is why we did this post-hoc analysis, where you can essentially make the three trials that we ran, CITI, DERBY, and OCHS, kind of more equal to each other by making the baseline lesions more pari passu.

Sure.

I'll do my best.

To also feedback the question I think you are asking.

Generally speaking are we open to other less traditional forms of financing in the context of.

Our acknowledged.

Capital raising needs.

And look we're certainly aware of is that correct Sean.

First of all.

Yeah sure.

Okay. Yeah. So we're aware of the current conditions that could impact our ability to raise capital and we're exploring all of those options those raised range from traditional equity debt Royal.

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 a benefit that we believe may be north of 25% in these patients with extra fovea lesions. All of that, and whether the FDA wants to take us out of that, of course, is going to be up to them, but we will submit all these data as one package. That's very helpful. And then, in terms of FDA interactions, you mentioned a disclosure by the end of the year, following your FDA meeting.

Royalty partnerships or sort of more strategic path. So.

Really we're looking at the entire range of things and.

We are.

Okay.

Basically also simultaneously as we mentioned.

Looking at our expenses to extend our runway while our cost of capital is where it is but.

At this point we're.

We're taking our time to do the right thing for shareholders. As we said, we'll look at all options.

Alright, thanks, so much.

Thank you so much.

Our next question comes from <unk> Rama with JMP J P. M. Your line is open.

Hey, guys. Thanks, so much for taking the question can you hear me all right.

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 event? Yeah, thank you so much, Phil.

Yes, we can hear you well and have them.

Alright cool.

Just a quick one on the <unk> 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.

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 would like to have in our hands. As it relates to approval, we set the second half of next year, and that is indeed premised on a priority review. So, all drugs in the retina for the last 20 years, as far as we know, have received priority review, and we believe that our products will fall in that category.

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

Thanks Pam.

You can hear me too. So yes, we're we're very very pleased with the progress of the <unk>.

What we're finding out 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 to see positive feedback on the process from not only from physicians, but also from patients, but once we got through the Rems and we go through the paperwork. That's required it takes on average between two to three weeks to transition a patient across.

Hopefully that answers your question.

Thanks, so much for taking a call.

<unk>.

Thank you and I'll, let Scott.

The last question from us, just on EmpaValley's launch, congratulations on the solid numbers for the quarter. You mentioned that most patients are switched. Are those, in fact, patients who require transfusions while on Ultramaris, the population that you're targeting, or are you getting a broader swath?

Our next question comes from Phil Nadeau with Cowen and company. Your line is open.

Good afternoon, congrats on the quarter and thanks for taking our questions a couple on GE from US and then one on <unk>.

In terms of the regulatory strategy.

We've had some kols suggests that the 18 month data could strengthen the package is that something you are considering and we've also had kols suggests that the consistency in the every other month dosing arm specifically the extra fulvio reasons would appeal to the FDA.

a broader swath of patients switched to Ampivelli in the early days.

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?

Is it possible to apply for approval just for every other month dosing and extra fulvio regions and is that something you'd be you'd be satisfied with.

Alright. Thank you so much Phil So let me first take those two questions with the 18 months that is not there wasn't care well call that specific that you have that.

Where does that was giving us feedback we have never guided that or mentioned that so that has been a misunderstanding I think came out of.

Yes, thanks, Phil. And thanks for the summary, Cedric. Yeah. Yeah. So, you know, of the 1,500 C5s,

One of the conferences.

As it relates to the every other month extra mobile data. We are of course very very happy with the data that we have there because every other month score for early patients is especially attractive, but we've been trials that.

of the 1,500 C5 treated patients. We are getting patients from across all of the segments, as Cedric describes, including the treatment-naive segment, 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 Empaveli. A large number 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 numbers. So, as Cedric said, and as the team is executing,

We believe represents a breakthrough in geographic atrophy for all patients the way we studied it in.

Studies.

There are three pieces to the application one is the safety, which I think.

Met or exceeded our own expectations second is does the drug works in that context. The data is very telling we also have the fellow eye analysis, which further confirms that can you expect from the drip.

The third one is what is the effect size and the effect size that is why we did this post hoc analysis, where you can essentially make the three trials that DRAM City Derby and Oaks.

And as the team is executing, we're getting patients from across all of those unmet need segments as well as treatment naive patients.

More equal to each other but I am making the baseline lesions.

More berry vessel and there we see success, we believes 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 a central divisions, all of that and whether the FDA wants to take us out of that of course is going to be up to them with repo.

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

Thank you. Good afternoon.

Congratulations on the quarter. You not only beat consensus, but I think you beat all 16 analyst estimates. So kudos for that. My question is actually about GA commercial, because you mentioned in your slide that you're preparing for a potential launch in GA. And I just want to drill down on that and ask, does that mean you're hiring a field force? Um, what does that look like?

All these data as one package.

That's very helpful. And then in terms of FDA interactions you've mentioned.

[noise] disclosure by the end of the year pushed your FDA meeting you're going to wait for the meeting minutes before making that disclosure or will you be in a position to do what you think right. After the meeting.

And then similarly on the review time lines I think you suggested an approval in the second half of the year.

Trying to just to clarify does that assume a six month review because this is a LIBOR adventure.

Yeah. Thank you so much Phil so we do not comment on it.

Uh, and is this an indication that you anticipate Apellis would be able to... I'm going to hand that one over to Adam. Thanks, Steve. Yeah, absolutely. 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.

Have your interactions until we have minutes. So we can make.

Appropriate and well pull a fair representation, so that wouldn't 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.

That is indeed premised on a priority region. So all drugs in the retina and the last 20 years as far as we know have received priority review and we believe that our product truthful in that category as well.

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

And then last question from US just on MTV always launch.

Congratulations on the solid number for the quarter you mentioned that most patients are switch are those in fact patients who require transfusions, while on ultra mirrors. The population that you're targeting are you getting a broader swath of patients switching temporarily in the early days.

Truly believe that we can launch this breakthrough product in GA, and we're preparing thoughtfully behind the scenes to get ready. Thanks.

Actually, maybe I'll ask one more, again, commercial, but back to PNH. The enabled device. Just maybe, could you update us on the progress there? Do you think it's still necessary, just given the strength of the launch? And when might that be coming to market?

Thank you so much.

Going to hand that one over to Adam, but we are very excited that we.

We are breaking into this segments of patients that have more normal hemoglobin levels.

May not necessarily be transfusion dependent Adam.

Yes, Thanks, Bill and thanks for the summer et cetera.

So of the 1500 <unk> treated patients.

Thanks again.

Thanks, Steve. We're big fans of the enabled device.

We are getting patients from across all of the segments as separate Cedric described including the treatment naive segments.

We're 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 processes were working as well as possible.

It's great I think that tells us that physicians and patients can see the benefit of elevating that standard of care with <unk> with <unk>.

About us if those patients, particularly the majority of the ultimate switches do you have low hemoglobin.

Wyatt transfusions, as we would've expected that the ones with the highest unmet need so centric type.

<unk> is executing we're getting patients from from across all of those.

These segments as well as treatment naive so.

Brexit is looking good.

As we get through the launch period into next year, we'll start to look at the best way of launching the Enable device. We think it will have a big benefit for patients, on top of the benefits they already see if they switch to Pemperverse.

Perfect. Thanks for taking my questions.

Thank you Phil.

Our next question comes from Steven <unk> with Raymond James Your line is open.

Great. Thank you good afternoon congrats.

Congrats on the quarter you not only beat consensus, but I think you'd be all 16 analyst estimates so kudos to that my question is actually about.

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

G. A commercial because you mentioned in your slides you're preparing for potential launch in <unk> and I just wanted to drill down on that.

Hey, everyone, thanks for taking our questions.

Does that mean, you're hiring a field force.

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 first half 22 filing. So, kind of, is it reasonable to assume that preparation to be

What does that look like.

Is this an indication that you anticipate appel us would be able to.

Independently launch in the U S without a commercial partner.

Thank you so much Steve.

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

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

Preparations are being made for an NDA to get a turnaround in relative... quick time after the FDA interactions. Thank you, madame; great to hear from you.

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 engine and we are preparing thoughtfully behind the scenes to get ready to do so.

We started working on the preparations for the MDA when we got the top-line data, so yes. Okay, and then on the other kind of expansion indications for Impaveli, with the caveat that some of them are being run by SOBE, so you might throw back to me as you go ask SOBE about them, how should we think about the design of some of these trials, and particularly we think about CAD versus the Satimlimab trial, or bone marrow TMA versus some of the other kinds of registrational trials as indications And with C3G, similarly, is there kind of scale and scope we should think about for how big these trials will be practically when they start? Yeah, thank you, Madhu.

Actually maybe I'll ask one more again commercial but back to <unk> enabled device.

Maybe could you update us on the progress or do you think its still necessary just given the strength of the launch.

When might that be coming to market. Thanks again.

We posted yet.

Big fans of the enabled device, we're also thrilled with.

How a patient support services are helping train <unk> patients.

I think there's a great opportunity for us to.

Continue to elevate the standard of care with the launch of the enabled device.

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.

Some 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 are seeing if I switch to Pepper valley.

Thank you.

Thank you Steve.

So there too, you know, when we design these trials, we look, 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 is not to mention the fact that we try to harmonize regulatory feedback from the various geographies as well. Fede, I don't know if you want to add something to that.

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

Hey, everyone. Thanks for taking our question so kind of a follow up on Phil's question about the timing for.

TEG approval in <unk>, so even with priority view to have a second half approval would imply a relatively early in the first half 'twenty two filings. So kind of is it reasonable to assume that preparation to be made for an NDA to going to a turnaround in relatively quick time after the FDA interactions by year end.

Thank you, Matt and great to hear you.

Have we started working on the preparations for the NDA.

When we go to the top line data so yes.

Okay, and then on the other expansion indications preemptive valley with the caveat that someone that are being run by <unk>. So you might throw back you'd be able to go out so it'll be about them. How should we think about the design of some of these trials, particularly we think about like CAE versus the September Nab trial.

Dr. I think you hit the spot. You know, we try, these are 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.

Bone marrow TMA versus some of the other kind of Registrational trials as indication like are they going to largely be in line with the kind of scale and scope of what's been seen previously.

Okay, great. Thanks.

<unk>. Similarly is there kind of a scale and scope, we should think about for how big These trials will be practically when they start.

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

Yes, Thank you, Matt so there too.

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 what impact, if any, COVID-19 and the Delta variant had on the third quarter? Thank you, Justin. Adam.

When we designed these trials, we look at obviously at what our competitors and others before us have done, but we evidenced we have our own interactions with the FDA, we make sure that we have alignment on the endpoints and the design of the studies.

That was the pledge for all four of the Registrational studies that we have and that's not to mention the fact that we try to harmonize the regulatory feedback from the various geographies as well.

I don't know if you want to add something to that.

No.

Hey, Scott.

Thanks, Justin. Yep. So we, you know, the demand that we're seeing from a stock form and physician REMS enrollment is

We try.

These are global development program, so not incorporating the FDA feedback.

But also the European regulatory bodies are very important.

And agnostic to our transition of early access program patients.

But they do not general deviate from from what you see out there.

Okay, great. Thank you very much everyone.

Thank you Madam.

Transcripts provided by Transcription Outsourcing, LLC.

Our next question comes from Justin Kim with Oppenheimer <unk> Company. Your line is open.

Hi, good afternoon, thanks for taking the questions just two one on commercial and one on <unk>.

[inaudible]

situation. 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

With the sort of start forms can you talk a little bit about how.

The pace of those farms might have been influenced by the early access programs are concluding and what impact if any COVID-19, and the Delta variant.

We've also, we pivoted very quickly to virtual interactions, so our ApellisCare educators who help train patients on how to administer the product, etc., at the request of physicians, they're interacting virtually, and we're getting hugely positive feedback on that as well. So we've adapted pretty well to virtual interactions as and when needed.

For the third quarter.

Thank you Justin Adam.

Thanks, Justin Yeah. So.

The demand that we're seeing from our Stockholm and decision ramp.

Coleman is agnostic to to our transition of early access program patients that are transitioning.

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.

We're also monitoring all of the situations, so we'll follow all of the COVID protocols, and as and when physicians change their process and allow face-to-face interactions, we'll make sure that we're very compliant with that. But we're using everything within our arsenal to interact with PNH physicians and PNH patients, and it's going well, launch to date, so we're happy with what the team's doing. Great

Just if you ask me if I wanted to launch a rare disease drug and 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 paas and at the moment.

And we're making the most of that impact in the calls, but we're also we pivoted very quickly to virtual interactions.

Our appellate cat educators to help train patients on how to administer the product mix et cetera at the request of physicians, they're interacting virtually and we are getting positive feedback on that as well, so we've pivoted pretty well to virtual interactions as and when needed. We're also monitoring.

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 for pegsidicope. And so just wondering, is this an enriched population and what are the motivations for having a phase two program as well there? Yeah, thank you, Justin.

All of the situations. So we'll follow all of the Covid protocols as and when physicians changed their process and allow face to face interactions will make sure that we're very compliant with that.

But we're using everything within our arsenal to interact with <unk> physicians and <unk> patients and it's going well launched it so.

With what the team's doing.

Great great.

Maybe just on <unk> with some of the posters presented at ASN and also sort of taking a look at Quinn trials, just wondering how the company thinks about the ICM PGN in CTG population post transplant and.

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, can be expected to be less efficacious in treating that.

In fact, there can you kind of alluded to maybe the fact that antibody mediated <unk>.

These could be an opportunity potentially for <unk>. So just wondering is this an enriched population and started the motivation for having a phase III program as well there.

Yes. Thank you Justin So we did not specifically studied <unk> in a phase II setting.

But we believe that the biology.

Third between the two diseases and for those on the call not familiar with that.

The real difference between <unk> and <unk> is the presence of anti bodies and the deposits.

Also, hand-in-hand with that is, of course, the post-transplant setting, where we believe the best-in-class profile will be very important. And we've always thought about C3G or ICMPGN patients in three buckets. Very early patients, typically adolescents, that have been newly diagnosed and 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 three that are present in the kidney so.

That's in place the classical pathways in all likelihood invoked and an alternative pathway inhibitor, such as the <unk> sector B or D molecules.

Can be expected to be less efficacious on that.

Also hand in hand with that is of course, the post transplant setting where we believe the best in class profile.

We will be very important and we've always thought about the CTG or icmp Jim.

<unk> in three buckets very early patients typically adolescence officers that have been newly diagnosed that made us 10 years or more until it gets to a final renal disease and where we believe there is a special case, where these oral products that are in development, including our own.

The second category is 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 some of the benefits that may come with these oral products. And 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 us. Understood. Thanks, and congrats on the prize. Our next question comes from Tazeen Ahmad of Bank of America. Your line is open.

Got you where he served patients that are getting closer to end stage renal disease.

And potentially the need for transplantation or hemodialysis of course.

There the advantage of having a best in class products will outweigh the benefits that may come with these oral products and then last but not least in the post transplant setting where convenience will always come second to having maximum efficacy. So that's how we think about the world and our trials are designed to be in lock step with that strategy.

Understood, Thanks, and congrats on the progress.

Thank you Justin.

Our next question comes from <unk> Ahmad of Bank of America. Your line is open.

Hi, Glenn.

One question for me.

Hi, one question for me.

Then as it relates to the preferences that you've listed about the types of financing.

With respect 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, you know, 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?

That the company is looking into is there one whether it be a royalty agreement or a partnership.

Some combination of debt that you think is your.

Our preferred option right now.

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 Youre looking for thank you.

Thank you. Thank you, Tazeen.

Thank you.

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 [inaudible] Douglas Goldstein, CFP®, Financial Planner & Investment Advisor

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 that's going to be important. So so of course, that's that is a consideration from a timing perspective.

Our next question comes from Colleen Kusy with AIRT.

Overall, I would say, we acknowledged that we would need to raise.

Capital in a way that is.

Colleen Kusy with AIRD. Your line is open.

<unk>.

As we always have so.

Great. Thanks so much for taking our questions, and congrats on the quarter. One question for us. I know you've presented the top-line Derby Health 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 U.S.-based physicians?

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.

Update you in due course, thanks for the question.

Our next question comes from Colin <unk> with Baird. Your line is open.

Yeah.

Great. Thanks for taking our questions and congrats on the quarter one question for us.

Thank you, Colleen. That's an excellent question, and the simple answer to that question is no. So we've already done a lot of outreach work in Europe, in the US, and other regions as well. And Adam, you were in charge of that work. Maybe you could give a quick update.

You presented the topline data at a number of medical meetings since that.

And there's also an interesting amount.

If you have any.

Have you had the opportunity to speak to any European Kols.

And how they might be the topline data differently.

From that.

Yes, thanks, Cedric. And thanks, Colleen.

Good question.

Thank you cleaned up some excellent question and the simple answer to that question is no. So we've done a lot of outreach work already in Europe and the U S.

So yes, we've, no surprise, right? So we presented some great data at ASRS and the Retina Society. And we've been interacting through various forms of market research with retina physicians all over the world, including in Europe. And we hear consistently, US, Europe, or international, that there is a real need for treatment and that data supports treating patients. And no surprise, very similar to what we're hearing in the US, that physicians are impressed with the safety, and they're also impressed with the ability to have 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 runs in Europe as, as, as the US there. So I hope

Other regions as well.

Adam you've been in charge of that work, maybe you can give a quick update on the results from that.

Yes, Thanks, Patrick and thanks, Colleen so yes, we have.

No surprise right. So we presented some great data ASR at the retina Society.

We've been interacting through various forms of market research with retinal physicians all of the world, including Europe.

And.

We're hearing that consistently U S Europe or international that there is a real need for a treatment and the data supports treating patients.

And no surprise is very similar to what we're hearing in the U S that physicians are impressed with the safety and Theyre also impressed with the ability of having some flexibility on dosing monthly and every other month and the ability to treat patients.

Yep, that's helpful. Thank you for taking our questions.

We get the same consistent feedback in our market research run in Europe is as as the USA. So hopefully that answers your question probably.

Our next question comes from Alethea Young with...

with cancer. Your line is open.

Yeah. That's helpful. Thank you for taking my question.

Hey guys, thanks for taking my questions and congrats on the early launch progress. I guess, two for me, one: when you're thinking of, 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 that might help evolve.

Thank you.

Our next question comes from Alicia Yap with Cantor Your line is open.

Hey, guys. Thanks for taking my questions and congrats on the early launch progress I guess two for me one.

Youre thinking about I know that the majority of switches, but maybe talk about some of the data that we might see as especially in the higher hemoglobin levels and how you think about that might help us.

Tazeen Ahmad, Annabel Samimy, Yigal Nochomovitz, Steven Seedhouse, Douglas Tsao, and Eliana Merle

Physicians to think about maybe trading more of their naive patients or maybe it's just a matter of time.

Before they go to the naive, that's my first question, and my second question is just, do you plan on having any other data with geographic attributes before you plan on filing the data that you would present in a public or either?

Before.

The experience of the switches before they go to the NIH. That's my first question and my second question is just do you plan on having any other like data with geographic atrophy before you plan on filing the data that you presented in a public are either via press release. Thanks.

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

Thank you so much at all since the first question Adam is wind.

Thanks, Alicia. Yeah, so we are actually seeing.

Thankfully here, yes, so we are actually seeing.

And preventing starts across all of the paradigm of the patient mix as I've described so.

All of the paradigms of the patient mixes I've described. So the 1,500 C-5 treated patients, we're seeing usage, the majority of usage at the moment within that.

1500, <unk> five treated patients, where we're seeing usage the majority of the usage at the moment within that lower falling hemoglobin requirement for transfusions.

But we're also getting usage in...

higher hemoglobin levels, and also in patients who have the signs and symptoms of

We're also getting usage and higher hemoglobin levels and also through patients who have the signs and symptoms of <unk>.

We are also getting Empavelli 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, but physicians keep telling us they want to try Emp

<unk> basically.

Also getting and probably start Sydney naive population, which is great. I think it's supported by the label and people understand the superiority data within the label I think the Ash abstracts, I mean help us get more data out there to have those discussions one thing we do consistently here as you know, it's a small prescriber base.

With a small patient population physicians keep telling us they want to try.

The valley in the hardest to treat patients those that have the highest unmet need and then start to broaden out to a wider population. So.

And I'll hand you back to Cedric for the second part of your question. Yeah, thank you, Alicia. So that's 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 the data that we believe will make a huge difference in the lives of these patients.

Typical with rare disease drug launches I think we'll start to see as we close the year and into next year that we'll be able to broaden that base of patients and physicians have got through that first second or third patients for example.

We expect to see that happen as we go into the first stages of the launch next year.

And you're back to Cedric for the second part of your question.

Yes, I think so.

The easy answer so.

Yes.

We made a deliberate effort as you know in September to has kind of very complete presentations at the retina Society, and the Srs and <unk> always going to be a recap and kind of concentrating again.

Yeah.

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

The data that we believe.

We'll make a huge difference in the lives of these patients.

Great. Thank you.

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

Thank you.

Okay.

Our next question comes from Yigal <unk> with Citi. Your line is open.

Hi, This is carly on for Yigal, Thanks for taking our questions.

We have two <unk> first to be were wondering what the regulatory precedent looks like in ophthalmology, when one phase III wax and one primary endpoint is there anything that you can lean on based on previous situations like this that the FDA had space.

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.

Thanks, so much.

Thank you so much so liquid regulatory.

So I look at regulatory precedents. Yes, there are regulatory precedents, but I think it's important to point out here what we've outlined before as well, which is 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 default value of 0.04 on two trials.

III precedents, yes, there are regulatory questions, but I think it's important to point out here.

What we've outlined before as well.

Is this from the Fda's perspective.

The P value chemicals on the border of point <unk>.

Needs to be contextualized with the extraordinary value that we had in books right I mean statistically.

And <unk> Oaks and the trials like Derby in combination are statistically more powerful than for example.

Therefore, the value of point or four 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 have an exquisite safety profile. We have a drug that we believe clearly works, where the fellow 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 the Oaks, with an effect size that ranges from 12 to 29%, where exactly does it fit?

The way I think the FDA will look at this.

We are going to present to them the way, we talked about it which is.

We had an exquisite safety profile, we have a drug that we believe clearly works.

Hello, and analysis again kind of clearly put that stake in the <unk>.

Ground and then third would be and that's really the key question. What does the success. When you have three trials between Chili's Derby and Oaks.

<unk> said that ranges from 12 months to 29% where exactly does it and again with that analysis, where you correct for the baseline imbalances in the groups you get quite a consistent picture.

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 and 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.

Again, indicating that this is going to be breakthrough treatments for these patients.

Then as it relates to every other month end market 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 <unk> and then also do you expect for your business. So all of that will be presented in the table discussion will be something that will come at the end of that process.

Okay. Thanks very much.

Our next question comes from Ellie Merle.

Sure.

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

Eliana Merle with UBS. Your line is open.

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 signups 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 and see how it goes before prescribing more, but I'd be curious about maybe the breakdown if there have been some sites that have submitted a lot of starter 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

Hey, guys. Thanks for taking the questions just a couple from US I guess just first.

First on commercial and peony I'm, just trying to get a sense of kind of the average number of script per site.

And then maybe like the proportion of bran site sign ups that are prescribed patients or <unk>.

You know kind of submitted the new start smart I know you've kind of alluded to the fact that initially physicians might want to start one or two patients and see how it goes before prescribing more but curious kind of maybe the breakdown at the airports on site.

Some of that a lot of start forms.

As I said glass on Sun.

Then just in terms of geographic atrophy.

Curious if you could give us any more color I'm wondering can expose to that that'd be CVA data or any more info on kind of what happened with the axial assay at the Derby I know that some of that gas where it had been ongoing but just curious kind of how that analysis is going and I guess, if we can expect to learn more.

to get the BCVA data or any more info on what happened with the Axios sites in Derby. I know that some of the Axios work had

Some of the FCS work has been ongoing, but I'm just curious about how that analysis is going, and I guess if we can expect to learn more at AAS. Thanks.

Thanks.

Thank you, Ali. Adam, do you want to take this first part? Yes.

Thank you Eddie.

Adam do you want to take the first bench.

Absolutely. Thanks Ali so yes.

Absolutely. Thanks, Ellie. So yeah, we're, you know, we're thrilled with the demand that we're seeing over here.

We're thrilled with the demand that we're seeing.

Over 115 physician signed up for and has over 100 start forms and.

Not getting into too many details, but we're seeing a nice geographical spread.

Across the U S. So it's.

We've seen physicians signed up for REMS, over 100 starter forms, and not to get into too many details, but we're seeing a nice geographical spread across the U.S.

It's a very healthy mix as patients with unmet need are showing up geographically across the U S. We do have multiple sites incentives that have submitted more than one start forms that we're getting follow on patient size you would as you would expect.

So it's...

A very healthy mix of patients with unmet needs is showing up geographically across the US. 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

I am thrilled that the demand seems to be widespread and that means that as I said before.

Physicians and patients.

<unk> and try and see.

The benefits of switching to Amp of Valeant, and then I think that the physicians will start to broaden that prescription as we as we get into the later stages of this is launching internet ship launch so.

I'm very happy with how we're seeing the early forms pop up around the And I'll hand you back to Cedric for the second part. Thank you, Adam. All right, and there were really two parts to your question there as well, Ali.

Very happy with how we're seeing the stockholders pop up around the U S.

And I'll hand, you back to <unk> for the second part.

Thank you Adam.

And there were really two parts to your question there as well the first one as it relates to the <unk> 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.

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 with XUS, US, etc., that is still ongoing, but as has become quite clear from the analysis that we did, again, with the covariance, that brings the data much closer to each other between the various studies, and that's something that, again, we will focus on and elaborate on at the American Academy of Ophthalmology.

As it relates to the investigation into what happened ex U S. U S et cetera that is still ongoing but.

S became quite clear from the from the analysis that we did again with the covariance that brings the data much closer to each other between the various studies and that's something that again, we will focus on an elaborate on as the American Academy of Ophthalmology, the safety profile the sector works with a fellow <unk>.

The safety profile, the fact that the drug works with the fellow eye analysis as a clear anchor in that, and the three trials, of course. And then the third piece, assessing what the real true effect size is of the drug, where that coherent analysis puts us in the ranges that we discussed before.

This is a clear anchor in that.

Three trials of course, and then the third piece.

What the real true census of the drug where does that coronary is analysis.

Puts us in the ranges that we discussed before.

Great, thanks so much.

Oh, great. Thanks, so much.

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

Thanks again.

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

Hi, thanks so much for taking the questions and congrats on the quarter. So first on P&H, in the past, you've talked about sort of 12 days average from the prescription of the first dose and was just being vague.

Hi, Thanks, so much for taking the questions and congrats on the quarter.

So first on <unk> in the past you've talked about.

Sort of 12 days average from prescription a first out so I was just wondering.

As the patient population has diversified a little bit, perhaps since last time,

Has the.

https://www.cdc.gov.au And then, secondarily,

The patient population is diversified a little bit perhaps since last quarter, if theres been any shift in that number or the inclusion of perhaps a little bit less severe patients.

I just was curious, there was no mention of it, if there's anything from an inventory perspective that we need to be mindful of.

And longer to get through the approval process.

Then secondarily.

to be mindful of this quarter as it relates to the P&H results. Thank you. Thank you, Matt. Adam?

Just was curious if 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 financial results. Thank you.

Yes, thank you, Matt. So, just on the inventory perspective, I'll start there. So, no. Basically, our specialty pharmacy holds a very low inventory.

Thank you Adam.

Yes, Thank you Matt.

Just on the inventory perspective, I'll start that so.

Yes.

Basically our specialty pharmacy holds a very low level of inventory. So it's not an issue.

For us moving forward, but as part of <unk>.

But as part of the progress, also, your first part of the question was, how long is it taking to transition patients? So at the moment, it's taking on average two to three weeks. And there are some really different reasons why some of that time period is there, and I'm not remotely worried about that time period. Not a surprise, patients have to follow up with their physicians, and follow-up appointments are required. So sometimes that delays them.

Part of the progress also your first part of the question was how long has it taken to transition patients. So at the moment, it's taking on average two to three weeks and then some rail <expletive>.

Different reasons why some of that at that time period is there I'm not remotely worried about at that time period.

Not a surprise.

Patients have to follow up with that physician.

And follow up appointments are required to sometimes that delayed the transition of his thoughtful to our commercial <unk> prescription.

Transcripts provided by Transcription Outsourcing, LLC. 2013 Transcription Outsourcing, LLC.

Also we want to make sure that we find everybody up who is winning an ops into our patient services and that also happens and then we would schedule the patient visits to help support and training physicians patients at their request so that activity is happening.

https://www.pearson.com.au

http://TheBusinessProfessor.com

So, a few things around Q4 to think about forward-looking, right?

How do you think it's around Q4 to think forward looking right I actually think there'll be some.

I think there'll be some seasonality in that, right? We're moving into Q4.

Some seasonality in that right, we're moving into Q4.

There are some holidays which have an impact on when patients want to transition from a staff 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.

Some holidays, which have an impact of when patients want to transition from a start form to a prescription.

Two of commercial products that we have.

Given 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 two to three weeks at the moment.

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

Feedback that we get once were.

In patient's hands through that transition period, and once we can train them and they are on the drug is very positive for our patient support programs. So I do hope as we transition to the broader population will be able to shrink that time from start form to commercial drug but it's.

So, I do hope as we transition to the broader population, we'll be able to shrink that time from stock form to commercial drug, but it's as I would expect it to be where we are in the long term. Mahalo.

So I would expect it to be where we are in the launch.

Matt hopefully that answer your question is on patients in inventory.

Matt, hopefully that answers your questions about patients and infants.

Yes. Thank you.

Thank you Matt.

And our next question comes from Congress Yahtzee with Jefferies. Your line is open.

Our next question comes from Kambiz Yazi with Jeffrey. Your line is open. Hi, team. This is a

Hi team. This is a comment on for Chris.

Hi team. This is Kambizan 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. Thank you so much. So we are, you know, in, we are still figuring out how these intermediate EMG studies need to be run. That is something that will take a little bit of time. What we've learned is that in the GA studies, when you look at the zone outside of the dead retina, right, it's not like the retina all of a sudden goes from dead to alive and well.

Learned and best practices from the entire Jcpenney experience.

Would you potentially apply adhere intermediate AMD study anything you would do differently directly because of that experience. Thank you very much.

Thank you so much so we are.

And we are figuring out how these intermediate Mds studies need to be run.

That is something that will take a little bit of time.

What we've learned is that.

In the GH studies, when you look at the zoom outside of the dead rent it out right.

It's not like the retina all of a sudden goes from did too alive and well there was a zone outside which is probably very similar to what we've seen intermediate AMD that is something that we study them presented last year and what we can.

There is a zone outside, which is probably very similar to what we see in intermediate EMG. That is something that we studied and presented last year, what we call this Irora to Cirora conversion. It's a very interesting way of measuring not pure geographic accuracy, but the earlier lesions. There's going to be a question as to how the FDA looks at that.

Just I will run through direct conversion.

It's a very interesting way of measuring north appears geographic atrophy earlier lesions theres going to be question, how the FDA looks at that.

Thank you very much thank.

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

Thank you.

Our next question comes from Joseph Stringer with Needham <unk> Company. Your line is open.

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

Hi, everyone. Congrats on the quarter and thanks for taking our questions just a quick one on the pipeline on.

I wanted to get your thoughts on.

Given the competitive landscape in enrollment.

What what are your thoughts are around the sort of the.

A threshold or a clinically meaningful read out from.

That study whether it be on the <unk>.

<unk> score or other relevant biomarkers. Thank you.

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

Thank you so much Joe so I'm going to hand that question over to <unk> to answer.

Hello.

We can hear you. Sorry. I couldn't. I mean, the question was, what threshold do we expect, or not?

Yes.

We got here.

Sorry.

I Couldnt have so the question was.

What threshold.

Do we expect or.

What, what would you, considering the competitive landscape today, you know, what would you expect from clinical studies in terms of the end point?

Considering the competitive landscape.

What you expect from the clinical studies in terms of the endpoint.

Yeah, so we're looking

Yes, so we are looking at.

At the combined mortality and efficacy, 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?

At the combined.

Mortality and efficacy.

We are.

Expecting on.

On function.

You'll have a change of around one unit per month.

On mortality to have a difference of 20% versus plus see what that's what we have powered the study has Paul.

Does that answer your question.

Yes. Thank you very much alright, thank you Gerry.

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

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

Your line is open. All right. Good afternoon, guys. Thanks very much for taking the time to answer the question. I've got two on GA. So, first, you know, I think earlier you commented, Cedric, clearly BCBA is probably not the best method to use to gauge visual acuity in GA patients. But I guess what I'm trying to understand is, if you could kind of contextualize, how do you see overall visual acuity actually fitting into the review process for PEG-CYPTACA plans?

Hi, Good afternoon, guys. Thanks, very much for taking the question I've got two on <unk>. So first.

I think earlier you commented Saturday clearly Ptv is probably not the best endpoint you use to gauge visual acuity and NGA 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 splitting into the review process.

Sure pegs to tackle plan.

Thank you, Laura. So BCVA with the FDA was specifically indicated as not relevant in the efficacy analysis. So that was a whole process that 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 of what goes on in the periphery of the macula.

Yes, Thank you Laura.

<unk> with the <unk>.

D able specifically indicated.

Not relevant in the efficacy analysis.

So it was a whole process that the NIH went through with the SBA couple of years ago, and we're one of the chambers and the same.

Same as we said I think we can all agree that a dying retina is a bad thing and the reason why <unk> is a poor measure for GE. As you know is that it's really a reflection of what happened in the <unk> and then also what goes on the periphery of the macula.

Okay, that's helpful. And then, kind of, one more related to GA, and then I guess one financial question for Tim. In GA, is there a precedent for any recent drug approval in the ophthalmology space where you get approval for 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 22, perhaps to just engage with partners in a little bit more detail?

Okay. That's helpful. And then kind of one more related to GAA and then I guess, one financial question for Tim.

Is there a precedent for any recent drug approval in the ophthalmology space we're in.

Get approval on one study and perhaps a subset analysis on a second one and then the.

Financing question for Tim or or probably also Cedric.

Are there scenarios in which you would push back the Gi submission further out than the first half of 'twenty to perhaps to just engage with partners and a little bit more detail. Thanks very much I appreciate it.

Thanks very much. I appreciate it. You're welcome.

You're welcome. So, on the precedent, I think, you know, an interesting precedent in wet AMD would be Vizudyne, 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, and Oakes, two of them with high statistical significance for a month and every other month, the third one being positive.

So on the precedent I think.

And interesting questions.

Andy would be busy doing.

But I think one of the features of this division at the FDA is very pragmatic right. I mean, we have three trials silly there'll be oaks.

Two of them with high statistical significance for a monthly and every other month.

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.

It is going to look at the totality of the data and make an assessment as to where they think.

And again as mentioned earlier, they will look at safety. They will look at whether the drug is biologically active and they will sign those whether it be exercise. It is clinically relevant. So those are kind of the steps we have to go through and we believe that this will become a breakthrough in the first therapy for these patients.

So, those are kind of the steps we have to go through, and we believe that this will become a breakthrough and the first therapy for these patients. And then on the GA submission, so it's very much our plan to submit it in the first half of next year. I don't know, Tim, if you want to add something to that.

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 that that's something to that.

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. Thanks very much, guys.

Yes, I would just say that I don't think we're going to change anything operationally around.

Financing.

Our view from an <unk> 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 go.

To that.

Thanks, very much guys.

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

Thank you Laura.

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

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. This does conclude the program.

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.

You guys for joining us today and have a wonderful rest of the week.

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

Thank you for participating. You may now disconnect.