Q2 2021 Apellis Pharmaceuticals Inc Earnings Call

[music].

Ladies and gentlemen, thank you for standing by and welcome Joe Kellys second quarter 2021 financial results Conference call.

Operator: Ladies and gentlemen, thank you for standing by, and welcome to Apellis' second quarter 2021 financial results 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 this session, you will need to press the start and the 1 key on your touchtone telephone. Please be advised that today's conference may be recorded. If you would like to call the operator's assistance, please press star then zero. I would now like to hand the conference over to your speaker host, Meredith Kaya, Senior Vice President of Investor Relations.

At this time all participants are in a listen only mode. After the speaker's presentation there'll be a question and answer session to ask the question. During the session you will need to press. The Star then the 1 key on you touched on the telephone.

Please be advised for today's conference maybe recorded.

You recall off the assistance. Please press Star then zero.

I would now like the end the conference of which you speak of host.

Meredith Kaya senior Vice President of Investor Relations. Please go ahead.

Meredith Kaya: Good afternoon, and thank you for joining us to discuss Apellis' second quarter 2021 financial results. With me on the call are Co-Founder and Chief Executive Officer, Dr. Cedric Francois, Chief Commercial Officer, Adam Townsend, Chief Medical Officer, Dr. Federico Grossi, and Chief Financial Officer, Tim Sullivan. Before we begin, I would like to point out that we will be making four forward-looking statements that are based on our

Yeah.

Good afternoon, and thank you for joining us to discuss our palace in the second quarter 2021 financial results.

With me on the call our co founder and Chief Executive Officer, Dr. Cedric Francois Chief Commercial Officer, Adam Townsend, Chief Medical Officer, Dr. Federico growth day, 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.

Meredith Kaya: Current Expectations and Beliefs. These statements are subject to certain risks and uncertainties and are actually...

For a certain risks and uncertainties and our actual results may differ materially.

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

I encourage you to consult the risk factors discussed in our SEC filings for additional detail now I'll turn the call over to Cedric.

Thank you Meredith and good afternoon to everyone joining us today for article from school.

Cedric Francois: Thank you, Meredith, and good afternoon to everyone joining us today for our conference. Also, a quick welcome to Meredith, who joined Apellis earlier this month and will be leading our investor relations effort. The second quarter was an exceptional period for Apellis, highlighted by the FDA approval of Empavedi or Pexitacocan, which is the first targeted C3 therapy. And PAVELI was approved with a broad label for the treatment of adults with paroxysmal nocturnal hemoglobinuria, or PNH, and it represents the first new class of complement medicine in nearly 15 years.

Also a Greek welcome to Meredith, who joined the <unk> earlier, this month and will be leading our investor relations efforts.

The second quarter was an exceptional period for <unk> highlighted by the FDA approval of <unk> or fixed at the coupon, which is the first targeted the <unk> therapy.

And by value was approved with a broad label for the treatment of adults with paroxysmal nocturnal hemoglobinuria for peonage and it represents the first new class of complement the medicine in the 15 years.

Cedric Francois: The approval of Empathy was a tremendous achievement for the P&H community and for Apedi, and I am very proud of our team for advancing this transformational medicine. Our commercial launch is off to a strong start, and our Chief Commercial Officer, Adam Townsend, will share additional details shortly.

The approval of integrity was a tremendous achievement for the <unk> community and for <unk> and I am very proud of our team for advancing the transformational medicine.

Our commercial launch is off to a strong start and our chief commercial officer, Adam Townsend will share additional details shortly.

Cedric Francois: The EMPA Value Approval was quickly followed by more good news, with positive results from the Phase 3 PRINCE study of our targeted P3 therapy in treatment nave PNH patients. Together with the PEGASIS data, the PRINCE results reinforce the potential for Empavedi to elevate the standard of care for all patients with PNA. And P&H is only the start of what is possible by targeting C3. In June, we hosted an R&D day where we showcased our growing pipeline across rare diseases, neurology, and ophthalmology. Our ambition is to be a global leader in complementary over the long term.

The anti of any approval was quickly followed by more good news with positive results from the phase III <unk> study of our target the C. III therapy in treatment nave <unk> patients.

Together with the Pegasus data the Prince results reinforce the potential for <unk> to elevate the standard of care for patients with B of niche.

And for BNS is the only the start of what is possible by targeting <unk> 3.

In June we hosted an R&D day, where we showcased our growing pipeline across rare disease urology and ophthalmology.

Our ambition is to be a global leader in confidence over the long term and we envy yields multiple new molecular entities across several modalities to deliver on that goal.

Cedric Francois: And we unveiled multiple new molecular entities across several modalities to deliver on that goal. In addition to advancing MPAVD in four registrational programs with our partner Sobe, we plan to transform the treatment of rare complement-driven diseases by developing new product candidates for existing and new indications and further enhancing the patient experience. In neurology, where C3 plays a key role in a wide range of neurodegenerative conditions, our world-class research team is pioneering targeted C3 therapies to help patients with these devastating diseases.

In addition to advancing <unk> in for Registrational programs with our partner Sobey ripple.

We plan to transform the treatment of rare complements driven diseases by developing new product candidates for existing and new indications and further enhancing the patient experience.

In urology, where C. III plays a key role in a wide range of neuro degenerative conditions. Our world Class research team is pioneering targeted C..3 therapies to help patients with these devastating diseases.

And then ophthalmology, where we aim to be number 1 in the retina. We look forward to the phase III results from <unk> in geographic atrophy or G. H.

Cedric Francois: And in ophthalmology, where we aim to be number one in the retina, we look forward to the phase 3 results from Paxilita Coplan in geographic atrophy, or GA. In addition, we are advancing novel molecular entities for GA, wet AMD, and intermediate AMD. At our R&D day, we also announced an exclusive research collaboration with Beam Therapeutics to apply Beam's proprietary base editing technology to discover novel treatments for complement-driven diseases. Complement is a new frontier for biology. And we look forward to working together with BEAM. We will explore base editing, silencing, and other approaches that may have the potential to modulate complement in the eye, the liver, and the brain.

In addition, we are advancing novel molecular entities for G. A what's the empty and intermediate M D.

At our R&D day, we also announced an exclusive research collaboration with beam therapeutics to apply beams proprietary base editing technology to discover novel treatments for compliments driven diseases.

Complement is a new frontier for base editing and we look forward to working together with beam.

We will explore base editing silencing in the other approaches that may have the potential to modulate complement in the eye the liver and the brain.

Our shared vision is to develop 1 time curative therapies for a wide range of debilitating diseases.

Cedric Francois: Our shared vision is to develop one-time curative therapies for a wide range of debilitating diseases. We are thrilled with the breadth and the depth of our expanded pipeline, which we believe positions Apellis to be a global leader in complementary medicine today, tomorrow, and in the future. Looking ahead, we are optimistic heading into the top line results from the phase 3 DERBY and OCHS studies of dexvitacoplan for the treatment of GA. This key readout in September is a potentially transformative event for the more than 5 million patients worldwide currently living with GA, as well as for the millions of patients with wet AMD, the majority of whom will develop atrophy over time.

We are thrilled with the breadth and the depth of our expanded pipeline, which we believe positions the applebee's to be a global leader in complement today tomorrow and into the future.

Looking ahead, we are optimistic heading into the top line results from the Phase III Derby and Oaks studies of Brexit the coupon for the treatment of all of the G. H.

The ski readout in September is there a potentially transformative event for the more than 5 million patients worldwide currently living with G as well as for the millions of patients with wet AMD, the majority of whom will develop atrophy over time.

Feedback from the retinal community shows great enthusiasm for fixed at the coal plant and the prospects of finally, having the first potential treatments for people living with G. H.

Cedric Francois: Feedback from the retinal community shows great enthusiasm for pexvitacoplan and the prospect of finally having the first potential treatment for people living with GA. I will now turn the call over to Adam Townsend to share more about our ongoing commercial launch of EmpaVidi for P&H. Adam.

I will now turn the call over to Adam Townsend to share more about our ongoing commercial launch of <unk> for Pn Itch Adam.

Thank you Cedric.

Adam J. Townsend: Thank you, Cedric. As Cedric mentioned, our Empa Valley commercial launch is off to a strong start, and I'm excited to share our initial results. Mpevele was approved on May 14th, so we are only in the very beginning stages. With that said, we are encouraged by the great progress we've made thus far and the positive feedback we have received from the P&H community. Our top launch priorities are outlined on this slide, all of which are designed to ensure that every eligible PNH patient who wants Empaveli will have access to this important new medicine.

Rick mentioned empathetic commercial launch is off to a strong start and I'm excited to share our initial results.

And the value was approved on May the 14th so we are only in the very beginning stages with that said we are encouraged by the great progress we've made thus far and the positive feedback we received from the <unk> community.

Our top launch priorities are outlined on this slide all of which are designed to ensure that every eligible P. N H patient who want Central Valley will have access to this important new medicine.

Beginning with the approval we were thrilled with the MPA value label, which included both patients currently being treated with the 5 inhibitors and those who are naive to treatment.

Adam J. Townsend: Beginning with the approval, we were thrilled with the Empaveli label, which included both patients currently being treated with C5 inhibitors and those who are naive to treatment. Recall that within the U.S., there are approximately 1,500 patients who are currently being treated with C5 inhibitors, so there is an ultramarine, and another 150 people diagnosed with PNH every year.

Recall that within the U S. There are approximately 1500 patients who are currently being treated with <unk> inhibitors, Soliris and <unk> and another 150 people diagnosed with peanut age every year.

Our initial launch focuses on P and H patients who have sub optimal control of their disease.

Adam J. Townsend: Our initial launch focuses on PNH patients who have suboptimal control of their disease, beginning with a third of patients on C5 inhibitors with the highest unmet need, those who require transfusions to address their falling hemoglobin levels. We then plan to expand to the broader P&H community, many of whom are also suffering from signs and symptoms like anemia and severe fatigue. We have received positive feedback from various stakeholders, and the quotes on the right side of the slide highlight the excitement for Empavelin from the P&H community.

Winning with the third of patients on the <unk> 5 inhibitors with the highest unmet need those who require transfusions to address the falling hemoglobin levels.

We then plan to expand to the broad of P. M H community.

Many of whom are also suffering from signs and symptoms like anemia and severe fatigue.

We have received positive feedback from various stakeholders and the quotes on the right side of the slide highlight the excitement for M. P value from the <unk> community.

At the end of July over 75 physicians have signed up for our Rems program since launch in the U S and we have received more than 60 stock homes.

Adam J. Townsend: At the end of July, over 75 physicians have signed up for our REMS program since its launch in the U.S., and we have received more than 60 initial forms. Each of these are not only early indicators of demand but also shows that physicians have identified that Empaveli can help better address their patients' treatment needs. We are finding that C5 inhibitor switch patients are the majority of new empivelli starts, with about 75% of switches coming from Altamira.

Each of these of not only early indicators of demands, but also that physicians have identified the end per valley can help better address that patient treatment needs.

We are finding that C..5 inhibitor switch patients of the majority of new M. P value starts with about 75 per cent of switches coming from ultimate price.

We have also received newly diagnosed patient start forms which is very encouraging and reflects a broad label.

Adam J. Townsend: We have also received newly diagnosed patient start forms, which is very encouraging and reflects our broad label. In terms of coverage breakdown, approximately 50% of Empire Valley patients have commercial private insurance, 25% have Medicaid, and 25% have Medicare, with all three payer channels submitting and approving prescriptions. We expect payer coverage to remain split 50-50 between private insurance and government programs for the foreseeable future.

In terms of coverage breakdown, approximately 50% of central valley patients have commercial private insurance.

95% have Medicaid and 25% have Medicare with all 3 per channel submitting Unapproved, Inc. Prescriptions.

We expect the payer coverage to remain split 50, 50 between private insurance and government programs for the foreseeable future.

And lastly on the pay upfront value.

Adam J. Townsend: And lastly, on the payoff. Our Value and Access team is engaging with high-priority payers, including the top 20 payers that cover approximately 85% of all US P&H patients. So far, four payers have accelerated Empaveli formulary reviews, and one has already placed Empaveli in a positive formulary. Given our strong progress to date, we are on track to be on formulary with approximately 90% of plans by the end of the year. To close, we are excited about the strong initial launch of Empaveli and are super proud to bring this important new product to the P&H community.

<unk> and access team is engaging with high priority payers, including the top 20 payers. The cover approximately 85% of U S. P. M. H patients so far for payers have accelerated empathetic formulary reviews, and 1 has already placed empathy and a positive formula.

Larry position.

Given our strong progress to date, we are on track to be on formulary with approximately 90% of plans by the end of the year.

To close.

We are excited about the strong initial launch event for value and our Super proud to bring this important new product to the PMA to community.

Some of the highlights I outlined from our launch activities are included on the left side of the slide.

Adam J. Townsend: Some of the highlights I outlined from our launch activities are included on the left side of this slide. We have done a lot of work to prepare the marketplace, and our integrated team, from the commercial field teams to medical affairs, is laser focused on successfully executing the law. On the right side of this slide, you can see end-of-year goals for engagement, market access, and patient experience. This includes engaging all priority accounts and 85% of priority physicians, as well as maintaining high patient satisfaction scores for self-infusion of Ampoveli.

We have done a lot of work to prepare the marketplace and our integrated team from the commercial field teams to medical Affairs is laser focused on successfully executing the launch.

On the right side of the slide you can see end of year goals for engagement market access and patient experience.

This includes engaging all priority accounts of 85% of priority physicians as well as maintaining high patient satisfaction scores for self infusion of empathetic.

While we are not planning to provide sales guidance in the near term, we do plan to provide certain launch metrics that help to illustrate our progress as we ramp up during this initial launch period.

Adam J. Townsend: While we are not planning to provide sales guidance in the near term, we do plan to provide certain launch metrics that help to illustrate our progress as we ramp up during this initial launch period. We look forward to keeping you updated as our teams continue to work to bring this transformative treatment to the P&H community. Our Apellis team is very proud to have the responsibility to help P&H patients with high unmet needs. At the same time, our commercial organization is looking forward to the upcoming Phase 3 GA results next month. Our US, European, and international teams are busy preparing the commercial foundation globally for this potential blockbuster opportunity. I will now turn the call over to Dr. Federico Grossi to review our clinical development.

We look forward to keeping you updated as our teams continue to work to bring this transformative treatments to the pnas community.

Our of Palace team is very proud to have the responsibility to help <unk> patients with high unmet needs at the same time, our commercial organization is looking forward to the upcoming phase III Gi results next month.

The U S European and international teams are busy preparing the commercial foundation globally for this potential blockbuster opportunity.

I will now turn the call over to the Doctor Federico groceries to review our clinical developments.

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Thank you Adam.

I'll begin briefly with the phase III study in peonage.

Federico Grossi: I'll begin briefly with the Phase 3 print study in PDF format.

In May we on the part of the Soviet We're thrilled to report positive top line result data from the Prima study of temporarily in treatment naive patients.

Federico Grossi: In May, we and our partner SOBI were thrilled to report positive top-line results from the print study.

Federico Grossi: The Print Study of Empaveli in Tritne-Nai, Pesha.

Part of any demonstrated statistical superiority of the co primary endpoints compared to standard of care, which did not include complement inhibitors at week 26.

Federico Grossi: And Paveli demonstrated statistical superiority on the co-primary endpoints compared to standard care, which did not include complement inhibitors at week 26.

And probably also achieved statistical superiority versus standard of care of several secondary endpoints, the meaningful to prescribers and patients dose.

Federico Grossi: And Paveli also achieves statistical superiority versus standard of care on several secondary endpoints that are meaningful to prescribers and patients. Those include improvement in hemoglobin levels and removing the need for transfusions. The safety profile of Empaveli was consistent with previous steps. These results add to the robust clinical profile of Empavelin and support the use of our targeted C3 therapy.

Of course include improvement in hemoglobin levels.

Moving the need for transfusions.

The safety profile of the barbell he was consistent with previous studies.

These results actually of the robust clinical profile of impact any kind of support the use of our target of cheaply therapy.

As a treatment for adults with B M H.

Federico Grossi: as a treatment for all adults with PNH

The M P and age we have for Registrational programs of the anti value with Saudi that are either ongoing or planned to start this year.

Federico Grossi: Beyond P&H, we have four registrational programs for Empaveli with SOBI that are either ongoing or planned to start in 2022.

Federico Grossi: to start this year.

Our rare disease programs, our focus of complement driven diseases, where patients are few or no treatment options.

Federico Grossi: Our disease programs are focused on complement-driven diseases with

Federico Grossi: Your patients have few or no treatment options, and we believe that targeting C3 has the potential to...

We believe that targeting <unk> 3 has the potential to offer a differentiated product profile.

Federico Grossi: A Differentiated Product Profile by Providing Comprehensive Controlled Components. I encourage you to watch the recording of our R&D day on our website to hear from several key opinion leaders on the administrative need, supportive clinical data, and potential for Empaveli to be a transformative treatment for patients suffering from this devastating disease. The upcoming milestones for the remainder of the year are outlined on this slide, including three-star initiations and enrollment completion of the

Providing comprehensive control of complement.

I encourage you to watch the recording of of I M. D day on their website to hear from several key opinion leaders on the.

The need support the clinical data and potential value to be of transfer of maybe treatment for patients suffering from this devastating disease.

GAAP coming milestones for the remainder of the year or all of <unk>.

<unk> on the Slide Inc.

Including 3 study initiations and enrollment completion of the Marianne study in ALS.

Federico Grossi: Meridian Study in ALS. Turning now to our ophthalmology.

Turning now to our ophthalmology franchise, a spread for the installation the.

Federico Grossi: As previously mentioned, the top-line results from the Phase III Derby and Nox studies of intravitreal plexus decouplant are expected in September. As shown on this slide, verbiage notes are identical.

Pablo yourselves from the phase III there'll be enough studies of each of each of books of the Copeland I expect that till September.

As shown on the slide there'll be a notes are identical multicenter randomized controlled studies that confirm the efficacy and safety of monthly and every other month aspects of the Copeland with sham treatment in 1258 patients with <unk>.

Federico Grossi: [inaudible]

Federico Grossi: and every other month Spexfetakoplan, with sham treatment in 1,258 patients with GA. The primary endpoint of both studies is the reduction in growth of GA lesions at Mk-12.

The primary end point of both studies is the reduction in the Gulf of GAA initials of.

Plus the.

For the study of this thing details can be seen of.

Federico Grossi: The full study design details can be seen on this slide.

The slight.

In September we plan 2 per cent of the results of the primary endpoint for the monthly and every other month.

Federico Grossi: In September, we plan to present the results of the primary endpoint for the monthly and every other month arms, as well as the safety profile of intravitreal bexeta couplands, including the rates of extubations and intraocular inflammation. Additional data from the studies are expected to be presented at medical meetings later this month. Although the primary endpoint will be analyzed at month 12, the studies will continue with treatment groups masked to month 24, and secondary functional endpoints will only be formally tested at month 24. Finally, I'd like to briefly discuss our plans for Baxeta-Coupland in intermediate.

Well as the safety profile both of them for.

The chart looks at the Copeland, including the rates of excavations unnamed truckload of inflammation.

And they said all the data from the studies.

It should be percentage and medical meetings later this year.

Although the primary endpoint will be analyzed a plus plus the studies will continue with trimming the group's Musk July 24.

Secondary functional endpoints will only be formally tested of plus 24.

Finally, I'd like to briefly discuss our plans for like for the Copeland and intermediate and the.

As he sees the currently has no approved treatments.

Federico Grossi: A disease that currently has no approved treatment. Targeting Intermediate and

Targeting the intermittent M D represents a significant opportunity to delay or prevent progression to a bunch of forms of M. D from.

Federico Grossi: The NDE represents a significant opportunity to delay or prevent progression to advanced forms of NDE and potentially prevent patient loss. Post hoc analysis of the Phase 2 FLE study demonstrated that GA patients receiving Pexota-Coupland had a lower rate of progression.

The potentially prevent the show a loss.

The post hoc analysis of the phase II filly study demonstrated the gea patients should we see the index at the Copeland, how the lower rate of progression from intermediate M. D through G E.

Federico Grossi: Intermediate MD to GA in retina areas outside of the GA lesion compared to shunt. These results support continued research.

But in the areas outside of the G illusion compared to Sham.

These results support the continued research and we are currently seeking feedback from regulators on the study design of regulatory pathway.

Federico Grossi: And we're currently seeking feedback from regulators on the studies.

Federico Grossi: and Study the Swine Regulatory Pathway.

Following the positive G every day.

Timothy E. Sullivan: Following a positive GA readout, we expect to initiate a pivotal study in the first half of next year. I will now turn the call over to Tim Sullivan for a review of the financial results.

We expect to really see it a pivotal study in the first half of next year.

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

Timothy E. Sullivan: of the Financial Results. Kim?

Thank you for Eddie.

Timothy E. Sullivan: Thank you, Cedric. Since we issued a press release earlier today with the full financial results, I will just focus on the highlights for the second quarter of 2021. Net product revenue was $623,000 in the second quarter of 2021. This reflects the first six weeks of recorded product revenue for Empaveli between FDA approval on May 14th through June 30th, 2021. The third quarter of 2021 will include the first full quarter of EmpaVeli net product revenue.

Since we issued a press release earlier today with the full financial results I will just focus on the highlights for the second quarter of 2021.

Net product revenue was 623000 in the second quarter of 2021 cause for.

Flex the first 6 weeks of recorded product revenue for the valley between FDA approval on May 14th through June 32021.

The third quarter of 2021 will include the first full quarter of empathy Ali net product revenue.

Research and development expenses were $145.9 million in the second quarter of 2021 compared to $87.1 million for the same period in 2020.

The increase in R&D expense was primarily attributable to the $50 million payment associated with the beam collaboration as well as medical and the quality of fairs expenses personnel costs, primarily due to the hiring of additional personnel and increase in costs associated with ongoing and planned clinical trials among others.

Timothy E. Sullivan: Research and development expenses were $145.9 million in the second quarter of 2021 compared to $87.1 million for the same period in 2020. The increase in R&D expenses was primarily attributable to the $50 million payment associated with the BEAM collaboration, as well as medical and quality affairs expenses, personnel costs primarily due to the hiring of additional personnel, and an increase in costs associated with ongoing and planned clinical trials, among others. R&D expenses were offset by contra R&D expenses related to the SOBI transaction.

R&D expenses were offset by Contra R&D expense related to the Soviet transaction of.

The decrease in contract manufacturing expenses and the capitalization of inventory following FDA approval of Emperor Valley.

We expect R&D expenses to continue to increase as the number of patients in our trials increases in the number of trials we are conducting increases.

General and administrative expenses were $49 million in the second quarter of 2020, 1 compared to $28.4 million for the same period in 2020.

The increase in general and administrative expenses was primarily attributable to general commercial preparation activities employee related costs per.

Recessionary consulting fees among others.

For the second quarter ended June 30th 2021 of Telus reported a net loss of $219.2 million compared to the net loss of $118.6 million for the same period in 2020.

As of June 30th 2021 of the palace had $599 million of cash cash equivalents and short term marketable securities.

Timothy E. Sullivan: A Decrease in Contract Manufacturing Expenses and the Capitalization of Inventory Following FDA Approval of Empaveli. We expect R&D expenses to continue to increase as the number of patients in our trials increases and the number of trials we are conducting increases. General and administrative expenses were $49 million in the second quarter of 2021, compared to $28.4 million for the same period in 2020. The increase in general and administrative expenses was primarily attributable to general commercial preparation activities, employee-related costs, professional, and consulting fees, among others.

We remain well capitalized to execute on the ongoing launch of MTV early in the <unk> and continued to advance our robust clinical development plan.

Our cash runway is expected to fund operations into the second half of 2022.

<unk> the $50 million paid the beam as part of our recent partnership.

In July we entered into certain agreements to exchange $201.1 million of the convertible notes for approximately 6 million shares of common stock, allowing us to lower our interest rate expense from further delever the balance sheet.

We began 2021 with approximately $520 million in aggregate principal amount of notes.

And with the 2 exchanges conducted in January and July of this year, we now have $192.7 million remaining at June 32021.

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

Cedric Francois: For the second quarter ended June 30, 2021, Apellis reported a net loss of $219.2 million, compared to a net loss of $118.6 million for the same period in 2020. As of June 30, 2021, Apellis had $599 million in cash, cash equivalents, and short-term marketable security. We remain well capitalized to execute on the ongoing launch of Empaveli and PNH and continue to advance our robust clinical development plan. Our cash runway is expected to fund operations into the second half of 2022, including the $50 million paid to BEAM as part of our recent partner. In July, we entered into certain agreements to exchange 201.1 million of the convertible notes for approximately 6 million shares of common stock, allowing us to lower our interest rate expense and further de-lever the balance sheet.

Thank you Tim.

Made excellent progress so far this year and have several important milestones upcoming as shown on the slide.

We look forward to continuing to advance our of growing pipeline across the rare disease ophthalmology and urology as for.

Part of our ambition to be a long term global leader in complement.

With the topline results of the Derby and Oaks studies expected next month, we would like to take this opportunity to recognize and thank the patients investigators caregivers partners employees and investors who have helped the advances for this key milestone.

We look forward to keeping you updated on our progress.

And now operator, please open the call for questions.

Thank you, ladies and gentlemen, as a reminder to ask the question on the phone line, you'll need the fastest start end of <unk> on you touched on the telephone do we kind of question for the pound key please standby of all the compile the Q&A roster.

And our first question coming from the line of from Rama with Jpmorgan. Your line is open.

Hey, guys. Thanks, so much for taking the question I'll just ask a quick 1 on and for valley on the average day from prescription to first dose being I think the slides at 12 days.

Cedric Francois: We began 2021 with approximately $520 million in aggregate principal amount of notes. And with the two exchanges conducted in January and July of this year, we now have $192.7 million remaining at June 30, 2021. I will now turn the call back over to Cedric for closing remarks.

Anecdotally can you put that 12 days into context here in terms of when it's a little bit higher than 12 days, and what's causing that and when when you might be able to get a patient on more quickly than say 12 days. Thanks. So much.

Thank you and the great to hear you I'm going to hand, it over to Adam to answer.

Thanks for the question out of Penn, So, yes, where we're actually very happy with the 12 days transition, it's very much in line with various other rare disease analogs.

Cedric Francois: Thank you, Tim. We've made excellent progress so far this year and have several important milestones ahead, as shown on this slide. We look forward to continuing to advance our growing pipeline across rare disease, ophthalmology, and neurology as part of our ambition to be a long-term global leader in complex, With the top-line results of the Derby and Oakes studies expected next month, we would like to take this opportunity to recognize and thank the patients, investigators, caregivers, partners, employees, and investors who have helped advance us to this key milestone. We look forward to keeping you And now, operator, please open the call for questions.

We obviously get them transition quicker than 12 days of the some transition of slightly longer than 12 days.

The main thing is we have to make sure. The the patients have the vaccinations before they stopped and that tends to drive that 12 day gap that seems to be the consistent thing. We're obviously working hard with all of our pnas community and patients to make sure that they have everything that they need as they transition them, but hopefully that answers your question.

None of them.

Thanks, so much for taking the question.

And our next question coming from the lineup of my boss.

<unk> with Evercore ISI your line is open.

Hi, guys. Thanks, so much for taking my question Cedric what percentage of the 38 per cent wet AMD converters in your phase 2 Philly technically had non leaky CMV at baseline and also what I remember 1 of the things that stood out when the phase 2 data came out was that folks that did cause.

Operator: Thank you. Ladies and gentlemen, as a reminder, to ask a question on the phone line, you will need to press the star and then the one key on your touchtone telephone. To withdraw your question, press the pound key. Please stand by while we compile the Q&A roster. And our first question comes from the line of Anupam Rama with J.P. Morgan. Your line is open.

From a debt to book that the convert have wet AMD conversion there'd be C V of scores than the worsening.

Anupam Rama: Hey guys, thanks so much for taking the question. I'll just ask a quick one on Empaveli on the average days from prescription to first dose being, I think, 12 days. Anecdotally, can you put that 12 days into context here in terms of when it's a little bit higher?

But my understanding is in 1 of your phase III do you do have micro parametric as well what would you expect in wet AMD converters on Microchemistry. Thank you very much.

Okay.

Thank you so much.

Well first of all of that start with the the city of trial and the non <unk>.

So.

Just a bit of a background for the people on the line and.

And the city trial, when we did of retrospective analysis and looked at the patients that had.

So called C N G.

Anupam Rama: Thank you.

Cedric Francois: Thank you Anupam, great to hear from you. I'm going to hand that over to Adam now.

What we were really looking at was ex judicious, so essentially leakage from neovascular membrane sitting in the rest of the number they're not supposed to be the.

Adam J. Townsend: Thanks for the question, Anupam. So yes, we're actually very happy with the 12 days transition. It's very much

The question, we ask ourselves is where the east neovascular membrane is there at the beginning of the study, but we're not picked up at the time of screening and that can happen because the technologies available. Sometimes this is missed so.

Adam J. Townsend: We're actually very happy with the 12 days transition. It's very much in line with various other rare disease analogs.

Adam J. Townsend: We obviously get transitions quicker than 12 days and some transitions slightly longer than 12 days. The main thing is that we have to make sure that the patients have their vaccinations before they start, and that tends to drive that 12-day gap. That seems to be the consistent thing. We're obviously working hard with all of our P&H community and patients to make sure that they have everything that they need as they transition, but hopefully that answers your question, Anupam.

So in the retrospective analysis of what we did is as the OTT, we looked at something called a double layer of saying, which is the separation of the Brooks membrane from the RPE cell theyre indicative of the membrane sitting there, but not being the key.

Now in the in the city of trial when doing that it became clear that a large percentage of the patients that ended up showing extra days later during the trial had that of or their sign at baseline and.

We'll have to kind of look back for exactly the number but I believe that it was around 75 per cent of the patients that develop that.

Operator: Now, next question coming from the line-up, Umer Raffat with Evercore ISI. Your line is open.

So that's as far as it relates to the city trial, but the very interesting observation that we will of course.

Umer Raffat: Hi guys, thanks so much for taking my question. Cedric, what percentage of the 38% wet AMD converters in your Phase II Philly technically had non-leaky CNVF?

Further interrogate with the phase III results and then as it relates to macro perimetry in those patients with the griddle Neovascular reservations for the macro Perimetry is an examination of where you're actually with the laser shine the light outside of the food yes.

Umer Raffat: And also, I remember one of the things that stood out when the Phase 2 data came out was that folks that did convert had wet AMD conversion. Their BCVA scores didn't worsen, but my understanding is that in one of your Phase 3s, you do have microparametry as well. What would you expect in wet AMD converters on microparametry?

In peripheral areas of the macula.

And here you know again in Philly, we did not do micro for inventory. So we don't really know whether there is or will it be an impact of explanations on macro perimetry, but macro for <unk> in the first phase is the way of creating a functional correlation so kind of the associating the ability to see the light and areas where Jupiter.

Cedric Francois: Thank you very much. Thank you so much, Umer. Well, first of all, let's start with the Philly trial and the non-leaky CNV. So, just a bit of background for the people on the line. In the Philly trial, when we did a retrospective analysis and looked at the patients that had the so-called CNV, what we were really looking at was exudations, so essentially leakage from neovascular membranes sitting in the retina where they're not supposed to be.

I think atrophy is growing so.

On the surface of itself and not really related to C. N V. But again in the phase III will have the first time to really look into the them.

And Cedric maybe just a follow up then if 75% of wet AMD converters likely had the double layer of baseline does that basically mean that based on the analysis thats being used in phase III. Your phase II wet AMD conversion rate was mid single digits I just want to confirm I'm hearing that right.

And and and also.

Can you just remind us all.

Cedric Francois: The question we asked ourselves is, were these neovascular membranes there at the beginning of the study but were not picked up at the time of screening? And that can happen because, with the technologies available, sometimes this is possible.

Since the since the last call before your phase III comes out can you remind us all of what interim have or have not happened and what blinded or an or of any interim data have you guys seen.

Sure. So so just with respect of the last question, we don't have any insights in the middle.

Cedric Francois: So in a retrospective analysis, what we did is on SDOCT, we looked at something called a double layer sign, which is a separation of the Brooks membrane from the RPE cell layer, indicative of that membrane sitting there but not being there. Now, in the Philly trial, when doing that, it became clear that a large percentage of the patients that ended up showing exudates later during the trial had that double layer sign at baseline. And Umer, I will have to kind of look back for exactly the number, but I believe that it was around 75% of the patients that developed.

That is something that will come in closer to the deadline.

Then as it relates to the.

It was breaking up sort of at the first part of your question could you repeat that please.

Oh, the first part of the question basically is remember how the phase II theory had wet AMD conversion rate of high teens.

And if we apply the double their definition that's been used in phase III. Considering you said 75 per cent of those high teens already had double their baseline would that mean that the new wet AMD conversions on on it was the only mid single digit from phase 2 is that right.

So the.

Is that kind of comes down to the definition of Red. So again the difference between choroidal Neovascular reservation and the expeditions, where you see leakage in the retina.

Cedric Francois: So that's as far as it relates to the Philly trial, but a very interesting observation that we will, of course, further interrogate with the phase three research. And then as it relates to microperimetry in those patients with choroidal neovascularization, microperimetry is an examination where you actually, with a laser, shine light outside of the fovea, so in peripheral areas of the macula. And here, you know, again, in Philadelphia, we did not do microperimetry, so we don't really know whether there is or will be an impact of exudations on microperimetry.

With the double layer, saying you don't really know whether there is the neovascular membrane. All of you noticed that there's the separation that is suspected of being a Colorado Neovascular complex the only way.

To measure a C. N V is to use something called the OCC and geography, which wasn't done in phase 2 of them, which even in the phase III of isn't.

Only the on a subset of patients so again.

By now to really know what the answer to that and member growth.

Again, the importance I think the pointed out is that with the OTT. It is very easy to detect small accidents in the retina that you may or may.

It may not be there at the beginning at screening because at screening you use kind of the the gold standard for wet AMD, which is fluorescent and geography and also the rest of the and geography, there may be of Neovascular complex prison, there's not the leak on that particular exam, but that later on the may have some small ex that you can.

Cedric Francois: But microperimetry, in the first place, is a way of creating a functional correlation, so kind of associating the ability to see light in areas where geographic atrophy is growing. So on the surface of itself, not really related to CNV, but again, in phase three, we'll have the first time to really look at it.

The honest Youll see T and 1 reference point that I would like to give you. The you know what's very interesting is that on the 26 cases that we had of extra days reported by the investigators in Sydney 17 patients at the time of the discovered the extra day received fluorescein angiogram.

The 10 only of those 17 patients at that point in time has come of friends with N. The based on for the rest of the geographies. So think about this you know of the 17 tested that had the extra days on as you'll see on the 10 could be concerned using for the rest of the geography all in line with what we've reported before.

Umer Raffat: And Cedric, maybe just to follow up then, if 75% of wet AMD converters likely had the double layer at baseline, does that basically mean, based on the analysis that's being used in Phase 3, your Phase 2 wet AMD conversion rate was mid-single digits? I just want to confirm that I'm hearing this.

Our belief that there was some investigator value isn't the phase 2 of that we have corrected for in the phase III.

Cedric Francois: And also, can you just remind us all, since this is the last call before your Phase 3 comes out, can you remind us all what the interim is?

Yeah.

Thank you very much.

Thank you.

Okay.

And our next question coming from the lineup and 2 of Kumar with Goldman Sachs. Your line is open.

Cedric Francois: Interim data have or have not happened, and what blinded and or any interim data have you guys seen?

Oh, Hey, thanks for taking our questions I'll step back from the risk question can I ask a more basic mechanistic question about about the D&B Darby oak how much do you think complement blockade of contribute.

Cedric Francois: Sure, so just with respect to the last question, we don't have any insight into

The emergence of CMV events as compared to things like the investigator bias.

Cedric Francois: That is something that, you know, will come when we're closer to the deadline. Then, as it relates to the – I was breaking up a little bit the first part of your question, Umer. Could you repeat that? Oh, the first part of the question, basically, is: remember how the Phase 2 Philly had wet AMDs?

Differences in baseline patient distribution of how much of it ultimately is just when you sufficiently blockade complementing the retina you get choroidal Neovascular edition had some biological free.

Yeah. Thank you so much of a medicine that has a very interesting question red so.

Umer Raffat: Tazeen Ahmad, Annabel Samimy, Yigal Nochomovitz, Steven Seedhouse, Douglas Tsao, and Eliana Merle

What is this imbalance that we saw in the phase 2 real or not.

Personally I think it was I just think of it what's the kind of versus the exaggerated based.

Umer Raffat: The double layer definition that's being used in Phase 3, considering you said 75% of those high teens already had double layer at baseline, would that mean that the new wet AMD conversions were only mid-single digits in Phase 2? Is that right?

Based on 2 important parameters, 1 of which you refer to the.

The investigator of base the second that we enrolled a lot of patients who at baseline had within the in the control of that rely while having G. E. In the study eye and put some numbers on that in the filly trial of 38% of the subjects in rules came from the background phenotype, whereas the normal distribution is closer to.

Cedric Francois: No, so that kind of comes down to the definition, right? So again, the difference between choroidal neovascularization and exudations, where you see leakage in the retina. With a double layer sign, you don't really know whether there is a neovascular membrane. All you know is that there is a separation that is suspected of being a choroidal neovascular complex. The only way, you know, technically, to measure ACNV is to use something called OCT angiography, which wasn't done in phase two and which, even in phase three, is only done on a subset of patients.

The 20 per cent. So I think in our phase III, we should all expect that number indeed to be closer to 20 per cent rather than of close to 40 of which was the case in Chile the.

As it relates to why is this happening and you know should we again see an imbalance.

It's a very interesting and fascinating observation and importantly, 1 that was not a safety concern again. These extra dates we're very small in nature detectable in the OCC and as mentioned earlier often not the technical answer the rest of in geography and then the question is is there are 4 <unk>.

Cedric Francois: So again, you know, hard by now to really know the answer to that, Umer, but again, important I think to point out is that with SDOCT, it is very easy to detect small exudates in the retina that may not be there at the beginning at screening because at screening, you use kind of the gold standard for wet AMD, which is fluorescent angiography. And in fluorescent angiography, there may be a neovascular complex present that does not leak on that particular exam but that later on may have some small exudates that you can detect on SDOCT.

All of these preexisting neovascular complexes and they become more leaky why is that the case.

All of its postulated that it could be that you induce of wound healing response, which can be associated with an increase in veg F. The accretion, which would then lead to a more of a leaky state. So it is you know net of not at all implausible that you know an increase in the extradition, which in this case again, what's the other safety concern for us.

Maybe actually associated with the repair responds that doesn't use back on for the control.

Okay, Great and then a question for Tim how should we think about SG&A and R&D expense.

The kind of through 2021, and through 2022 and kind of how condition of that around what happens in Derby Oaks and kind of the still be.

Cedric Francois: And one reference point that I would like to give you that is very interesting is that in the 26 cases that we had of exudates reported by the investigators in Philly, 17 patients at the time of that discovered exudate received a fluorescent angiogram, and 10 only of those 17 patients at that point in time had confirmed wet AMD based on fluorescent angiography. So think about this; of the 17 tested that had exudates on SDOCT, only 10 could be confirmed using fluorescent angiography. This is in line with what we've reported before, our belief that there was some investigator bias in phase two that we have corrected for in phase three.

Our operations on the.

Phase III trials around the value.

Yeah. Thanks, a lot of others. So as you as you know, we don't give any specific guidance to what.

With respect to those line items.

But 1 thing to keep in mind is that our cash of $599 million is sufficient to get us into the second half of 2022 and that does consider of positive readout in the Derby and Oaks.

Bearing in mind that we do plan to scale up for commercialization ourselves globally.

But for <unk> for G&A expenses for the year, you should also expect probably a bit of of ramp up even even towards the end of this year of little bit.

In our commercial spending in conjunction with the launch of if the Valeant P and H.

And then related to R&D.

Operator: Now, next question coming from the line-up, Madhu Kumar with Goldman Sachs. Your line is open.

You can see there's actually a pretty good breakout of the R&D expenses in our in our 10-Q, we go into quite a bit of detail in the in the table and I think some of the ongoing ones are pretty easy to project, what sort of a mild increase as you look in the at the increase in the sort of.

Madhu Sudhan Kumar: Hey, thanks for taking our questions. I'll step back from the prescriptions and ask you about a more basic mechanism.

Madhu Sudhan Kumar: Transcribed by https://otter.ai

The number of clinical trials of the pivotal trials that were for.

Madhu Sudhan Kumar: Transcripts provided by Transcription Outsourcing, LLC.

We have ongoing in addition to our Derby and Oaks, which again will roll into a into an extension study. So that will continue on for 3 years after Derby and Oaks. So you can you.

Cedric Francois: Yeah, thank you so much, Madhu. So that is a very interesting question, right? So, was this imbalance that we saw in phase two real or not? You know, personally, I think it was. I just think it was kind of vastly exaggerated based on two important parameters. One, which you referred to, is the investigator bias. The second is that we enrolled a lot of patients who at baseline had glaucoma within the contralateral eye while having GA in the study eye.

You can kind of think it of a pretty decent sense of how things look for over the next over the next year or 2.

Okay, great. Thanks for taking my <unk>.

Thanks Martin.

And our next question coming from the line of Golf Alcoholics with Citi. Your line is open.

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

The first question is related to is Eric the announcement that the FDA had requested change and the primary endpoint analysis. Further study we were just wondering if the current expectation at the FDA well ask for similar slope of analysis for Derby and Oaks. In addition to that rate of change in Appalachia region area.

Cedric Francois: And to put some numbers on that, in the Philly trial, 38% of the subjects enrolled came from that background phenotype, whereas the normal distribution is closer to 20%. So, I think in our phase three trials, we should all expect that number, indeed, to be closer to 20%, rather than close to 40%, which was the case in Philly.

Yeah. Thank you so much for the question the short answers for that question is no. So a you know again not not.

Not to notice the credit because of course about the special protocol assessment is often or typically requested from the EBITDA when it is unclear.

Cedric Francois: Then as it relates to why this is happening and should we again see an imbalance, it's a very interesting and fascinating observation and, importantly, one that was not a safety concern. Again, these exudates were very small in nature, detectable as DOCT and, as mentioned earlier, often not detectable on fluorescent angiography. And then the question is, if there are, for example, these pre-existing neovascular complexes and they become more leaky, why is that?

And of what type of analysis.

With the agreed to and that is often inspired by a request from the sponsor that maybe view of this unusual in the context of all of that analysis. So my suspicion is that that is the process that went through.

From our perspective I can tell you that after the filly trial, we submitted our protocol with the proposed statistical analysis plan.

And the fish for a meeting and we had for the agreements with the FDA on that so there was no need for a spot since what we proposed was the standard that the MTA. That's among other supposed to use for example, and the <unk> victory trials that'd be the Roche tenancy.

Cedric Francois: And we have always postulated that it could be that you induce a wound healing response, which can be associated with an increase in VEGF secretion, which would then lead to a more leaky state. So it is not at all implausible that an increase in exudation, which in this case, again, was not a safety concern for us, may actually be associated with a repair response that is induced by complement control.

Okay, great. Thank you and then we were just wondering if there's anything more you could say at this point on how the range of missed injections and great of dropouts in Derby and Oaks compared to what was the therapy and I think in the past you've mentioned plans to conduct some additional analyses that could potentially account for the impact of of.

Madhu Sudhan Kumar: Okay, great. And then a question for Tim, how should we think about SG&A and R&D expense through 2021 and through 2022? And kind of how conditioned is that around what happens at Darby Oaks and kind of still be collaborations on phase three trials for Empa Valley? Yeah, thanks a lot, Madhu.

Net.

And we were just wondering if those would be included in the top line a lot of share in September as well. Thank you.

Sure no problem so.

As we of its weighted before and as we talked about at length during our R&D day in the in June.

We've been tracking very very closely over the best of 2 years or you're in the health I should say what the impact was of Covid on the missed injections in the trial and as we indicated at the R&D day for the primary endpoint analysis of the monthly injections, we feel very good about the minimum impact.

Timothy E. Sullivan: So, as you know, we don't give any specific guidance with respect to those line items. But one thing to keep in mind is that our cash of $599 million is sufficient to get us into the second half of 2022, and that does take into account a positive readout in Derby and Oaks.

Of Covid on that analysis and that is the analysis that will give us our approval for every other month injections, where you know 1 Mr injection could be an interval of as long as for months and the trial that is 1 of your long.

Timothy E. Sullivan: Bearing in mind that we do plan to scale up for commercialization ourselves globally, for G&A expenses for the year, you should also expect probably a bit of a ramp up, even towards the end of this year, a little bit in our commercial spending in conjunction with the launch of Empa Valley and P&H. And then, related to R&D, you can see there's actually a pretty good breakdown of the R&D expenses in our 10-Q.

There of course of the risk is higher but as we pointed out at our R&D day.

Every other month is something that we used to interpret and understand you know what's the PK PD PD relationship of the drug is but for approval, we need the monkey and there'll be feel very confident that the impact of COVID-19 is under control.

Okay. Thank you so much.

You're welcome.

Now next question coming from the line of film of 2 with Cowen. Your line is open.

Hi, Hi deemed as the only Rodriguez for Phil. Thank you for taking my call.

Timothy E. Sullivan: We go into quite a bit of detail in the table below. And I think some of the ongoing ones are pretty easy to project with sort of a mild increase as you look at the increase in the number of clinical trials, the pivotal trials that we have ongoing, in addition to our Derby notes, which again, will roll into an extension study, so that will continue on for three years after Derby notes. You can kind of get a pretty decent sense of how things will grow over the next year or two.

Mentioned some of the positive feedback you have received from the lunch on your goals for the year. We were curious if you have identified any barriers that would.

Preclude you from achieving those goals and expectations for the launch.

And then N G E.

Positively the results on the FDA approval.

What's the group within the patient population do you expect physicians will first approach in training.

<unk> do you think.

The change depending on the level of reduction of the USG from day 1 day.

Madhu Sudhan Kumar: Okay, great. Thank you. Thank you, Mike.

September results. Thank you.

Thank you so much I'll, let Adam answer the first part of your question and then I will take the second.

Operator: Now the next question comes from the line of Yigal Nochomovitz with Citi. Your line is open.

Yeah. Thanks for the.

The question, Yeah, we're very happy with our progress to date with the launch.

Carly: Hi, this is Carly on behalf of Yigal. Thanks for taking our questions. Our first question is related to Iverick's announcement that the FDA had requested a change in the primary endpoint analysis for their study. We were just wondering if you expect the FDA will ask for a similar slope analysis for Derby and Oakes in addition to the rate of change in absolute.

Everything is going well and as you can tell by the the.

The Rams the number of physicians going through brands and the number of start forms where on a very strong launch trajectory.

We're very happy and believe the Al Q4, 'twenty 1 goals are very achievable and we are working incredibly well with the payers to make sure that we can get every patient who needs access access and those are ongoing discussions as you remember sometimes they take between 3 to 6 months to allow us to get access to their formularies.

Carly: Absolute TA Legion Area. Yeah, thank you so much for that question. The short answer to that question is no.

Cedric Francois: So, you know, again, not, not, you know, not.

And we're continuing to have some success there. So that's something that we'll continue to work on but everything is pointing in the right direction for the antibody low interest.

Cedric Francois: So, let's start with the first question. What is a special protocol assessment? So, a special protocol assessment is a process that is not, you know, not to speak for Iveric, of course, but a special protocol assessment is often or typically requested from the FDA when it is unclear what type of analysis the FDA would agree to. And that is often inspired by a request from the sponsor that may be viewed as unusual. After the Philly trial, we submitted our protocol with the proposed statistical analysis plan at an end-of-phase So, there was no need for a SPA since what we proposed was the standard that the FDA had, among others, also used, for example, in the Cro-Mans factory trials with Rose Genentech.

Happy to help the <unk> community.

And then it of Mr. For your second part of your question. So I'm happy to have the because it's something that we of course.

You don't have done a lot of research on the as well.

Which you know well. This is what is the patient population that physicians will be interested in how do we see this product being implemented and there are 2 I think important takeaways to communicate the first 1 is that should we have a good safety profile for our drug right I mean should the exhibition to be very well under control and.

If this is a product with a clinically meaningful effect on the growth of atrophy.

And then you know this is in our opinion going to be of drug product that of retinal specialists book prescribed to the majority if not all of their patients for G. Because of that is how medicine works right. So.

I think that is something that is probably not fully appreciate it yet how we think the skills fit into the flow of the retinal specialist like ends of it just found their way into the flow of the treatment of wet AMD and then as it relates to so basically all patients and then the question, Okay at which point in time would you intervene in the disease.

Cedric Francois: Okay, great. Thank you. And then we were just wondering if there's anything more you could say at this point about how the rate of missed injections and rate of dropouts in Derby and Oakes compared.

Carly: to what was observed in Philly, and I think in the past you've mentioned plans to conduct

And that's very interesting read because intuitively you may say well.

Even when you speak with the retinal specialist.

Carly: Thank you.

Cedric Francois: As we have discussed before, and as we talked about at length during our R&D day in June, we've been tracking very, very closely over the past two years or year and a half, I should say, what the impact was of COVID on the missed injections in the trial. And as we indicated at the R&D day, for the primary endpoint analysis of the monthly injections, we feel very good about, you know, a minimum impact of COVID on that analysis.

I'm going to start with my worst of patients.

Blind in 1 eye advanced the geographic atrophy of the Contra lateral eye and while the intuitively that makes sense logically it does not because of again assuming that this drug is the save as we think and hope it will be you want to treat geographic atrophy as early as possible right at the first sign of the G. When you start losing sort of reset.

Yourselves.

Ex fully expect physicians and patients to make the commitment to saving as many sort of the receptor yourselves as they can to as much as possible of prolonged the path to blindness. So I think something that should the drug find its way into the market that I believe will happen is that patients will be treated early and the you know of old patients.

Cedric Francois: And that is the analysis that will give us our approval. For every other month injections, where, you know, one missed injection could be an interval of as long as four months in a trial that is one year long, there, of course, the risk is higher. But as we pointed out at our R&D day, every other month is something that we use to interpret and understand, you know, what the PK-PD relationship of the drug is. But for approval, we need mockney. And there we feel very confident that the impact of COVID is under control.

Exceptions.

You know it should be interested in being treated with this product.

Yeah.

Thank you very helpful.

Thank you our next question coming from the line of Colin Christie with Baird. Your line is open.

Hi, good afternoon, thanks for taking our questions. So 1 of G. A I guess following up on that day.

Really oh gee of patients could be.

Amenable to the street that I guess, what sort of bottlenecks would you expect.

Assuming all of the same positive data and approval of what sort of bottlenecks would you expect would there be any sort of capacity restrictions or limitations for the intramuscular injection.

Operator: The next question comes from the line of Phil Nadeau with Colin. Your line is open.

Yeah, So I mean, I'll give the medical angle and then I will handle it to 2 items.

Talk a little bit more kind of about the practical implementations because we've done work on that as well of course, but the medically I think again you know.

Ernie Rodriguez: Hi, hi team, this is Ernie.

Ernie Rodriguez: Rodriguez for Phil. Thank you for taking our call. You mentioned some of the positive feedback you have received on the launch and your goals for the year. We were curious if you had identified any barriers that could preclude you from achieving those goals and expectations for the launch? And then, in GA, assuming positive results and an FDA...

If the safety profile of this drug is good at that.

Point in time I think.

<unk>.

It will be important to educate physicians it would be the first treatment for a disease that is currently untreated the bill it will be important to find patients in the generalist ophthalmology practice that may not be referred to retinal doctor right now because there's no treatment available and even earlier in the optometrists office, but I think of that point in the.

Ernie Rodriguez: In the GA patient population, do you expect physicians will first approach and treat them with Empavelia? And do you think...

Ernie Rodriguez: Do you think this will change depending on the level of reduction?

And really the main focus should be on building awareness and the fact that there is now.

Cedric Francois: Thank you. Thank you so much.

Adam J. Townsend: I'll let Adam answer the first part of your question and then I will take the second. Yeah, thanks for the question. Yeah, we're very happy with our progress today with the launch. Everything is going well, and as you can tell by the REMS, the number of physicians going through REMS, and the number of start forms, we're on a very strong launch trajectory. We're very happy and believe that our Q421 goals are very achievable.

For will then at that point, hopefully be a treatment available and Adam I don't know if he wants to add something to that.

Yeah, just to add on the capacity piece of the question. We did some research with injecting ophthalmologists and retinal specialists.

They've had many years of getting experience of doing introvert trio of injections and increasing patient numbers.

So we believe with the new edition and the new.

New approved product N G E.

Adam J. Townsend: We're working incredibly well with the payers to make sure that we can get every patient who needs access to the medicine. And those are ongoing discussions. And as you remember, sometimes they take between three to six months to allow us to get access to their formularies.

That will have the capability of expanding capacity based on our discussions and our market research with them.

You know they know that they currently have the bolus of Gi patients within the clinics and the best sites of which there are no current treatment. So we don't expect capacity to be a rate limiting step as we launched the stroke.

Adam J. Townsend: And we're continuing to have some success there, so that's something that we'll continue to work on. But everything's pointing in the right direction for the Empire Valley launch.

Great. That's helpful. Thank you and then 1 follow up on intermediate M D.

Cedric Francois: So we're very happy to help the P&H community. And then, Ernesto, for the second part of your question, so I'm happy you asked that because it's something that we, of course, have done a lot of research on as well, which is, what is the patient population that physicians will be interested in? How do we see this product being implemented?

Could you talk about any initial thoughts you have on the potentially pivotal study design in terms of the size or endpoint.

Yeah, we're not commenting yet on what the design will be but I think the again the notion of doing a trial in the intermediate and the goes hand in hand, with what I mentioned earlier about wanting to treat patients as early as possible and the fact that in a post hoc analysis of Philly, we actually discovered.

Cedric Francois: And there are two, I think, important takeaways to communicate. The first one is that we should have a good safety profile for our drug, right? I mean, should the exudations be very well under control?

That in the region outside of the atrophic area of the retina in other words, the retina that you can still see on your auto for the restaurant image, but the retina that is of course, the affected and as if she wants to go into the kind of of surrogates for intermediate Andi and where we saw post hoc the significance of slow.

Cedric Francois: And, you know, if this is a product with a clinically meaningful effect on the growth of atrophy, then, you know, this is, in our opinion, going to be a drug product that a retinal specialist will prescribe to the majority, if not all, of their patients with GA because that is how medicine works, right? So I think that is something that is probably not fully appreciated yet, how we think this will fit into the flow of the retinal specialist like anti-VEGFs found their way into the flow of the treatment of wet AMD. And then as it relates to, basically, all patients, and then the question, okay, at which point in time would you intervene in the disease? And that's very interesting, right?

Down on the conversion to full geographic atrophy. So no design details yet, but the patient population that we are particularly interested in excess of it.

Yeah.

Yeah.

Great. Thanks, so much.

Thank you so much Quinn.

Our next question coming from the line of Casino Hoffman with Bank of America. Your line is open.

Hi, good afternoon, Thanks for taking my question.

Quickly on the on the Th studies I, assuming that they are both positive should we expect that you would be able to apply for approval of this calendar year and what would be the rate limiting capital left in your application of assuming positive data and then as we talk about the commercial landscape can you maybe give us your view about.

The potential for a C 5 as 1 of the T.

The 1 Q complement inhibitor entering the market and how.

Your products would be differentiate it from the Inc.

Cedric Francois: Because intuitively, you may say, well, even when you speak with a retinal specialist, you know, I'm gonna start with my worst patients, you know, blind in one eye, advanced geographic atrophy in the contralateral eye. And while intuitively that makes sense, logically, it does not. Because again, assuming that this drug is as safe as we think and hope it will be, you want to treat geographic atrophy as early as possible, right? At the first sign of GA, when you start losing photoreceptor cells, you know, I fully expect physicians and patients to make a commitment to saving as many photoreceptor cells as they can.

Thank you so much does the and I'm gonna, hence the approval question.

The to fit the Rico, and then Adam will take the commercial question.

Thank you Cedric and thank you for the question.

Looking for for the the results.

Of the readout of the studies come in September and our teams are ready to jump into each of the submissions.

Be able to submit as soon as possible, we're not guiding on the timing of the submissions, but we're fully prepared.

To tackle the analyses not only of the.

Some of the primary endpoints would be reported to them, but the full analyses for climate for the submission under the that as soon as possible.

Yeah.

Thank you for the <unk> and then well I was just had the mistakes team here some other commercial question.

That's the question on data.

Cedric Francois: Tazeen Ahmad, Annabel Samimy, Yigal Nochomovitz, Steven Seedhouse, Douglas Tsao, and Eliana Merle

Look I think at the end of the day you.

We will see what happens with the competition. It is our conviction that the the mechanism by which the retina surfers in geographic atrophy is driven by the accumulation of <unk> III products on the rest of that which is not appropriately being removed and it's not being appropriately removed because the same cellular mechanisms.

Cedric Francois: I believe what will happen is that patients will be treated early and that, barring exceptions, you know all patients should be interested in being treated within.

Operator: Thank you. For our next question, coming from the line of Colleen Kusy with Baird, your line is open.

Colleen Margaret Kusy: Hi, good afternoon. Thanks for taking our questions. So one on GA, I guess following up on that, that really, you know, all GA patients could be

Competes for removal of C..3 as those that work on the visual cycle, we know from our <unk> studies that <unk> has no effect on the accumulation of C..3 so it would be sort of fresh to us should of C..5 inhibitor that'd be successful, especially in light of the fact that NTIC fab has failed twice already.

Colleen Margaret Kusy: Amenable to this treatment, I guess; what sort of bottlenecks would you expect?

Colleen Margaret Kusy: Assuming, obviously, positive data and approval, what sort of bottlenecks would you expect, and would there be any sort of capacity restrictions?

Both when administered systemically as well as intra day trading.

Colleen Margaret Kusy: Restrictions or limitations for the intravitreal injection

Cedric Francois: Yeah, so I mean, I'll give the medical angle, and then I will hand it over to Adam to talk a little bit more about practical implementations, because we've done work on that as well, of course. But medically, I think, again, you know, if the safety profile of this drug is good, at that point in time, I think it will be important to educate physicians. It would be the first treatment for a disease that is currently untreatable.

1 is on the other hand, the interesting interesting targets.

There are 2 you don't have kind of the broad control of complement that we believe you need.

As you do with fixes that could someday also covering the lectin pathway and the alternative pathway. So I think.

The proof is in the pudding, but it's also important to note the.

You know the.

The only competitor of course of course is a very ex program and we look forward to evaluating the when it becomes available.

Cedric Francois: It will be important to find patients in the generalist ophthalmology practice that may not be referred to a retinal doctor right now because there's no treatment available, and even earlier in the optometrist's office. But I think at that point in time, really, the main focus should be on building awareness and the fact that there is now, or will then, hopefully, be a treatment available. And Adam, I don't know if you want to add something to it.

Yeah, I think I hope that answers your question the dozen yeah, that's really helpful. Patrick.

I mean, I think if you were to talk about 1 thing that could be differentiated in your program for severe would you pivot more to efficacy.

Well I think you know.

Again.

What we have done and what I like about our program is that it has been the program, where we deliberately chose to be highly consistent overtime.

Adam J. Townsend: Yeah, just to add on the capacity piece of the question, we did some research with injecting ophthalmologists and retina specialists. And, you know, they've had many years of experience doing intravitreal injections and increasing patient numbers. So we believe with a new edition and a new approved product in GA, they'll have the capability of expanding capacity based on our discussions and our market research with them. You know, they know that they currently have a bolus of GA patients within their clinics and at their sites for which there are no current treatments. So we don't expect capacity to be a rate-limiting step as we launch this drug.

In other words we.

Did the for the trailing 2015 really to mimic what Genentech Roche at the time was doing with their non policing about program. We knew that they had the interactions with the FDA what is the expectation for in terms of endpoints in the phase 2 clinical trial was really designed to anticipate the phase III trial with minimum change right. So.

For all of you that have studied Philly in Derby and Oaks Theyre pretty much of carbon copy from of each other with very very tiny changes and if anything just more quality and robustness in the Derby and Oaks trial. So you know are there ex program without any criticism is kind of much more very.

But the right I mean, there was the part 1 part 2 of the Phase..2 then they went through the span of the phase III. It's a different approach we wish them success.

Colleen Margaret Kusy: Great, that's helpful. Thank you. And then one follow up on intermediate AMD. Could you talk?

But I think for us standing of the course and.

Really building on the initial hypothesis has been the case.

Okay. Thank you.

Thank you.

Colleen Margaret Kusy: Potentially pivotal study design in terms of size or end point. Yeah, but we're not commenting yet.

Yeah.

The next question coming from the line of Steve <unk> with Raymond Raymond James Your line is open.

Cedric Francois: Yeah, we're not commenting yet on what the design will be, but I think, again, the notion of doing a trial in intermediate AMD goes hand-in-hand with what I mentioned earlier about wanting to treat patients as early as possible, and the fact that in a post-hoc analysis of Philly, we actually discovered that in the region outside of the atrophic area of the retina, in other words, retina that you can still see on your ultrafluorescent image, but retina that is, of course, affected, and is, if you want to call it that, a kind of a surrogate for intermediate AMD, and where we saw post-hoc a significant slowdown on the conversion to full geographic atrophy. So no design details yet, but a patient population that we are particularly interested and excited about.

Yes, Hi, this is Tim we're running up on for Steve The House.

So the they have a quick question on teenage commercial are giving you a point $6 million in revenue is it fair to assume you have around 15 to 20 of patients on therapy or is that revenue most of the for inventory build and then in terms of geographic distributions have you seen any trend you know a bolus of orders coming from of certain.

Geographic area in the U S or is that too early to tell.

Thank you so much I will hand, it over to Adam sensor.

Yeah. Thank you very much for the questions. So.

We're not going to guide on product revenue for the foreseeable future, but you know the the.

The initial 6 million is of great sign of of how empathetic and elevate the standard of care. So.

We had over 75 physicians sign up for Rems and Opus 60 start forms which is the should give you a very strong sign of the demand.

Operator: Our next question coming from the line out, Tazeen Ahmed with Bank of America. Your line is open. Hi, good afternoon.

More to come there and on your second part of the question. We've seen success all across the U S. So we've seen start forms and rent submissions as well as actual patients come from each of the the large main centers that you would expect within the <unk> community and also from smaller.

Tazeen Ahmed: Thanks for taking my questions. Quickly on

Tazeen Ahmed: of GA Studies. Assuming that they're both positive, should we expect that you would be able to apply for approval this calendar year? And what would be the rate-limiting steps left in your application?

Sensors geographically dispersed across the U S. So where we're having an impact across the whole country hopefully that answers your question.

Tazeen Ahmed: and Assuming positive data

Tazeen Ahmed: And then, as we talk about the commercial landscape, could you maybe give us your view on...

Tazeen Ahmed: The potential for a C5 as well as a C1Q complement inhibitor to enter the market

Yeah, Yes think of and then maybe a question on G. A commercialization for the third and US. So in terms of you know in terms of where you potentially need to be of versus where you are now I mean, you. Just are you just starting out versus you know what percent of our sales force do you still need to hire you'll probably in early stages.

Tazeen Ahmed: Transcripts provided by Transcription Outsourcing, LLC.

Cedric Francois: Thank you so much, Tazeen. I'm going to hand the approval question to Federico, and then Adam will take the commercial question.

Cedric Francois: to Federico, and then Adam will take e-commerce. Thank you, Cedric, and thank you for the question. We are looking forward to the results, the readout of the studies coming in September, and our teams are ready to jump into the submissions and be able to submit as soon as possible. We're not advising on the timing of the submissions, but we're fully prepared to tackle the analysis, not only of the primary endpoints that will be reported soon, but the full analysis required for that. Thank you, Philip. And then, well, I was just, Adam is texting me here.

To give us an idea.

Yeah, I'll take that 1 too it's Adam So we have obviously built in the infrastructure, which we can carry across the certain pieces of commercialization for geographic atrophy. We've also created the leadership teams commercial and medical affairs in the U S.

The International head office in Switzerland.

And in Germany, and in Australia. So we have the core infrastructure as soon as we see data we are rapidly start to expand on that infrastructure through sales force and medical affairs and everything else that you would expect so we're in a good place we're looking for it to see the data and we have identified candidates out of the Mark.

Cedric Francois: It's not a commercial question. It's a question about data. Look, I think at the end of the day, you know, we will see what happens with the competition. It is our conviction that the mechanism by which the retina suffers from geographic atrophy is driven by the accumulation of C3 products on the retina, which is not properly removed. And it's not being properly removed because the same cellular mechanisms compete for removal of C3 as those that work on the visual side.

Who are willing to join our pallets and excited to join the palace post positive <unk> data.

Thank you very much.

Thank you our next question coming from the line of Alicia Young with Cantor. Your line is open.

Hey, guys. Thanks for taking my question.

2 just 1 can you talk a little bit about how COVID-19 has kind of impacted things of how you think going forward. It may what kind of I guess some of the Delta Varian Lam the Varian and take every variant you have going and then maybe the second question is just from a scenario of a it sounds like you know how do you think about kind of you know having levels of kind of you know on the safety of front, whether it be the <unk>.

Cedric Francois: We know from our PNH studies that C5 has no effect on the accumulation of C3, so it would be a surprise to us should a C5 inhibitor be successful, especially in light of the fact that anti-C5 has failed twice already, both when administered systemically as well as intratribally. C1 is, on the other hand, an interesting target, but there, too, you don't have the kind of broad control of complement that we believe you need, and as you do with pexitaclopan, by also covering the lectin pathway and the alternative pathway.

By the end up though.

Or whether it be the.

That's the day of events like how do you think about like if they were the same in this trial read out what do you think that means commercially versus the potentially of were slightly lower you know kind of maybe lay out some of your scenarios on that thanks.

Thank you so much of the center I assume that your first question regarding to Covid also applies to the study correct of the duo study.

All of that play out from the panic shockingly [laughter] ex it well I will I will hand, it over to Adam them to give them. Some reached the size of them because that's the country well actually kind of.

Yeah. Thanks for Lithia, yes, the the joys of launching a product.

During the global pandemic, so we've actually seen impacts of live interactions increase so our prior to our approval they were lower than 10% of our interactions were live in now roughly 40 per cent of all of our interactions of live in person. We also continue to use virtual technologies to engage with.

Cedric Francois: So I think, you know, the proof is in the pudding, but it's also important to note that, you know, the only competitor closest, of course, is the Iverix program, and we look forward to evaluating that when it becomes available.

Physicians now my bias tells me that the Delta Varian could slow this down a little bit the in person engagements, but we you know we're going to closely monitor all of the regional COVID-19 restrictions and we'll make sure that we're following those with the HCP as of now offices.

Cedric Francois: Yeah, I think I hope that answers your question, Tazeen.

Tazeen Ahmed: Yeah, that's really helpful, Cedric. I mean, if you were to talk about one thing that...

Tazeen Ahmed: Transcripts provided by Transcription Outsourcing, LLC.

But we think we have the right skill set and obviously, we prepared to do a virtual launch and we're having some great success with that as well so between the balance of in person and on the virtual we think we're in a really good spot to continue the great progress on the PMA channel.

Cedric Francois: Would you pivot more to efficacy?

Cedric Francois: I think, you know, again... But what we have done.

Cedric Francois: What we have done and what I like about our program is that it has been a program where we deliberately chose to be highly consistent over time. In other words, we did the Philadelphia trial in 2015, really to mimic what Genentech Roche at the time was doing with their Lampalizumab program. We knew that they had interactions with the FDA, what the expectations were in terms of endpoint, and the phase two clinical trial was really designed to anticipate a phase three trial with minimum change.

Thank you Adam and then Alicia as it relates to your second question related to safety. So.

I want to start off by saying that in the filly trial. The safety profile was such that we did not have to make any changes in the phase III. So first of all of as it relates to the expeditions and as alluded to earlier the tanks.

Thanks for the ex additions, we had were never a safety concern and by correcting for that investigator of bias and the fact that the demographic will be adjusted we expect in the phase III clinical trial, the extradition rates to be lower than they were at in phase II, but again.

Cedric Francois: For all of you that have studied Philly and Derby and Oakes, they're pretty much a carbon copy of each other with very, very tiny changes and, if anything, just more quality and robustness in the Derby and Oakes trial. So, you know, the AVERIX program, without any criticism, is. [inaudible] Okay, thank you.

And the investigators in the phase III trials with no of course, those dates are very well from the phase II <unk> rates to be acceptable for the enrollment in the phase III trial, which if it hadn't been for Covid.

Probably even faster than any phase III trials done before.

Then as it relates to the cases of infection endophthalmitis. So we had 2 cases in the filly trial.

Operator: Our next question comes from the line of Steve Seedhouse with Raymond James.

Steven Seedhouse: So we have a quick question on P&H Commercial, given that you have $0.6 million in revenue.

That was on a total of approximately 1400 intra articular injections that's right.

And the infectious endophthalmitis is in line with what you've signed in the phase II clinical trials with anti VEGF or with steroids for example, so.

Steven Seedhouse: Thank you.

Cedric Francois: Thank you so much. Well, I will hand that over to Adam.

Adam J. Townsend: Thank you very much for the questions. We're not going to guide on product revenue for the foreseeable future, but, you know, the initial 0.6 million is a great sign of how Empaveli can elevate the standard of care. We've had over 75 physicians sign up for REMS and over 60 start forms, which should give you a very strong indication of the demand. So there is more to come there. And on your second part of the question, we've seen success all across the US. So we've seen initial forms and REM submissions as well as actual patients come from each of the large main centers that you would expect within the P&H community and also from smaller centers geographically dispersed.

This is an entry pathogen and this is the complication that is inherent to the procedure itself. There is right now absolutely no indication that that rate would be higher because of some circumstance then of this under normal circumstances and typically what you see is that in the phase II clinical trial of a certain rate and phase III gets better and then <unk>.

Virtually it further improves as physicians get used to the procedure. So Luca.

It is our expectation that.

The safety profile of fixes the coupon will be safe.

And that we will be able to with the focus on efficacy against.

Against the background of feeling.

Great. Thank you.

Thank you so much.

Our next question coming from the line of Ellie Merle with UBS. Your line is open.

Hey, guys. Thanks, so much for taking the question I'm just first in terms of Activations N. G. I guess, maybe what we might know him from the natural history around like how activations.

Adam J. Townsend: Transcripts provided by Transcription Outsourcing, LLC. Hopefully, that answers your question. Yes, thank you. And then maybe a question on...

My impact T a growth or any of <unk>.

Adam J. Townsend: Transcripts provided by Transcription Outsourcing, LLC.

Adam J. Townsend: Yeah, I'll take that one too. It's Adam. So we have obviously built an infrastructure which we can carry across for certain pieces of commercialization for geographic attributes. We've also created leadership teams commercially in medical affairs in the US, at our international head office in Zug, Switzerland, and in Germany and in Australia. So we have the core infrastructure. As soon as we see data, we'll rapidly start to expand on that infrastructure through salesforce and medical affairs and everything else that you would expect. So we're in a good place, we're looking forward to seeing the data, and we've identified candidates out in the market who are willing to join Apellis and excited to join Apellis post-positive GA data.

Correctly either of your data or in the natural history and then second question just in terms of the commercial outlook for Ta ex U.

You also I guess, just curious how youre thinking about you know potential commercial preparations ex U S for Gi and just any differences in terms of you know diagnosis rate or you know any particular, maybe appetite from endpoints versus yeah. The you asked or anything different there in terms of the commercial strategy per se.

Yeah. Thanks.

Thank you so much of the well so as it relates to expeditions and we don't talk a lot about this because we're really not talking about the anecdotal numbers, but if you look back at the filly trial.

And you look at those patients that develop expeditions for whom we have the follow up data for geographic atrophy.

Operator: Thank you. Our next question comes from the line of Alethea Young with Kansor. Your line is open. Hey, guys, thanks.

There's quite a remarkable slowdown N G and beyond what the metrics for example in the primary endpoint, but these are of such small numbers that will have to find out in the phase III clinical trial, if they materialize.

Or not.

Alethea Young: Hey guys, thanks for taking my questions. Um, two, just one: can you talk a little bit about, you know, how COVID has kind of impacted things and how you think going forward it may with kind of, I guess, some of this Delta variant, Lambda variant, take every variant you have going. And then maybe the second question is just from a scenario basis, like, you know, how do you think about kind of, you know, having levels of, you know, on the safety front, whether it be infections or endoptosis, or, you know, whether it be the, um,

So again, that's something to look forward to.

But it's definitely an intriguing observation that goes hand in hand with kind of of the hypothesis that maybe the extra days go hand in hand with a.

1 of the healing of beat their process.

And then as it relates to the ex U S deployments, which is the.

Wonderful undertaking that Adam is taking on I'll hand, it over to him.

Yeah. Thank you. Thanks for the question. So quickly obviously in the G. A there's a million patients in the U S and.

And about $2.6 million in Europe, and 5 million globally. So you can see that there is a totally global opportunity for geographic atrophy or of palace, and we're preparing to execute against that global opportunity. So we have built out and the infrastructure and so again, Switzerland.

Alethea Young: Thank you so much, Alicia. And I assume that your first question regarding COVID also applies. I will hand that over to Adam then to give some brief insights because that's going very well.

Our experienced commercial and medical affairs leaders and we have already started to build out of region in Germany.

Cedric Francois: Thanks, Alethea. Yes, the joys of launching a product during a global pandemic. And we've actually seen that.

Based in Munich, and also Australia, and the affiliate so we're ready to make sure that we can meet the needs of G. A physician's NGA patients very quickly ex U S. It's an exciting opportunity and we're doing all of it we can to be ready for that.

Adam J. Townsend: We've actually seen in-person live interactions increase. So prior to our approval, they were lower than 10% of our interactions were live. Now, roughly 40% of all of our interactions are live in-person. We also continue to use virtual technologies to engage with physicians. Now, my bias tells me that the Delta variant could slow this down a little bit, the in-person engagements. But we, you know, we're going to closely monitor all of the regional COVID-19 restrictions, and we'll make sure that we're following those with HCPs in our offices. But we think we have the right skill set.

Now I will hand, the regulatory side to Cedric and fed day on what's likely to be expected in Europe that was the third part of your question.

Thank you so much so so in Europe as it relates to the regulatory process.

Like in the U S. The growth of geographic atrophy as the primary endpoint.

The that we look for.

The general feedback from the European regulators has been that we would like to see of directional change in the functional endpoints in alignment with the essence.

Adam J. Townsend: And obviously, we're preparing to do a virtual launch, and we're having some great success with that as well. So between the balance of in-person and virtual, we think we're in a really good spot to continue the great progress on the PMH launch. Thank you, Adam.

Essentially the loss of photoreceptor cells as measured through the anatomical endpoints, but not with the expectation of showing that statistically and other data that we will gather at the 24 month time point and adds to our filings in Europe.

The answer your question.

That's really helpful. Thank you.

Thank you so much.

Yeah.

Okay.

The next question coming from the line of Justin Kim with Oppenheimer. Your line is open.

Cedric Francois: And then, Alitya, as it relates to your second question related to safety, I want to start off by saying that in the Philadelphia trial, the safety profile was such that we did not have to make any changes in Phase III. So, first of all, as it relates to the exudations, and as alluded to earlier, the types of exudations we had were never a safety concern. And by, you know, correcting for that investigator bias and the fact that the demographics will be adjusted, we expect in the Phase III clinical trial the exudation rates to be lower than they were in Phase II.

Hi, good afternoon, thanks for taking our question.

Just had a couple of at this point.

I know you had covered this a little bit before but with the intermediate AMD study, depending on the Derby and Oaks of success can you just discuss how important regulatory buy in an IRA to see where all of our progression of designing empowering our potentially pivotal study in intermediate AMD and sort of what aspects of the Derby and Oaks study will.

And for them that design and powering as well.

Thank you so much and great to hear you I'm going to hand that over to for that.

As the others.

Thank you Joseph for the question.

Cedric Francois: But, again, the investigators in the Phase III trial, who know, of course, those data very well, found the Phase II exudation rates to be acceptable for the enrollment in the Phase III trial, which, if it hadn't been for COVID, would probably have been faster than any Phase III trial done before. Then, as it relates to the cases of infectious endophthalmitis, we had 2 cases in the Philly trial that had a total of approximately 1,400 intravitril injections. That rate of infectious endophthalmitis is in.

Well.

It's really important and we are.

You know of discussing with the.

The regulators on the imports on the all of the change from IRA.

So they are buying and an agreement on the definition under the 6 of us.

The the endpoint to look for the studies as the inspector of the important.

And we are having ongoing discussions with them. So we'll know more.

In the next few months.

Okay, Great and maybe just 1 on empathy Ali appreciating that the label of already quite broad just wondering if there are any plans at this point too.

And formally incorporate the Prince study data into the label and any sort of timeframe for that as well as the potential scientific publication.

Cedric Francois: And typically, what you see is that in a Phase II clinical trial, you have a certain rate, in Phase III it gets better, and then commercially, it further improves as physicians get used to the procedure. Look, it is our expectation that the safety profile of Plexi-Tacoplan will be safe, and that we will be able to focus on efficacy against the background of Philly.

Thank you so of assistant so the.

That has not been decided yet to your point of the label is very broad.

And the will be something we will follow up of them.

Okay, great. Thanks, so much for taking the questions and look forward to the results of next month.

Thank you so much.

Our next question coming from the line of Matthew Luchini with BMO capital markets. Your line is now open.

Cedric Francois: Our next question, coming from the line of Ellie Merle with UBS, your line is open. Hey guys, thanks so much for taking the question.

Alright. Thanks, everyone. This is Nick 1 other on for Matthew I, just 1 quick follow up for us.

The G&A smarts is going pretty well as you said and I believe you said the majority of patients are still 5 switches <unk> 75 per cent of that being from out from the Arris is that something we can expect going forward or is that kind of it kind of change at the time of any incremental color on that would be really great.

Eliana Rachel Merle: Just first, in terms of exudations in GA, and I guess maybe what we might know from the natural history around how exudations might impact GA growth or just, you know, any associations we've seen historically, either in your data or in the natural history. And then second question, just in terms of the commercial outlook for GA ex-US, I guess I'd just curious, you know, how you're thinking about, you know, potential commercial preparations ex-US for GA and just any differences in terms of, you know, diagnosis rate or, you know, any particular maybe emphasis on endpoints versus, you know, the U.S. or anything different there in terms of the commercial strategy versus the U.

Okay.

Thank you so much I'm going to hand that 1 over to Adam as well.

So yes. Thanks for the question, you're correct with thing of switch being the majority of our and P value stocks.

And the 75% of those switches are coming from all from Altamira as a quick reminder, the.

The 1 third of the 1500 <unk> 5 treated patients. We believe is a target population of the beginning of approach of not that has the highest unmet need they have of low and pulling the hemoglobin on net currency 5 treatment and that continually being transfused.

That is the patient population that we're seeing and so see 5 switches will be the bolus of all starts moving forward.

Eliana Rachel Merle: Thank you so much Ali. Well, so as it relates to exudations, and we don't talk a lot about this because we're really not talking about anecdotal numbers, but if you look back at the Philly trial and you look at those patients that developed exudations for whom we have the follow-up data for geographic atrophy, there's quite a remarkable slowdown in GA, you know, beyond what we measured, for example, in the primary end.

I expect that to be a balance between altamira of sensor the rest with the ultimate likely being the majority of them as we move forward and then we'll continue to progress through the unmet need in the 1500 C 5 treated patients.

Great. Thank you.

Okay.

Thank you so much.

Okay.

And our next question coming from the lineup Joseph Stringer with Needham Your line is open.

Eliana Rachel Merle: But these are such small numbers that we'll have to find out in a phase three clinical trial if they materialize or not. So again, that's something to look forward to, but it's definitely an intriguing observation and goes hand-in-hand with kind of that hypothesis that maybe these exudates go hand-in-hand with a wound healing repair process. And then, as it relates to the XUS deployment, which is a wonderful undertaking that Adam is taking on, I'll hand it over to him.

Yes.

Hi, everyone. Thanks for taking our questions per quarter.

If the belly in terms of gross to net recognized that its early on of the lunch.

But just given your commentary around commercial versus government, the payor mix and how that's.

Going to continue in the future.

So the early sense of the gross to net early on and of.

You know, what what you sort of see that kind of.

The steady state on an annual basis. Thank you.

Thank you so much and what you want to take this 1.

Eliana Rachel Merle: Yeah, thank you. Thanks for the question. So, quickly, obviously, in GA, there are a million patients in the U.S. and about 2.6 million in Europe and 5 million globally. So, you can see that there is a totally global opportunity for geographic atrophy for Apellis, and we're preparing to execute against that global opportunity. So we have built out an infrastructure in Zug, Switzerland, with very experienced commercial and medical affairs leaders, and we have already started to build out our

Yeah, absolutely. Thanks, Jerry you're right. It's the it's a bit too premature for us to comment on gross to net at this point in the launch we are in line with the other across the net rare disease models and to your point I expect our gross to net to tick down as we progress into the later stages of the launch as we transition patients to 20 per valley. So early days.

In the launch window for them.

I mean still thrilled with how we're progressing with the hemp of early launch.

Great. Thanks for taking our questions.

Thank you some of that's expressed <unk>.

Next question coming from the line of I don't know of transplant Roth capital. Your line is open.

Cedric Francois: I'd also like to thank our partners at the FDA, based in Munich, and also our Australian affiliates. So, we're ready to make sure that we can meet the needs of GA physicians and GA patients very quickly outside the US. It's an exciting opportunity, and we're doing all that we can to be ready for that. Now, I will hand the regulatory side to Cedric and Feday on what's likely to be expected in Europe. Thank you so much.

Yes, Hi, maybe just for housekeeping question from Tim the cost of the research collaboration from beam Therapeutics would that'd be an ongoing the line items separately at him.

Thank you and all of them are ultimately know that that is unlikely to be it'll be baked into research and development expense, we broke that out showing the upfront because it had the large impact on the R&D expense. This quarter as you know we're obligated to pay another $25 million a year from now and.

Cedric Francois: So in Europe, as it relates to the regulatory process, like in the U.S., the growth of geographic atrophy is the primary endpoint that we look for. The general feedback from the European regulators has been that they would like to see a directional change in the functional endpoints in alignment with essentially the loss of photoreceptor cells as measured through the anatomical endpoints, but not with the expectation of showing, And that is data that we will gather at the 24 month time point and add to our findings.

Ultimate.

After that the ongoing expense would be fairly de minimis at this as a research collaboration initially so it will be baked into R&D.

Kind of get them and maybe a clarification from Adam Adam you mentioned that and this is related to the lead time of 12 days to get patients on drug.

Cedric Francois: Did that answer your question, Ali? Yes, really helpful. Thank you.

That vaccination is ease of component there.

Hum.

The human Covid vaccination, because I thought that the most.

Operator: Our next question comes from the line of Justin Kim with Oppenheimer. Your line is open.

The most of these patients are sick patients. So they had been previously vaccinated.

Justin Alexander Kim: I know you covered this a little bit before, but with the Intermediate AMD study dependent on Derby and Oakes' success, can you just discuss how important regulatory buy-in on iRORA to see RORA progression is to designing and powering a potentially pivotal study in Intermediate AMD, and what aspects of the Derby and Oakes study will help inform that design and powering?

Yeah, and it's a no it's actually vaccination of instead of required by label 2 weeks before the start of that in the valley to get on to the valley. So it's the following the labor guidance.

It is not COVID-19 vaccine related.

So even though these people were previously vaccinated because they received out of my rest of day, they would have to receive an order of vaccine.

Justin Alexander Kim: Studies will help inform that design empowering as well.

Cedric Francois: Thank you so much, Justin. Great to hear from you. I'm going to hand that over to Federico. Thank you, Stennis, and thank you, Justin, for the question.

Yeah the upon.

So in the label Guy the guidelines from the vaccination 2 weeks prior to the first types of type of product.

Okay. Okay. Thank you so much right now.

Federico Grossi: It's really important, and we are discussing with the regulators the importance of the change from IRR to IRR, so they're buying an agreement on the definition of the disease and the end point to look for in the studies, etc.

Thank you so much of the mirror.

And I think that was the last question.

In closing thank you all for joining us on our second quarter Conference call. We look forward to presenting top line results from our Derby and Oaks studies in September and keeping you updated on our commercial and pipeline progress in the months ahead.

Federico Grossi: Thank you very much. Okay, great. And maybe just one on Empaveli, appreciating that the label is already quite broad, just wondering if there are any plans at this point to

We are around later today and tomorrow, if you have any additional questions and feel free to reach out to Meredith.

Operator: https://www.youtube.com

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

Justin Alexander Kim: https://www.kenhub.com Thank you so much, Justin. So that has not been decided yet. To your point, the label is very broad.

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

Cedric Francois: And, you know, that will be something we'll follow up on. Great. Thanks so much for taking the questions. I look forward to the results.

Okay.

Okay.

[music].

Justin Alexander Kim: Great. Thanks so much for taking the questions. I look forward to the results next month.

Operator: Our next question comes from the line of Madhu Luchini with BMO Capital Markets. Your line is open.

Madhu Sudhan Kumar: Hi, thanks, everyone. This is Nick going out on for Matthew.

Nick: Just one quick follow-up for us. It seems like the P&H launch is going pretty well, as you said, and I believe you said the majority of patients are C5 switches, 75% of that being from ultramarines. Is that something we can expect going forward? Or is that going to kind of change over time? Any incremental color on that would be really great. Thank you.

Cedric Francois: Thank you so much. I'm going to hand that one over to you now.

Adam J. Townsend: So, yep, thanks for the question. You're correct.

Adam J. Townsend: We're seeing a switch in the majority of our Empire Valley starts, and 75% of those switches are coming from Altamiris. As a quick reminder, one-third of the 1,500 C5-treated patients we believe is our target population at the beginning of launch, and that third has the highest unmet need. They have a low and falling hemoglobin on their current C5 treatment, and they're continually being transfused. So, that is the patient population that we're seeing, and so C5 switches will be the bolus of our start moving forward. I expect there to be a balance between Altamiris and Soliris, with Altamiris likely being the majority as we move forward, and then we'll continue to progress through the unmet need among the 1,500 C5-treated patients.

Adam J. Townsend: My next question comes from the line of Joseph Stringer with Needham. Your line is open.

Operator: Hi, everyone. Thanks for taking our questions. A quick one on HIPAA Valley in terms of pros and cons. I recognize that it's early on at the launch, but just getting your commentary around commercial versus government payer mix and how that I'm going to continue in the future. Just wanted you to give us an early sense of the growth in that early on and what you sort of see in a steady state.

Joseph Stringer: Thank you. Thank you so much. Adam, do you want to take this one? Yes, absolutely. Thanks, Joey. You're right.

Adam J. Townsend: It's a bit too premature for us to comment on growth-to-net at this point in the launch, but we are in line with other growth-to-net rare disease models. And to your point, I expect our growth-to-net to tick down as we progress into the later stages of the launch, as we transition patients to Empaveli. So, early days in the launch window, but I'm still thrilled with how we're progressing with the Empaveli launch.

[music].

Joseph Stringer: Great, thanks for taking our questions.

Adam J. Townsend: Thank you so much. Next question.

Operator: Our next question comes from the line of Alomar Priests with RAAD Capital, Yolanda Sullivan.

Alomar Priests: Yes, hi. Maybe just the housekeeping.

Alomar Priests: Housekeeping question from Tim: the cost of the research collaboration from Beam Therapeutics, would that be an ongoing line item separately, Tim?

Timothy E. Sullivan: Thank you, Elmer. Ultimately, no, that is unlikely to be; it'll be baked into the research and development expense. We broke that out, showing the upfront cost because it had a large impact on the R&D expense this quarter. As you know, we're obligated to pay another $25 million a year from now. And ultimately, after that, the ongoing expense will be fairly de minimis, as this is a research collaboration, initially, so it'll be baked into R&D.

Timothy E. Sullivan: Thank you. Thank you, Tim. And maybe some clarification from Adam. Adam, you mentioned that, and this is related.

Adam J. Townsend: It to the lead time of 12 days.

Adam J. Townsend: Transcribed by https://otter.ai

Adam J. Townsend: I did not get a vaccination because I thought that most of these patients are switch patients, so they were previously vaccinated.

Adam J. Townsend: Yeah, it's not, it's actually vaccinations that are required by label two weeks before the start of Empaveli to get on to Empaveli. So it's following the label guidance. It is not COVID vaccine related. So even though these people were previously vaccinated because they received the Delta virus, they would have to receive another vaccine.

Adam J. Townsend: Yep, they're following the label guidelines on vaccination two weeks prior to the first dose of. Thank you so much. Thank you so much, Elomer. And I think that was the last question. In closing, thank you all for joining us on our second quarter conference call. We look forward to presenting top-line results from our Derby and Oakes studies in September and keeping you updated on our commercial and pipeline 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 day.

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

Operator: ??? ??? ??? ??? ??? ??? ??? ??? ??? ??? ??? ??? ??? ??? ??? ??? ??? [inaudible] ?? Tazeen Ahmad, Annabel Samimy, Yigal Nochomovitz, Steven Seedhouse, Philip Nadeau, Douglas Tsao, Eliana Merle, Madhu Kumar, Joseph Stringer, Derek Archila, Douglas Tsao, Adam Townsend, Timothy Sullivan, John Miller, Colleen Kusy, Graig Suvannavejh, David Acheson, Timothy Sullivan, Anupam Rama, Meredith Kaya, Jonathan Miller, Akash Tewari, Siyue Wang, Philip Nadu, Steve Sites, Tazeen Ahmed, Apellis Pharmaceuticals, Inc. Tazeen Ahmad, Annabel Samimy, Yigal Nochomovitz, Steven Seedhouse, Philip Nadeau, Douglas Tsao, Eliana Merle, Madhu Kumar, Joseph Stringer, Derek Archila, Tazeen Ahmad, Annabel Samimy, Yigal Nochomovitz, Steven Seedhouse, Philip Nadeau, Douglas Tsao, Eliana Merle, Madhu Kumar, Joseph Stringer, Derek Archila, John Miller, Adam Townsend, Timothy Sullivan, Colleen Kusy, Graig Suvannavejh, David Acheson, Timothy Sullivan, Siyue Wang, Phil Nadu, Steven Sites, Tazeen Ahmed, Apellis Pharmaceuticals, Inc.

Ladies and gentlemen, thank you for standing by, and welcome to Apellis' second quarter 2021 financial results 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 this session, you will need to press the start and the 1 key on your touchtone telephone. Please be advised that today's conference may be recorded. If you would like to call the operator's assistance, please press star then zero. I would now like to hand the conference over to your speaker host, Meredith Kaya, Senior Vice President of Investor Relations. Please go ahead.

[music].

Good afternoon, and thank you for joining us to discuss Apellis's second quarter 2021 financial results. With me on the call are co-founder and chief executive officer, Dr. Cedric Francois, chief commercial officer, Adam Townsend, chief medical officer, Dr. Federico Grossi, and chief financial officer, Tim Sullivan. Before we begin, I would like to point out that we will be making four forward-looking statements that are based on our current expectations and beliefs. These statements are subject to certain risks and uncertainties, and our actual results may differ materially.

I encourage you to consult the risk factors discussed in our SEC filings for additional detail. Now, I'll turn the call over to Cedric. Thank you, Meredith, and good afternoon to everyone joining us today for our conference. Also, a quick welcome to Meredith, who joined Apellis earlier this month and will be leading our investor relations effort. The second quarter was an exceptional period for Apellis, highlighted by the FDA approval of Empavedi, or Pexita Coplan, which is the first targeted C3 therapy.

And Paveli was approved with a broad label for the treatment of adults with paroxysmal nocturnal hemoglobinuria, or PNH, and it represents the first new class of complement medicine in nearly 15 years. The approval of Empath Eddy was a tremendous achievement for the P&H community and for App Eddy. And I am very proud of our team for advancing this transformational medicine. Our commercial launch is off to a strong start, and our Chief Commercial Officer, Adam Townsend, will share additional details shortly.

The AMPA Ready approval was quickly followed by more good news, with positive results from the Phase 3 PRINCE study of our targeted C3 therapy in treatment nave PNH patients. Together with the PEGASIS data, the PRINCE results reinforce the potential for empavedi to elevate the standard of care for all patients with PNA. And P&H is only the start of what is possible by targeting C3. In June, we hosted an R&D day where we showcased our growing pipeline across rare diseases, neurology, and ophthalmology. Our ambition is to be a global leader in complementary over the long term.

And we unveiled multiple new molecular entities across several modalities to deliver on that goal. In addition to advancing MPAVD in four registrational programs with our partner SOBE, we plan to transform the treatment of rare complement-driven diseases by developing new product candidates for existing and new indications and further enhancing the patient experience. In neurology, where C3 plays a key role in a wide range of neurodegenerative conditions, our world-class research team is pioneering targeted C3 therapies to help patients with these devastating diseases.

And in ophthalmology, where we aim to be number one in the retina, we look forward to the phase 3 results from pexitacoplam in geographic atrophy, or GA. In addition, we are advancing novel molecular entities for GA, wet AMD, and intermediate AMD. At our R&D day, we also announced an exclusive research collaboration with Beam Therapeutics to apply Beam's proprietary base editing technology to discover novel treatments for complement-driven diseases. Complement is a new frontier for biology. And we look forward to working together with BEAM. We will explore base editing, silencing, and other approaches that may have the potential to modulate complement in the eye, the liver, and the brain.

Our shared vision is to develop one-time curative therapies for a wide range of debilitating diseases. We are thrilled with the breadth and the depth of our expanded pipeline, which we believe positions Apellis to be a global leader in complementary medicine today, tomorrow, and in the future. Looking ahead, we are optimistic heading into the top line results from the phase 3 DERBY and OCHS studies of plexitycoplan for the treatment of GA. This key readout in September is a potentially transformative event for the more than 5 million patients worldwide currently living with GA, as well as for the millions of patients with wet AMD, the majority of whom will develop atrophy over time.

[music].

Feedback from the retinal community shows great enthusiasm for pexitacoplam and the prospect of finally having the first potential treatment for people living with GA. I will now turn the call over to Adam Townsend to share more about our ongoing commercial launch of EmpaVidi for P&H. Adam.

Thank you, Cedric. As Cedric mentioned, our Empa Valley commercial launch is off to a strong start, and I'm excited to share our initial results. Mpevele was approved on May 14th, so we are only in the very beginning stages. With that said, we are encouraged by the great progress we've made thus far and the positive feedback we have received from the P&H community. Our top launch priorities are outlined on this slide, all of which are designed to ensure that every eligible PNH patient who wants Empaveli will have access to this important new MedStar.

Ladies and gentlemen, thank you for standing by and welcome Joe Kelley of second quarter 2021 financial results conference call at.

At this time all participants are in a listen only mode.

Beginning with the approval, we were thrilled with the Empaveli label, which included both patients currently being treated with C5 inhibitors and those who are naive to treatment. Recall that within the U.S., there are approximately 1,500 patients who are currently being treated with C5 inhibitors, so there is an ultramarine, and another 150 people diagnosed with PNH every year.

After the Speakers' presentation there'll be a question and answer session to ask the question. During the session you will need to press. The Star then the 1 key on you touched on the telephone.

Please be advised for today's conference maybe recorded.

The call offer assistance. Please press Star then zero.

I would now like the end the conference of what you speak of house.

The cargo senior Vice President of Investor Relations. Please go ahead.

Okay.

Good afternoon, and thank you for joining us to discuss the palace for the second quarter 2021 financial results with me on the call our co founder and Chief Executive Officer, Dr. Cedric Francois Chief Commercial Officer, Adam Townsend, Chief Medical Officer, Dr. Federico Gretzky.

Our initial launch focuses on PNH patients who have suboptimal control of their disease, beginning with a third of patients on C5 inhibitors with the highest unmet need, those who require transfusions to address their falling hemoglobin levels. We then plan to expand to the broader P&H community, many of whom are also suffering from signs and symptoms like anemia and severe fatigue. We have received positive feedback from various stakeholders, and the quotes on the right side of the slide highlight the excitement for Empaveli from the P&H community.

The 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 of certain risks and uncertainties and our actual results may differ materially.

I heard you to consult the risk factors discussed in our SEC filings for additional detail now I'll turn the call over to Cedric.

Thanks for Meredith and good afternoon to everyone joining us today for articles from school.

Also a quick welcome to Meredith, who joined US earlier, this month and will be leading our investor relations efforts.

At the end of July, over 75 physicians have signed up for our REMS program since its launch in the U.S., and we have received more than 60 initial forms. Each of these are not only early indicators of demand but also shows that physicians have identified that Empaveli can help better address their patients' treatment needs. We are finding that C5 inhibitor switch patients are the majority of new empivelli starts, with about 75% of switches coming from Altamira.

The second quarter was an exceptional period for <unk> highlighted by the FDA approval of empathy or makes it the coupon which is the first targeted for Q3 therapy.

And then he was approved with a broad label for the treatment of adults with paroxysmal nocturnal hemoglobinuria or P and H and the represents the first new class of complement the medicine in the.

15 years.

The approval of integrity was a tremendous achievement for the <unk> community and for at the at each and I am very proud of our team for advancing the transformational medicine.

We have also received newly diagnosed patient start forms, which is very encouraging and reflects our broad label. In terms of coverage breakdown, approximately 50% of Empire Valley patients have commercial private insurance, 25% have Medicaid, and 25% have Medicare, with all three payer channels submitting and approving prescriptions. We expect payer coverage to remain split 50-50 between private insurance and government programs for the foreseeable future.

Our commercial launch is off to a strong start and our chief commercial officer, Adam Townsend will share additional details shortly.

The anti of any approval was quickly followed by more good news with positive results from the phase III study of <unk>. So I get the C..3 therapy in treatment naive <unk> patients.

Together with the Pegasus data the French results reinforced the potential for impact of Eddie to elevate the standard of care for patients with B of niche.

And lastly, on the payoff. Our Value & Access team is engaging with high priority payers, including the top 20 payers that cover approximately 85% of all US P&H patients. So far, four payers have accelerated Empavelli formulary reviews, and one has already placed Empavelli in a positive formulary position. Given our strong progress to date, we are on track to be on formulary with approximately 90% of plans by the end of the year.

And <unk> is the only the start of what is possible by targeting the <unk> III.

In June we hosted an R&D day, where we showcased our growing pipeline across rare disease urology and ophthalmology.

Our ambition is to be a global leader in continents over the long term and we envy of multiple new molecular entities across several of the modalities to deliver on that goal.

In addition to advancing <unk> in for Registrational programs with our partner Sobey.

We plan to transform the treatment of rare complements driven diseases by developing new product candidates for existing and new indications and further enhancing the patient experience.

To close, we are excited about the strong initial launch of EmpaVeli and are super proud to bring this important new product to the P&H community. Some of the highlights I outlined from our launch activities are included on the left side of this slide. We have done a lot of work to prepare the marketplace, and our integrated team, from the commercial field teams to medical affairs, is laser focused on successfully executing the law.

In urology, whereas the 3 plays a key role in the wide range of neuro degenerative conditions. Our World Class research team is pioneering targeted T..3 therapies to help patients with these devastating diseases.

And in ophthalmology, where we aimed to the number 1 in the retina. We look forward to the phase III results from Brexit that Copeland and geographic atrophy or <unk>.

On the right side of this slide, you can see end-of-year goals for engagement, market access, and patient experience. This includes engaging all priority accounts and 85% of priority physicians, as well as maintaining high patient satisfaction scores for self-infusion of empyrovalin. While we are not planning to provide sales guidance in the near term, we do plan to provide certain launch metrics that help to illustrate our progress as we ramp up during this initial launch period.

In addition, we are advancing novel molecular entities for G. A what's the empty.

The empty and intermediate and the.

At our R&D day, we also announced an exclusive research collaboration with beam therapeutics to apply beams proprietary base editing technology to discover novel treatments for compliments driven diseases.

Complement is a new frontier for base editing and we look forward to working together with Dean.

We will explore base editing silencing and the other approaches that may have the potential to modulate compliment and the other.

We look forward to keeping you updated as our teams continue to work to bring this transformative treatment to the P&H community. Our Apellis team is very proud to have the responsibility to help P&H patients with high unmet needs. At the same time, our commercial organization is looking forward to the upcoming Phase 3 GA results next month. Our US, European, and international teams are busy preparing the commercial foundation globally for this potential blockbuster opportunity. I will now turn the call over to Dr. Federico Grossi to discuss our clinical development.

The liver and the brain.

Our shared vision as to these other onetime curative therapies for a wide range of debilitating diseases.

We are thrilled with the breadth and the depth of our expanded pipeline, which we believe positions the applebee's to be a global leader in complement today tomorrow and into the future.

Looking ahead, we are optimistic heading into the top line results from the Phase III Derby and Oaks studies of the exit that kirkland's for the treatment of the G. H.

This key readout in September is there a potentially transformative event for the more than 5 million patients worldwide currently living with GE.

I'll begin briefly with the phase 3 print study in PNA. In May, we and our partner Sobe were thrilled to report positive top-line results from the print study of Empaveli in treatment-nave patients.

As well as for the millions of patients with wet AMD from.

The majority of whom will develop atrophy over time.

And Paveli demonstrated statistical superiority on the co-primary endpoints compared to standard care, which did not include complement inhibitors at week 26.

Feedback from the retinal community shows great enthusiasm for picks at the Coke then and the prospects of finally, having the first potential treatments for people living with G E.

And Paveli also achieves...

Statistical superiority versus standard of care on several secondary endpoints that are meaningful to prescribers and patients, including improvement in hemoglobin levels and removing the need for transfusions. The safety profile of Empaveli was consistent with previous steps. These results add to the robust clinical profile of Empavelin and support the use of our targeted C3 therapy as a treatment for all adults with PNH. Beyond P&H.

I will now turn the call over to Adam Townsend to share more about our ongoing commercial launch of empathy for Pn itch Adam.

Thank you Cedric.

Cedric mentioned empathetic commercial launch is off to a strong start and I'm excited to share our initial results.

Value was approved on May the 14th so we are only in the very beginning stages with that said we are encouraged by the great progress we've made thus far and the positive feedback we received from the <unk> community.

We have four registrational programs for Empaveli with SOBI that are...

Our top launch priorities are outlined on this slide all of which are designed to ensure that every eligible patient who 1 central valley will have access to this important new medicine.

that are either ongoing or plan to start this year.

[inaudible]

Tazeen Ahmad, Annabel Samimy, Yigal Nochomovitz, Steven Seedhouse, Douglas Tsao, Eliana Merle, Madhu Kumar, Joseph Stringer, Derek Archila, Douglas Tsao, Eliana Merle, Jonathan Miller, Colleen Kusy, Graig Suvannavejh, Steven Sites, Tazeen Ahmed, Apellis Pharmaceuticals, Inc. Tazeen Ahmed, Apellis Pharmaceuticals, Inc. Tazeen Ahmed, Annabel Samimy, Yigal Nochomovitz, Steven Sites, Tazeen Ahmed, Apellis Pharmaceuticals,

Beginning with the approval we were thrilled with the NPV of the label, which included both patients currently being treated with the 5 inhibitors and those who are naive to treatment.

Recall that within the U S. There are approximately 1500 patients who are currently being treated with the 5 inhibitors soliris and Ulta merits and another 150 people diagnosed with <unk> every year.

I encourage you to watch the recording of our R&D day on our website to hear from several key opinion leaders on the admin need.

Supportive clinical data and potential for Paveli to be a transformative treatment for patients suffering from this devastating disease. The upcoming milestones for the remainder of the year are outlined on this slide, including three study initiations and enrollment completion of the Meridian.

Our initial launch focuses on P and H patients who have sub optimal control of their disease.

Meaning with the third of patients on <unk> inhibitors, with the highest unmet need those who require transfusions to address the willing hemoglobin levels.

of the Meridian Study in ALS.

Turning now to our ophthalmology.

We then plan to expand to the broader pnas community.

As previously mentioned, the top-line results from the Phase 3 DERBY and NOV studies of intravitreal plexus decoupling.

Many of whom are also suffering from signs and symptoms like anemia and severe fatigue.

Expected in September. As shown on this slide, Derby and Oaks are identical, multi-center, randomized, controlled studies that compare the efficacy and safety of monthly and every other month of Bexar-Tacoplan with sham treatment in 1,000 patients...

We have received positive feedback from various stakeholders and the quotes on the right side of the slide highlight the excitement for M per value from the <unk> community.

At the end of July over 75 physicians have signed up for our Rems program since launch in the U S and we have received more than 60 stock homes.

2,258 patients with GA. The primary endpoint of both studies

About studies

The full study design details can be seen on this slide.

Each of the it's not only early indicators of demands, but also that physicians have identified the end per valley can help better address that patient treatment needs.

As well as the safety profile of intervention by Exeter Copeland.

Including the rates of extubations and intraocular inflammation.

Additional data from the studies is expected to be presented,

We are finding that the C..5 inhibitor switch patients of the majority of new M. P value stocks with about 75% of switches coming from ultimately for us.

Although the primary endpoint will be analyzed at month 12, the studies will continue with treatment groups masked to month 24, and secondary functional endpoints will only be formally tested at month 24. Finally, I would like to briefly discuss our plans for Pexeta-Copeland in intermediate

We have also received newly diagnosed patient start forms which is very encouraging and reflects a broad label.

In terms of coverage breakdown, approximately 50% of central valley patients have commercial private insurance.

A disease that currently has no approved treatment.

95% have Medicaid and 25% have Medicare with all 3 per channel submitting Unapproved, Inc. Prescriptions.

Targeted Intermediate MD represents a significant opportunity to delay or prevent progression to advanced forms of MD.

We expect the payer coverage to remain split 50, 50 between private insurance and government programs for the foreseeable future.

and potentially prevent vision loss.

A post hoc analysis of the Phase 2 Philly study demonstrated that GA patients receiving petrotocoplan had a lower rate of progression from intermediate LDL to advanced LDL.

And lastly on the payer front.

The value and access team is engaging with high priority payers, including the top 20 payers of the cover approximately 85% of all.

Intermediate MD to GA in retina areas outside of the GA lesion.

These results support continued research, and we are currently seeking feedback from regulators on study design and regulatory pathways. Following a positive GA readout, we expect to initiate a pivotal study.

U S <unk> patients so far for payers have accelerated and provide the formulary reviews and 1 has already placed empathy and a positive formulary position.

Given our strong progress to date, we are on track to be on formulary with approximately 90% of the plans by the end of the year.

Thank you.

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

of the Financial Results, Kim. Thank you, Cedric.

For clothes.

Excited about the strong initial launch event of the value and our Super proud to bring this important new products for the PMA to Covid.

Since we issued a press release earlier today with the full financial results, I will just focus on the highlights for the second quarter of 2021. Net product revenue was $623,000 in the second quarter of 2021. This reflects the first six weeks of recorded product revenue for Empaveli between FDA approval on May 14th through June 30th, 2021. The third quarter of 2021 will include the first full quarter of Ampivelli net product revenue.

Some of the highlights I outlined from our launch activities are included on the left side of the slide.

We have done a lot of work to prepare the marketplace and our integrated team from the commercial field teams to medical Affairs is laser focused on successfully executing the launch.

On the right side of the slide you can see end of year of golf for engagement market access and patient experience.

Research and development expenses were $145.9 million in the second quarter of 2021 compared to $87.1 million for the same period in 2020. The increase in R&D expenses was primarily attributable to the $50 million payment associated with the BEAM collaboration, as well as medical and quality affairs expenses, personnel costs primarily due to the hiring of additional personnel, an increase in costs associated with ongoing and planned clinical trials, among others. R&D expenses were offset by contra R&D expenses related to the SOBI transaction.

This includes engaging all priority accounts of 85 per cent of priority physicians as well as maintaining high patient satisfaction scores for self infusion of empathetic.

While we are not planning to provide sales guidance in the near term we do plan to provide some launch metrics that help to illustrate our progress as we ramp up during this initial launch period.

We look forward to keeping you updated as our teams continue to work to bring this transformative treatment to the pnas community.

All of the palace team is very proud to have the responsibility to help <unk> patients with high unmet needs at the same time, our commercial organization is looking forward to the upcoming phase III results next month.

A Decrease in Contract Manufacturing Expenses and the Capitalization of Inventory Following FDA Approval of Empaveli. We expect R&D expenses to continue to increase as the number of patients in our trials increases and the number of trials we are conducting increases. General and administrative expenses were $49 million in the second quarter of 2021, compared to $28.4 million for the same period in 2020. The increase in general and administrative expenses was primarily attributable to general commercial preparation activities, employee-related costs, professional, and consulting fees, among others.

The U S European and international teams are busy preparing the commercial foundation globally for this potential blockbuster opportunity.

I will now turn the call over to the Doctor Federico groceries to review our clinical developments.

<unk>.

Thank you Adam.

I'll begin briefly with the phase III study in peonage.

In May we on the part of the Soviet We're thrilled to report positive top line result data from the study of Empire Bailey in treatment naive patients.

Per Bailey demonstrated statistical superiority of the co primary endpoints compared to standard of care, which did not include complement inhibitors at week 26.

And probably also achieved statistical superiority versus standard of care of several secondary endpoints, the meaningful to prescribers and patients those.

For the second quarter ended June 30, 2021, Apellis reported a net loss of $219.2 million, compared to a net loss of $118.6 million for the same period in 2020. As of June 30, 2021, Apellis had $599 million in cash, cash equivalents, and short-term marketable security. We remain well capitalized to execute on the ongoing launch of Empaveli and PNH and continue to advance our robust clinical development plan. Our cash runway is expected to fund operations into the second half of 2022, including the $50 million paid to BEAM as part of our recent partnership.

Those include improvement in hemoglobin levels.

Moving the need for transfusions.

The safety profile of them for value was consistent with previous guidance.

These results actually of the robust clinical profile of the battery and support the use of our target of seafood therapy.

That's the treatment for adults with <unk>.

The M P and age we have for where interest ratio of programs of that value with Saudi that are either ongoing or planned to start this year.

Our rare disease programs, our focus of complement driven diseases, where patients have few or no treatment options.

We believe that targeting see free has the potential to offer a differentiated product profile.

Providing comprehensive control of component.

I encourage you to watch the recording of the R&D day on our website to hear from several key opinion leaders on the.

In July, we entered into certain agreements to exchange 201.1 million of the convertible notes for approximately 6 million shares of common stock, allowing us to lower our interest rate expense and further de-lever the balance sheet. We began 2021 with approximately $520 million in aggregate principal amount of notes. And with the two exchanges conducted in January and July of this year, we now have $192.7 million remaining at June 30, 2021. I will now turn the call back over to Cedric for closing remarks. Cedric?

The net supportive clinical data and potential impact of any to be of transform IV treatment for patients suffering from this devastating disease.

GAAP coming milestones for the remainder of the year or all of <unk>.

On the Slide Inc.

Including 3 study initiations and enrollment completion of the Marianne study in a L. S.

Turning now to our ophthalmology franchise is prevalent dimension the.

Topline results from this phase III there'll be enough studies of each of each of Opex of the Copeland I expect that till September.

As shown on the slide that'd be the notes are identical multi center randomized controlled studies that confirm the efficacy and safety of monthly and every other month aspects of the carbon with channel treatment in 1258 patients with <unk>.

Thank you, Tim. We've made excellent progress so far this year and have several important milestones ahead, as shown on this slide. We look forward to continuing to advance our growing pipeline across rare diseases, ophthalmology, and neurology as part of our ambition to be a long-term global leader in cancer. With the top-line results of the Derby and Oakes studies expected next month, we would like to take this opportunity to recognize and thank the patients, investigators, caregivers, partners, employees, and investors who have helped advance us to this key milestone. We look forward to keeping you updated on our progress. And now, operator, please open the call for questions.

The primary end point of both studies is the reduction in the Gulf of GAA Neutrals of Mt.

Plus.

The full of the study design details can be seen of the slides.

In September we plan 2 per cent of the results of the primary endpoint for the monthly and every other month.

Well of the safety profile both of them for the so like I said, the copeland, including the rates of observations and in trial collecting from Asia.

And they said all the data from the studies.

It should be presented at medical meetings later this year.

Thank you. Ladies and gentlemen, as a reminder, to ask a question on the phone line, you will need to press the star and then the one key on your touchtone telephone. To withdraw your question, press the pound key. Please stand by while we compile the Q&A roster. And our first question comes from the line of Anupam Rama with J.P. Morgan. Your line is open.

Although the primary endpoint will be analyzed most of the studies will continue the trend in groups must July 24.

Secondary of functional endpoints will only be formally tested of plus 24.

Finally, I'd like to briefly discuss our plans for banks of the compound in intermediate and the.

As he sees the currently has no approved treatments.

Targeting and for me to an M. D represents a significant opportunity to delay or prevent progression to a bunch of forms of Andy from.

Hey, guys. Thanks so much for taking the question. I'll just ask a quick one on empivelli about the average day from prescription to first dose being, I think the slide said 12 days. Anecdotally,

From potentially prevent tissue loss.

The post hoc analysis of the phase II filly study demonstrated the <unk> patients receiving picks of the Copeland kind of a lower rate of progression from intermediate and the 2 G E.

Can you put that 12 days into context here in terms of when it's a little bit higher than 12 days and what's causing that, and when you might be able to get a patient on?

But in the areas outside of the bids the illusion compared to sham.

These results support the continued research and we are currently seeking feedback from regulators.

A patient is gone more quickly than, say, 12 days. Thanks so much.

Thank you, Anupam. Great to hear from you. I'm going to hand that over to Adam to answer.

The study the sign a regulatory pathway.

Following the positive data readout, we expect to initiate a pivotal study in the first half of next year.

Thanks for the question, Anupam. So, yes, we're actually very happy with the 12-day transition. It's very...

I will now turn the call chicken Sony value for a review of the financial results.

Yeah.

Thank you Sandy.

Very much in line with various other rare disease analysts. And we, we

Since we issued a press release earlier today with the full financial results I will just focus on the highlights for the second quarter of 2021 net.

various other rare disease analogs. We obviously get transitions quicker than 12 days and some transitions slightly longer than 12 days. The main thing is that we have to make sure that the patients have their vaccinations before they start, and that tends to drive that 12-day gap. That seems to be the consistent thing. We're obviously working hard with all of our P&H community and patients to make sure that they have everything that they need as they transition, but hopefully that answers your question, Anupam.

Net product revenue was 623000 in the second quarter of 2021. This reflects the first 6 weeks of recorded product revenue for them for belly between FDA approval on May 14th through June 32021.

The third quarter of 2021 will include the first full quarter of empathy Ali net product revenue reset.

The research and development expenses were $145.9 million in the second quarter of 2021 compared to $87.1 million for the same period in 2020 the.

The increase in R&D expense was primarily attributable to the $50 million payment associated with the beam collaboration as well as medical and the quality of fairs expenses personnel costs, primarily due to the hiring of additional personnel and increase in costs associated with ongoing and planned clinical trials among others.

Now, next question coming from the line-up, Umer Raffat with Evercore ISI. Your line is open.

Thanks so much for taking my question. Cedric, what percentage of the 38% wet AMD converters in your Phase II Philly technically had non-leaky CNV at baseline? And also, I remember one of the themes that stood out when the Phase II data came out was that folks that did

R&D expenses were offset by Contra R&D expense related to the sobey transaction.

The decrease in contract manufacturing expenses and the capitalization of the inventory following FDA approval of event the value.

We expect R&D expenses to continue to increase as the number of patients in our trials increases in the number of trials we are conducting increases.

Convert from folks that did convert have what AMD converts

General and administrative expenses were $49 million in the second quarter of 2020, 1 compared to $28.4 million for the same period in 2020.

Microparametric as well. What would you expect in wet AMD converters on microparametric?

Thank you very much.

Thank you so much, Umer. Well, first of all, let's start with the Philly trial and the non-leaky CNV. So, just a bit of background for the people on the line. In the Philly trial, when we did a retrospective analysis and looked at the patients that had... [inaudible] So in the retrospective analysis, what we did was on SDOCT, we looked at something called a double layer sign, which is a separation of the Brooks membrane from the RPE cell layer indicative of that membrane sitting there, but not being there.

The increase in general and administrative expenses was primarily attributable to general commercial preparation activities employee related costs.

First of all in consulting fees among others.

For the second quarter ended June 30th 2021 of Telus reported a net loss of $219.2 million compared to the net loss of $118.6 million for the same period in 2020.

As of June 32021 of Palace had $599 million of cash cash equivalents and short term marketable securities.

We remain well capitalized to execute on the ongoing launch of empathy early in the <unk> and continued to advance our robust clinical development plan.

Our cash runway is expected to fund operations into the second half of 2022 <unk>.

Now in the Philly trial, when doing that, it became clear that a large percentage of the patients that ended up showing exudates later during the trial had that double layer sign at baseline. And Umer, I will have to kind of look back for exactly the number, but I believe that it was around 75% of the patients that developed. So that's as far as it relates to the Philly trial, but a very interesting observation that we will, of course, further interrogate with the phase three research. And then as it relates to micropyramidry in those patients with choroidal neovascularization. So micropyramdry is an examination where you actually, with a laser, shine light outside of the foveas.

Including the $50 million paid the beam as part of our recent partnerships and.

In July we entered into certain agreements to exchange $201.1 million of the convertible notes for approximately 6 million shares of common stock, allowing us to lower our interest rate expense and further delever the balance sheet.

We began 2021 with approximately $520 million in aggregate principal amount of notes and the.

The 2 exchanges conducted in January and July of this year, we now have $192.7 million remaining at June 32021.

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

Thank you Tim we've made excellent progress so far this year and have several important milestones upcoming as shown on the slide.

We look forward to continuing to advance our of growing pipeline across rare disease, ophthalmology and urology as part of our ambition to be a long term global leader in complement.

and peripheral areas of the macula. And here, you know, again, in Philadelphia, we did not do microperimetry, so we don't really know whether there is or will be an impact of exudations on microperimetry. But microperimetry, in the first place, is a way of creating a functional correlation, so kind of associating the ability to see light in areas where geographic atrophy is growing. So, on the surface of itself, not really related to CNV, but again, in phase three, we'll have the first time to really look into it.

With the topline results of the Derby and Oaks studies expected next month, we would like to take this opportunity to recognize and thank the patients investigators caregivers partners employees and investors who have helped advance as to this key milestone.

Look forward to keeping you updated on our progress.

And now operator, please open the call for questions.

Thank you, ladies and gentlemen, as a reminder to ask the question on the phone line, you'll need the fastest start end of <unk> on you touched on the telephone to withdraw your question press the pound key please standby, while we compile the Q&A of Oscar.

And Cedric, maybe just to follow up then, if 75% of wet AMD converters likely had the double layer at baseline, does that basically mean, based on the analysis that's being used in Phase 3, your Phase 2 wet AMD conversion rate was mid-single digits? I just want to confirm I'm hearing that right. And also, can you just remind us all,

And our first question coming from the line of I know from Rama with Jpmorgan. Your line is open.

Hey, guys. Thanks, so much for taking the question I'll just ask a quick 1 on the valley on the average day from prescription to first dose being I think the slides at 12 days.

Anecdotally can you put that 12 days into context here in terms of when it's a little bit higher than 12 days, and what's causing that and when when you might be able to get a patient on more quickly than say 12 days. Thanks. So much.

Since this is the last call before your Phase 3 comes out, can you remind us all what interests us?

What interims have or have not happened, and what blinded and or any interim data have you guys seen?

Thank you and great to hear you I'm going to hand, it over to Adam for answer.

Thanks for the question out of time, so yes, we were actually very happy with the 12 days transition, it's very much in line with various other rare disease analogs.

Sure, so just with respect to the last question, we don't have any insights into the middle.

and that is something that you know will come when we're closer to each other.

We obviously get transitioned quicker than 12 days of some transition of slightly longer than 12 days.

Tazeen Ahmad, Annabel Samimy, Yigal Nochomovitz, Derek Archila, Douglas Tsao, Eliana Merle, Oh, the first part of the question, basically, is do you remember how the Phase II Philly had wet AMD conversions?

The main thing is we have to make sure. The the patients have the vaccinations before they stopped and that tends to drive that 12 day gap that seems to be the consistent thing. We're obviously working hard with all of our <unk> community and patients to make sure that they have everything that they need as they transition.

rate of high teen. And if we apply the double layer definition that's being used in phase three,

Using Phase 3, considering you said 75% of those high teens already had double layer at baseline, would that mean that the new wet AMD conversions were only mid-single digits in Phase 2? Is that right?

Hopefully that answers your question out of them.

Thanks, so much for taking the question.

And our next question coming from the lineup of mobile.

<unk> with Evercore ISI your line is open.

Hi, guys. Thanks, so much for taking my question Cedric what percentage of the 38 per cent wet AMD converters in your phase II filly technically had non leaky CMV at baseline and also what I remember 1 of the things that stood out 1 of the phase 2 day that came out was that folks that did.

Now, so that kind of comes down to the definition, right? So again, the difference between choroidal neovascularization and exudations, where you see leakage in the retina. With a double layer sign, you don't really know whether there is a neovascular membrane. All you know is that there is a separation that is suspected of being a choroidal neovascular complex. The only way, you know, technically, to measure ACNV is to use something called OCT angiography, which wasn't done in phase two and which, even in phase three, is only done on a subset of patients.

From a debt to book that did convert have wet AMD conversion the BCBS scores than the worsening.

But my understanding is in 1 of your phase III, you do have micro parametric as well.

Would you expect in wet AMD converters on Microchemistry. Thank you very much.

So again, you know, hard by now to really know the answer to that, Umer, but again, important, I think, to point out is that with SDOCT, it is very easy to detect small exudates in the retina that may not be there at the beginning at screening because at screening, you use kind of the gold standard for wet AMD, which is fluorescent angiography. And on fluorescent angiography, there may be a neovascular complex present that does not leak on that particular exam but that later on may have some small exudates that you can detect on SDOCT.

Thank you so much.

Well first of all of that start with the the city of trial and the non <unk>. So.

Just a bit of a background for the people on the line and the.

For the trial when we did of retrospective analysis and looked at the patients that have <unk>.

So called C N G.

What we were really looking at force ex judicious, so essentially leakage from neovascular membrane sitting in the rest of them, where they're not supposed to be the question. We ask ourselves is where does the east neovascular membrane is there at the beginning of the study, but we're not picked up at the time of screening and that can happen because with the technology.

Available sometimes this is missed so in the retrospective analysis of what we did is on the OTT, we looked at something called a double layer of saying, which is the separation of the Brooks membrane from the RPE cell theyre indicative of the membrane sitting there, but not being the key now in the in the city of trial.

And one reference point that I would like to give you that is very interesting is that in the 26 cases that we had of exudates reported by the investigators in Philly, 17 patients at the time of that discovered exudate received a fluorescent angiogram, and 10 only of those 17 patients at that point in time had confirmed wet AMD based on fluorescent angiography. So think about this; of the 17 tested that had exudates on SDOCT, only 10 could be confirmed using fluorescent angiography. This is in line with what we've reported before, our belief that there was some investigator bias in phase two that we have corrected for in phase three. Thank you very much. Thank you.

When doing that it became clear that a large percentage of the patients that ended up showing extra days later during the trial had that deliver their sign at baseline.

I will have to kind of look back for exactly the number but I believe that it was around 75 per cent of the patients that develop that so that's as far as it relates to the city trial, but a very interesting observation that we will of course.

Further interrogate with the phase III results and then as it relates to macro perimetry in those patients with the coronal neovascular reservations for the macro Perimetry isn't the examination of where you're actually with the laser shine the light outside of the school of yes, so in peripheral areas of the macula.

Now, next question coming from the line-up, Madhu Kumar with Goldman Sachs. Your line is open.

And here you know again in Philly, we did not do micro for inventory. So we don't really know whether there is or will be an impact of explanations on macro perimetry, but the macro <unk> in the first phase is the way of creating a functional correlation so kind of the associating the ability to see light in areas where.

Oh, hey, thanks for taking our questions. I'll step back from Umer's questions and ask him more when he's in.

Douglas Goldstein, CFP®, is the director of Profile Investment Services and the host.

You mentioned investigator bias, but I'm not sure with differences in baseline patient distribution how much of it...

Geographic atrophy is growing so.

Yeah, thank you so much, Madhu. That is a very interesting question, right? So, was this imbalance that we saw in phase two real or not? You know, personally, I think it was. I just think it was kind of vastly exaggerated based on two important parameters, one which you referred to, the investigator bias. The second, that we enrolled a lot of patients who, at baseline, had wet AMD in the contralateral eye while having GA in the study eye.

On the surface of itself not really related to C. N V. But again in the phase III will have the first time to really look into the them.

And Cedric maybe just to follow up then if 75% of wet AMD converters likely had the double layer of baseline does that basically mean that based on the analysis, that's being used in phase III. Your phase II wet AMD conversion rate was mid single digits I just want to confirm I'm hearing that right.

And also can.

Can you just remind us all.

And to put some numbers on that, in the Philly trial, 38% of the subjects enrolled came from that background phenotype, whereas the normal distribution is closer to 20%. So, I think in our phase three, we should all expect that number to be closer to 20% rather than close to 40%, which was the case in Philly.

Since this is the last call, but for your phase III comes out can you remind us of what interim have or have not happened and what blended or an or of any interim data have you guys seen.

Sure. So so just with respect to the last question, we don't have any insights in the middle.

That is something that will come in closer to the deadline.

Then as it relates to the.

Then as it relates to why this is happening and should we again see an imbalance, it's a very interesting and fascinating observation and, importantly, one that was not a safety concern. Again, these exudates were very small in nature, detectable as DOCT and, as mentioned earlier, often not detectable on fluorescent angiography. And then the question is, if there are, for example, these pre-existing neovascular complexes and they become more leaky, why is that?

Breaking up sort of at the first part of your question could you repeat that please.

Oh, the first part of the question basically is remember how the phase II theory had wet AMD conversion rate of high teens and if we apply the double their definition, that's being used in phase III. Considering you said 75 per cent of those high teens already had double layer at baseline would that mean that the <unk>.

New wet AMD conversions on on it was the only mid single digits from phase 2 is that right.

No.

That's kind of comes down to the definition of Red. So again, the difference between choroidal Neovascular reservation and expeditions, where you see leakage in the retina.

And we have always postulated that it could be that you induce a wound healing response which can be associated with an increase in vagus secretion which would then lead to a more leaky state. So it is not at all implausible that an increase in exudation, which in this case, again, was not a safety concern for us, may actually be associated with a repair response that is induced by complement control.

With the double layer, saying you don't really know whether there is the neovascular membrane. All of you noticed that there was the separation that is suspected of being for choroidal Neovascular complex the only way.

Technically to measure of <unk> is to use something called the OCC and geography, which wasn't done in phase 2 of them, which even in the phase III is only the on a subset of patients so again.

The hardest by now to really know what the answer to that and member of boats.

Okay, great. And then a question for Tim: how should we think about SG&A and R&D expense kind of through 2021 and through 2022? And kind of how conditioned is that around what happens at Darby Oaks and kind of the SOBE collaborations on phase three trials?

Again, the importance I think the pointed out is that with the OTT. It is.

It's very easy to detect smoked exited in the retina that you made you know the.

It may not be there at the beginning at screening because at screening you use kind of the gold standard for wet AMD, which is fluorescence and geography and also the restaurant and geography, there may be of Neovascular complex prison, there's not the leak on that particular exam, but that later on the may have some small exits that you can.

on on phase three trials for emphysema. Yeah, thanks a lot Madhu. So, as you know, we don't give any specific guidance with respect to those line items. But one thing to keep in mind is that our cash of $599 million is sufficient to get us into the second half of 2022, and that does take into account a positive readout in Derby and Oakes.

The effect on us the OCD and 1 reference point that I would like to give you the.

The interesting is that on the 26 cases that we had of extra days reported by the investigators in Sydney 17 patients at the time of the discovered the exited received for the Russians Angiogram and 10 only of those 17 patients at that point in time.

Bearing in mind that we do plan to scale up for commercialization ourselves globally, but for G&A expenses for the year, you should also expect probably a bit of a ramp up, even towards the end of this year, a little bit in our commercial spending in conjunction with the launch of EmpaValley and P&H. And then, related to R&D, you can see there's actually a pretty good breakdown of the R&D expenses in our 10-Q.

Confirmed with N. The based on for the rest of the geographies. So think about this.

Of the 17 tested that had the extra days honest the OCD on the 10 could be concerns using for the rest of the geography.

In line with what we've reported before our belief that there was some investigator bias in the phase 2 of that we have corrected for in the phase III.

Thank you very much.

Thank you.

Yeah.

And our next question coming from the line up until Kumar with Goldman Sachs. Your line is open.

Oh, Hey, thanks for taking our questions I'll step back from the risk question can I ask a more basic mechanistic question about about CMV Darby Oaks.

We go into quite a bit of detail in the table below. And I think some of the ongoing ones are pretty easy to project with sort of a mild increase as you look at the increase in the number of clinical trials, the pivotal trials that we have ongoing, in addition to our Derby Noakes trial, which again, we'll roll into an extension study, so that will continue on for three years after Derby Noakes. You can kind of get a pretty decent sense of how things will grow over the next year. Okay, great. Thanks for taking my call.

Do you think complement blockade of contribute to the emergence of CMV events as compared to things like you maintained investigator bias.

The baseline patient distributions how much of it ultimately is just when you sufficiently blockade complementing the retina you get choroidal Neovascular edition had some biological frequency.

Yeah. Thank you so much of a medicine that has a very interesting question red so.

The next question comes from the line of Yigal Nochomovitz with Citi: the line is open.

What is this imbalance that we saw in the phase 2 real or not.

Hi, this is Carly on behalf of Yigal. Thanks for taking our questions. Our first question

Personally I think it was I just think of it what's the kind of versus the exaggerated based.

Questions related to Iverick's announcement that the...

Based on 2 important parameters, 1 which you referred to the.

Annabelle Samimy, Yigal Nochomovitz, Steven Seedhouse, Douglas Tsao, Eliana Merle, Madhu Kumar, Justin Kim, Laura Chico, Adam Townsend, Timothy Sullivan, John Miller, Akash Tsao, Eliana Merle, Madhu Kumar, Steven Sites, Tazeen Ahmed, Apellis Pharmaceuticals, Inc.

The investigator of bias the second that we enrolled a lot of patients who at baseline had within the in the control of that rely while having GAA and the study I.

Put some numbers on that in the filly trial of 38% of the subjects enrolled came from the background phenotype, whereas the normal distribution is closer to 20 per cent. So I think in our phase III, we should only expect that number indeed to be closer to 20% rather than the close to 40 of which was the case in Chile.

Thank you so much for that question. The short answer to that question is no.

So, you know, again, not, not, you know, not.

From our perspective, I can tell you that after the Philly trial, we submitted our protocol with the proposed statistical analysis plan at an end-of-phase-2 meeting, and we had full agreement with the FDA on that. So there was no need for a SPA since what we proposed was the standard that the FDA had, among others, also used, for example, in the Cro-Magn spectra trials with Roche.

Then as it relates to why is this happening and you know should we again see an imbalance.

It's just it's a very interesting and fascinating observation and importantly, 1 that was not a safety concern again.

This extra day, it's we're very small in nature detectable.

And as mentioned earlier, often not the technical answer the rest of in geography and then the question is is there are for example, these preexisting neovascular complexes and they become more leaky why is that the case.

Okay, great. Thank you. And then we were just wondering if there's anything more you could say.

We have always postulated that it could be that you induce of wound healing response, which can be associated with an increase in velocity accretion, which would then lead to more the key state. So it is you know net is not.

Thank you for your time.

So, as we have discussed before and as we talked about at length during our R&D day in June, we've been tracking very, very closely over the past two years or year and a half, I should say, what the impact was of COVID on the missed injections in the trial. And as we indicated at the R&D day, for the primary endpoint analysis of the monthly injections, we feel very good about, you know, a minimum impact of COVID on that analysis.

Not at all implausible that.

The increase in expedition, which in this case again it was the other safety concerns for us maybe actually associated with the repair responds that doesn't use of that comes from the control.

Okay, Great and then a question for Tim how should we think about SG&A and R&D expense and the kind of through 2021 and through 2022 and kind of how condition is that around what happens in Derby Oaks and kind of the still be collaborations on the pod.

Phase III trials around the value.

And that is the analysis that will give us our approval. For every other month injections, where, you know, one missed injection could be an interval of as long as four months in a trial that is one year long, there, of course, the risk is higher. But as we pointed out at our R&D day, every other month is something that we use to interpret and understand, you know, what the PK-PD relationship of the drug is. But for approval, we need to do it monthly.

Yeah. Thanks, a lot of my do so as you as you know we don't give any specific guidance too.

With respect to those line items.

But 1 thing to keep in mind is that our cash of $599 million is sufficient to get us into the second half of 2022 and that does consider of positive readout in Derby and Oaks.

Bearing in mind that we do plan to scale up for commercialization of ourselves globally.

But for Etsy for G&A expenses for the year, you should also expect probably a bit of of ramp up even even towards the end of this year of little bit in <unk>.

In our commercial spending in conjunction with the launch event the Valeant <unk>.

And there, we feel very confident that the impact of COVID is under control. Thank you so much. You're welcome. The next question comes from the line of Phil Nadeau with Colin Hill.

And then related to R&D.

You can see there's actually a pretty good breakout of the R&D expenses in our in our 10-Q, we go into quite a bit of detail in the table and I think some of the ongoing ones that are pretty easy to project with sort of a mild increase as you look in the at the increase in the sort of.

Hi. Hi, Tim. This is Ernie Rodriguez speaking for Phil.

Thank you for taking our call. You mentioned some of the positive feedback you received on the launch and your goals for the year, and we were curious if you had identified any barriers that could preclude you from achieving those goals and expectations for the launch. And then, in GA, assuming positive results and FDA approval, what subgroup within the GA patient population do you expect physicians will first approach and treat with Pavelia?

The number of clinical trials of the pivotal trials that were for.

We have ongoing in addition to our tariff, which again will roll into a into an extension study. So that will continue on for 3 years. After Durbin book. So you can do.

You can kind of think it of a pretty decent sense of how things look for over the next over the next year or 2.

Okay, great. Thanks for taking my.

Thanks Manav.

And our next question coming from the line of the call Nicole <unk> with Citi. Your line is open.

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

And do you think this will change depending on the level of reduction that you achieve in the... September results. Thank you so much. I'll let Adam answer the first part of your question, and then I will take the second.

The first question is related to either Eric the announcement that the FDA had requested change in the primary endpoint analysis. Further study we were just wondering if it's your expectation that the FDA will ask very similar slope analysis, great Derby and Oaks. In addition to the rate of change in Appalachia region area.

Yeah, thanks for the question. Yeah, we're very happy with our progress today with the launch. Everything is going well.

Everything is going well, and as you can tell by the REMS, the number of physicians going through REMS, and the number of start forms, we're on a very strong launch trajectory. We're very happy and believe that our Q421 goals are very achievable. We're working incredibly well with the payers to make sure that we can get every patient who needs access. And those are ongoing discussions, and as you remember, sometimes they take between three to six months to allow us to get access to their formularies, and we're continuing to have some success there. So that's something that we'll continue to work on, but everything's pointing in the right direction for the Empire Valley launch, so we're very happy to help the P&H community.

Yeah. Thank you so much for the question the short answer to that question is no. So a.

You know again not nuts.

Not not the speak for a very good of course of the special protocol assessment is often or typically requested from the EBITDA when it is unclear.

And of what type of analysis.

With the agreed to and that is often inspired by a request from the sponsor that maybe for you. This unusual in the context of all of that analysis. So my suspicion is that that is the process that as Eric went through.

From our perspective I can tell you that after the filly trial, we submitted our protocol with the proposed statistical analysis plan and at the end of Phase 2 of meeting and we had for the agreement with the FDA on that so there was no need for a spot since what we proposed was the standard is that the MTA. That's among others also used for <unk>.

Example, in the <unk> victory trials with Roche tenancy.

Okay, great. Thank you and then we were just wondering if there's anything more you could say at this point on how the range of missed injections and great of dropouts in Derby and Oaks compare to what was observed in Philly and I think in the past you've mentioned plans to conduct some additional analyses that could potentially account for the impact of that.

And then, Ernesto, for the second part of your question, so I'm happy you asked that, because it's something that we, of course, have done a lot of research on as well, which is, what is the patient population that physicians will be interested in? How do we see this product being implemented? And there are two, I think, important takeaways to communicate. The first one is that we should have a good safety profile for our drug, right? I mean, should the exudations be very well under control?

The net.

Covid and we're just wondering if those would be included in the top line a lot of share in September as well. Thank you.

Sure no problem so.

As we have it's weighted before and as we talked about at length during our R&D day in June.

And, you know, if this is a product with a clinically meaningful effect on the growth of atrophy, then, you know, this is, in our opinion, going to be a drug product that a retinal specialist will prescribe to the majority, if not all, of their patients with GA, because that is how medicine works, right? So, I think that is something that is probably not fully appreciated yet, how we think this will fit into the flow of the retinal specialist, like anti-VEGFs found their way into the flow of the treatment of wet AMD.

We've been tracking very very closely over the past 2 years or you're in the health I should say what the impact was of Covid on the missed injections in the trial and as we indicated at the R&D day for the primary endpoint analysis of the monthly injections, we feel very good about.

Minimum impact of Covid on that analysis and that is the analysis that will give us our approval for every other month injections, where 1 Mr injection could be an interval of as long as for months and the trial that is 1 year along the.

And then as it relates to, basically, all patients, and then the question, okay, at which point in time would you intervene in the disease? And that's very interesting, right? Because intuitively, you may say, well. Even when you speak with a retinal specialist, you know, I'm going to start with my worst patients, you know, blind in one eye, advanced geographic atrophy in the contralateral eye, and while intuitively that makes sense, logically it does not, because again, assuming that this drug is as safe as we think and hope it will be, you want to treat geographic atrophy as early as possible, right?

There of course of the risk is higher but as we pointed out at our R&D day.

Every other month is something that we used to interpret and understand what's the PK PD PD relationship of the drug is but for approval we need the monthly and there we feel very confident that the impact of Covid is under control.

Okay. Thank you so much.

You're welcome.

And our next question coming from the line of Bill of <unk> with Cowen Your line is open.

Hi, Hi, Tim This is there any rodriguez for Phil. Thank you for taking my call.

You mentioned some of the positive feedback you have received from the launch on your growth for the year. We were curious if you have identified any barriers that would.

Preclude you from achieving those goals and expectations for the launch.

And then in GAA.

Assuming positive results on the FDA approval.

The group within the <unk> patient population do you expect physicians will first approach in treating with.

At the first sign of GA, when you start losing photoreceptor cells, you know, I fully expect physicians and patients to make commitments to saving as many photoreceptor cells as they can to, as much as possible, prolong the path to blindness. So I think something that, should this drug find its way into the market, that I believe will happen is that patients will be treated early and that, you know, all patients, barring exceptions, should be interested in being treated.

<unk> do you think.

The change depending on the level of reduction of that USG from day 1 there.

The September results. Thank you.

Thank you so much I'll, let Adam answer to the first part of your question and then I will take the second.

Yes. Thanks.

The question, Yeah, we're very happy with our progress to date with the launch.

Everything is going well and as you can tell by the.

The Rams the number of physicians going through brands and the number of stops homes. We're on a very strong launch trajectory.

Thank you. Hi, good afternoon. Thanks for taking our questions.

We are very happy and believe the our Q4 'twenty 1 goals are very achievable.

Thank you so much for taking our questions. So one on GA, I guess following up on that, that really, you know, all GA patients could be

The working incredibly well with the payers to make sure that we can get every patient who needs access access and those are ongoing discussions as you remember sometimes they take between 3 to 6 months to allow us to get access to their formularies and we're continuing to have some success. There. So that's something that we'll continue to work on.

Amenable to this treatment, I guess what sort of bottlenecks would you expect, assuming obviously positive data and approval, what sort of bottlenecks would you expect, and would there be any sort of capacity restrictions or limitations for the intravitreal injection?

But everything is pointing in the right direction for the MTR.

Of the launch so we're very happy to help the nature of community.

Yeah, so I mean, I'll give you the medical angle, and then I will hand it over to Adam to talk a little bit more about practical implementations, because we've done work on that as well, of course. But medically, I think, again, you know, if the safety profile of

And then Ed of Mr. For your second part of your question. So I'm happy you asked that because it's something that we of course.

You don't have done a lot of research on the as well.

Well. This is what is the patient population that physicians will be interested in how do we see this product being implemented and there are 2 I think important takeaways to communicate the first 1 is that should we have a good safety profile for our drug right I mean should the ex additions would be very well under control and.

The profile of this drug is good at that point in time.

If this is a product with a clinically meaningful effect on the growth of atrophy.

You know, it will be important to educate physicians. It would be the first treatment for a disease that is currently untreatable. It will be important to find patients in the generalist ophthalmology practice that may not be referred to a retinal doctor right now because there's no treatment available, and even earlier in the optometrist's office. But I think at that point in time, really, the main focus should be on building awareness and the fact that there is now...

And then this is in our opinion going to be of direct product that of retinal specialists book prescribed through the majority if not all of their patients with <unk> because of that is how medicine works right. So.

I think that is something that is probably not fully appreciate it yet how we think this will fit into the flow of the retinal specialist like end of it just found their way into the flow of the treatment of wet AMD and then as it relates to so basically all patients and then the question, Okay at which point in time would you intervene in the dish.

And that's very interesting read because intuitively you may say well.

And Adam, I don't know if you want to add something to it or not.

Even when you speak with the retinal specialist.

I'm going to start with my worst patients.

<unk> advanced <unk> geographic atrophy of the Contra lateral eye and while the intuitively that makes sense logically it does not because of again assuming that this drug is as safe as we think and hope it will be you want to treat geographic atrophy as early as possible right at the first sign of the G. When you start losing photo receptor.

Yeah, just to add on the capacity piece of the question, we did some research with injecting ophthalmologists and retina specialists. And, you know, they've had many years of experience doing intravitreal injections and increasing patient numbers. So we believe with a new edition and a new approved product in GA, they'll have the capability of expanding capacity based on our discussions and our market research with them. You know, they know that they currently have a bolus of GA patients within their clinics and at their sites for which there are no current treatments. So we don't expect capacity to be a rate-limiting step as we launch this drug.

Yourselves ex.

For the expect physicians and patients to make the commitment to saving as many sort of reset yourselves as they can to as much as possible prolonged the path to blindness. So I think something that should the drug find its way into the market that I believe will happen is that patients will be treated early and the old patients.

Exceptions.

It should be interested in being treated with this product.

Great, that's helpful. Thank you. And then, on intermediate AMD, could you talk about any initial thoughts you have on the potentially pivotal study design in terms of size or endpoints? Yeah, we're not commenting yet.

Yeah.

Thank you very helpful.

Thank you our next question coming from the line of Colin Christie with Baird. Your line is open.

Okay.

Hi, good afternoon, thanks for taking our questions. So 1 of the G. A I guess following up on that.

Oh Gee of patients could be.

Yeah, we're not commenting yet on what the design will be, but I think, again, the notion of doing a trial in intermediate AMD goes hand-in-hand with what I mentioned earlier about wanting to treat patients as early as possible, and the fact that in a post-hoc analysis of Philly, we actually discovered that in the region outside of the atrophic area of the retina, in other words, retina that you can still see on your ultrafluorescent image, but retina that is, of course, affected, and is, if you want to call it that, a kind of a surrogate for intermediate AMD, and where we saw post-hoc a significant slowdown on the conversion to full geographic atrophy. So, no design details yet, but a patient population that we are particularly interested in exploring.

Amenable to the Street, Matt I guess, what sort of bottlenecks would you expect.

Assuming all the same positive data and approval what sort of bottlenecks would you expect.

Would there be any sort of capacity restrictions or limitations for the intramuscular injection.

Yeah, So I mean, I'll give the medical angle and then I will handle it the Adam to talk a little bit more kind of about the practical implementations because we've done it where it comes out as well of course, but the medically I think again you know.

If the safety profile of this drug is good.

The point in time I think.

It will be important to educate physicians it would be the first treatment for a disease that is currently untreatable, but will be important to find patients in the generalist ophthalmology practice that may not be refer to retinal doctor right now because there's no treatment available and even earlier in the optometrists office, but I think at that point in the.

And really the main focus should be on building awareness and the fact that there is now.

Our next question comes from the line of Tazeen Ahmed with Bank of America. Your line is open.

Or will then at that point, hopefully be a treatment available and the other.

Hi, good afternoon. Thanks for taking my questions.

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

Yeah, just to add on the capacity piece of the question. We did some research with injecting ophthalmologists and retina specialists.

Quickly on the GA studies, assuming that they're both positive, should we expect that you would be able to apply for...

They've had many years of getting experience of doing introvert trio of injections and increasing patient numbers. So we believe with the new edition and the new approved product in G. H.

For more information, please visit www.cdc.gov.

And then, as we talk about the commercial landscape, could you maybe give us your view on...

At www.tazeenahmed.com.

That will have the capability of expanding capacity based on our discussions and our market research with them.

Differentiated from those

Thank you so much, Tazeen. I'm going to hand the approval question...

They know that they currently have the bolus of Gi patients within the clinics and that the sites of which there are no current treatments. So we don't expect capacity to be a rate limiting step as we launch this drug.

The approval question to Federico, and then Adam will take the commercial question.

Thank you, Cedric, and thank you for the question.

We are looking forward to the results.

Great. That's helpful. Thank you and then 1 follow up on intermediate AMD.

The readout of the studies comes in September, and our teams are ready to jump into the submissions and be able to submit as soon as possible. We're not guiding on timing of the submissions, but we're fully prepared to tackle the analysis not only of the primary endpoints that will be reported soon but the full analysis required for the submission and do that as soon as possible.

Could you talk about any initial thoughts you have on the potentially pivotal study design in terms of size of endpoint.

Yeah, we're not commenting yet on what the design will be but I think the again the notion of doing a trial in the intermediate and the goes hand in hand, with what I mentioned earlier about wanting to treat patients as early as possible and the fact that in the post hoc analysis of Philly, we actually discovered.

2013 University of Georgia College of Agricultural and Environmental Sciences UGA Extension Office

That in the region outside of the atrophic area of the retina in other words, the retina that you can still see on your ultra for the restaurant image. The addressing the other is of course affected and as if she wants to close out the kind of of surrogates for intermediate and the and where do we sell post hoc the significance slowed.

Thank you, and then, well, I was just, Adam is texting me here, it's not a commercial question, it's a question about data. Look, I think at the end of the day, you know, we will see what happens with the competition. It is our conviction.

Down on the conversion to full geographic atrophy. So no design details yet, but the patient population that we are particularly interested in extent of it.

The reason that the retina suffers from geographic atrophy is driven by the accumulation of C3 products on the retina, which is not properly being removed. And it's not being properly removed because the same cellular mechanisms compete for removal of C3 as those that work on the visual side. We know from our PNH studies that C5 has no effect on the accumulation of C3, so it would be a surprise to us should a C5 inhibitor be successful, especially in light of the fact that anti-C5 has failed twice already, both when administered systemically as well as intravitrally.

Great. Thanks, so much.

Thank you so much Quinn.

Our next question coming from the line of Casino Aman with Bank of America. Your line is open.

Hi, good afternoon, Thanks for taking my question.

Quickly on the Ta studies, assuming that they are both positive should we expect that you would be able to apply for approval of this calendar year and what would be the rate limiting capital left in your application of assuming positive data and then.

We talk about the commercial landscape can you maybe give us your view about.

C1 is, on the other hand, an interesting target, but there, too, you don't have the kind of broad control of complement that we believe you need, and as you do with pexitaclopan by also covering the lectin pathway and the alternative pathway. So I think, you know, the proof is in the pudding, but it's also important to note that, you know, the only competitor close to us, of course, is the Iverix program, and we look forward to evaluating that when it becomes available.

The potential for the 5 as well as the C..1 Q complement inhibitor.

Turning the market and how.

Newer products would be differentiate it from the thanks.

Thank you so much does the and I'm gonna, hence the approval question.

For the Rico, and then Adam will take the commercial question.

Thank you Cedric and thank you for the question.

Looking for for the the results of.

Of the readout of the studies come in September and our teams are ready to jump into each of the submissions in.

Be able to submit as soon as possible, we're not guiding on the timing of the submissions, but we're fully prepared to tackle the the analysis not only of the.

That when it becomes available. [inaudible] Yeah, I think I hope that answers your question.

Of the primary endpoints would be reported.

2 of them, but if all the analyses with flow for the submission under the that as soon as part of it.

Okay.

Thank you for the <unk> and then well I was just had the mistakes thing to hear some other commercial question.

Yeah, that's really helpful, Cedric. I mean, if you were to talk about one thing that could be differentiated in your program versus theirs, would you pivot?

Western on data.

Look I think at the end of the day.

We will see what happens with the competition. It is our conviction that the the mechanism by which the retina suffers in geographic atrophy is driven by the accumulation of <unk> III products on the rest of that which is not appropriately being removed and it is not being appropriately removed because of the same cellular mechanisms.

Transcripts provided by Transcription Outsourcing, LLC.

I think, you know, again... What we have done and what I like about our program is that it has been a program where we deliberately chose to be highly consistent over time. In other words, we did the Philadelphia trial in 2015 really to mimic what Genentech Roche, at the time, was doing with their Lampalizima program. We knew that they had interactions with the FDA, what the expectations were in terms of endpoints, and the phase two clinical trial was really designed to anticipate a phase three trial with minimum change.

Compete for removal of C. III as those that work on the visual cycle, we know from our P&A studies. The seaside has no effect on the accumulation of C..3 so it would be sort of fresh to us should of C..5 inhibitor that'd be successful, especially in light of the effect that the NTIC fab has failed twice already.

Both when administered systemically as well as intra day trading.

1 is on the other hand, the interesting interesting.

Interesting targets, but they are 2 you don't have kind of the broad control of complement that we believe you need.

For all of you that have studied Philly and Derby and Oakes, they're pretty much a carbon copy of each other with very, very tiny changes. And if anything, just more quality and robustness in the Derby and Oakes trial. So, you know, the AVEX program without, you know, any criticism is. [inaudible] Okay, thank you. The next question is coming.

And as you do with fixes that could someday also covering the lectin pathway and the alternative pathway. So I think.

The proof is in the pudding, but it's also important to note that.

The only competitor of course of course is a very ex program and we look forward to evaluating the when it becomes available.

Yeah, I think I hope that answers your question.

Our next question comes from the line of Steve Seedhouse with Raymond James. Your line is open. Yes, hi, this is...

Yeah, that's really helpful. Patrick.

And I think if you were to talk about 1 thing that.

<unk> could be differentiated in your program for us as Darren would you pick up more of the efficacy.

Around 15 to 20 patients on therapy, or is that revenue mostly for inventory build? And then, in terms of geographic distribution, have you seen any trends, you know, a bolus of orders coming from a certain geographic area in the U.S., or is that too early to tell?

Well I think.

Again.

Yeah.

But what we have done and what I like about our program is that it has been the program, where we deliberately chose to be highly consistent overtime.

In other words we.

The difficulty of trailing 2015 really to mimic what genentech Roche at the time was doing with their non bodies in that program. We knew that they had the interactions with the FDA what the expectations for in terms of endpoints in the phase 2 clinical trial was really designed to anticipate the phase III trial with minimum change right. So.

Thank you so much. Well, I will hand that over to Adam to answer.

Thank you very much for the questions. We're not going to guide on product revenue for the foreseeable future.

Thank you for watching.

Transcripts provided by Transcription Outsourcing, LLC. We've had over 75 physicians sign up for REMS and over 60 start forms, which should give you a very strong indication of the demand. So more to come there.

For all of you that have studied failure in Derby and Oaks theyre pretty much of carbon copy from of each other with very very tiny changes and if anything just more quality and robustness in the Derby and Oaks trial. So you know other ex program without any criticism.

Kind of a much more.

And on your second part of the question, we've seen success all across the US. So we've seen initial forms and REM submissions, as well as actual patients come from each of the large main centers that you would expect within the P&H community and also from smaller centers, geographically dispersed across the US. So we're having an impact across the whole country. Hopefully, that answers your question. Yes, thank you. And then maybe a question on GA commercialization for therapy.

Variable the right I mean, there was the part 1 part 2 of the phase III the.

Then they went through the span of the phase III, it's the dish.

From the approach we wish them success.

But I think for us standing of the course.

You know really building on the initial hypothesis has been the case.

Okay. Thank you.

Thank you.

Yeah.

And our next question coming from the line of Steve <unk> with Raymond Raymond James Your line is open.

Yes, Hi, this is Tim we're running up on for Steve for the House.

So the they have a quick question on teenage commercial giving you a point $6 million in revenue is it fair to assume you have around 15 to 20 patients on therapy or is that revenue mostly for inventory build and then in <unk>.

So in terms of, you know, in terms of where you potentially need to be versus where you are now, I mean, you're just, are you just starting out versus, you know, what percent of your sales force do you still need to hire? You're probably in the early stages, but just to give us an idea. Yeah, I'll take that one too. So we have obviously built an infrastructure which we can carry across for certain.

Terms of geographic distributions have you seen any trend of bolus of orders coming from of certain geographic area in the U S or is that too early to tell.

Thank you so much I will hand, it over to Adam sensor.

Yes, thank you very much for the questions. So.

We're not going to guide on product revenue for the foreseeable future.

The the initial 6 million is of great sign of of how empathetic and elevate the standard of care. So.

We've obviously built an infrastructure which we can carry across for certain pieces of commercialization for geographic attributes. We've also created the leadership teams commercially in medical affairs in the U.S., at our international head office in Zug, Switzerland, and in Germany and Australia.

We had over 75 physicians sign up for Rems and Opus 60 start forms which is the should give you a very strong sign of the demand.

So more to come there and on your second part of the question.

So we have the core infrastructure. As soon as we see data, we'll rapidly start to expand on that infrastructure through Salesforce and medical affairs and everything else that you would expect. So we're in a good place. We're looking forward to seeing the data. And we've identified candidates out in the market who are willing to join Apellis and excited to join Apellis post-positive GA data.

<unk> seen success all across the U S. So we've seen start forms and rent submissions as well as actual patients come from each of the the large main centers that you would expect within the <unk> community and also from smaller centers geographically dispersed across the U S.

We're having an impact across the whole country.

That answers your question.

Yes, Yes think of and then maybe a question on G. A commercialization for the third and US. So in terms of you know in terms of where you potentially need to be of versus where you are now I mean, you. Just are you just starting out versus what percent of our sales force do you still need to hire.

Thank you. Our next question comes from the line of Alethea Young with Canthar. Your line is open. Hey, guys, thanks.

Hey guys, Thanks for taking my questions. Two, just one, can you talk a little bit about, you know, how COVID has kind of impacted things and how you think going forward it may with kind of, I guess, some of this Delta variant, Lambda variant, take every variant you have going? And then maybe the second question is just from a scenario basis, like, you know, how do you think about having levels of, you know, on the safety front, whether it be infections or endoptosis or, you know, whether it be exudative events?

Really in early stages, but just to give us an idea.

Yeah, I'll take that 1.2 of its Adam.

We have obviously built in the infrastructure, which we can carry across the set and pieces of commercialization for geographic atrophy.

We've also created the leadership team's commercially in medical affairs in the U S.

International head offices in Switzerland, and in Germany, and in Australia. So we have the core infrastructure.

And as we see data we are rapidly start to expand on that infrastructure through sales force the medical affairs and everything else that you would expect so we're in a good place we're looking for it to see the data and we have identified candidates out in the market who are willing to join our pallets and excited to join the palace post positive <unk> data.

How do you think about, like, if they were the same in this trial readout, what does that mean commercially versus if, you know, they were potentially slightly lower? You know, kind of just maybe lay out some of your scenarios on that. Thanks.

Okay.

Thank you very much.

Thank you our next question coming from the line of Alicia Young with Cantor. Your line is open.

Thank you so much, Alicia. And I assume that your first question regarding COVID also applies http://www.pnh.org.au

Hey, guys. Thanks for taking my question.

Just 1 can you talk a little bit about how COVID-19 has kind of impacted things of how you think going forward. It may what kind of I guess some of the Delta Varian Lam the Varian and take every variant you have going and then maybe the second question is just from a scenario of it sounds like you know how do you think about kind of having levels of kind of on the safety front, whether it be the infection.

Thanks, Alethea. Yes, the joys of launching a product during a global pandemic. So we've actually seen in-person live interactions increase. Prior to our approval, less than 10% of our interactions were live, and now roughly 40% of all of our interactions are live in person. We also continue to use virtual technologies to engage with physicians. My bias tells me that the Delta variant could slow this down a little bit, the in-person engagements, but we're going to closely monitor all of the regional COVID-19 restrictions, and we'll make sure that we follow those with HCPs in their offices.

At the end of auto or whether it be the <unk>.

The day of events like how do you think about like if they were the same in this trial readout. What do you think that means commercially versus the potentially were slightly lower kind of just maybe lay out some of your scenarios on that thanks.

Thank you so much of the center I assume that your first question regarding to Covid also applies to the study correct of the <unk> I was actually out of Montana shockingly.

Well I will I will hand, it over to its out of them to give them some ratio size of them because that's the country well actually kind of yeah. Thanks, the lithia, yes, the joys of launching a product during a global pandemic. So we've actually seen.

Impasse in light of interactions increase so prior to our appraisal day were lower than 10% of our interactions were live in now roughly 40% of all of our interactions of live in person. We also continue to use virtual technologies to engage with physicians now.

But we think we have the right skillset, and obviously, we're prepared to do a virtual launch, and we're having some great success with that as well. So between the balance of in-person and virtual, we think we're in a really good spot to continue the great progress on the PNH.

My bias tells me that the Delta Varian could slow this down a little bit the in person engagements, but we.

We're going to closely monitor all of the regional COVID-19 restrictions and we'll make sure that we're following those with the HCP isn't the offices.

Thank you, Adam. And then, Alitia, as it relates to your second question related to safety, I want to start off by saying that in the Philadelphia trial, the safety profile was such that we did not have to make any changes in Phase III. So, first of all, as it relates to the exudations, and as alluded to earlier, the types of exudations we had were never a safety concern. And by, you know, correcting for that investigator bias and the fact that the demographic will be adjusted, we expect in the Phase III clinical trial the exudation rates to be lower than they were in Phase II.

But we think we have the right skill set and obviously, we prepared to do a virtual launch and we're having some great success with that as well so between the balance of in person.

Virtual we think we're in a really good spot to continue the great progress on the P&I trench.

Thank you Adam and then Alicia as it relates to your second question related to safety. So.

I want to start off by saying that in the filly trial. The safety profile was such that we did not have to make any changes in the phase III. So first of all as it relates to the expeditions and as alluded to earlier the types of expeditions. We had were never a safety concern and by correcting for that investigator of bias in the.

That the demographic will be adjusted we expect in the phase III clinical trial, the extradition rates to be lower than they were in the phase II, but again.

But, again, the investigators in the Phase III trial, who know, of course, those data very well, found the Phase II exudation rates to be acceptable for the enrollment in the Phase III trial, which, if it hadn't been for COVID, would probably have been faster than any Phase III trial done before. Then, as it relates to the cases of infectious endophthalmitis, we had two cases in the Philly trial that were on a total of approximately 1,400 intravitreal injections.

The investigators in the phase III trials with no of course those dates are very well found for the phase II <unk> rates to be acceptable for the enrollment in the phase III trial, which if it hadn't been for Covid, which is probably even faster than any phase III trials done before.

Then as it relates to the cases of infection endophthalmitis. So we had 2 cases in the filly trial.

That was on a total of approximately 1400 intra articular injections that's right.

That rate of infectious endophthalmitis is in line with what you find in Phase II clinical trials with anti-VEGF or with steroids, for example. So this is an entry pathogen, and this is a complication that is inherent to the procedure itself. There is absolutely absolutely no indication that that rate would be higher because of some circumstance than it is under normal circumstances. And typically, what you see is that in a Phase II clinical trial, you have a certain rate, in Phase III it gets better, and then commercially, it further improves as physicians get used to the procedure. Look, it is our expectation that the safety profile of Teixeira Co-Plan will be safe and that we will be able to focus on efficacy against the background of Philly.

Infectious endophthalmitis.

In line with what you've signed in the phase II clinical trials with anti VEGF or with steroids for example, so.

This is an entry pathogen and this is the complication that is inherent to the procedure itself. There is right now absolutely no indication that that rate would be higher because of some circumstance then of this under normal circumstances and typically what you see is that in the phase II clinical trial of a certain rate and phase III gets better and then <unk>.

Inversely it further improves as physicians get used to the procedure. So Luca.

It is our expectation.

The safety profile of fixes the coupon will be safe.

And that we will be able to focus on efficacy.

Against the background of feeling.

Our next question, coming from the line of Eileen Merle with UBS, your line is open. Hey guys, thanks so much for taking the question.

Great. Thank you.

Thank you so much.

Our next question coming from the line of Ellie Merle with UBS. Your line is open.

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

Just first, in terms of exudations in GA, and I guess maybe what we might know from the natural history around how exudations might impact GA growth or just, you know, any associations we've seen historically either in your data or in the natural history. And then second question, just in terms of the commercial outlook for GA exus, I guess I'd just curious, you know, how you're thinking about potential commercial preparations exus for GA and just any differences in terms of, you know, diagnosis rate or, you know, any particular maybe emphasis on endpoints versus, you know, the U.S. or anything different there in terms of the commercial strategy versus the U.S. thing.

Just first in terms of Activations and Gi and I guess, maybe what we might know him from the Nashville has for Ya around like how activations of my impact T a growth or cash.

Of the association of please stand as.

Historically either of your data or in the natural history.

Then second question just in terms of the commercial outlook for Ta ex.

You also I guess just curious how are you.

Youre thinking about potential commercial preparations ex you asked for G&A and just any differences in terms of you know diagnosis rate or.

Any particular, maybe appetite for him.

And clients versus the you asked or anything different there in terms of the commercial strategy versus the theory.

Thank you so much, Ali. Well, so as it relates to exudations, and we don't talk a lot about this because we're really not talking about anecdotal numbers, but if you look back at the Philly trial and you look at those patients that developed exudations for whom we have the follow-up data for geographic atrophy, there's quite a remarkable slowdown in GA, you know, beyond what we measured, for example, in the primary end.

Thank you so much of the well so as it relates to expeditions.

We don't talk a lot about this because we're really not talking about the anecdotal numbers, but if you look back at the filly trial.

And you look at those patients that developed expeditions for whom we have the follow up data for geographic atrophy.

It's quite a remarkable slowdown N G and beyond what the metrics for example in the primary endpoint, but these are of such small numbers that will have to find out in the phase III clinical trial, if they materialize.

But these are such small numbers that we'll have to find out in a phase three clinical trial if they materialize or not. So again, that's something to look forward to, but it's definitely an intriguing observation and goes hand-in-hand with kind of that hypothesis that maybe these exudates go hand-in-hand with a wound healing repair process. And then, as it relates to the ex-US deployments, which is a wonderful undertaking.

Or not.

So again, that's something to look forward to.

But it's definitely an intriguing observation that goes hand in hand with kind of of the hypothesis that maybe this extra day to go hand in hand with a.

The root healing of repair process.

And then as it relates to the ex U S deployments.

Which is the.

A wonderful undertaking that Adam is taking on. I'll hand it over to him.

Wonderful undertaking that Adam is taking on I'll hand, it over to him.

Yeah, thank you. Thanks for the question. So, quickly, obviously, in GA, there are a million patients in the U.S. and about 2.6 million in Europe and 5 million globally. So, you can see that there is a totally global opportunity for geographic atrophy for Apellis, and we're preparing to execute against that global opportunity. So we have built out an infrastructure in Zug in Switzerland of very experienced commercial and medical affairs leaders, and we have already started to build out our region in Germany based in Munich and also our Australian affiliates. So we're ready to make sure that we can meet the needs of GA physicians and GA patients very quickly outside the US. It's an exciting opportunity, and we're doing all that we can to be ready for it.

Yeah. Thank you. Thanks for the question. So quickly obviously in the GI there's a million patients in the U S and about $2.6 million in Europe and $5 million globally. So you can see that there is a totally global opportunity for geographic atrophy or of palace, and we're preparing to execute against the.

Global opportunity. So we have built out and the infrastructure and so again, Switzerland.

Very experienced commercial and medical affairs leaders and we have already started to build out of region in Germany.

The Munich, and also Australia and the affiliate so we are ready to make sure that we can meet the needs of Gi physicians and patients very quickly ex U S. It's an ex.

Citing opportunity and we're doing all that we can be ready for that now I will hand, the regulatory side to Cedric and fed day on what's likely to be expected in Europe that was the third part of your question.

Now, I will hand the regulatory side to Cedric and Feday on what's likely to be expected in Europe. That was the third part of your question. Thank you so much. So in Europe, as it relates to the regulatory process, like in the US, the growth of geographic atrophy is the primary endpoint that we look for. The general feedback from the European regulators has been that they would like to see a directional change in the functional endpoints in alignment with essentially the loss of photoreceptor cells as measured through the anatomical endpoint. And that is data that we will gather at the 24 month time point and add to our findings.

Thank you so much so so in Europe as it relates to the regulatory process.

Like in the U S. The growth of geographic atrophy as the primary endpoint.

We look for.

The general feedback from the European regulators has been that we would like to see a directional change in the functional endpoints in alignment with the.

Essentially the loss of photoreceptor cells as measured through the anatomical endpoints, but not with the expectation of showing that statistically and other data that we will get there at the 24 month time point and adds to our filings in Europe.

Did that answer your question, Annie? Yes, really helpful. Thank you.

So the answer your question.

That's really helpful. Thank you.

Thank you so much.

Our next question comes from the line of Justin Kim with Oppenheimer. Your line is open.

Yes.

The next question coming from the line of Justin Kim with Oppenheimer. Your line is open.

Hi, good afternoon. Thanks for taking our questions. Just a couple at this point. With the Intermediate AMD study dependent on Derby and Oakes' success, can you just discuss how important regulatory buy-in on iRORA to cRORA progression is to designing and powering a potentially pivotal study in Intermediate AMD, and sort of what aspects of the Derby and Oakes study will.

Hi, good afternoon, thanks for taking our question.

Just had a couple of at this point.

I know you had covered that a little bit before but with the intermediate AMD study depending on therapy of notes of success can you just discuss how important regulatory buying an IRA to see where all of our progression of designing empowering our potentially pivotal study in intermediate AMD and sort of what aspects of the Derby and Oaks study will.

And for them that design empowering as well.

Tazeen Ahmad, Annabel Samimy, Yigal Nochomovitz, Derek Archila, Douglas Tsao, Eliana Merle

Thank you so much and great to hear you I'm going to hand that over to fit the eco. Thank.

Thank you Cedric and thank you for dosing for the question.

Well.

Thank you so much, Justin. It's great to hear from you.

It's really important and we are discussing.

For discussing with the.

Our regulators on the imports on the of the change from IRA.

I'm going to hand that over to Federico. Thank you, Cedric, and thank you, Justin, for the question. Well, you know, it's really important, and we are, as you know, discussing with the regulators the importance of the change from...

So they are buying and an agreement on the definition under the seeds of.

The the endpoint to look for the studies as the inspector of the important.

And we are having ongoing discussions with them. So we'll know more.

In the next few months.

...

[inaudible] Okay, great. And maybe just one on Empaveli, appreciating that the label is already quite broad, just wondering if there are any plans at this point to

Okay, Great and maybe just 1 on empathy Ali.

Appreciating that the label of already quite broad just wondering if there are any plans at this point too.

https://www.youtube.com

And formally incorporate the Prince study data into the label and any sort of timeframe for that as well as the potential scientific publication.

Thank you so much, Justin. So, that has not been decided yet. To your point, the label is very broad. And, you know, it will be something we'll follow up on. Great. Thanks so much for taking the questions. I look forward to the results.

Thank you so of assistance so the.

That has not been decided yet to your point of the label is very broad.

Great. Thanks so much for taking the questions. I look forward to the results next month.

And the.

It will be something we will follow up on.

Okay, great. Thanks, so much for you of taking the questions and look forward to the net results next month.

Thank you so much.

Our next question comes from the line of Mathieu Luchini with BMO Capital Markets. Your line is open.

And our next question coming from the line of Matthew Luchini with BMO capital markets. Your line is now open.

Hi, thanks, everyone. This is Nick Lenard on for Matthew.

Yes.

Alright. Thanks, everyone. This is Nick 1 other on for Matthew I, just 1 quick follow up for us.

Just one quick follow-up for us. It seems like the P&H launch is going pretty well, as you said, and I believe you said the majority of patients are C5 switches, with 75% of that being from ultramarines. Is that something we can expect going forward, or is that going to kind of change over time, and any incremental color on that would be really great? Thank you.

The G&A smarts is doing pretty well as you said and I believe you said the majority of patients are still 5 switches <unk> 75 per cent of that being from off of mirrors is that something we can expect going forward or is that kind of kind of changed here at the time of any incremental color on that would be really great. Thanks.

Thank you so much. I'm going to hand that one over to Adam as well. So, yep, thanks for the question. You're correct. We're seeing switch being the majority.

Thank you so much I'm going to hand that 1 over to Adam as well.

So yes. Thanks for the question you are correct.

Sure thing of switch being the majority of all of empathy.

So yeah, thanks for the question; you're correct. We're seeing a switch in the majority of our Empire Valley starts, and 75% of those switches are coming from Altamiris. As a quick reminder, one-third of the 1,500 C5 treated patients we believe is our target population at the beginning of launch, and that third has the highest unmet need. They have a low and falling hemoglobin on their current C5 treatment, and they're continually being transfused.

In parallel the starts and the 75% of those switches are coming from from Altamira as a quick reminder.

The 1 third of the 1500 <unk> 5 treated patients we believe is <unk>.

Target population of the beginning of approach of not that has the highest unmet need they have of low and pulling the hemoglobin on net currency 5 treatment and that continually being transfused. So that is the patient population that we're seeing.

So that is the patient population that we're seeing, and so C5 switches will be the bolus of our start moving forward. I expect there to be a balance between Altamiris and Soliris, with Altamiris likely being the majority as we move forward. And then we'll continue to progress through the unmet need in the 1,500 C5 treated patients.

And so the <unk> switches will be the bolus of all starts moving forward.

I expect.

Got to be balanced between Altamira sensor the rest with the ultimate likely being the majority as we move forward and then we will continue to progress through the unmet need in the 1500 <unk> treated patients.

Great. Thank you.

Our next question, coming from the line of Joseph Stringer with Needham Nealon, is open.

Okay.

Thank you so much.

And our next question coming from the lineup Joseph Stringer with Needham Your line is open.

Hi, everyone. Thanks for taking our questions. A quick one on HIPAA Valley in terms of pros and cons. I recognize that it's early on in the launch, but just giving your commentary around commercial versus government payer mix and how that Thank you.

Hi, everyone. Thanks for taking our questions.

1 on the belly in terms of gross to net recognized that its early on in the launch.

But just given your commentary around commercial versus government, the payor mix and how that's.

<unk> going to continue in the future.

Thank you so much. Adam, you want to take this one? Yes, absolutely. Thanks, Joey. You're right.

Can you get us an early sense of the gross to net early on in.

You know, what what you sort of see that kind of.

The steady state on an annual basis. Thank you.

Thank you so much Adam you want to take this 1.

It's a bit too premature for us to comment on growth-to-net at this point in the launch, but we are in line with other growth-to-net rare disease models. And to your point, I expect our growth-to-net to tick down as we progress into the later stages of the launch as we transition patients to EmpaVeli. So, early days in the launch window, but I'm still thrilled with how we're progressing with the EmpaVeli launch.

Yes, absolutely if I can share you're right. It's the it's a bit too premature for us to comment on gross to net at this point in the launch we are in line with the other across net rare disease models and to your point.

Based on gross to net to tick down as we progress into the later stages of the launch as we transition patients to 'twenty per value. So early days.

In the launch window.

Hum still thrilled with how we're progressing with the temporary launch.

Great, thanks for answering our questions.

Great. Thanks for taking our questions.

Thank you so much. Next question.

Thank you some of it.

Thanks Christopher.

Our next question comes from the line of Elinor Priess with RAAD Capital and Yolana Soltysin.

Question coming from the line of I don't know of transplant Roth capital. Your line is open.

Yes, hi. Maybe just a housekeeping question from Tim. The cost of the research collaboration from BEAM Therapeutics, would that be an ongoing line item separately, Tim? Thank you, Elmer.

Yes, Hi, maybe just for housekeeping question from Tim.

The cost of the research collaboration from beam Therapeutics would that be an ongoing the line items separately Tim.

Thank you and all of them are ultimately know that that is unlikely to be it'll be baked into research and development expense, we broke that out showing of the upfront because it had the large impact on the R&D expense. This quarter as you know we're obligated to pay another $25 million a year from now and other.

Ultimately, no, that is unlikely to be; it'll be baked into research and development expense. We broke that out, showing the upfront because it had a large impact on the R&D expense this quarter. As you know, we're obligated to pay another $25 million a year from now. And ultimately, after that, the ongoing expense will be fairly de minimis, as this is a research collaboration initially, so it'll be baked into R

For the.

After that the ongoing expense would be fairly de minimis. As this is the research collaborations initially so it will be baked into R&D.

Thank you. Thank you, Tim. And maybe some clarification from Adam.

Kind of get them and maybe a clarification from Adam Adam you mentioned that.

Adam, you mentioned that, and this is related to the lead time of 12 days to get patients on the drug, that vaccination...

And this is related to the lead time of 12 days.

Net patients on drug.

That vaccination is ease of component there.

Transcribed by https://otter.ai

Did you mean the COVID vaccination? Because I thought that most of these patients are switch patients, so they've been previously vaccinated.

The human Covid vaccination, because I thought that the.

Most of these patients are switch patients. So they had been previously vaccinated.

Yeah.

Yeah, it's, no, it's actually vaccinations that are required by label two weeks before the start of Empaveli to get on to Empaveli. So it's following the label guidance; it is not COVID vaccine related. So even though these people were previously vaccinated because they received Altamiris,

It's no it's actually vaccination of instead of required by label.

2 weeks before the start of the potbelly to get all of them to unfairly. So it's following the labor guidance.

It is not COVID-19 vaccine related.

So even though these people were previously vaccinated because they received out of my risk they would have to receive in other vaccine.

Altamiris, they would have to receive another vaccine.

Yep, they're following the label guidelines on vaccination two weeks prior to the first dose of vaccine. Thank you so much.

Yeah the Apollo.

Following the label Guy the guidelines from the vaccination 2 weeks prior to the first types of empathy.

Okay. Okay. Thank you so much right now.

Thank you so much, Elomer. And

Thank you so much of the mirror.

And I think that was the last question.

And I think that was the last question. In closing, thank you all for joining us on our second quarter conference call. We look forward to presenting top-line results from our Derby and Oakes studies in September and keeping you updated on our commercial and pipeline 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.

In closing thank you all for joining us on our second quarter Conference call. We look forward to presenting top line results from our Derby and Oaks studies in September and keeping you updated on our commercial and pipeline progress in the months of heads.

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 the rest of the week.

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

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