Q4 2024 Apellis Pharmaceuticals Inc Earnings Call

Okay.

Unknown Executive: Good morning, ladies and gentlemen. Thank you for standing by, and welcome to the Apellis Pharmaceuticals' fourth quarter and full year 2024 earnings conference call. At this time, all participants are in a listen-only mode.

Speaker Change: Good morning, ladies and gentlemen, thank you for standing by and welcome to the appellate Pharmaceuticals fourth quarter and full year 2024 earnings conference call. At this time all participants are in a listen only mode. After the speaker's presentation. There will be a question and answer session to ask a question. During the session you will need to press star one one.

Unknown Executive: After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you will need to press star 11 on your telephone. You will then hear an automated message advising that your hand is raised. To withdraw your question, please press star 11 again. Please be advised that today's conference is being recorded.

Speaker Change: On your telephone you will then hear an automated message advising that your hand is raised to withdraw. Your question. Please press star. One again, please be advised that today's conference is being recorded I would now like to turn the call over to Meredith Kaya Senior Vice President Investor Relations and strategic Finance. Please go ahead.

Meredith Kaya: I would now like to turn the call over to Meredith Kaya, Senior Vice President, Investor Relations and Strategic Finance. Please go ahead. Good morning, and thank you for joining us to discuss Apellis' fourth quarter and full year 2024 financial results.

Meredith Kaya: Good morning, and thank you for joining us.

Speaker Change: Fourth quarter full year 2024 financial results with me on the call our co founder and Chief Executive Officer, Dr. Cedric Francois Executive Vice President of commercial David Anderson, Chief Medical officers Dr. Carolyn.

Meredith Kaya: With me on the call are co-founder and chief executive officer Dr. Cedric Francois, executive vice president of commercial David Acheson, chief medical officer Dr. Caroline Baumal, and chief financial officer Tim Sullivan. Before we begin, let me point out that we will be making forward-looking statements that are based on our current expectations and beliefs. These statements are subject to certain risks and uncertainties, and actual results may differ materially. I encourage you to consult the risk factors discussed in our SEC filings for additional detail.

Meredith Kaya: Chief Financial Officer, Jim Sullivan.

Meredith Kaya: Before we begin let me point out that we will be making forward looking statements that are based on our current expectations and beliefs.

Meredith Kaya: These statements are subject to certain risks and uncertainties and actual results may differ materially I encourage you to consult the risk factors discussed in our SEC filings for additional detail now I'll turn the call over to Cedric.

Cedric Francois: Now I'll turn the call over to Cedric. Thank you, Meredith, and thank you all for joining us this morning. As we close out another year, I would like to recognize the progress our team has made. We achieved important milestones in 2024, strengthening our business while navigating some headwinds along the way. Saifovre generated over 120% year-over-year U.S. net revenue growth. We presented positive phase 3 valine data with MPAVINI and C3G and ICF-BGN. We advanced our earlier stage pipeline. fortified our financial position.

Cedric Francois: Thank you.

Cedric Francois: And thank you all for joining us this morning.

We closed out another year I would like to recognize the progress our team has made.

Cedric Francois: Achieved important milestones in 2020 for strengthening our business well navigating some headwinds along the way.

Cedric Francois: So I feel free generated over 120% year over year U S net revenue growth.

Cedric Francois: We presented positive phase III data.

Cedric Francois: T T G I C and D.

Cedric Francois: We advanced our earlier stage pipeline.

Cedric Francois: Before decide our financial position.

Cedric Francois: Looking ahead, our strategy is focused on three key pillars. First. transform the treatment of geographic atrophy with safe Second, to maximize Mbaveri's impact in rare diseases. And third, to advance our innovative pipeline, leveraging our expertise in complement science. Starting with pillar number 1, Sypho-free is the market-leading treatment for geographic atrophy in the U.S. More than 510,000 injections administered through the... Recent regulatory developments within the competitive landscape confirm our view that safe ovary is the leading treatment. Syphovre's unmatched prescribing label, which includes increasing effect over time and flexible dosing, will enable us to further strengthen Syphovre's market leadership over time.

Cedric Francois: Looking ahead, our strategy is focused on three key pillars first to transform the treatment of geographic atrophy, which said feel free.

Cedric Francois: Second.

Cedric Francois: To maximize <unk>.

Cedric Francois: In rare diseases.

Cedric Francois: Third.

Cedric Francois: Our innovation pipeline leveraging our expertise in complement sites.

Cedric Francois: Starting with pillar number one state footprint and market leading treatment for geographic atrophy in the U S.

Cedric Francois: 510000 injections administered through December.

Cedric Francois: Recent regulatory developments within the competitive landscape.

Cedric Francois: Are you, let's say for <unk> as the leading treatment for it yet.

Cedric Francois: So it will feature unmatched prescribing level, which includes increasing effects overtime and flexible dosing will enable us to further strengthen central market theater shifts over time.

Cedric Francois: Saifovri has generated nearly $900 million in sales in less than two years, making this one of the most successful launches in recent history. With only two approved treatment options available and no new competitors on the horizon, we are in a strong position.

Cedric Francois: Central venous generated nearly $900 million in sales and less than two years, making this one of the most successful launches in recent history.

Cedric Francois: With only two approved treatment options available and no new competitors on the horizon.

Cedric Francois: We are in a strong position.

Cedric Francois: Our two key priorities heading into the rest of 2025 are to secure CIFORI's leadership and to grow the overall GA. We are still in the early phases of growth and estimate that only half of diagnosed GA patients are seen by an eye care professional. All of those, less than 10% are... Building a new market takes time, but we have the right product, strategy, and team.

Cedric Francois: Our two key priorities heading into the rest of 2025.

Cedric Francois: I hope to secure set for his leadership and.

Cedric Francois: And to grow the overall market.

Cedric Francois: We are still in the early phases of growth estimate that only helps okay.

Speaker Change: Patients are seen by an eye care professional.

Speaker Change: Its dose less than 10% are receiving treatment.

Speaker Change: Building, a new market. It takes time, but we have the right product strategy team to execute.

Cedric Francois: The U.S. is our primary commercial focus for Cyfo Green, but we will continue to explore select international markets. We were pleased to receive approval from the Therapeutics Goods Administration in Australia last month, and our regulatory review in Switzerland is ongoing.

Speaker Change: The U S. As our primary commercial focus for sexual REIT, but we will continue to explore select international markets.

Speaker Change: We were pleased to receive approval from the Therapeutics goods administration in Australia last month.

Speaker Change: It's a regulatory review in Switzerland is ongoing.

Cedric Francois: As we continue to focus our efforts on the CIFOR relaunch, we are also working to develop the next generation do this, we are combining safe APL 3007 RSIRM. This approach is designed to comprehensively block complement activity in the retina, as well as the choroids, through local and systemic C3 inhibition. plan to initiate a Phase II trial in the second quarter.

Speaker Change: As we continue to focus our efforts on the Safeway relaunch. We are also working to develop the next generation treatment for each game.

Speaker Change: To do this.

Speaker Change: We are combining sexual freedom and APL zero-zero, seven alright R&D.

Speaker Change: This approach is designed to comprehensively blocks complement activity at the risk of that as well as the choroid.

Speaker Change: Local and systemic C three inhibition.

Speaker Change: We plan to initiate a phase II trial in the second quarter.

Cedric Francois: Shifting gears then to our second pillar. Maximizing the Impact of Empathy and Rarity. And Baveri continues to elevate the standard of care in PMA.

Speaker Change: Shifting gears then to our second pillar.

Speaker Change: <unk> amazing the impact of empathy and rare diseases.

Speaker Change: But any continues to elevate the standard of care <unk>.

Cedric Francois: We also look forward to becoming a leader in nephrology, starting with the anticipated launch of MPAVETI in C3G and primary. We recently filed a supplemental NDA for El Paveri based on the positive phase 3 value . These results hit the tri-sector with unprecedented reduction. Inuria, significant clearance of C3 deposits, and stabilization of EGFR. more compelling was that these results were consistent regardless of disease type, transplant status or age. If approved, we expect to launch in the second half of 2025. Our partner SOBE recently received validation of its application. And then one step closer to making this life-changing treatment available to patients.

Speaker Change: We also look forward to becoming a leader in nephrology, starting with the anticipated launch of <unk> and primary ICL P. J.

Speaker Change: We recently filed a supplemental NDA for it Eddie.

Speaker Change: Based on the positive phase III.

Speaker Change: Data <unk>.

Speaker Change: These results.

Speaker Change: Sector with unprecedented reductions in proteinuria significant clearance of <unk> deposits.

Speaker Change: The utilization of Egfr.

Speaker Change: Even more compelling was that these results were consistent regardless of disease type transplant status or age.

Speaker Change: If approved we expect to launch in the second half of 2020 sites.

Speaker Change: Our partner so be it.

Speaker Change: We recently received validation of its application.

Speaker Change: One step closer to making this life changing treatment available to patients in the EU.

Cedric Francois: In the second half of 2025, we are also planning to initiate Phase III trials for empyvedia in two new nephrology indications. Focal segmental glomerulosclerosis and delayed graft.

Speaker Change: In the second half of 2025, we are also planning to initiate phase III trials for <unk> and two new nephrology indications focal segmental glomerular sclerosis.

Speaker Change: Delayed graft function.

Cedric Francois: Lastly, our third pillar, our innovative pipeline. We are excited to be advancing the first ever gene editing approach, targeting the neonatal FC gamma receptor with our partner, Beam Therapeutics. We look forward to sharing more about this program and our broader emerging pipeline with all of you soon. We are excited about the future of that. We have two potential blockbuster products, which are Fulvry and Dabaveni, a robust development pipeline of clinical and preclinical programs, and a clear path to profit.

Speaker Change: Lastly, our third pillar.

Speaker Change: This pipeline we.

Speaker Change: We are excited to be advancing the first ever gene editing approach targeting the neonatal FC gamma receptor with our partner <unk> Therapeutics.

Speaker Change: Look forward to sharing more about this program and our broader emerging pipeline with all of you soon.

Speaker Change: We are excited about the future of that business, we have two potential blockbuster products, let's say February and IBD.

Speaker Change: A robust development pipeline of clinical and preclinical programs.

Speaker Change: A clear path to profitability.

David Acheson: I will now turn the call over to David Acheson, our new Executive Vice President of Government. I'm sure many of you are familiar with David from previous earnings calls and investor events, and we are thrilled that he is now leading our commercial organization. Thank you, Cedric, and good morning, everyone.

David Anderson: I will now turn the call over to David.

Speaker Change: Our new executive Vice President of commercial.

Speaker Change: I'm sure. Many of you are familiar with David from previous earnings calls and Investor events and we are.

Speaker Change: But he is now leading our commercial organization is it.

Cedric Francois: Thank you Cedric and good morning, everyone let.

David Acheson: Let me start with SIFOBRI. With over 510,000 injections administered and nearly $900 million in net sales, SIFOBRI has had a remarkable launch. Our focus going forward is to both strengthen our leadership position and grow the overall market. The recent regulatory update from our competitor provides us more confidence than ever in the strength of Cyphobry's differentiated profile.

Cedric Francois: Let me start with that footprint with over 510000 injections administered nearly $900 million in net sales sorry February has had a remarkable launch our focus going forward is to both strengthen our leadership position and grow the overall market.

Cedric Francois: The recent regulatory update from our competitor provides us more confidence than ever in the strength of <unk> differentiated profile.

David Acheson: Three things now are very clear. Syphobry has consistently demonstrated robust and increase in effects over time. Syphobry is the only GA product approved for as few as six doses per year. And syphobry is the only product in a preferred position with many payers. In the fourth quarter, CyfoBri maintained its market leadership with approximately 94,000 doses delivered to physician offices, including 89,000 commercial doses and 4,600 samples. Total market share remained stable at over 60%, and new patient share trended positively, ending the year approaching 50%. As of December, there are more than 2,300 sites of care that have ordered SIFO.

Cedric Francois: Three things that now are very clear.

Cedric Francois: <unk> has consistently demonstrated robust and increase in effects over time.

Cedric Francois: <unk> is the only gea product approved first view of six doses per year.

Cedric Francois: <unk> is the only product in a preferred position with many payors.

Cedric Francois: In the fourth quarter <unk> maintained its market leadership with approximately 94000 doses deliberate to physician offices, including 89000 commercial doses and 4600 samples total.

Cedric Francois: Total market share remained stable at over 60% and new patient share trended positively ending the year approaching 50%.

Cedric Francois: As of December there are more than 2300 sites of care that are ordered sight February.

David Acheson: Syphobry's fundamentals remain strong. In the first two months of 2025, we are seeing continued growth in the number of syphobry injections administered, which is the true measurement of demand.

Cedric Francois: So I have ovaries fundamentals remained strong in the first two months of 2025, we are seeing continued growth in the number of site footprint injections administered which is the true measurement of demand.

David Acheson: There are, however, a few temporary factors expected to affect orders of commercial vials and net revenue in the first. First, the overall GA market growth in the quarter has been tempered due to typical Q1 dynamics like Medicare re-verifications and winter storms affecting distribution and patient visits. And second, we have also seen a spike in sample usage over the past two months. We believe retina specialists are using more samples because of a reported funding gap at non-for-profit co-pay assistant organizations. We estimate there could be 5,000 or more incremental samples used in this quarter as compared to the average quarterly sample volume in 2020.

Cedric Francois: There are however, a few temporary factors expected to affect orders of commercial vials and net revenue in the first quarter.

Cedric Francois: First the overall market growth in the quarter has been tempered due to typical Q1 dynamics like Medicare re verifications and winter storms affecting distribution and patient visits.

Cedric Francois: And second we have also seen a spike in sample usage over the past two months, we believe retina specialists are using more samples because of that reported funding gap at non for profit co pay assistant organizations, we estimate there could be 5000 or more incremental samples using this quarter as compared to the average quarterly sample volume.

Cedric Francois: In 2024.

David Acheson: The momentum we are seeing in injection demand to date sets the stage for continued growth in 2025 and beyond.

Cedric Francois: The momentum we are seeing an injection demand to date sets the stage for continued growth in 2025 and beyond.

David Acheson: Maximizing the GA opportunity will require a long-term and strategic approach. We need to make sure each patient has access to a retina specialist who can treat them. We need higher utilization from those physicians who are already treating patients with syphogory, as well as adoption by retina specialists who may have initially been hesitant to utilize GA. And we must continue to further strengthen our formulary positions, being the only GA products with preferred status provides a significant competitive advantage. We're executing across key initiatives to achieve these goals, including broadening our reach to the eye care community, amplifying real-world data through key forums, educating payers on cyfovir's differentiated value proposition, and connecting with patients through our DTC campaign.

Cedric Francois: Maximizing the <unk> opportunity will require a long term and strategic approach.

Cedric Francois: We need to make sure each patient has access to our retina specialists, who can treat them with even higher utilization from those physicians, who are already treating patients with <unk> as well as adoption by retina specialists, who may have initially been hesitant to utilize Gi treatments.

Cedric Francois: And we must continue to further strengthen our formulary positions being the all HCA products with preferred status provides a significant competitive advantage.

Cedric Francois: Executing across key initiatives to achieve these goals, including broadening our reach to the eye care community amplify and real world data through key forums educating payers on safe ovaries differentiated value proposition.

Cedric Francois: Back to you with patients through our DTC campaign.

David Acheson: We recently launched phase two of our DTC campaign, featuring Henry Winkler. This campaign focuses on increasing awareness of GA and cyphobry, and ensuring GA patients are able to connect to a retina specialist who can treat.

Cedric Francois: We recently launched phase two of our DTC campaign, featuring Henry Winkler. This campaign focuses on increasing awareness of gea insightful and ensuring Gi patients are able to connect to a retina specialist who can treat them.

David Acheson: Now, let me shift to Infobel. The commercial and medical teams are ramping up their efforts in anticipation of F of LA's potential label expansion into C3G and ICMPGN later this year. We are in the process of hiring a field-based team, which will allow us to hit the ground running and make a significant impact in the early phases of the launch. Ahead of approval, we are executing several pre-launch activities focusing on disease state awareness. These include participation in key nephrology conferences, building relationships with key physician accounts, KOL and payer engagement, and patient education. These activities maximize the likelihood of a successful launch in C3G and ICM3.

Cedric Francois: Now, let me shift to <unk>.

Cedric Francois: Our commercial and medical teams are ramping up their efforts in anticipation of <unk> potential label expansion into <unk> and <unk> later this year.

Cedric Francois: We are in the process of hiring a field based team, which will allow us to hit the ground running and make a significant impact in the early phases of the launch.

Cedric Francois: Ahead of approval, we are executing several prelaunch activities focusing on disease state awareness. These include participation in key nephrology Congresses.

Cedric Francois: Building relationships with key physician accounts.

Speaker Change: Oh, well in payer engagement and patient education.

Speaker Change: These activities maximize the likelihood of a successful launch in <unk> and <unk>. They also reinforce our commitment to rare nephrology with our programs in Dts and SCS.

David Acheson: They also reinforce our commitment to rare nephrology with our programs in DGF and FSGS. The commercial opportunity is significant with an estimated 5,000 C3G and ICM-PGN patients in the U.S. Empivelli is the only drug to be studied in a broad patient population. Given the strength of the phase 3 data, we believe Empivelli will be used across all patient groups and disease severity. Physician feedback has been consistent that treatment choice will be based on efficacy over the route of administration, given the severity of C3G and ICMPG. Many patients, even those with mild to moderate disease, will eventually suffer kidney In P&H, Ampivelli generated approximately $23 million in U.S.

Speaker Change: The commercial opportunity is significant with an estimated 5000 <unk> patients in the U S. <unk> is the only drug to be studied in a broad patient population given the strength of the phase III data, we believe <unk> will be used across all patient groups and disease severity.

Speaker Change: Physician feedback has been consistent that treatment choice will be based on efficacy over the route of administration, given the severity of <unk> and IC and PGN.

Speaker Change: Many patients even those with mild to moderate disease will eventually separate kidney failure.

Speaker Change: <unk> and <unk> generated approximately $23 million in U S. Net product revenue in the fourth quarter compliance rates remained high at 97% and the safety profile remains consistent with our previous updates.

David Acheson: net product revenue in the fourth quarter. Compliance rates remain high at 97%, and the safety profile remains consistent with our previous efforts.

David Acheson: We expect continued competitive pressure in 2025, but this should be more than offset by initial revenue generated from C3G and ICMG.

Speaker Change: We expect continued competitive pressure in 2025, but this should be more than offset by initial revenue generated from <unk> and <unk>.

Caroline Baumal: With that, I will now turn the call over to Thanks, David. And good morning, everyone. I'll start with syphovir. We continue to see evidence supporting syphovir's strong efficacy and consistent benefit to GA patients over long periods of time. Earlier this month, we presented 48-month data from our Gale Extension Study that reinforced syphobres increasing effects over time. These data demonstrated that early treatment with syphobre leads to preservation of retina tissue at magnitudes of approximately 1.5 disc areas on average at 48 months in non-syphobrial GA patients dosed monthly. For context, 1.5 disc areas is the size of approximately two phobia areas, which is considered highly meaningful by retinal specialists.

Carolina: With that I will now turn the call over to Carolina.

Carolina: Thanks, David and good morning, everyone.

Carolina: I'll start with iPhone.

Carolina: We continue to see evidence supporting safety.

Carolina: Efficacy.

Carolina: System benefit PTA patients over long periods of time.

Carolina: Earlier. This month, we presented 48 month data from our extension study that reinforced April rates increasing effects over time. These.

Carolina: These data demonstrated that early on with Tysabri lead to preservation of retina tissue at magnitudes of approximately 1.5 disc areas on average at 48 months.

Carolina: <unk> patients dosed monthly.

Carolina: For context, one five disc areas is the size of approximately two phobia areas, which is considered highly meaningful by retinal specialists.

Caroline Baumal: We are also beginning to see real-world evidence of the benefits of typhoid treatment. An independent analysis of real-world data concluded that by month 9 of treatment, cyfovir reduced the annualized growth rate of GA by over 40%. Separately, another analysis of real-world data following cyfovir treatment showed stable visual acuity over multiple injections. While there are always limitations to independent analyses, these results add to the extensive clinical data set for cyfovir and strengthen confidence in its treatment benefits.

Carolina: We are also beginning to see real world evidence of the benefits of stifle treatments.

Speaker Change: An independent analysis of real World data concluded that by line of treatment.

Speaker Change: <unk> reduced the annualized growth rate of G&A by over 40%.

Speaker Change: Separately.

Further analysis of real World data following <unk> treatment showed stable visual acuity over multiple injections.

Speaker Change: While there are always limitations to independent analyses. These results add to the extensive clinical data set for say celebrate and strengthen confidence and its treatment benefit.

Caroline Baumal: As Cedric mentioned, we are also developing a next-generation treatment for GA. We believe combining cyfovir and our siRNA APL 3007 may provide comprehensive complement blockade in the retina and in the choroid. Specifically, cyfovir inhibits complement in the retina, and APL 3007 is intended to target systemic complement activity in the eye. With less C3 present in the eye following administration of APL 3007, there may be an even higher degree of efficacy contribution from Cyfo-Ova. Last month, we shared Phase 1 data with APL 3007 and Healthy Volunteers showing greater than 90% knockdown of C3 products as measured by the remaining levels of protein in the blood.

Cedric Francois: As Cedric mentioned, we are also developing a next generation treatment for Ges.

Cedric Francois: We believe combining sighful debris and Rsi RNA APL 3007 may provide comprehensive complement blockade in the retina and choroid, specifically say February inhibits complement in the retina and APL 3007 is intended to target.

Cedric Francois: <unk> complements activity in the eye.

Cedric Francois: With less seats, we present in the following administration of APL 2007.

Cedric Francois: Maybe an even higher degree of efficacy contribution from sites over.

Cedric Francois: Last month, we shared phase one data with APL 2007 in healthy volunteers, showing greater than 90% knockdown of ctrip products as measured by the remaining levels of protein in the blood.

Caroline Baumal: We expect to initiate a Phase 2 study with Cyfovir and APL 3007 in GA patients in the second quarter.

Cedric Francois: We expect to initiate a phase two study with Tysabri and APL 3007, <unk> patients in the second quarter.

Caroline Baumal: Shifting to Empaveli, the phase three valiant results provided further confidence in Empaveli's ability to control complement and provide a meaningful difference to patients with rare kidney diseases. Based on these data and a strong rationale for complement inhibition, we plan to initiate two pivotal studies with enfibelity in the second half of this year. One in primary focal segmental glomerulosclerosis or FSGF and one in delayed graft function or DGF. The complement pathway plays a significant role in both diseases, and there are currently no FDA-approved therapies. FSGS is a rare kidney disease that causes scarring of the glomeruli.

Cedric Francois: Shifting to and develop the phase III Valeant results provided further confidence in <unk> ability to control complement and provide a meaningful difference to patients with rare kidney diseases.

Cedric Francois: Just on these data and a strong rationale for complement inhibition, we plan to initiate two pivotal studies with <unk> in the second half of this year.

Cedric Francois: One in primary focal segmental glomerular sclerosis, or S SGS and one in delayed graft function or D. G F.

Cedric Francois: The complement pathway plays a significant role in both diseases and there are currently no FDA approved therapies.

Cedric Francois: SGS is a rare kidney disease that causes scarring of the <unk> Sim.

Caroline Baumal: Similar to C3G and IC-MPGN, FSGS results in end-stage kidney disease within 5 to 10 years for approximately half a patient. There are an estimated 13,000 primary FSGS patients in the United States. DGS is a complication in kidney transplantation where the transplanted kidney fails to function and typically requires dialysis within the first week of transplant. This negatively affects the long-term survival of the kidney and overall patient outcome. In 2023, there were an estimated 21,000 transplants in the U.S. using deceased donor kidney. DGF occurred in 30% to 35% of these transplants. FSGS and DGF were chosen due to their high unmet need, significant complement involvement, and our ability to move directly into pivotal programs with potential approvals by 2030.

Cedric Francois: Similar to <unk>, and IC and PGN STS resulted in stage kidney disease within five to 10 years for approximately half of patients.

Cedric Francois: There are an estimated 13000 primary at STS patients in the United States.

Cedric Francois: Bgs is a competition in kidney transplantation, where the transplanted kidney fails to function and typically requires dialysis within the firstly of transplant.

Cedric Francois: This negatively affects the long term survival of the kidney and overall patient outcomes in.

Cedric Francois: In 2023.

Cedric Francois: Estimated 21000 transplants in the U S using deceased donor kidneys.

Cedric Francois: Occurred in 30% to 35% these transplants.

Cedric Francois: SGS and DTF were chosen due to their high unmet need.

Cedric Francois: And if I can complement involvement and our ability to move directly into pivotal programs with potential approvals by 2030.

Caroline Baumal: Given our leadership and expertise in complement, we are uniquely positioned to bring treatments to patients with these devastating conditions.

Cedric Francois: Given our leadership and expertise in complement we are.

Cedric Francois: Uniquely positioned to bring treatments to patients with devastating diseases.

Timothy Sullivan: For more information visit www.FEMA.gov I will now turn the call over to Tim for a review of the financials. Tim? Thank you, Caroline. I will now provide an overview of our financial. Additional details are available in the press release that we issued earlier this morning. Total revenue for the fourth quarter of 2024 was approximately $213 million, including $168 million in SIFO and $23 million in Empa Valley U.S. Net Product Revenue.

Tim: I will now turn the call over to Tim for a review of the financials Tim.

Tim: Thank you Caroline I will now provide an overview of our financials and additional details are available in the press release that we issued earlier this morning.

Tim: Total revenue for the fourth quarter of 2024 was approximately $213 million, including $168 million in <unk> and $23 million <unk> U S net product revenue.

Timothy Sullivan: Total revenue for the full year 2024 was $781 million, a nearly 100% increase as compared to 2023. Turning to the rest of the P&L. For the fourth quarter, cost of sales was $40.9 million. R&D expenses were $76.4 million. SG&A expenses were $121.5 million, and we reported a net loss of $36.4 million. Regarding cyfovery, gross to net remains stable relative to the third quarter. We anticipate gross to net to be in the low to mid 20% range through 2025. We took a 1% price increase on January 1st that is intended to help offset some of the ASP erosion while managing customer reimbursement.

Tim: Total revenue for the full year, 2024 was $781 million and nearly 100% increase as compared to 2023.

Tim: Turning to the rest of the P&L.

Tim: For the fourth quarter cost of sales was $40 9 million R&D.

Tim: Our R&D expenses were $76 4 million.

Tim: G&A expenses were $121 $5 million and we reported a net loss of $36 4 million.

Regarding faithful gross to net remained stable relative to the third quarter, we anticipate gross to net to be in the low to mid 20% range through 2025.

Tim: We took a 1% price increase on January one that is intended to help offset some of the ASP erosion, while managing customer reimbursement.

Timothy Sullivan: We continue to execute against our strategy while maintaining financial discipline. We made strong progress from a financial perspective in 2024.

Tim: We continue to execute against our strategy, while maintaining financial discipline we've.

Tim: We made strong progress from a financial perspective in 2024.

Timothy Sullivan: As you can see on slide 17, our total revenue in 2024 nearly matches our non-GAAP expenditures. With $411 million in cash and cash equivalents at the end of 2024, we remain confident in our financial position. We anticipate operating expenses in 2025 to be relatively stable compared to 2024. We expect our existing cash combined with our future product sales to be sufficient to fund our core business to profitability.

Tim: As you can see on slide 17, our total revenue in 2024 nearly matches our non cap expenditure.

Tim: With $411 million in cash and cash equivalents at the end of 2024.

Tim: Remain confident in our financial position.

Tim: We anticipate operating expenses in 2025 to be relatively stable compared to 2024 <unk>.

We expect our existing cash combined with our future product sales to be sufficient to fund our core business to profitability.

Cedric Francois: I will now hand the call back over to Cedric for closing remarks. Thanks.

Tim: I'll now hand, the call back over et cetera for closing remarks.

Cedric Francois: We have started 2025 from a position of strength and are focused on building on the success of Cyphovry, preparing for our second commercial launch with Empavedi and C3G and ICMPGN, progressing our pipeline, and solidifying our finance. By doing this, we remain confident in our ability to create significant value for patients and shareholders over the coming years.

Tim: We have started 2020 phase from a position of strength and are focused on building on the success of aesthetics.

Speaker Change: Preparing for our second commercial launch with <unk> in CTG and ICF BGN progressing our bank line and so to say our financial position Baidu.

Tim: By doing this.

Tim: <unk> confident in our ability to create significant value for patients and shareholders over the coming years.

Unknown Executive: As a reminder, to ask a question, please press star 11 on your telephone and wait for your name to be announced. To withdraw your question, please press star 11 again. Please limit yourself to one question and a follow-up.

Tim: As a reminder question. Please press star one on your telephone and wait for your name to be announced to withdraw. Your question. Please press star one again, please limit yourself to one question and a follow up please standby, while we compile the <unk>.

Unknown Executive: Please stand by while we compile the Q&A roster.

Speaker Change: Q&A roster.

John Miller: And our first question will be coming from John Miller of Evercore ISI. Your line is open. Hi, guys. Thanks so much for taking my question and congrats on all the progress. One on ampivelli and the kidney indications, I guess, and a quick follow-up on that. Obviously, your primary endpoint showed really great results with the spot test in UACR, but the competitor had a 24-hour endpoint. I know you said in the past that you looked at 24 hours, but we haven't seen it yet. Do you plan on presenting that publicly? I assume it was included in the submission to the FDA.

Speaker Change: And our first question will be coming from John Miller of Evercore ISI. Your line is open.

John Miller: Hi, guys. Thanks, so much for taking my question and congrats on all the progress.

John Miller: One on <unk> in the kidney indications I guess and then a quick follow up on that.

John Miller: Hi.

Speaker Change: Obviously your primary endpoint showed really great results with the spot tests of new ACR, but the competitor had a 24 hour endpoint I know you said in the past that you looked at 24 hours, but we haven't seen it yet do you plan on presenting that publicly I assume it was included in the submission to the FDA do you have a sense of.

John Miller: Do you have a sense of which metric the FDA is most focused on? That's a commentary, and that would be great.

Speaker Change: Which metric the FDA is most focused on some commentary that would be great.

Cedric Francois: Hi, John. Thank you so much for that question. So, look, we're very excited about the submission with MPAVETI, of course, and looking forward to feedback in short order. The 24 hours was consistent with what we saw with the spots, but the endpoint, of course, was the spot. I think what is really important here is not just the proteinuria, right, but the consistency that we had across all the phenotypes of this disease and across all three important metrics that exist. There is, of course, the proteinuria, which had such a highly clinically meaningful reduction, but we also had the EGFR stabilization.

Speaker Change: Thank you so much for that question.

Speaker Change: We're very excited about the submission with Mpeg video of course, and looking forward to feedback in short order.

Speaker Change: 24 hours was consistent with what we saw with the spots at the endpoint of course was the spot I think what is really important here is not just the protein here yet, but the consistency that we had across all of these types of this disease.

Speaker Change: And across all three important metrics that exist. There is of course, the proteinuria, which had such a highly clinically meaningful reduction.

Cedric Francois: And in addition to that, and I cannot overemphasize that, the impressive results on the histopathology, right? I mean, so when you look at these kidneys, you see the C3 deposits go away, you know, melting like snow in the sun, quite frankly, over the course of a couple of months. And after six months, as much as 70% of patients have no more detectable C3 deposits. So that's something really important to bear in mind. We're excited about the submission, about what we can do for patients, and the submission or the publication will come out tomorrow.

Speaker Change: You also have the Egfr stabilization and then addition to that and I cannot overemphasize that.

Speaker Change: Impressive results on the Histopathology right I mean, so when you look at these kidneys you see the C. Three deposits go away.

Speaker Change: Melting like slow into some quite frankly over the course of a couple of months and after six months as much as 70% of patients.

Speaker Change: No more detected those <unk> deposits, so thats something really important to bear in mind. We are excited about the submission about what we can do for patients.

Speaker Change: And.

Speaker Change: The submission for publication will come out soon as well.

John Miller: All right, thank you.

John Miller: Maybe just as a quick follow-up, given recent news coming out of the agency, I'd love to get a sense of your confidence level that you'll be able to launch in the second half of 2025, that the agency will be able to meet its PDUFID requirements, and you'll get a timely review. Yeah, so, of course, we have no control over macro, but at the current point in time, there is no indication at all that there is any type of delay. Thanks so much.

Speaker Change: Alright. Thank you maybe just as a quick follow up.

Speaker Change: Given recent news coming out of the agency I would love to get a sense of your confidence level.

Speaker Change: That youll be able to launch in the second half of 'twenty five that the agency will be able to meet its <unk> requirements and Youll get a timely review.

Speaker Change: Yes so.

Speaker Change: Controlling for macro but at the current point in time, there is no indication at all.

Speaker Change: <unk> was delayed.

Unknown Executive: Thank you and good night.

Speaker Change: Thanks, so much.

Speaker Change: Thank you.

Tazeen Ahmad: for our next question. Our next question will be coming from Tazeen Ahmad of Bank of America Securities. Your line is open. Great, thank you. Good morning, guys. I have a couple questions regarding SIFOVRI.

Speaker Change: For our next question.

Speaker Change: Our next question will be coming from <unk> Ahmad of Bank of America Securities Banc of America Securities. Your line is open.

Speaker Change: Great. Thank you good morning, guys.

Speaker Change: Question is regarding <unk> so.

Tazeen Ahmad: So, just based on the metrics that you cited, or really trends in the first quarter, how should we be thinking about results in the first quarter relative to 4Q? Could it be that sales would be lower this quarter for the reasons that you mentioned? And then regarding the beneficial status in Medicare Advantage, do you think that that's going to have an early and noticeable impact on new patient share in the year, or do you think that's something that would happen more gradually? And then I have a follow-up thing.

Speaker Change: Based on the metrics that you cited.

Speaker Change: Trends in the first quarter.

Speaker Change: How should we be thinking about.

Speaker Change: From the first quarter relative to Q could it be that sales will be lower this quarter for the reasons that you mentioned and then.

Speaker Change: Regarding the the beneficial status and Medicare advantage do you think that that is going to have.

Speaker Change: And early a noticeable impact on new patient share.

Speaker Change: In the year or do you think thats something that would happen more gradually and then I have a follow up thanks.

David Acheson: I'm going to hand it over to David. Hey, Tazeen. It's David. I hope you're doing well. Thank you for the question. So, like we talked about in the call, some of the things that we're seeing in Q1 are transit impact to what we think will impact net revenue. And while they're anticipated to be temporary, we do think that Q1 will be lower than Q4 as a result. And we're not going to guide on anything for Q1 beyond that, but that's where we are currently, at least with what we've seen so far. Oh, and the other thing to note, too, by the way, is one of the things that is really positive for us is that the good news, we're seeing injections, which we talked about in the call as well, grow in Q1 versus Q4, which is very positive for us.

David Anderson: Yes, I'm going to hand, it over to David.

David Anderson: Dave It's David I Hope you're doing well. Thank you for the question so like we talked about.

David Anderson: In the call some of the things that we're seeing in Q1, our transit impact to what we think will impact net revenue.

David Anderson: While there.

David Anderson: Dissipated to be temporary we do think that Q1 will be lower than Q4 as a result.

David Anderson: And we're not going to guide on anything for Q1 beyond that but that's that's where we are currently.

David Anderson: At least with what we've seen so far.

David Anderson: Yeah.

David Anderson: The other thing to note too by the way is.

David Anderson: One of the things that is really positive for us is that the good news, we're seeing injections, which we talked about in the call as well grow in Q1 versus Q4.

David Anderson: <unk> is very positive for us and we expect so once we get somebody is temporary.

David Acheson: And we expect so, you know, once we get some of these temporary impacts against the Q1 numbers out of the way, we should see and continue to see and expect to see 2025 to have growth.

David Anderson: Impacts against the Q1 numbers out of the way, we should see it continue to see and expect to see 2025 to have growth.

David Acheson: Okay, and then my follow-up is about the label change that was made for the competing product. How important is it that the label for iSurvey will say monthly injection relative to every other month? Because it does seem, based on our doc check, that up until now, docs seem to have adopted every other month. Do you think that that practice will change? Yeah, so look, I think it's a little bit early here, right? In regards to the label change, I think there's still some things here that folks are still trying to figure out.

David Anderson: Okay and then my follow up is about the label change that was made for the competing product.

David Anderson: <unk> important is it that the label for ice survey will say monthly injection relative to every other month because it does floor based on our dock chalk that up until now.

Doc seem to have adopted every other month do you think that will change.

David Anderson: Sure.

Speaker Change: Yes, So look I think it's a little early here right in regards to those label change I think theres still some things here that folks are still trying to figure out I will tell you.

David Acheson: I will tell you, myself and Caroline, which I'll hand to in a second for some comment, we were at the Immaculate Society when this came out, which is a prestigious meeting that was held in Florida. And the general talk and discussion was around Cyfovery and the every other month dosing. I think the more important part was the follow on to that, which is we had a lot of robust data that was presented at that meeting that really helped us to solidify even further that Cyfovery's consistent increased effects over time is going to have impact. And does it have an impact?

Speaker Change: Myself, and Caroline, which I'll get to in a second for some comment we are at the Macula Society. When this came out which is a prestigious meeting that was held in Florida.

Speaker Change: The general target discussion was around site <unk> and every other month dosing I think the more important part was the follow on to that which is we had a lot of robust data that was presented at that meeting.

Speaker Change: That really helped us to solidify even further that side full rates consistent increase in effects over time, it's going to have impact.

Caroline Baumal: That was a lot of the discussion. Plus, we're the only product that can be treated and it's in the label for as few as six doses a year. And we're the only product that has preferred positions with payers. That was the conversation at Immaculate Society.

Speaker Change: Does it have an impact that was a lot of the discussion.

Speaker Change: We're the only product that can be treated and it's in the label for as few as six doses a year and we're the only product that has preferred positions with payers that was the conversation at Macula Society.

Caroline Baumal: So I'll hand it over to Thank you. Hi, Tazeen. You know, what I hear from my colleagues and what I know from being a physician is that efficacy and convenience are really important driving factors for patients, physicians, and payers, and we have consistently demonstrated efficacy with every-other-month dosing.

Carolina: I'll hand, it over to Carolina for additional comments.

Speaker Change: Thank you <unk>.

Speaker Change: What I hear from my colleagues when I know from being in a position is that efficacy and convenience really driving factors board for patients physicians and payers and we have consistently demonstrated efficacy with every other month dosing.

Caroline Baumal: This has not been demonstrated with a survey in a clinical trial, and, you know, the FDA did not approve the for-every-other-month dosing. So our label includes all of our benefits, our efficacy, increasing effects over time in a flexible dosing regimen that includes monthly and every-other-month dosing.

Speaker Change: It has not been demonstrated with <unk> and the clinical trial and Tommy.

Speaker Change: The FDA did not approve that for every other month dosing. So our label includes all of our benefits are efficacy increasing opex overtime.

Speaker Change: Flexible dosing regimen that includes monthly and every other month dosing.

Anupam Rama: One moment for our next question. Our next question will be coming from Anupam Rama of J.P. Morgan. Your line is open. Hi, thanks for taking the question.

Speaker Change: Okay.

Speaker Change: One moment for our next question.

Speaker Change: Our next question will be coming from and your Pam Rama of J P. Morgan Your line is open.

Malcom Kuno: This is actually Malcom Kuno, Auditor-Auditor. So, with the iSurvey headwinds over the last several months and the updated label, what are you hearing from payers on the potential for preferred tiering for a SIFO?

Malcolm Kunal: Hi, Thanks for taking the question. This is actually Malcolm Kunal Ultra auto pump.

Malcolm Kunal: So we would see is a bit of headwinds over the last several months and the updated label. What are you hearing from payers on the potential for preferred tearing fore sight debris.

David Acheson: Yes, welcome. Thank you. It's David. Thanks for the question. So, we're really fortunate to have a number of payers and sizable plans that have us in a preferred position. I think it's a little hard to forecast what that looks like, but I will tell you, when we look at and have conversations with the payers, it really comes down to every other month dosing and the fact that we have it in the label with the efficacy that matches up to that. So, those are the things to keep in mind, and we'll see what happens in the future, but I can't really predict what will happen moving forward with the payers, at least at this point.

Malcolm Kunal: Yes.

Malcolm Kunal: Yes, Michael Thank you it's David Thanks for the question. So we're really fortunate to have a number of pairs and sizable plans that have us in a preferred position I think it's a little hard to forecast what that looks like but.

But I will tell you.

Malcolm Kunal: When we look at and have conversations with the payers. It really comes down to every other month dosing and the fact that we have it in the label with the efficacy that matches up to that so those those are the things to keep in mind.

Malcolm Kunal: We will see what happens in the future, but I can't really predict what will happen moving forward with the payers at least at this point in time.

Unknown Executive: Great, thank you. Thank you.

Malcolm Kunal: Great. Thank you.

Salveen Richter: One moment for our next question. Our next question will be coming from Salveen Richter of Goldman Sachs. Your line is open. Good morning. Thanks for taking my question.

Malcolm Kunal: Thank you one moment for our next question.

Malcolm Kunal: Our next question will be coming from <unk> Richter of Goldman Sachs. Your line is open.

Richter: Good morning, Thanks for taking my question could you give us a little bit more color on how we should think about the cadence at this site for free.

Salveen Richter: Could you give us a little bit more color on how we should think about the cadence of the cyfovery launch here in 2025, just given that the commentary on 1Q being lower than 4Q, but there's growth in 2025, and also in the context of, you know, a potential label update for our survey and the formulary status and expansion XUS. Thank you. Thank you, Salveen. So I think, first of all, really important to bear in mind, injections continue to grow, right? And that is a reflection of the unmet need in this disease. Remember, fewer than 10 percent of patients with geographic atrophy have been treated and only about half of patients are currently being seen by agri-professionals.

Richter: Sure in 2025, just given the commentary on <unk> being lower than <unk>, but there is growth in 2025.

Richter: Also in the context of potential label update prior survey in the formulary status and expansion ex U S. Thank you.

Speaker Change: Thank you <unk>, so I think first of all medium versus injection.

Richter: Injections continue to grow right.

Richter: That is reflection of the unmet need in this disease remember fewer than 10% of patients with geographic atrophy has been treated.

Richter: And only about half of patients are currently being seen by accurate professionals. So youll opportunity there to do good for patients and to <unk>.

Cedric Francois: So the opportunity there to do good for patients and to generate revenue is enormous, as it has always been. So that is as far as the overall market is concerned. Competitively, quite frankly, I think we are in an enviable position right now. You know, last year, of course, we went through several motions. But at the end of the day, I think it's important to bear in mind that the CRL for our competitor, you know, beyond whether it's resolved or not now, really called out the shortcomings that our competitor has, most notably the fact that there is or that there was a 12-month limitation initially, which a lot of physicians did not know.

Richter: Generate revenue.

Richter: As enormous as it has always been so.

Richter: That is as far as the overall market is concerned competitively quite frankly, I think we are in an enviable position right now.

Richter: Last year of course, we went through several motions that at the end of the day.

Richter: I think it's important to bear in mind that the CRM for our competitor.

Richter: Beyond whether its resolved or not now.

Richter: Really called out the shortcomings that our competitor has most notably the fact that there is sort of if there was a 12 month limitation initially which will help physicians did not know and then of course also the lack of data for every other month dosing. So I think it was important to kind of level set the knowledge around.

Cedric Francois: And then, of course, also the lack of data for every other month's dosing. So I think it was important to kind of level set the knowledge around two products so that physicians can take the right.

Richter: Two products, so that physicians can take the retrofits. So we're very excited about 2025 is headaches.

Cedric Francois: So we're very excited about where 2025 is heading.

Richter: And beyond as well.

Richter: Okay.

Yigal Nochomovitz: Thank you and one moment for our next question. Our next question will be coming from Yigal Nochomovitz of Citigroup. Your line is open.

Richter: Thank you and one moment for our next question.

Speaker Change: Our next question will be coming from your gallon no Joe <unk> of Citigroup. Your line is open.

Yigal Nochomovitz: Hey, Cedric and team. Thanks for the question. I had a question on the combo trial with O7 and Cyfovir. How are you thinking about the phasing of the dosing there, given the intravitreal and the systemic? Are you going to interweave them or can you just talk more about the strategy for that combo dosing? And then will this phase two have any comparison arm or is it just going to be a single arm study?

Speaker Change: Hey, Sanjay can team thanks for the question.

Speaker Change: I had a question on the combo trial with <unk> seven safe over how are you thinking about the phasing of the dosing there given the <unk> and the systemic.

Speaker Change: You are going to enter with them or can you just talk more about the strategy for that combo dosing and then well this phase II have any.

Speaker Change: Comparison harm or is it just going to be.

Cedric Francois: Thank you. Thank you so much, Yigal. So we're super excited about our 3007 program.

Speaker Change: Single arm study thank you.

Speaker Change: Thank you so much Hugo so we're super excited about our <unk> seven program and you're asking as usual and exited the question, which is we stopped carefully.

Cedric Francois: And you are asking, as usual, an excellent question, which is we've thought carefully how to implement this in a physician setting, right? So the idea there is that with a subcutaneous injection, you lower the systemic levels of C3. So turning off the faucet, if you want, and you give a stoichiometric advantage, so a dosing advantage to cyfovir, which you still need in the eye to control the enzymatic activity of the complement cascade. We will synchronize those injections to every two months and every three-month administrations, both of which, so the intravitril and the subcutaneous, both of which would happen in the physician's office.

Speaker Change: To implement this in a physician right. So the idea there is that with a subcutaneous injection that you lowered the systemic levels of <unk> III.

Speaker Change: So turning off the faucet, if you want to can you give us. Thank you metric advantage. So dosing advantage Tuesday February which you still need NDA to control the antiemetic activity of the complement Cascade, we will synchronize those injections to every two months and every three months administrations.

Speaker Change: Most of which to the attributes and the subcutaneous both of which would happen in the physician's office. So I think thats something really important.

Cedric Francois: So I think that's something really important. There will be a dosing component to this, as per usual, so that we can explore those two separate pathologies. But, you know, in the broader strategic context, I mean, we're looking forward to this year to, you know, growing the market in GA, truly establishing ourselves, you know, as we are the market leader, but growing that share that we have, and then also to what's going to happen in the future.

Speaker Change: There will be a dosing components to this as per usual so that we can explore those two separate pathologies.

Speaker Change: But the broader strategic context, I mean, we're looking forward to this year growing to mercury the NGA.

Speaker Change: Truly establishing ourselves.

Speaker Change: We are the market leader, but growing that share that we have and then also to once we subjectively of course belief will be one of the if not the most exciting developmental program and geographic cash receipt by the end of this year and into 2026.

Cedric Francois: Objectively, of course, but the belief will be one of the, if not the most exciting developmental program in geographic atrophy by the end of this year and into 2020.

Timothy Sullivan: Thanks. And maybe one for Tim. Just on Empaveli, obviously you have a ton of really interesting larger indications coming down the pipe, as you've alluded to, the C3G, the CCMPGN, FSGS potentially, GAGF. So as far as the patent looks like, do you have any comments on how you might extend that even further, given the potential for very significant revenues on these follow-on indications? Yeah, sure. If I heard you correctly, you asked if there was a way to kind of extend our exclusivity. Is that, did I understand that from a patent perspective? Yeah. So, so look, we have composition of matter through kind of 2033-ish and 2035 with customary extensions.

Speaker Change: Thanks, and maybe one for Tim just on <unk>.

Speaker Change: Obviously, you have a ton of really interesting larger indications coming down the pipe.

Speaker Change: Alluded to the <unk>, <unk> and PGN <unk> <unk> potentially GFS DHS. So.

Far as the pattern looks like do you have any comments on how you might extend that.

Speaker Change: Even further given given the potential for a very significant revenues on these follow on indications.

Speaker Change: Yes, sure if I heard you correct correctly.

Speaker Change: If there is a way to kind of extend our exclusivity is that did I understand patent personnel.

Speaker Change: So look we have composition of matter through 2033 ish.

Speaker Change: In 2035 with customary extension so yes.

Timothy Sullivan: So, you know, that's still a pretty reasonable runway for the indications that we discussed. And we discussed that those, you know, those are both chosen because we believe that we would have the ability to launch those with a significant amount of patent life left. You know, there are other things, you know, that we have in mind. We also have, as Cedric mentioned, some combination product work ongoing that could really change, change our, the profile of our systemic administration of Exeter-Copeland. So, we're looking at lifecycle management initiatives as well.

Speaker Change: Yes, that's still pretty reasonable runway for the indications that we discussed and we've discussed those.

Speaker Change: Those are both chosen because we believe that we would have the ability to launch those with a significant amount of patent life left or are there other things that.

Speaker Change: We have in mind, we also have.

Speaker Change: Rick mentioned some combination product.

Speaker Change: <unk> ongoing.

Speaker Change: That could really change changed the profile of our systemic administration of exit of cobalt. So we're looking at lifestyle lifecycle management initiatives as well.

Timothy Sullivan: But from a composition of matter perspective, 2035 is really, is really where that runs out. Okay, gotcha. Thank you.

Speaker Change: But from a composition of matter perspective, 2035 is really is really worried that runs out.

Speaker Change: Okay got you. Thank you.

Colleen Kusy: One moment for our next question. Our next question will be coming from Colleen Kusy of Baird. Your line is open, Colleen. Great. Good morning. Thanks for taking our questions. Congrats on the progress. So you've had some strong momentum on the payer front last year.

Speaker Change: One moment for our next question.

Our next question will be coming from Colin Crosby of Baird. Your line is open Colleen.

Colin Crosby: Great. Good morning, Thanks for taking my questions. Congrats on the progress that you've had some strong momentum on the payer front last year can you put into context what percent of the market you have preferred position again and how much more growth on the payer front do you expect to achieve in 2025.

David Acheson: Can you put into context, you know, what percent of the market you have preferred positioning in and how much more growth on the payer front do you expect to achieve? Thank you, Colleen. And good to have you back.

David Acheson: So I'm going to hand it over to David. Hey, Colleen. Good to hear from you. And thank you for the question. So we've got some big plans, like Aetna is a great example that, as of January 1st, has us in a preferred position, and a patient has to start with CycoVid before they could move to the competitive product. So there's some big plans that are out there. I think percentage-wise, it's a little bit hard to talk through that because there's so many intricacies in the plans on how they actually look and the downstream accounts, in particular to the PBMs, can make their own decisions on what they want to do with that.

Speaker Change: Thank you Kelly and good to have you back so I'm going to hand, it over to David Hagan Ali good to hear from you and thank you for the question. So we've got some big plans like Aetna is a great example, as of January 1st.

Speaker Change: Is this an appropriate preferred physician and patient has to start with <unk> before they could move to the competitive product. So there is some big plans are out there I think percentage wise, it's a little bit hard to to talk through that because theres. So many intricacies of the plans on how they actually look at this in the downstream accounts in particular to the Pbms can make their own decisions on.

Colleen Kusy: But I will tell you, we have a number of sizable plans and two major PBMs that have us in a preferred policy position for their downstream accounts to make those decisions. Great, that's helpful. Thank you.

Speaker Change: What they wanted to do with that.

Speaker Change: So, but I will tell you we have a number of sizable plants and two major pbms that habits in our preferred policy position further downstream account to make those decisions on.

Colleen Kusy: And then for C3G and ICMPGN, have European regulators and U.S. regulators historically approached that review similarly? Since we've seen some positive momentum on the European opinion front, just wondering how that decision might have reached through to the U.S. review. Yeah, so thank you so much for that question, Colleen. So our partners Sobe and Apellis have been in lockstep through all of this. And, you know, we're very excited about the global deployment of Empavel in the U.S. and Aspavel in the ex-U.S., of course. I think what's, and again, kind of highlighting what we've mentioned many times, in the U.S., for example, we estimate there are approximately 5,000 patients.

Speaker Change: Great. That's helpful. Thank you and then for <unk> IC and PGN has it European regulators and U S. Regulators historically approach that review similarly, because we see some positive momentum on the European.

Speaker Change: Opinion front, just wondering how that decision might have read through to the U S. Caribbean.

Speaker Change: Yes. It was thank you so much for that question, calling so our partners <unk> and <unk> given it looks stepped through all of this.

Speaker Change: And we're very excited about the global deployment.

Speaker Change: And by building use in this study ex U S.

Speaker Change: Of course.

Speaker Change: I think whats and again kind of highlighting what we've mentioned many times.

Speaker Change: The U S. For example, we estimate there are approximately 5000 patients. We estimate then we believe that we will only be competing with all the other products should it be approved that may be on the market by the time, we get there we're about at thousands of onto those lifestyles. So.

David Acheson: We estimate and we believe that we will only be competing with the only other product should it be approved that may be on the market by the time we get there for about 1,000 out of those 5,000. So it's a really special opportunity for us, and the numbers in Europe are quite a bit higher than 5,000. A really unique opportunity that deserves the prioritization that it gets within Apellis as well as with our partners.

Speaker Change: It's a really special opportunity for us and the numbers aren't.

Speaker Change: But it is higher than 5000, but with unique opportunities.

Speaker Change: Deserves the prioritization that it fits within our base as well as with FERC.

Colleen Kusy: Great, thanks for taking our questions and congrats on. Thank you.

Speaker Change: Great. Thanks for taking my questions and congrats on progress.

Phil Nadeau: One moment for our next question. Our next question will be coming from Phil Nadeau of T.D. Cohen. Your line is open. Good morning. Thanks for taking our questions. First, a follow-up and then another question.

Speaker Change: Sure.

Speaker Change: Thank you one moment for our next question. Our next question will be coming from Phil Nadeau of Cowen. Your line is open.

Phil Nadeau: Good morning, Thanks for taking my questions.

Phil Nadeau: The follow-up is on your comments you made about the sampling. Can you go into a little bit more detail on the dynamics of why there's a funding shortage and what gives you confidence that this is just a Q1 issue and it won't persist later in the year? Sure, thank you so much, Phil. So, look, the sampling are a reflection of a couple of factors, but one that stands out is what we spoke about before, which are these organizations that provide support to physicians to, you know, help with the co-pay of the product. That is not just for cyphory, but for all intravenous injections.

Speaker Change: First a follow up.

Speaker Change: Another question on the follow up is on your comments you made about the sampling can you go into a little bit more detail on the dynamics of why there is a funding shortage.

Speaker Change: What gives you confidence.

Speaker Change: Just a Q1 issue and it wont persist later in the year.

Phil Nadeau: Sure. Thank you so much Phil So look this is simply a reflection of a couple of sectors.

Phil Nadeau: But one that stands out is what we spoke about before we started these organizations that provide support to physicians to.

Phil Nadeau: Help with some of the product that is not just for <unk>, but for all the attributes for the injections.

Phil Nadeau: And it's important to note that we do not have real visibility on, you know, how this is managed. This is by design. That is, it should be appropriately, these are independent organizations that determine how they manage their fundings. So, we contribute, others contribute. We typically contribute at the beginning of the year, but it can happen throughout the year from other organizations. And it has happened before that they run out. So, what then typically happens is that physicians will go towards sampling to be able to still take care of those patients, right? So, I would say that the increase in samples is a reflection of the fact that these patients are in need.

Phil Nadeau: It's important to note that we do not have real visibility.

Phil Nadeau: <unk>.

Phil Nadeau: How does this managed this is by design that is should be appropriately.

Phil Nadeau: So our independent organizations that determine how the advantage there.

Phil Nadeau: Funding so we.

Phil Nadeau: <unk> contributes others contributes we typically contribute at the beginning of the year, but it can happen throughout the year from other organizations and it has happened before that they run outs. So what typically happens is that physicians will go towards sampling.

Phil Nadeau: To be able to still take care of those patients threat. So I would say that the increase in samples is reflection of the fact that these patients are in need there is hopefully in my own expectations temporary funding gap.

Phil Nadeau: There is a, hopefully, and by all expectations, temporary funding gap that physicians compensate for that with samples. Got it. That is helpful.

Phil Nadeau: Physicians compensate for that the template.

Phil Nadeau: And then I brought a question on MPaveli and C3G and ICMPGN in the slide deck you outlined. for buckets of patients with that disease. Can you talk about how you're gonna focus? Your marketing, for example, will you focus on post-transplant patients where you're likely to be the only option, or are there other elements or physicians that you think are highest priority?

Got it that's helpful and then.

Speaker Change: First a question on <unk>, and <unk> and I see in PJM in the slide deck you opine.

Phil Nadeau: Four buckets of patients.

Phil Nadeau: The disease can you talk about how youre going to focus.

Phil Nadeau: Marketing for example, where you focus on post transplant patients, where you're likely to be the only option.

Phil Nadeau: Or.

Are there other other elements or physicians that you think are our highest priority.

Phil Nadeau: Yeah, well, thank you so much, Phil. So, you know, again, I think you point out something that we're particularly proud of, which is that when we studied these diseases, we went very broad, right? We said we're going to study C3G, as well as ICMPGN, which are split about 50-50 in the population that we are targeting. We looked at pre-transplant, but also post-transplant, which is a segment that often gets neglected. We studied pediatric patients, as well as adults. And we studied, you know, what happens in these diseases. Sometimes C3 is depleted, sometimes it's not. We studied everything.

Phil Nadeau: Yes.

Phil Nadeau: Well thank you so much.

Phil Nadeau: Again I. Thank you.

Phil Nadeau: Probably not something that we're particularly proud of which is that when we studied these diseases. We went very broad right. We said, we're going to study <unk> as well as the <unk>, which are split about 50 50.

Phil Nadeau: It's a population that we are trying to think.

Phil Nadeau: We look at pre transplant, but also post transplant, which is the segment that often gets neglected we studied pediatric patients as well as adults and we studied what happens in this disease is sometimes <unk>, sometimes it's not we studied everything and everywhere, we sell with a consistent response as far as.

Phil Nadeau: And everywhere we saw a consistent response, as far as the impact on the disease was concerned. So what that means moving forward, because I think what you're asking us is where are the initial demographics? I think the post-transplant segment is a particularly interesting one. I think it's also worth noting that within this small community of transplant nephrologists, EmpaVedi is taking on quite a pristine reputation, not just because of the data that we had in Valiant, but also because all of the recent xenotransplants, so you may have seen in the news, the kidney transplants that are happening from genetically modified pigs, are transplants that were either rescued with EmpaVedi or are now, in all cases, as far as we know, proactively being protected with EmpaVedi.

Phil Nadeau: Good.

Phil Nadeau: The impact on the disease was concerned.

Speaker Change: So what that means moving forward, because I think what youre asking.

Phil Nadeau: It is.

Speaker Change: Where are the initial deal.

Speaker Change: Graphics, I think the post transplant segments as it particularly interesting one I think it's also worth noting that within this small community of transplant nephrologists.

Speaker Change: He is taking on.

Speaker Change: Quite a pristine reputation not just because of the data that we had at Valeant.

Speaker Change: But also because of the recent casino transplants that you may have seen in the news that kidney transplants that are happening from genetically modified pigs.

Speaker Change: Our defense does that were either rescues.

Speaker Change: Or are now in all cases as far as we know proactively being.

Speaker Change: Protected with empathy, so the I'd say the reputation of the ability to be able to control compliments within the kidney is growing steadily and something that of course bodes well for our launch later this year.

Phil Nadeau: So I'd say the reputation of EmpaVedi to be able to control complement within the kidney is growing steadily and something that, of course, bodes well for our launch later.

Phil Nadeau: That's very helpful. Thank you.

Speaker Change: That's very helpful. Thank you.

Speaker Change: Thank you.

Speaker Change: One moment for our next question.

Unknown Executive: Our next question comes from.

Speaker Change: Our next question comes from.

Akash Tiwari: Akash Tiwari of Jefferies, your line is open.

Speaker Change: Our cash to worry of Jefferies. Your line is open.

Akash Tiwari: Hi, this is Kathy on For a Cost. So on Estelle's earning call, they stated that docs were essentially warehousing patients and pausing their iSurvey doses until the 24-month label update, rather than switching them to CyphoVri, and then as such, they were expecting a bullet in March once dosing resumed. So given that iSurvey's label got updated a couple weeks before the PDUFA with the 2-year data on the label, but without every other month dosing, what are you seeing in terms of CyphoVri versus iSurvey use within the past few weeks? And then what should we expect regarding dynamics on CyphoVri versus iSurvey going forward?

Speaker Change: Hi, this is kathy on for our costs.

Speaker Change: On the shelf with earning call. They stated that docs were essentially warehousing patients and pausing their survey doses until the 24 month label update rather than switching from Tuesday February and then as such they are expecting a bolus in March once dosing regimes. So given that <unk> label updated a couple of weeks before that.

Speaker Change: With the two year data on the label.

Speaker Change: But without every other month dosing what are you seeing in terms of FIFO reverses survey with over the past few weeks and then what should we expect regarding dynamics.

Akash Tiwari: And then what do you think your team needs to do to change doctors' perception? Thank you.

Speaker Change: Seifer LTE versus <unk> going forward and then what do you think your team needs to do to change doctors perception. Thank you.

Cedric Francois: Yeah, so I think I will answer the first part and then I will hand it over to Caroline to talk about doctor perception, which of course is very important. But I think, look, there may have been some warehousing with certain physicians with certain patients to take home very clearly here is that we are definitive market leader and we are growing that. That is very clear from all of the intelligence that we have. at Apellis and something that, you know, is rooted in the data that we have, right?

Speaker Change: Yes, so I think.

Speaker Change: I will answer the first part and then I will hand. It opens you can't relate to talk about buckler perception that occurs very unfortunate, but I think.

Speaker Change: Look there may have been some warehousing with certain physicians with servicing patients.

Speaker Change: The take home very clear here is that we aren't definitive market leader and we are growing steps leadership that is very clear from all of the intelligence that we have internally at <unk> and there's something that is rooted in the data that we have right. So.

Caroline Baumal: So, I think that is the key message for us and I'll hand it over to Caroline to talk about how Thank you, Cedric. Well, we hear a lot from our physician colleagues. We just attended three major meetings, most recently the MACA Society, and physicians are very enthusiastic about our differentiated efficacy data and our long-term data. I mean, we presented tissue saves and how much tissue that was. That was over a disc and a half of retinal tissue that saved with syphovore use, and we presented long-term data, patients who've been treated with syphovore for 48 months.

Speaker Change: I think that is the key message for us and I'll hand, it over to Ken relate to talk about.

Ken: Obviously subscribed if your thoughts thank you Cedric.

Speaker Change: We hear a lot from our physician colleagues from just attended three major meetings. Most recently the Macula Society and physicians are very enthusiastic about our differentiated.

Speaker Change: C data and our long term data we presented.

Speaker Change: Tissue save so much tissue that was that was over a disk and half of retinal tissue that saved with FIFO for Houston, We presented long term data patients who've been treated with <unk> for 48 months. So this is really unprecedented.

Akash Tiwari: So, this is really unprecedented, and this is the key driver amongst physicians. I think that in the end, that physicians really speak to the scientific data, and it's very meaningful for them. Okay, understood. Thank you.

Speaker Change: This is the key driver amongst physicians I think that.

Speaker Change: In the end that physicians really speak to the scientific data and it's very meaningful for them.

David Acheson: And then just like a super quick follow-up, it seems like, like, because you provide some more color on inventory in Q4, because it seems like quarter-over-quarter sales growth was about 10% versus vol growth was about 5%. But you mentioned that you had stable growth in that dynamics. Thank you.

Speaker Change: Okay understood. Thank you and then just like a super quick follow up.

Speaker Change: It seems like like could you provide some more color on inventory in Q4.

Speaker Change: Because it seems like quarter over quarter sales growth was about 10% versus BOL growth was about 5%, but you mentioned that you had stable gross to net dynamics. Thank you.

David Acheson: Yep, this is David. So thank you for the question. You know, coming out of Q4, and usually you'll see in any given quarter, at the end of a quarter, some move, you know, in regards to orders that will move inventory a little bit. We saw a little bit of that, of course, you know, coming out of Q4, and sometimes you'll see a little bit more around the holidays. But it did not put us in a situation that we were out of the typical two- to three-week range that we have. And we may see a little bit of drawdown, you know, in the front of Q1, but for the most part, it was not a significant number that we would be concerned about anyway.

David: Yes. This is David.

Speaker Change: Thank you for the question.

David: Coming out of Q4, usually.

David: Usually youll see in any given quarter at the end of a quarter. Some move in regards to orders that will move inventory a little bit we saw a little bit out of course, you know coming out of Q4, and sometimes you'll see a little bit more around the holidays, but it did not but as to the situation that we were out of the typical two to three week range that we have and we may see a little bit of drawdown.

David: On the front of Q1, but for the most part it was not a significant number that we would be concerned about in any way.

David Acheson: Got it. Understood. Thank you.

David: Got it understood. Thank you.

Ellie Merle: One moment. For our next question. Our next question will be coming from Ellie Merle of UBS. Your line is open. Hey, guys. Thanks for taking the question. In terms of TA, I guess what's the latest that you're seeing in terms of patient adherence and what you're seeing in terms of any discontinuations? I guess sort of how we should be thinking about long-term what the discontinuation rate or compliance on therapy might be. And then just a second question, in terms of your expectations for the number of samples beyond 1Q, I guess what do you expect in terms of this dynamic in 2Q and the rest of the year?

David: Thank you one moment.

David: Our next question.

Speaker Change: Our next question will be coming from Ellie Merle of UBS. Your line is open.

Speaker Change: Hey, guys. Thanks for taking my question.

Speaker Change: In terms of <unk> I guess, what's the latest that you're seeing in terms of patient adherence and what youre seeing in terms of any discontinuation I guess sort of how we should be thinking about long term, what the discontinuation rate our compliance on therapy might be.

Speaker Change: And then just a second question in terms of your expectations for the number of samples beyond <unk> you I guess, what do you expect.

Speaker Change: The dynamic in Tokyo in the rest of the year. You mentioned this was a temporary funding gap and the patient assessment organization.

David Acheson: You mentioned this is a temporary funding gap in the patient assistant organizations, but just curious what you expect over the course of the year in terms of the number of samples. Thanks.

Speaker Change: But just curious why you expect over the course of the year in terms of the number of samples. Thanks.

Cedric Francois: Yes, thank you so much, Ali. So, first of all, as it relates to the adherence, you know, we actually see adherence levels for cyfovir be similar to what we have or what you find with anti-VHFs, which is, you know, a very positive trend considering that anti-VHF is kind of more viewed as an acute treatment with an immediate benefit, whereas with cyfovir, as we all know, you make an investment in the future protection and, you know, the large amounts of tissue that you can preserve. If you are fatal to the product. So that is something that we have no concerns around.

Speaker Change: Thank you so much so first of all as it relates to DSD routes.

Speaker Change: We actually see adherence levels for <unk> will be similar to what we have or what you signed with <unk>.

Speaker Change: Which as you know.

Speaker Change: A very positive trend considering that Jeff is kind of more viewed as an acute treatment as an immediate benefit, whereas I would say from a risk. We all know you make an investment in the future protection.

Speaker Change: These these large amounts of tissue that you can preserve issue are.

Speaker Change: Faithful to the product so.

That is something that.

David Acheson: As it relates to the samples, I will have David. Yeah, so I think a couple things. And just remember up front, I think it's important to remember that samples being requested and put into a patient for treatment is a sign of demand, which is very positive for us. And we're seeing the injections increase in Q1 versus Q4. So we feel good about that. I think a couple things. First of all, we believe this is temporary, and we anticipate that, you know, these issues that we're working on, that the samples are being used in place of a commercial product, will be fixed over time.

Speaker Change: I have no concerns around.

Speaker Change: It is through the surplus I'll have David answer, yes. So I think a couple of things I just remember upfront I think it is important to remember that samples being requested.

Speaker Change: Got into a patient for treatment.

Speaker Change: As a sign of the demand, which is very positive for us and we're seeing the injections increase in Q1 versus Q4, so we feel good about that.

Speaker Change: A couple of things first of all we believe this is temporary and we anticipate that these issues that we're working on that the samples are being used in place of a commercial product will be.

Unknown Executive: We don't know what that looks like as far as timing. And the funding gap and when all those things kind of come together that Cedric mentioned, it's really, it's in the control of the groups that manage this with patients and with physicians. So we really don't have an answer to that. But we will continue to supply samples if needed and put patients in a place where they can be treated. Got it. Thanks. Thank you. One moment for our next question.

Speaker Change: <unk> fixed over time, we don't know what that looks like as far as timing and the funding gap and when all those things kind of come together et cetera mentioned.

Speaker Change: It's really it's in the control of that.

Speaker Change: Groups that manage this with patients with physicians. So we really don't have an answer to that.

Speaker Change: But we will continue to display samples if needed and if a patients in a place where they can be treated.

Speaker Change: Got it thanks.

Speaker Change: Thank you one moment for our next question.

Annabel Samimy: Our next question comes from Annabel Samimy of CFO. Your line is open, Annabel. Hi, thanks for taking my question. So, I'm just trying to understand the competitive dynamics a little bit better for cyphovery. Can you help us square away comments about leadership position of greater than 60% share, but then new patients is more like 50-50 and then we've got competitive headwinds coming from the label expansion, but then you talk about positive trends in injection growth, preferred formulary status, and positive feedback that you're getting from the community around efficacy and flexibility of cyphovery. So, I guess, maybe you can help us really understand what that competitive headwind is that is pushing the new patient share to 50-50.

Speaker Change: Our next question comes from Annabel Sammy of Stifel. Your line is open Annabel.

Annabel Sammy: Hi, Thanks for taking my question.

So I'm just trying to understand the competitive dynamics a little bit.

Speaker Change: Better for <unk> can you help us square your comments about leadership position with greater than 60% share, but then.

Speaker Change: New patients is more like 50, 50, and then we've got <unk>.

Speaker Change: <unk> headwinds coming from the label expansion, but then you talked about positive trends in injection growth preferred formulary status and positive feedback that youre getting from the community around efficacy and flex flexibility of <unk>. So I guess, maybe you can help us really understand what that competitive headwind is.

Speaker Change: That that is pushing the new patient share to 50 50.

Annabel Samimy: Because it looks like everything's sort of lining up well for cyphovery, but I'm not sort of able to square away why it's still 50-50 for the new patient share.

Speaker Change: Because it looks like everything sort of lining up well for tysabri, but I'm not.

Speaker Change: Sort of able to square away why its still 50 50 for the new patient share.

Annabel Samimy: Yeah, thank you Annabel. I think, look, c. You know, where the direction is positive for us, right, but I think most importantly Even a couple of months ago, I think, you know, we were in a competitive situation where the data or the knowledge around our competitor was, I would say, weak in the retina community as far as it relates to what does this drug actually do, you know, what does it do in the long run. A lot of physicians, as I mentioned, didn't know that this drug was only approved initially for a one-year period, so that was called, you know, an act of surprise.

Speaker Change: Yeah. Thank you Annabel I think Luke.

Speaker Change: Sure.

Speaker Change: We'll see.

Speaker Change: Ultimately, we'll end up of course right.

Speaker Change: The direction is supposed to do for us right. So.

Speaker Change: But I think most importantly.

Speaker Change: Even a couple of months ago, I think we were in a competitive situation, where the data or the knowledge around or our competitor was I would say weak and the rest of that community as far as it relates to what does disrupt actually do.

Speaker Change: What does it do in the long run.

Speaker Change: Low physicians as I mentioned that this drug was only approved initially for a one year period, so that lets call it.

Cedric Francois: So I think that there's, you know, we are now playing in a level playing field, and in a level playing field, the differentiation of efficacy is... That is being recognized by retina doctors. And that's not just on the magnitude basis, it is also on the longitudinal data.

Speaker Change: Like the surprise, so I think that there.

Speaker Change: We are now playing in a level playing field and the level playing field the differentiation on the efficacy.

Speaker Change: As you know.

Speaker Change: Incredibly robust right and the other thing that's about retina doctors and that's not just on the magnitude basis and there is also other luxury tuna those data and I would say that's a real turning point for us.

Caroline Baumal: And I would say that's a real turning point for us. You know, that we're looking forward to working from I don't know, Caroline if you want to add something.

Speaker Change: We're looking forward to to.

Speaker Change: I'm working from I don't know.

Caroline Baumal: Well, I think one of the things that really differentiates us with physicians is the every-other-month dosing. And, you know, we use clinical studies to guide us. And the robust data we have, the heterogeneous, broad patients that were studied all demonstrate the efficacy into year four with every-other-month dosing, which will just increase the convenience and help patients stay compliant. So, I mean, physicians continually come up to me, are grateful for what we're presenting, and show that this long-term and every-other-month dosing speaks to their patient population. Okay, great.

Speaker Change: Karen I just want to add something.

Speaker Change: Well I think one of the things that really differentiates us with physicians is that every other month dosing and we use clinical studies.

Speaker Change: And the.

Speaker Change: Robust data, we have that heterogeneous broad patients that were studied.

Speaker Change: I'll show, the Devin demonstrate the efficacy and tier four with every other month dosing, which will just increase the convenience and help patients stay compliant. So physicians continually come up to me a great. So far but we're presenting and show that this long term and every other month dose.

Speaker Change: It speaks to their patient population.

Annabel Samimy: And if I could just ask a question on C3G, MPG, and LAUNCH, what are your expectations there? You know, you're not, Fivalta is clearly going to come out a little bit earlier, but you did mention that physicians are a little bit more focused on, or a lot more focused on efficacy. But I'm curious.

Speaker Change: Okay, great and if I could just ask a question on.

Speaker Change: <unk> launch what are your expectations there.

Speaker Change: Youre not.

Speaker Change: Clearly, that's something that a little bit earlier, but you did mention that physicians are a little bit more focused on are a lot more focus on efficacy.

Speaker Change: But I'm curious.

Cedric Francois: The level of urgency patients have to get on treatment, and so what can we expect for, I guess, an early launch trajectory for that product? Yeah, thank you Annabel. I think the key thing is that we see a demand in the requests that we already get for compassionate use and expanded use access, right? So demand is very important. Remember, these are younger patients, about half of whom over a 10 year period, which is not a lot when you're 20 or 30, have a 50% chance of losing their kidneys. So the need is incredibly high. And again, I want to emphasize that, you know, based on the data that we have, we will probably be competing probably only for about 20% of that overall bucket of patients.

Speaker Change: The level of urgency patients have to get on treatment and so what can we expect for I guess, the early launch trajectory for that product.

Speaker Change: Yeah. Thank you and then Bill I think the key thing is that we.

Speaker Change: We see the demands and the.

Speaker Change: And the requests that we already get for compassionate use and extended use excess spread.

Speaker Change: So the demand is very important to remember these are younger patients about half of whom over her tenure.

Speaker Change: Periods, which is not a lot, but you are 20 or 30.

Speaker Change: A 50% chance of losing their kidneys so that.

Speaker Change: The need is incredibly high and again I want to emphasize that.

Speaker Change: Based on the data that we have we will probably be competing probably only for about 20% of that overall bucket of patients. So.

Annabel Samimy: So a really important opportunity for us and for patients. Okay, great. Thank you.

Speaker Change: A really important opportunity for us and for patients.

Speaker Change: Okay, great. Thank you.

Unknown Executive: One moment for our next question.

Speaker Change: Thank you.

Speaker Change: One moment for our next question.

Douglas Tsao: Our next question will be coming from Douglas Tsao of H.C. Wainwright. Douglas, your line is open. Hi, good morning. Thanks for taking the questions. First question I had was in terms of the SIRNA plus Cypho-3 product, Cedric. I know in the past you've spoken about Cypho-3 having a very powerful effect on preservation of photoreceptors and less so on RPE cells.

Speaker Change: Our next question will be coming from Douglas Tsao of H C. Wainwright Douglas Your line is open.

Douglas Tsao: Hi, good morning, Thanks for taking the questions.

Douglas Tsao: First question I had was in terms of the sirna plus.

Douglas Tsao: Photography product centric.

Pat you've spoken about say appropriate having a very powerful effect on preservation of photo receptors and less so on RPE cells.

Cedric Francois: And so I'm just curious, with this approach, is this sort of what you're specifically targeting by going after the chloric, which is sort of adjacent to the RPE as well? Well, Doug, I'm very impressed with that question. You are correct. This is, so the impact that cytophobia has on the photoreceptors, you know, is near perfect, right, about 100% when you look in the first six months. I mean, it is, it's an incredibly robust impact on those photoreceptors. The RPE cells are the ones that continue to die, of course, meaningfully slowed down. And then the question that we're trying to answer here is, since if we, on the choroidal side, right, on the back of the eye, if we can lower C3 levels, will we be able to impact the RPE cells in a way that is similar to the photoreceptors?

Douglas Tsao: So I'm just curious with this approach is this sort of what you're specifically targeting.

Douglas Tsao: By going after the core equities.

Douglas Tsao: Which is sort of adjacent to the <unk> as well.

Douglas Tsao: Well im very impressed with that question.

Douglas Tsao: You are correct. This is.

Douglas Tsao: So the impact will be as of the third photo receptors.

Douglas Tsao: It's near perfect threat to about 100% when you look in the first six months I mean it is a.

Douglas Tsao: It's just an incredibly robust impact just one receptor.

Douglas Tsao: The RPE cells are the ones that continue today of course of course meaningfully slowed down and then the question that we're trying to answer here is since.

Douglas Tsao: The Colorado side right on the back of the year, if we can lower C. Three levels, we will be able to impact the RFP itself in a way that is similar to this one receptors. So excellent question against <unk>.

Timothy Sullivan: So excellent question, and the answer is yes. Okay, great.

Timothy Sullivan: And if I just a quick follow up for David, just I'm curious, you know, to the extent that you anticipate seeing an impact on the Medicare redesign for this year, or if you can qualify, you know, sort of quantify this. Okay, thank you for the question. I think quantifying that is challenging for us. And I would hate to take a guess at it. So it's something we're looking at. We've got a whole team, of course, that manages all the things that we do with payers, especially in our space with CMS. But I don't think I can quantify that at least Okay, great.

David: Okay, Great and then just a quick follow up for David just I'm curious to.

Douglas Tsao: To the extent that you anticipate seeing an impact on the Medicare redesign for this year.

David: Or if you can sort of quantify that at this point.

David: Okay. Thank you for the question I think quantifying that is challenging for us and I would hate to.

David: To take a guess at it.

David: So it's something we're looking at we've got a whole team of course that manages all of the things that we do with payers, especially in our space for CFS, but I don't think I can quantify that at least at this time.

Timothy Sullivan: Thank you so much.

Speaker Change: Okay, great. Thank you so much.

Joseph Stringer: One moment for our next question. Our next question will be coming from Joseph Stringer of Needham & Company. Your line is open, Joseph. Hi, good morning. Thanks for taking our questions too from us. I just wanted to get your updated commentary on any on the switching dynamics between cyphoborine and IZERVAY. And secondly, I know prior question asked about adherence rates, but just curious about compliance rates for cyphoborine, for example, patient Using or skipping injection.

David: Thank you.

David: One moment for our next question.

David: Our next question will be coming from Joseph Stringer of Needham <unk> Company. Your line is open Joseph.

Joseph Stringer: Hi, good morning, and thanks for taking our questions supervised.

Joseph Stringer: Just wanted to get your updated commentary on any.

Joseph Stringer: On the switching dynamics between Zach O'brien.

Joseph Stringer: And secondly, I know prior question asked about.

Joseph Stringer: Adherence rates, but just curious what about compliance rates for <unk>.

Joseph Stringer: Probably for example patients.

David Acheson: How does that look, or how has that changed over time?

Joseph Stringer: Skipping injection, how does that work or how has that changed over time. Thank you.

David Acheson: So, this is David. Thank you for the question. A couple of things. I think Cedric and Caroline touched on already some of the compliance where we fall with cyfobrine, and it's about in the same range as anti-VEGF. So, actually, I feel good about that because for us to be in the GA treatment area with something that's that compliant, I think it's very positive because it is a disease that's definitely slower than wet AMD. As far as the question on the dynamics of switching, so, you know, we look at this on a regular basis. I will tell you that we've had, you know, a number of weeks, especially during the CRL period that they had for the competitive product that we saw a number of switches, and I still think we're seeing that today in the first part of the front end of Q1.

Joseph Stringer: So so this is David Thank you for the question a couple of things I think Cedric and Carolina touched on already some of the compliance where we fall with Sidefoot Murray and it's about in the same range as the anti VEGF. So actually I feel good about that because for us to be in the under the GAA treatment area with something that's that can play in.

Joseph Stringer: <unk>.

Joseph Stringer: Think as very positive because it is a disease that was definitely slower than what.

Joseph Stringer: What AMD.

Joseph Stringer: As far as.

Joseph Stringer: As far as the question on the dynamics of switching.

Joseph Stringer: No.

Joseph Stringer: Look at this on a regular basis I would tell you that we've had.

Joseph Stringer: Number of <unk>.

Joseph Stringer: Weeks, especially during the <unk>.

Joseph Stringer: Period that they had or the competitive product that we saw a number of switches.

Joseph Stringer: And I still think we're seeing that today in the first part of the front end of Q1.

David Acheson: And the good thing is, and I think what's driving my thinking around that is the fact that we are seeing an increase in injections in Q1 versus Q4, and I think that we're in a good place to see growth overall in 2025.

Joseph Stringer: And the good thing is and I think what's driving.

Joseph Stringer: Im thinking around that is the fact that we are seeing an increase in injections in Q1 versus Q4.

Joseph Stringer: And I think that we're in a good place to see growth overall in 2025.

Lachlan Hanbury-Brown: One moment for our next question. Our next question will be coming from Lachlan Hanbury-Brown of William Blair. Your line is open. Hey guys, thanks for taking the question. I wanted to ask more about the efforts that you've made to get doctors off the sideline. You know, you've said that the sort of shift towards the efficacy-focused messaging is resonating well with physicians, but I'm wondering if you can sort of translate that into any changes of actual prescribing behaviours or new prescribers. Yeah, so that is that is what we are seeing. And thank you for that question.

Joseph Stringer: One moment for our next question.

Speaker Change: Our next question will be coming from Lachlan Hanbury Brown of William Blair. Your line is open.

Speaker Change: Hey, guys. Thanks for taking the question I wanted to ask more about the efforts that you've made to get doctors off the sideline you said that the sort of shift towards the efficacy focused focused messaging is resonating well with physicians, but I'm wondering if you can sort of translate that into any changes of actual prescribing behaviors or new.

Speaker Change: <unk>.

Speaker Change: Yes. So that is that is what we are seeing I. Thank you for that question.

Cedric Francois: I think what is what is gratifying after, you know, three years of launch now is that the data becomes very clear, right? We have the extension study, the data becomes, you know, much more concise to communicate.

Speaker Change: What is.

Speaker Change: What is gratifying after.

Speaker Change: Three years of launch now as that data becomes very clear that we have the extension study data becomes.

Speaker Change: Much more concise.

Cedric Francois: And, you know, the main message at Magdalena Society, which is one that I think really resonates the most, is that if you are on four years of treatments with cyfovir, you can have up to three square millimeters of retina preserved, right? And three square millimeters of retina is one and a half disc areas. It's a huge amount of real estate in tobacco. That is, you know, when you tell physicians that it resonates incredibly well, that is the reality of this drug and one that we can now really use moving forward. The safety situation is very stable and efficacy is becoming as impactful.

Speaker Change: So communicate and.

Speaker Change: The main message at Macula Society was just one that I think really resonates. The most is that if you are on four years of treatments with sexual free you could have up to three square meter meters of retina preserves right three square millimeters of breakfast is one of the health care, yes, it's a huge amount of real estate and tobacco.

Speaker Change: That is.

Speaker Change: So physicians that it resonates incredibly well that is the reality of this drug and one that we.

Speaker Change: They are not really who's moving forwards.

Speaker Change: The safety situation is very stable and efficacy becoming disciplined focus.

Lachlan Hanbury-Brown: Thanks.

Timothy Sullivan: And a follow-up, if I may, sort of following up on, I think, Yigal's earlier question on patent life for Empavelli. I was curious if you can give any color on what you had assumed for IRA price negotiations when you were doing the sort of business cases for FSGS and DGF. I realize there's probably still more questions than answers there, but just would be great to get your thoughts on sort of. What you'd assumed.

Speaker Change: Thanks Anna.

Speaker Change: The follow up if I may sort of following up on <unk> question on patent law firm to valley.

Speaker Change: Curious if you can give any color on what you had assumed for raw price negotiations. When you were doing the sort of business cases for <unk> and DTF I realize there's probably still more questions than answers there, but just would be great to get your thoughts on sort of.

Speaker Change: What you'd assumed.

Timothy Sullivan: Yeah, thank you so much. So these are, look, we did a thorough analysis after the readout of Valiant in the kidney based on the premise that we have clearly exquisite target engagements in the kidney, in the glomerulus, and we did the usual work that you do in that situation, the competitive analysis, the biology, what can we do with the pathogen life of the drug, and that is where these two diseases emerge. So much more will follow, but we're excited about these indications and we'll be And one more.

Speaker Change: Yes.

Speaker Change: Yes. Thank you. So much. So these are look we did a thorough analysis after the readout of Valeant indicate.

Speaker Change: It could be based on the premise that we have clear the exquisite target engagements.

Speaker Change: Bear with us.

Speaker Change: As we did the usual work that you're doing that situations are competitive analysis. The biology, what can we do.

Speaker Change: That's the life of the drug and that is where are these two diseases emerge. So much more will follow but we're excited about these indications.

Speaker Change: And one more question.

Ryan Deshner: One moment for our next question. Our next question will be coming from Ryan Deshner. Raymond James, your line is open, Ryan. Good morning, and thanks for the question.

One moment for our next question.

Our next question will be coming from Ryan Deschner of Raymond James Your line is open right.

Ryan Deschner: Hi, good morning, and thanks for the question.

Timothy Sullivan: Have your expectations for gross to net in 2025 in a steady state evolved at all in the last few months and Can you give us any more detail on what you're expecting to see in terms of timing and duration of the impact of the new DTC campaign on sales in 2025 and beyond, based on what you saw in the prior campaign? Yeah, thank you very much for the question.

Ryan Deschner: Expectations for gross to net in 2025.

Ryan Deschner: <unk> stayed evolved at all in the last few months and.

Speaker Change: Can you give us any more detail on what youre expecting to see in terms of timing and duration of the impact of a new DTC campaign on sales in 2025 and beyond.

Ryan Deschner: Based on what you saw in the prior campaign. Thank you.

David Acheson: I'll take the gross net piece and then hand it over to David for the impact of the DTC. So, the simple answer is no, our view on gross net hasn't changed at all. At the end of the third quarter, we did guide to low to mid-20s throughout the course of 2025, and that remains the same.

David Anderson: Yes. Thank you very much for the question I'll take the gross to that piece and then hand, it over to David for the impacts of the CTC.

David Anderson: The simple answer is none of our demand growth so that hasnt changed at all at the end of the third quarter, We did guide to.

David Anderson: Low to mid twenties throughout the course of <unk>.

David Anderson: 25, and that that remains the same and David Yes. Thank you Tim.

David Acheson: David? Yep. Thank you, Tim.

David Acheson: So, I appreciate the question on DTC. It's a little early. We started running that commercial on television with Henry Winkler in mid-January, but I can give you one piece of information that happened that will give you an indicator of some of the early impact that we can see. We did have the commercial run during the Saturday Night Live 50th Anniversary Special. We had about 15 million views on the commercial, which was attributed to driving about 3,000 visits to our website at that time. So, we can see things like that early. It's going to take time for us to see the total impact throughout the next several months.

David Anderson: So I appreciate the question on DTC, It's a little early we started running that commercial on TV with Henry Winkler January in mid January but I can give you one piece of information that happens that will give you an indicator of some of the early impact that we can see we did have the commercial run during the Saturday night live 50th anniversary special.

David Anderson: At about 15 million views on the commercial.

David Anderson: <unk> was.

David Anderson: Attributed to driving about 3000 visits to our website.

David Anderson: At that time, so we can see things like that early it's going to take time for assessing the total impact.

David Anderson: Throughout the next several months.

David Acheson: Excellent.

Unknown Executive: Thank you very much. And we do have time for one more question.

David Anderson: Okay.

David Anderson: Excellent. Thank you very much.

David Anderson: And we do have time for one more question.

Derek Achila: And our last question will be coming from Derek Achila of Wells Fargo. Your line is open. Hey, good morning, and thanks for taking the question.

David Anderson: Okay.

David Anderson: And our last question will be coming from Derrick Sheila.

David Anderson: Sheila of Wells Fargo. Your line is open.

David Anderson: Hey, good morning, and thanks for taking the question maybe just two for Tim I guess, how should we think about opex growth in 2025 relative to 'twenty four.

Derek Achila: Maybe just two for Tim. I guess, how should we think about, you know, OpEx growth in 2025 relative to 2024? You know, is there going to be a lot of growth coming from, you know, some of the R&D initiatives that you guys talked about? And just, you know, based on some of the seasonal factors and one cue in the sampling, I guess, how should we be thinking about gross margin trends through 2025? Sure. So From the perspective of OPEX versus 2024, you know, as we said in our prepared remarks, that we expect those to be more or less the same.

David Anderson: Is there going to be a lot of growth coming from some of the R&D initiatives that you guys talked about and just based on some of the seasonal factors and <unk> and the sampling I guess, how should we be thinking about gross margin trends through 'twenty five.

David Anderson: Sure so.

David Anderson: From the perspective of Opex versus 2024, we said in our prepared remarks that we expect those to be more or less the same.

Timothy Sullivan: I think that's probably the case when you think about what we've, some cost savings from our European infrastructure, some of which we scaled down, that will be offset by some R&D expenditure that gets increased. And then from the gross margin perspective, you know, we don't guide on that. There's a lot that goes into gross margin that sort of moves around. But from a sampling perspective, you know, I think we gave you everything we could from the perspective of color on how we project that. We really don't have any visibility. What we do know, what we did talk about, is that we see, you know, an approximately 5,000, you know, vial estimated increase of samples in this quarter.

David Anderson: Think that's probably the case when you think about what we've.

David Anderson: Cost savings from our European infrastructure.

Some of which we scaled down.

David Anderson: That'll be offset by some R&D expenditure that gets increased.

David Anderson: And then from a gross margin perspective.

David Anderson: Guide on that.

David Anderson: A lot that goes into gross margin that sort of moves around but from a sampling perspective.

David Anderson: I think we gave you everything we could from that.

David Anderson: Perspective of color on how we project that we really don't have any visibility, but we do know what we did talk about is that we see in approximately 5000.

David Anderson: Vial estimated increase of samples in this quarter and so doing the math on that you can kind of get to a reasonable idea of what our revenue is provide you can understand what that would be.

Timothy Sullivan: And so doing the math on that, you can kind of get to a reasonable idea of what our revenue is per vial. You can understand what that would be. And frankly, that's, you know, that's... That's the piece that we can right now kind of get into our risk margin impact in the first quarter, at least as an estimate. Beyond that, we really have no visibility on. Yeah, thank you.

David Anderson: And frankly that settlement.

David Anderson: No that's.

David Anderson: That's the piece that we've got right now kind of.

David Anderson: Gross margin impacted them just in the first quarter pizza as an estimate beyond that we really have no visibility. Unfortunately.

David Anderson: Got it thank you.

Cedric Francois: And I would now like to turn the call back to Cedric Francois for closing remarks. Thank you so much, and thank you, everyone, for joining us this morning. If you have any follow-up questions, please feel free to reach out to Meredith. Thank you.

Cedric Francois: And I would now like to turn the call back to Cedric bench Wahl for closing remarks.

Cedric Francois: Thank you so much and thank you everyone for joining us. This morning, if you have any follow up questions. Please feel free to reach out to Meredith. Thank you so much.

Unknown Executive: And this concludes today's conference call. Thank you for participating. You may now disconnect.

Speaker Change: And this concludes today's conference call. Thank you for participating you may now disconnect.

Cedric Francois: Yeah.

Cedric Francois: Okay.

Cedric Francois: [music].

Unknown Executive: Thank you for watching!

Cedric Francois: Okay.

Cedric Francois: Okay.

Cedric Francois: [music].

Cedric Francois: Okay.

Cedric Francois: Okay.

Cedric Francois: Okay.