Apellis Pharmaceuticals, Inc.
APLSBusiness Summary
Apellis Pharmaceuticals, Inc. is a commercial-stage biopharmaceutical company focused on discovering, developing, and commercializing novel therapeutic compounds by inhibiting the complement system. The company currently markets two drugs targeting C3: SYFOVRE (pegcetacoplan injection), approved by the FDA in February 2023 for geographic atrophy (GA) secondary to age-related macular degeneration, and EMPAVELI (pegcetacoplan), approved by the FDA in May 2021 for paroxysmal nocturnal hemoglobinuria (PNH) and in July 2025 for C3 glomerulopathy (C3G) and primary immune complex membranoproliferative glomerulonephritis (primary IC-MPGN) 1. Apellis believes SYFOVRE has the potential to be the standard of care for GA, a disease affecting an estimated 1.5 million people in the United States 2. The company has exclusive worldwide commercialization rights for SYFOVRE, with a focus on the U.S. and select international markets like Australia, where it received marketing approval in January 2025 3. For EMPAVELI, Apellis holds exclusive U.S. commercialization rights, while Swedish Orphan Biovitrum AB (Publ) (Sobi) holds exclusive ex-U.S. commercialization rights for systemic pegcetacoplan 4.
The core business model revolves around the discovery, development, and commercialization of complement system inhibitors. Revenue is generated primarily through product sales of SYFOVRE and EMPAVELI, as well as royalties from collaboration partners like Sobi. Primary customer segments include patients with rare diseases such as PNH, C3G, primary IC-MPGN, and GA. The company leverages its expertise in complement immunology to develop new pipeline candidates, either as independent treatments or as supplements to pegcetacoplan's effects 5.
SYFOVRE (pegcetacoplan injection) is commercialized as a monotherapy for GA. GA is an advanced stage of age-related macular degeneration, characterized by progressive loss of retinal cells, leading to irreversible vision loss. An estimated 1.5 million people in the United States are living with GA 6. SYFOVRE aims to prevent or reduce retinal cell death by inhibiting complement activation at the C3 level, with increasing treatment effects observed over time in Phase 3 trials 7. It is administered intravitreally, with dosing flexibility of once every 25 to 60 days 8. For the years ended December 31, 2025 and 2024, SYFOVRE generated $586.9 million and $611.9 million, respectively, in U.S. net product revenue 9.
EMPAVELI (pegcetacoplan) is approved for PNH, C3G, and primary IC-MPGN. PNH is a rare, chronic blood disorder affecting approximately 4,700 patients in the United States 10. EMPAVELI targets C3 to address both intravascular and extravascular hemolysis in PNH. For C3G and primary IC-MPGN, rare kidney diseases affecting an estimated 5,000 people in the United States, EMPAVELI is designed to prevent C3 activation and protect the kidney from injury 11. For the years ended December 31, 2025 and 2024, EMPAVELI generated $102.4 million and $98.1 million, respectively, in U.S. net product revenue 12. Royalties from Sobi for ex-U.S. sales of Aspaveli were $13.2 million and $18.4 million for the years ended December 31, 2025 and 2024, respectively 13.
For the fiscal year ended December 31, 2025, Apellis Pharmaceuticals, Inc. reported total revenue of $702.5 million 14. The company achieved a net income of $22.4 million 15, a significant improvement from net losses of $197.9 million in 2024 and $528.6 million in 2023 16. The accumulated deficit as of December 31, 2025, was $3.0 billion 17. Cash and cash equivalents stood at $466.2 million 18. The company generated net cash from operating activities of $45.3 million in 2025, compared to net cash usage of $87.9 million in 2024 and $594.7 million in 2023 19. Total debt as of December 31, 2025, included $375.0 million under the Sixth Street Financing Agreement and approximately $93.9 million principal amount of Convertible Notes 20.
Year-over-year, U.S. net product revenue from SYFOVRE decreased from $611.9 million in 2024 to $586.9 million in 2025 21. Conversely, U.S. net product revenue from EMPAVELI increased from $98.1 million in 2024 to $102.4 million in 2025 22. Royalties from Sobi decreased from $18.4 million in 2024 to $13.2 million in 2025 23. The shift from a net loss in 2024 to net income in 2025 indicates a positive inflection point in the company's financial performance, driven by revenue generation and potentially controlled expenses.
Significant operational developments during the period include the FDA approval of EMPAVELI for C3G and primary IC-MPGN in July 2025 24. In January 2025, the TGA in Australia approved SYFOVRE for every-other-month treatment of adult patients with GA 25. The company initiated a Phase 2 multi-dose clinical trial of a combination therapy of SYFOVRE with APL-3007 (a small interfering RNA) in patients with GA in June 2025 26. Two pivotal clinical trials with EMPAVELI were initiated in the fourth quarter of 2025 for primary focal segmental glomerulosclerosis (FSGS) and delayed graft function (DGF) 27. In July 2025, Apellis entered into a Royalty Buy-Down Agreement with Sobi, receiving an upfront payment of $275.0 million and agreeing to reduce Sobi's royalty payment obligations by 90% 28. In August 2025, Apellis opted into a license agreement with Beam Therapeutics for APL-9099, an FcRn gene editing treatment, triggering an upfront milestone payment of $3.8 million 29. The company also launched a single package for SYFOVRE (co-pack) in the fourth quarter of 2025 to standardize administration and streamline distribution 30.
Business Outlook
Apellis Pharmaceuticals, Inc. aims to transform the treatment of GA with SYFOVRE, maximize EMPAVELI's impact in rare diseases, and advance its innovative pipeline by leveraging its complement expertise in 2026 31. The company anticipates achieving net operating income based on its current operating plan, though it notes that profitability may not be sustained 32.
A major growth area is the development of a next-generation treatment for GA by combining SYFOVRE with APL-3007, a small interfering RNA (siRNA) designed to comprehensively block complement activity in the retina and choroid 33. A Phase 2 multi-dose clinical trial of this combination in patients with GA was initiated in June 2025 to evaluate safety, biologic activity, and pharmacodynamics 34. The company believes that with less C3 present in the eye following APL-3007 administration, there may be a greater degree of efficacy contribution from SYFOVRE 35.
Another significant growth vector is the expansion of EMPAVELI's indications in nephrology. Two pivotal clinical trials with EMPAVELI were initiated in the fourth quarter of 2025 for primary focal segmental glomerulosclerosis (FSGS) and delayed graft function (DGF) 36. FSGS is a rare kidney disease affecting an estimated 13,000 primary FSGS patients in the United States, with approximately half suffering end-stage kidney disease within 5-10 years 37. DGF is a complication in kidney transplantation, occurring in 30-35% of the estimated 21,000 U.S. deceased donor kidney transplants in 2023 38. There are currently no FDA-approved therapies for either FSGS or DGF, presenting a significant unmet medical need 39. The FSGS study (APL2-FSG-319) is a sequential Phase 2/3 trial evaluating efficacy and safety of twice-weekly subcutaneous infusions of pegcetacoplan, with a primary objective of reducing proteinuria 40. The DGF study (APL2-DGF-318) is a randomized, double-blind, placebo-controlled trial with a primary endpoint of time to freedom from dialysis to Day 90 41.
The company is also advancing its innovative pipeline through its collaboration with Beam Therapeutics, Inc. for APL-9099, a treatment targeting the neonatal Fc receptor (FcRn) 42. Preclinical studies for APL-9099 have commenced, with the potential for a first-in-class gene editing treatment offering one-time dosing for future target indications 43. In August 2025, Apellis opted into a license agreement with Beam for the FcRn program in the liver, triggering an upfront milestone payment of $3.8 million 44. Under this agreement, Beam is eligible to receive up to $168.8 million in regulatory and development milestones and up to $215.0 million in sales-based milestones, along with low single-digit royalties on annual net sales 45.
Regarding operational outlook, the company plans to submit for regulatory approval of a single dose, sterilized prefilled syringe for SYFOVRE in the first half of 2026, which is expected to provide physicians with a new, more convenient administration method 46. The company continuously reviews its supply chain risk and implements mitigation plans 47.
Planned capital allocation includes continued significant expenses for commercializing EMPAVELI and SYFOVRE, prioritizing ongoing development of pegcetacoplan, and focusing research initiatives on high-potential opportunities like APL-3007 and APL-9099 48. The company believes its cash and cash equivalents of $466.2 million as of December 31, 2025, combined with anticipated cash from product sales, will be sufficient to fund projected operating expenses and capital expenditures for at least the next 12 months, as well as longer-term cash requirements 49.
Management explicitly flagged structural headwinds and execution risks, including the potential for SYFOVRE to be less effective or cause safety issues not identified in clinical trials, such as the reported retinal vasculitis events 50. A change in the perception of SYFOVRE's benefit/risk profile could reduce market acceptance and adversely affect product revenues 51. The company also faces substantial competition in GA from avacincaptad pegol and in PNH from eculizumab, ravulizumab, and iptacopan, with iptacopan also competing in C3G 52. The regulatory approval process is expensive, time-consuming, and uncertain, with no guarantee of obtaining approvals for SYFOVRE in additional jurisdictions or for EMPAVELI in other indications 53. The European Commission's negative opinion on SYFOVRE's MAA in the EU in 2024 is noted as potentially impacting approval prospects in other jurisdictions 54. Furthermore, the company relies on third parties for manufacturing, storage, and distribution, increasing the risk of insufficient quantities or unacceptable costs 55.
Geographic, regulatory, and macro factors identified as constraints include the uncertainty surrounding the FDA's draft Diversity Action Plan (DAP) guidance and how it will consider DAPs in connection with NDA reviews 56. The EU's new Clinical Trials Regulation (EU) No 536/2014, effective January 2022, could delay clinical studies in the EU if not navigated properly 57. The ongoing review of EU pharmaceutical legislation, with proposed changes potentially reducing regulatory exclusivity protection, is expected to be adopted by mid-2026 and take effect in mid-2028 58. The U.S. Inflation Reduction Act of 2022 (IRA) has implications for Medicare Part D, including price negotiations for certain costly single-source drugs starting in 2026, which could subject Apellis's products to maximum fair price negotiations and impact profitability 59. The Trump Administration's Executive Orders and proposed pilot programs like GLOBE and GUARD, aiming to reduce pharmaceutical prices and implement reference pricing, also introduce significant uncertainty and potential adverse effects on business 60.
Risk Factors
Apellis faces material risks including the potential for SYFOVRE or EMPAVELI to be less effective or cause safety issues not identified in clinical trials, such as the reported retinal vasculitis events with SYFOVRE, which could compromise market acceptance and reduce product revenues 61. The company faces substantial competition in GA from avacincaptad pegol and in PNH from eculizumab, ravulizumab, and iptacopan, with iptacopan also competing in C3G 62. The regulatory approval process is expensive, time-consuming, and uncertain, with the European Commission's negative opinion on SYFOVRE's MAA in the EU in 2024 potentially impacting approval prospects in other jurisdictions 63. Dependence on third parties for manufacturing, storage, and distribution increases the risk of supply interruptions or unacceptable costs 64. Macroeconomic and geopolitical risks include the uncertainty surrounding the FDA's draft Diversity Action Plan (DAP) guidance, the EU's new Clinical Trials Regulation, and the ongoing review of EU pharmaceutical legislation, which could reduce regulatory exclusivity 65. The U.S. Inflation Reduction Act of 2022 (IRA) and Trump Administration's Executive Orders and proposed pilot programs (GLOBE and GUARD) aiming to reduce pharmaceutical prices and implement reference pricing, could subject Apellis's products to Medicare price negotiations and impact profitability 66. The company also carries $375.0 million of indebtedness under its financing agreement with Sixth Street and approximately $93.9 million principal amount of Convertible Notes maturing in September 2026 67, with covenants including maintaining liquidity of at least $50.0 million if market capitalization is below $3.0 billion 68.
Management Priorities
Management's message to shareholders emphasizes a continued focus on compassion and commitment to patients, aiming to transform the treatment of GA with SYFOVRE, maximize EMPAVELI's impact in rare diseases, and advance an innovative pipeline leveraging complement expertise in 2026 69. They explicitly state the anticipation of achieving net operating income based on the current operating plan, while cautioning that profitability may not be sustained 70. Key strategic priorities include the ongoing commercialization of EMPAVELI and SYFOVRE, prioritizing the ongoing development of pegcetacoplan, and focusing research initiatives on high potential opportunities such as APL-3007 and APL-9099 71. Management believes that the cash and cash equivalents of $466.2 million as of December 31, 2025, combined with anticipated cash from sales of EMPAVELI and SYFOVRE, will be sufficient to fund projected operating expenses and capital expenditure requirements for at least the next 12 months, as well as anticipated longer-term cash requirements and obligations 72.
View Source Annual Report on SEC.gov ↗
References
- [1] Item 1, Business — Overview
- [2] Item 1, Business — Overview
- [3] Item 1, Business — Overview
- [4] Item 1, Business — Overview
- [5] Item 1, Business — Our Strategy
- [6] Item 1, Business — Geographic Atrophy
- [7] Item 1, Business — Benefits of Our Approach
- [8] Item 1, Business — Benefits of Our Approach
- [9] Item 1, Business — Overview
- [10] Item 1, Business — Paroxysmal Nocturnal Hemoglobinuria (PNH)
- [11] Item 1, Business — EMPAVELI in Nephrology
- [12] Item 1, Business — Overview
- [13] Item 1, Business — Overview
- [14] Item 7, MD&A — Consolidated Results
- [15] Item 1A, Risk Factors — Risks Related to Our Financial Position and Need for Additional Capital
- [16] Item 1A, Risk Factors — Risks Related to Our Financial Position and Need for Additional Capital
- [17] Item 1A, Risk Factors — Risks Related to Our Financial Position and Need for Additional Capital
- [18] Item 1A, Risk Factors — Risks Related to Our Financial Position and Need for Additional Capital
- [19] Item 1A, Risk Factors — Risks Related to Our Financial Position and Need for Additional Capital
- [20] Item 1A, Risk Factors — Risks Related to Our Financial Position and Need for Additional Capital
- [21] Item 1, Business — Overview
- [22] Item 1, Business — Overview
- [23] Item 1, Business — Overview
- [24] Item 1, Business — Overview
- [25] Item 1, Business — Overview
- [26] Item 1, Business — Overview
- [27] Item 1, Business — Overview
- [28] Item 1, Business — Overview
- [29] Item 1, Business — Research Collaboration with Beam
- [30] Item 1, Business — Product Development
- [31] Item 1, Business — Our Strategy
- [32] Item 1A, Risk Factors — Risks Related to Our Financial Position and Need for Additional Capital
- [33] Item 1, Business — SYFOVRE and APL-3007
- [34] Item 1, Business — SYFOVRE and APL-3007
- [35] Item 1, Business — SYFOVRE and APL-3007
- [36] Item 1, Business — Overview
- [37] Item 1, Business — EMPAVELI in Nephrology
- [38] Item 1, Business — EMPAVELI in Nephrology
- [39] Item 1, Business — EMPAVELI in Nephrology
- [40] Item 1, Business — EMPAVELI in FSGS
- [41] Item 1, Business — EMPAVELI in DGF
- [42] Item 1, Business — Overview
- [43] Item 1, Business — Overview
- [44] Item 1, Business — Research Collaboration with Beam
- [45] Item 1, Business — Research Collaboration with Beam
- [46] Item 1, Business — Product Development
- [47] Item 1, Business — Manufacturing
- [48] Item 1A, Risk Factors — Risks Related to Our Financial Position and Need for Additional Capital
- [49] Item 1A, Risk Factors — Risks Related to Our Financial Position and Need for Additional Capital
- [50] Item 1A, Risk Factors — Risks Related to Commercialization and Product Development
- [51] Item 1A, Risk Factors — Risks Related to Commercialization and Product Development
- [52] Item 1A, Risk Factors — Risks Related to Commercialization and Product Development
- [53] Item 1A, Risk Factors — Risks Related to Regulatory Approval and Marketing of Our Product Candidates and Other Legal Compliance Matters
- [54] Item 1A, Risk Factors — Risks Related to Regulatory Approval and Marketing of Our Product Candidates and Other Legal Compliance Matters
- [55] Item 1A, Risk Factors — Risks Related to Our Dependence on Third Parties
- [56] Item 1A, Risk Factors — Risks Related to Regulatory Approval and Marketing of Our Product Candidates and Other Legal Compliance Matters
- [57] Item 1A, Risk Factors — Risks Related to Regulatory Approval and Marketing of Our Product Candidates and Other Legal Compliance Matters
- [58] Item 1A, Risk Factors — Risks Related to Regulatory Approval and Marketing of Our Product Candidates and Other Legal Compliance Matters
- [59] Item 1A, Risk Factors — Current and future legislation may increase the difficulty and cost for us and our collaborators to obtain reimbursement of and commercialize our product candidates and affect the prices we, or they, may obtain.
- [60] Item 1A, Risk Factors — Current and future legislation may increase the difficulty and cost for us and our collaborators to obtain reimbursement of and commercialize our product candidates and affect the prices we, or they, may obtain.
- [61] Item 1A, Risk Factors — We or others may later discover that EMPAVELI or SYFOVRE is less effective than previously believed or causes safety issues that were not identified in clinical trials, which could compromise our ability, or that of our collaborators, to market the product.
- [62] Item 1A, Risk Factors — We face substantial competition, which may result in others discovering, developing or commercializing products before or more successfully than we do.
- [63] Item 1A, Risk Factors — The regulatory approval process is expensive, time consuming and uncertain and may prevent us or our collaborators such as Sobi from obtaining approvals for the commercialization of pegcetacoplan or any of our product candidates that we develop.
- [64] Item 1A, Risk Factors — We contract with third parties for the manufacture, storage and distribution of commercial supply for EMPAVELI, SYFOVRE, and clinical supply for our product candidates and expect to continue to do so in connection with our future development and commercialization efforts.
- [65] Item 1A, Risk Factors — The regulatory approval process is expensive, time consuming and uncertain and may prevent us or our collaborators such as Sobi from obtaining approvals for the commercialization of pegcetacoplan or any of our product candidates that we develop.
- [66] Item 1A, Risk Factors — Current and future legislation may increase the difficulty and cost for us and our collaborators to obtain reimbursement of and commercialize our product candidates and affect the prices we, or they, may obtain.
- [67] Item 1A, Risk Factors — The terms of our indebtedness could adversely affect our operations and limit our ability to plan for or respond to changes in our business.
- [68] Item 1A, Risk Factors — The terms of our indebtedness could adversely affect our operations and limit our ability to plan for or respond to changes in our business.
- [69] Item 1, Business — Our Strategy
- [70] Item 1A, Risk Factors — Risks Related to Our Financial Position and Need for Additional Capital
- [71] Item 1A, Risk Factors — Risks Related to Our Financial Position and Need for Additional Capital
- [72] Item 1A, Risk Factors — Risks Related to Our Financial Position and Need for Additional Capital
Analysis on 5/22/2026