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July 29, 2025 EMPAVELI® (Pegcetacoplan) FDA Approval in C3 Glomerulopathy (C3G) and Primary Immune Complex Membranoproliferative Glomerulonephritis (IC -MPGN)
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2 Q & A S E S S I O N O P E N I N G R E M A R K S A N D K E Y H I G H L I G H T S Cedric Francois, M.D., Ph.D., Co-Founder, President & CEO D I S E A S E O V E R V I E W, T R I A L D ATA , A N D L A B E L H I G H L I G H T S Caroline Baumal, M.D., Chief Medical Officer E M PAV E L I C 3 G & I C- M P G N U . S . L A U N C H P L A N S David Acheson, Executive Vice President of Commercial Agenda
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3 Forward-looking statements Statements in this presentation about future expectations, plans and prospects, as well as any other statements regarding matters that are not historical facts, may constitute “forward-looking statements” within the meaning of The Private Securities Litigation Reform Act of 1995. The words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “will,” “would” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including whether the results of the Company’s clinical trials for EMPAVELI, SYFOVRE, or any of its future products will warrant regulatory submissions to the FDA or equivalent foreign regulatory agencies; whether systemic pegcetacoplan will receive approval from the FDA or equivalent foreign regulatory agencies for C3G and IC-MPGN or any other indication when expected or at all; rate and degree of market acceptance and clinical utility of EMPAVELI, SYFOVRE and any future products for which we receive marketing approval will impact our commercialization efforts; whether SYFOVRE will receive approval from foreign regulatory agencies for GA when expected or at all; whether the Company’s clinical trials will be completed when anticipated; whether results obtained in clinical trials will be indicative of results that will be generated in future clinical trials or in the real world setting; whether the period for which the Company believes that its cash resources will be sufficient to fund its operations; and other factors discussed in the “Risk Factors” section of Apellis’ Annual Report on Form 10-K with the Securities and Exchange Commission on February 28, 2025 and the risks described in other filings that Apellis may make with the Securities and Exchange Commission. Any forward-looking statements contained in this presentation speak only as of the date hereof, and Apellis specifically disclaims any obligation to update any forward-looking statement, whether as a result of new information, future events or otherwise.
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4 For the first time, patients with C3G and primary IC -MPGN can be treated with a C3 -targeted therapy EMPAVELI is indicated for the treatment of adult and pediatric patients aged 12 years and older with C3G or primary IC-MPGN, to reduce proteinuria. NOW APPROVED
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5 EMPAVELI is the only product to achieve the trifecta of outcomes across all three key markers of disease Proteinuria Reduction eGFR Stabilization Substantial clearance of C3 deposits Well-established safety profile in line with existing label
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6 EMPAVELI's broad label addresses significantly underserved patient populations First and only FDA-approved treatment for adult and pediatric (12+ years) patients with primary IC-MPGN Only FDA-approved treatment for pediatric (12+ years) C3G patients Only FDA-approved treatment for post-transplant C3G disease recurrence
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7 Leveraging the power of C3 to deliver life -changing medicines to patients Third FDA approval in just four years, including SYFOVRE in GA1 (2023) and EMPAVELI in PNH2 (2021) Expansion of EMPAVELI franchise in rare kidney disease, with initiation of pivotal studies in FSGS3 and DGF4 by year end 1 GA: Geographic atrophy 2 PNH: Paroxysmal nocturnal hemoglobinuria 3 FSGS: Focal segmental glomerulosclerosis 4 DGF: Delayed graft function
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DISEASE OVERVIEW, TRIAL DATA, AND LABEL HIGHLIGHTS Caroline Baumal, M.D., Chief Medical Officer
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9 C3G and primary IC -MPGN: two debilitating kidney diseases characterized by complement overactivation and C3 deposition Significant Unmet Need • Patient diagnosis often occurs in late teens to mid-20s • ~50% of patients progress to kidney failure within 5-10 years of diagnosis1-3 • Kidney failure requires kidney transplant or lifelong dialysis • 90% of patients who receive transplants experience disease recurrence4 Chase Living with C3G 1. Smith RJH, et al. Nat Rev Nephrol. 2019;15(3):129-143. 2. Servais A, et al. Kidney Int. 2012;82(4):454-464. 3. Zand L, et al. J Am Soc Nephrol. 2014;25(5):1110-1117. 4. Tarragón, B, et al. C3 Glomerulopathy Recurs Early after Kidney Transplantation in Serial Biopsies Performed within the First 2 Years after Transplantation. Clinical Journal of the American Society of Nephrology. August 2024; 19(8)1005-1015. doi: 10.2215/CJN.0000000000000474.
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10 1Subjects entering VALE, the planned long -term extension study, will not complete the follow -up period. Phase 3 VALIANT study design Group 1 + 2 (n=124) Pegcetacoplan + SOC Group 1 (n=62) Pegcetacoplan + SOC Group 2 (n=62) Placebo + SOC Standard of Care (SOC) (n=124) Screening SC infusion, twice weekly Randomized, double-blind placebo-controlled period Wash Out Population: Patients 12 years+ with C3G or primary IC-MPGN pre- and post - transplant and evidence of active renal disease. Primary endpoint: Log- transformed ratio of urine protein -to-creatinine ratio (uPCR) at Week 26 vs. baseline. Selected secondary endpoints: Change in kidney function measured by eGFR. Reduction in C3c staining. VALE extension study Up to 10 weeks 26 weeks Primary endpoint readout Open-label period 26 weeks Follow-up1 8 weeks SC infusion, twice weekly
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11 The Trifecta: EMPAVELI showed positive effects on all three key disease markers 68.1% (57.3, 76.2) P<.0001 relative reduction1 (95% confidence index ) in pegcetacoplan vs placebo arms 1 Percentages calculated by converting the ratio of geometric means to percentages 71.4% of pegcetacoplan-treated patients achieved zero intensity staining at week 26 vs 8.8% for placebo Clearance of C3c Staining Demonstrated stabilization of kidney function based on 6-month eGFR Stabilization of eGFRReduction in Proteinuria Baseline Week 26 +6.3 mL/min/1.73m2 pegcetacoplan vs placebo P=.03 (nominal) Consistent effects across subgroups based on disease type, age, and transplant status Favorable safety and tolerability, consistent with established profile
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12 Indication Statement • EMPAVELI is indicated for the treatment of adult and pediatric patients aged 12 years and older with C3 glomerulopathy (C3G) or primary immune-complex membranoproliferative glomerulonephritis (IC-MPGN), to reduce proteinuria Dosing and Administration • Recommended dosage for adults is 1,080 mg administered subcutaneously twice weekly • Recommended dosage for pediatric patients is dependent upon patient weight Safety • Boxed warning for meningococcal infections and for risk of serious infections caused by encapsulated bacteria • REMS program requires prescriber enrollment; prescribers must educate patients and ensure vaccination • Contraindications for hypersensitivity and unresolved serious infection caused by encapsulated bacteria • Warnings about serious infections and infusion-related reactions • Most common adverse reactions in patients with C3G or primary IC-MPGN ( ≥10%): infusion site reactions, pyrexia, nasopharyngitis, influenza, cough, and nausea EMPAVELI: overview of prescribing information
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EMPAVELI C3G & Primary IC-MPGN U.S. LAUNCH PLANS David Acheson, Executive Vice President of Commercial
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14 5,000 C3G and primary IC -MPGN patients in the U.S. 1. 2024 claims data analysis (patients with confirmed diagnosis). Servais et al. Kidney Int. 2012; 82(4): 454. Iatropoulos et al, Mol Immunol. 2016; 71: 131 Note: Scale is an approximation based on APLS internal estimates. ~5K C3G / IC-MPGN patients estimated in U.S. 1 Primary IC-MPGN EMPAVELI is on the path to blockbuster status Post-Transplant / Pediatric C3G Adult C3G, native kidney Competitor label
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15 Meaningful overlap between C3G and primary IC -MPGN patients and PNH-target facilities 1. Apellis internal assessment based on claims data and HCP-HCO affiliation analysis. C3G/IC-MPGN Nephrology Primary HCO Targets1 ~900 overlapping accounts include: ~60% of C3G / IC-MPGN patients ~60% of prescribing nephrologists PNH Primary HCO Targets OVERLAPPING HCO TARGETS 25% overlap between C3G/IC-MPGN and PNH primary HCO targets
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16 Maximizing the potential of EMPAVELI in C3G and Primary IC-MPGN Raise awareness about the availability of a disease-modifying therapy • With EMPAVELI now approved, the underlying cause of disease can be directly targeted through C3 inhibition Establish EMPAVELI as the treatment of choice • Trifecta of outcomes (proteinuria, eGFR, C3 staining) • Equate early use of EMPAVELI with the preservation of kidney function and long-term disease control Secure broad access as soon as possible • Helping patients with insurance support, disease education, and more • Actively engaging with payers to ensure broad coverage Highly Experienced Commercial Team
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CLOSING REMARKS Cedric Francois, M.D., Ph.D., Co -Founder, President & CEO
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July 29, 2025 EMPAVELI® (Pegcetacoplan) FDA Approval in C3 Glomerulopathy (C3G) and Primary Immune Complex Membranoproliferative Glomerulonephritis (IC -MPGN)