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Boldly delivering life-changing medicines Cedric Francois, M.D., Ph.D. Co-Founder, Chief Executive Officer and President January 13, 2025
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2 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. Such forward-looking statements include the Company’s plans, strategies and expectations for its preclinical, clinical and commercial development of its products and product candidates, its expectations regarding the sNDA for pegcetacoplan for the treatment of for C3G and primary IC-MPGN and the potential commercialization thereof, its plans to initiate Phase 3 studies of pegcetacoplan in FSGS and DGF and the Company’s expectations regarding achieving profitability and the timing thereof. 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 adjustments to the Company’s preliminary revenue figures resulting from, among other things, the completion of financial closing and review procedures for the quarter and year ended December 31, 2024; 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 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 (SEC) on February 27, 2024, in Apellis’s Quarterly Report on Form 10-Q filed with the SEC on August 1, 2024 and the risks described in other filings that Apellis may make with the SEC. 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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3 Our mission We combine courageous science and compassion to develop life -changing medicines for some of the most challenging diseases patients face ROB Living with GA
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4 Apellis is positioned for sustainable value creation Maximizing two blockbuster opportunities with SYFOVRE and EMPAVELI Leveraging expertise in complement science to advance our pipeline and drive the next wave of therapeutic innovation On a path to profitability
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5 Building a top-tier biotech company through clinical and commercial execution 2009 – 2021 Pioneered a new class of complement medicines Advanced therapies that target C3 to provide comprehensive control of complement 2021 – 2024 Became leaders in C3 therapies Delivered first new class of complement medicines in 15 years 2025+ Unlocking blockbuster potential & driving the next wave of innovation Reach more patients with SYFOVRE & EMPAVELI Deliver multiple kidney launches Advance innovative pipeline leveraging complement expertise Our ambitions:
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6 On track to deliver long-term profitable growth Cash and cash equivalents of $410 million as of December 31, 20241 Expect existing cash and projected revenues to fund operations to profitability 1. Estimated 2024 cash and cash equivalents are unaudited, preliminary and based on management’s estimate as of the date of this presentation and are subject to completion of the Company’s financial closing and review procedures. 2. Non-GAAP Operating Expenses are adjusted for stock-based compensation, depreciation and amortization. Nine months ending September 30, 2023 Nine months ending September 30, 2024 Total Revenue Non-GAAP OpEx + Cost of Sales 128% YOY Total Revenue growth ~$620M ~$250M ~$570M ~$600M 2
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7 Our three strategic pillars Transform the treatment of GA with SYFOVRE Maximize EMPAVELI’s impact in rare diseases Advance innovative pipeline, leveraging our expertise in complement
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8 Strategic pillar #1: transform the treatment of GA with SYFOVRE • Strengthen SYFOVRE’s position as standard of care • Develop leading next-gen therapy: SYFOVRE + APL-3007 (siRNA) • Become a leader in nephrology, starting with C3G/IC-MPGN • Expand into additional rare, nephrology indications • Develop novel, gene-edited FcRn therapy Transform the treatment of GA with SYFOVRE Maximize EMPAVELI’s impact in rare diseases Advance innovative pipeline leveraging expertise in complement
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9 has increased efficacy over time is approved for use beyond 12 months SYFOVRE is the market-leading treatment for GA in the U.S. is approved for as few as 6 doses per year is in a preferred position with many payers ONLY SYFOVRE
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10 SYFOVRE maintains U.S. leadership in GA category with >120% annual sales growth in FY 2024 1. Estimated 2024 SYFOVRE net product revenue are unaudited, preliminary and based on management’s estimate as of the date of this presentation and are subject to completion of the Company’s financial closing and review procedures. ~$886 million Since launch through December 31, 2024 62K >510K injections through December 31, 2024, including clinical trials 2023 2024 SYFOVRE Injections (incl. clinical trials) 160K 510K 2023 2024 SYFOVRE U.S. net product revenue $611M $275M
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11 Strengthening SYFOVRE’s position as standard of care Secure SYFOVRE as the market leader Grow the GA market Executing on two key priorities: 5 ~1.5M GA patients estimated in U.S.1 GA patients currently in ECP office <10% total currently treated GA patients in ECP office2 1. Friedman DS et al., Arch Ophthalmol 2004; Apellis analysis and assumptions. 2. Qdata AMD, as of October 2024, provided by Verana Health, Inc.
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12 SYFOVRE is well-positioned for continued growth and leadership Strong execution Strong value proposition ~70% non-PE-backed practices Apellis data on file. Diverse customer mix >170 congresses >200 peer-to-peer education programs >2,300 sites of care have ordered SYFOVRE >95% of Medicare lives with broad coverage 0 Payers with a 12-month restriction Only preferred GA therapy ~30% PE-backed practices
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13 Key initiatives to bring SYFOVRE to more GA patients Broaden reach to eyecare community Amplify real-world data with clinical analyses & third -party evidence Connect with patients through new DTC campaign Educate payers on SYFOVR E’s differentiated value proposition
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14 New SYFOVRE DTC campaign launching this month!
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15 SYFOVRE + APL-3007: potential next generation treatment aimed at comprehensively blocking complement activity in the retina and choroid APL-3007 (siRNA) Phase 1 study in healthy volunteers Mean change from baseline in C3 • Strategic goal: evaluate potential for SYFOVRE + APL-3007 to show superiority vs SYFOVRE alone • APL-3007 reduced circulating C3 concentration by up to 90% in a single dose, Phase 1 healthy volunteer study • Expect to initiate Phase 1b/2 multi-dose study in 2Q 2025 1. Phase 1b/2 study will evaluate safety, biologic activity, and pharmacodynamics of multiple doses of APL-3007 in combination with SYFOVRE. -100 -80 -60 -40 -20 0 Mean (±SE) % Change from Baseline in Complement C3 (mg/dL) Time Point (Day) Dose 1 Dose 2 Dose 3 Dose 4 Pooled Dose Pooled Placebo
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16 Strategic pillar #2: maximize EMPAVELI’s impact in rare diseases • Strengthen SYFOVRE’s position as standard of care • Develop leading next-gen therapy: SYFOVRE + APL-3007 (siRNA) • Become a leader in nephrology, starting with C3G/IC-MPGN • Expand into additional rare, nephrology indications • Develop novel, gene-edited FcRn therapy Transform the treatment of GA with SYFOVRE Maximize EMPAVELI’s impact in rare diseases Advance innovative pipeline leveraging expertise in complement
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17 EMPAVELI on track to become a blockbuster opportunity 1. Estimate based on available epidemiological literature and claims data. 2021 PNH Hematology 2025 C3G & IC-MPGN Rare Nephrology 2028+ DGF & FSGS Rare Nephrology ~1.5K patients 1 ~5K patients 1 ~30K patients 1
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18 As of December 31 , 2024: • ~$23 million in 4Q 2024 U.S. net product revenue • ~97% patient compliance rate • Continued strong safety profile with zero meningococcal infections due to encapsulated bacteria • Robust efficacy sustained long -term EMPAVELI continues to elevate the standard of care in PNH 1. Estimated 2024 EMPAVELI net product revenue are unaudited, preliminary and based on management’s estimate as of the date of this presentation and are subject to completion of the Company’s financial closing and review procedures.
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19 C3G and IC -MPGN: two debilitating kidney diseases • Rare kidney diseases with no approved therapies • Progress to kidney failure in ~50% of patients within 5-10 years of diagnosis ‒ Leads to kidney transplant or lifelong dialysis, neither curative • ~5,000 1 people with C3G/IC-MPGN in U.S. 1. Based on moderate & severe patient population. C3G: ClearView Analysis using physician and literature consensus
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20 C3G/IC-MPGN: EMPAVELI showed positive effects on 3 key disease markers in 6 Months in Phase 3 VALIANT study 68.1% relative reduction1 (95% CI) in pegcetacoplan vs placebo arms (57.3, 76.2) P<.0001 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/1.73m 2 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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21 Feedback from C3G patient in VALIANT study Joining the [VALIANT] trial and receiving pegcetacoplan has changed my and my family’s lives. I am back to my old self again. I have the energy not only to walk around the block, but to climb mountains and to run marathons. I have been able to reduce the number of medications I was taking to less than half. Simply put, you have given me hope, and that is the best thing patients like myself can ask for. 1. Individual patient results may vary.
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22 Anticipate broad EMPAVELI adoption in C3G and IC-MPGN 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 ~5K C3G / IC-MPGN patients estimated in U.S. 1Severe Post transplant Moderate Mild
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23 ~70% of C3G/IC -MPGN patients covered by overlapping PNH targets 1. Apellis internal assessment based on claims data and HCP-HCO affiliation analysis. C3G/IC -MPGN Nephrology Primary HCO Targets 1 ~900 overlapping accounts include: ~70% 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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24 Focused commercial footprint covers majority of target nephrologists and patients HCO accounts Each sales-based employee covers ~20 HCO accounts Of the ~900 target HCO accounts, commercial footprint requires less than 50 sales-based employees
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25 Expanding EMPAVELI into new rare, kidney indications PRIMARY FOCAL SEGMENTAL GLOMERULOSCLEROSIS (FSGS) DELAYED GRAFT FUNCTION (DGF) Plan to initiate two Phase 3 trials in 2H 20251 1. FDA interactions are planned in 1H 2025 for both indications.
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26 Primary FSGS is a rare, progressive kidney disease Approximately 13,000 patients in the US have primary FSGS1 FSGS DISEASE OVERVIEW • Rare kidney disease that causes scarring in the glomeruli and can lead to ESRD UNMET NEED • No FDA-approved therapies • ~50% of patients progress to end-stage kidney disease ( ESKD) within 5-10 years1 • Persistent proteinuria is a major predictor of progression and remains difficult to control RATIONALE FOR EMPAVELI • Low levels of C3 correlate with higher disease activity, poorer outcomes, and higher risk of progression to ESKD • Complement proteins are detected in glomeruli of patients 1. Prevalence estimated using claims data and published literature for FSGS incidence and sub-types. 2. Bensink, Mark E et al. Kidney Med. 2023;6(2):100760 (USRDS Analysis).
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27 DGF presents a significant challenge in kidney transplantation DGF DISEASE OVERVIEW • A condition where the transplanted kidney fails to function, requiring dialysis <1-week post-transplant UNMET NEED • No FDA-approved therapies • DGF leads to a higher incidence of transplant rejection including re-transplantation • Risk of graft failure and mortality persist after DGF resolution RATIONALE FOR EMPAVELI ● Complement plays a significant role in transplantation process ● Comprehensive C3 inhibition may both prevent and treat complement overactivation associated with DGF DGF occurs in approximately 30- 35% of deceased donor kidneys (~21,000 in the US in 2023)1 1. Organ Procurement and Transplantation Network.
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28 Key EMPAVELI milestones in 2025 Early 2025 Plan to submit U.S. supplemental NDA for C3G / IC -MPGN 2H 2025 U.S. launch of EMPAVELI in C3G/IC -MPGN, if approved Early 2025 Sobi expected to submit application in EMA for C3G / IC -MPGN 2H 2025 Anticipate initiation of two Phase 3 trials in nephrology
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29 Strategic pillar #3: advance innovative pipeline • Strengthen SYFOVRE’s position as standard of care • Develop leading next-gen therapy: SYFOVRE + APL-3007 (siRNA) • Become a leader in nephrology, starting with C3G/IC-MPGN • Expand into additional rare, nephrology indications • Develop novel, gene-edited FcRn therapy Transform the treatment of GA with SYFOVRE Maximize EMPAVELI’s impact in rare diseases Advance innovative pipeline leveraging expertise in complement
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30 Developing first-ever gene editing approach to FcRn OPPORTUNITY FOR: First-ever, gene-edited FcRn Neonatal Fc receptor (FcRn) One-time dosing Pre-clinical studies ongoing
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31 PRODUCT DISEASE PRECLINICAL PHASE 1 PHASE 2 PHASE 3 APPROVED OPHTHALMOLOGY SYFOVRE® (pegcetacoplan injection) GA APL-3007 + SYFOVRE GA RARE DISEASE EMPAVELI® (pegcetacoplan)* PNH C3G / IC-MPGN HSCT-TMA FSGS DGF NEUROLOGY RNA therapies Undisclosed MULTIPLE THERAPEUTIC AREAS Gene-edited FcRn therapy (Beam) Undisclosed Gene-edited complement therapies (Beam) Undisclosed Oral complement inhibitor Undisclosed *Sobi has global co-development and ex-U.S. commercialization rights for systemic pegcetacoplan The safety and efficacy of the agents for the indications under investigation have not been established. Advancing innovative pipeline leveraging expertise in complement Marketed in the US Marketed in the US Plan to Initiate Ph3 in H2 2025 Plan to Initiate Ph1b/2 in Q2 2025 Plan to Initiate Ph3 in H2 2025
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32 Apellis is positioned for sustainable value creation Maximizing two blockbuster opportunities with SYFOVRE and EMPAVELI Leveraging expertise in complement science to advance our pipeline and drive the next wave of therapeutic innovation On a path to profitability