Apellis Pharmaceuticals, Inc. · NASDAQ:APLS
Apellis Pharmaceuticals — Technical Presentation (2018)
21 slides from Apellis Pharmaceuticals's technical presentation, 2018
Slide 1: APL-2 in GA: Phase II FILLY Trial 18-Month Results
APL-2 in GA: Phase II FILLY Trial 18-Month Results • Nathan Steinle, MD
Slide 2: Financial Disclosures
Financial Disclosures • Speaker for Regeneron • Speaker for Genentech • Speaker for Alimera Sciences • Consultant for Regenerative Patch Technologies • Consultant for Regeneron • Consultant for Genentech • Consultant for Alimera Sciences • Consultant for Vortex Surgical • Consultant for Notal Vision
Slide 3: Key Takeaways
Key Takeaways • APL-2 reduced the progression of GA secondary to AMD in the largest Phase 2 GA trial (n=246) • Results correlated to treatment frequency with increasing effect size over time • Further confidence in results from intra-patient control • Upon discontinuation of APL-2, treatment effect
Slide 4: Accumulation of complement fragments in plasma and in the eyes of AMD patients
Accumulation of complement fragments in plasma and in the eyes of AMD patients (A): C3d, (B): C3dg/C3b, (C): iC3b, in drusen, choroid, sub-RPE space Scholl, H. P. N. et al. Systemic complement activation in age-related macular degeneration. PLoS One 3, 1–7 (2008). C5 staining – “soft” drusen Membran
Slide 5: The Complement Pathway and Geographic Atrophy
The Complement Pathway and Geographic Atrophy Lectin Pathway Classical Pathway Alternative Pathway APL-2 C3 Factor D Cell removal, Inflammation C3a C3b Antigen uptake by APCs C5 Cell death, secretion, Inflammation C5a C5b MAC lysis, or proliferation 5
Slide 6: FILLY - Phase 2 study of APL-2 in Geographic Atrophy
FILLY - Phase 2 study of APL-2 in Geographic Atrophy Sham APL-2 injections APL-2 injections Injections every other month every month n= 81 n= 79 n= 86 APL-2 APL-2 APL-2 0 mg 15 mg 15 mg 6
Slide 7: Study Design
Study Design Apellis Eligible Patients with Geographic Atrophy* 246 subjects in 43 sites’ GO . _ SS | Single Masked Randomized 2:2:4:1 APL-2 15 mg APL-2 15 mg Sham Every Other Month ni Every Other Month (AEOM) (SEOM) N=79 N=40 TreatmentPeriod * Follow up SEee8888 ~~ Be 8 «= oo oe 7 3 = Bu *Confirmed
Slide 8: FILLY – timeline and endpoints
FILLY – timeline and endpoints Primary efficacy endpoint is the primary registration endpoint Change in geographic atrophy (GA) lesion size from baseline to month 12. images Primary safety taken at 0 2 6 12 18 endpoint months months months months Number and severity of local and systemic treatment e
Slide 9: Key Inclusion/Exclusion Criteria
Key Inclusion/Exclusion Criteria • Inclusion Criteria: ‒ Age ≥ 50 years ‒ GA due to AMD confirmed by the central reading center using FAF images: § Total GA area 2.5 to 17.5 mm2 (1 to 7 DA) at Screening § For multifocal GA, at least one lesion with ≥ 1.25 mm2 (0.5 DA) § Completely visualized GA on t
Slide 10: Baseline characteristics
Baseline characteristics Sham APL-2 every APL-2 injections other month monthly N=81 N=79 N=86 Bilateral GA, n (%) 72 (90.0%) 64 (82.1%) 71 (85.5%) History of CNV in Fellow Eye, n (%) 29 (35.8%) 28 (35.4%) 36 (41.9%) GA lesion size, mean, mm2 (SD) 8.2 (4.1) 8.9 (4.5) 8.0 (3.8) BCVA score, mean letter
Slide 11: APL-2 slows GA growth at 12 months (square root)
APL-2 slows GA growth at 12 months (square root) sham APL-2 every APL-2 injections other month monthly 0.5 Change from baseline in square root 0.4 GA lesion growth (mm) 0.35 20% lesion growth difference 0.3 p=0.067 vs Sham 0.28 0.25 29% lesion 0.2 growth difference p=0.008 vs Sham 0.1 0 Modified Int
Slide 12: Lesion growth by six-month periods (square root)
Lesion growth by six-month periods (square root) – 12 months Sham APL-2 injections APL-2 injections injections every other month every month 0-6 6-12 0-6 6-12 0-6 6-12 months months months months months months 0 0 0 0.1 0.1 0.1 Lesion growth 0.2 0.2 0.2 0.3 0.3 0.3 (mm) 0.4 0.4 0.4 0.5 0.5 0.5 33% l
Slide 13: FILLY sham group behaved consistently with recent publication
FILLY sham group behaved consistently with recent publication 0.5 sham APL-2 every APL-2 Change from baseline in square root injections other month monthly 0.4 GA lesion growth (mm) 0.35 0.3 0.28 0.25 0.2 0.1 0 2 months 6 months 12 months Holz, F.G., et al., Efficacy and Sham Lampalizumab, 10 mg Saf
Slide 14: GA growth resumes after cessation but treatment effect maintained through 18 months
After cessation of treatment at 12 months, GA growth resumes but treatment effect is maintained through 18 months (square root) sham APL-2 every APL-2 injections other month monthly 0.5 0.49 16% lesion growth difference 0.41 p=0.097 vs Sham Change from baseline in square root 0.4 0.39 20% lesion GA
Slide 15: Lesion growth by six-month periods (square root) – 18 months
Lesion growth by six-month periods (square root) – 18 months Sham APL-2 injections APL-2 injections injections every other month every month 0-6 6-12 12-18 0-6 6-12 12-18 0-6 6-12 12-18 months months months months months months months months months 0 0 0 0.1 0.1 0.1 Lesion growth 0.2 0.2 0.2 0.3 0.3
Slide 16: GA growth comparison: fellow eye vs study eye post hoc analysis
GA growth comparison: fellow eye vs study eye post hoc analysis Sham APL-2 injections APL-2 injections Injections every other month every month n= 72 n= 63 n= 69 10% 23% Difference Difference Change from baseline in square root 0.4 0.4 0.4 p > 0.1 p = 0.083 GA lesion growth (mm) 0.3 0.3 0.3 Fellow F
Slide 17: Best-corrected Visual Acuity
Best-corrected Visual Acuity 17
Slide 18: Adverse Event Profile
Adverse Event Profile APL-2 Every Adverse Event APL-2 Monthly Sham Pooled Other Month n (%) of subjects with events N=86 N=81 N=79 Ocular SAEs in study eye* 4 (4.7%) 2 (2.5%) 1 (1.2%) Systemic (non-ocular) SAEs 19 (22.1%) 24 (30.4%) 23 (28.4%) Treatment related ocular AEs in the study eye 22 (25.6%)
Slide 19: New onset exudation – 18 months
New onset exudation – 18 months APL-2 Monthly APL-2 EOM Sham Pooled All Subjects n = 86 n =79 n = 81 Subjects with wAMD in Study eye (%) 18 (20.9%) 7 (8.9%) 1 (1.2%) With History of CNV in Fellow Eye n = 36 n =28 n = 29 Subjects with wAMD in Study eye (%) 13 (36.1%) 5 (17.9%) 0 No CNV History in Fel
Slide 20: New onset exudation
New onset exudation • Subjects that developed exudation had minor loss of vision and were treated with anti-VEGF • 6 patients developed wet AMD in the 12-18 month non-treatment period (5/6 had fellow eye wet AMD) Illustrative OCT scan of an exudative AMD with Subject 2 (monthly): Exudative AMD (Mont
Slide 21: Key Takeaways
Key Takeaways • APL-2 reduced the progression of GA secondary to AMD in the largest Phase 2 GA trial (n=246) • Results correlated to treatment frequency with increasing effect size over time • Further confidence in results from intra-patient control • Upon discontinuation of APL-2, treatment effect
Apellis Pharmaceuticals — Technical Presentation (2018) on 6ix