Retina Pipeline 2021

RETINA PIPELINE 2021 Suppress inflammation Alternative Classical Lectin A VIEW INTO ONGOING Targeting the Complement Cascade DRY AMD ANX007 (Annexon) — C1q Inhibition INNOVATION pegcetacoplan (Apellis) — C3 Convertase Inhibition CB2782 (Catalyst) — C3 Convertase Inhibition avacincaptad pegol (IVERIC bio) — C5 Convertase Inhibition ALXN1720 (Alexion) — C5 Convertase Inhibition Autophosphorylation Antibody HMR59 (Hemera) — MAC Inhibition by sCD59 C3 Antigen C1q danicopan (Achillion) — Complement Factor D Inhibition COMPLEMENT COMPLEMENT C1r + C1s MBL Ionis-FB-LRx (Ionis/Roche) — Complement Factor B Inhibition Factor D Factor B GEM103 (Gemini) — Complement Factor H Therapy C4 GT005 (Gyroscope) — Complement Factor I Therapy Any Cell iC3b C3 Convertase (non-activating surface) MASPs OMS721 (Omeros) — Blocks MASP-2 PROPERDIN Amplification Loop OMS906 (Omeros) — Blocks MASP-3 C2 TT30 (Alexion) — Blocks C3 Opsonization COMPLEMENT C3 C3 IBI302 (Innovent Biologics) — sCR1 Inhibition/Anti-VEGF iC3b Factor H T Cell TMi-018 (Translatum Medicus Inc) — Blocks M1 Transcriptome Expression C3bBb AVD-104 (Aviceda Therapeutics) — Enhances CFH Binding to C3b COMPLEMENT KNP-301 (Kanaph Therapeutics) — Blocks C3b/Anti-VEGF Factor I C4b2a

C3b macrophage • Opsonization, phagocytosis • IC solubilization C3a Other approaches • B cell activation (CR2 and C3dg) • Clearance of debris and apoptotic cells © sciencesource.com Inflammasome Inhibition C5 Convertase • Activation of T cells and APCs (C4b2a3b, C3bBbC3b) kamuvudine (Inflammasome Therapeutics) Xiflam (OcuNexus) C5 C5a Matrix Modulation T Cell doxycycline (Oracea) Neuroprotection HtrA1 inhibitor Any Cell C5b FHTR2163 (Genentech/Roche) T Cell IC500 (IVERIC bio) macrophage Repair mitochondrial dysfunction/oxidative stress • Activation of T Cells and APCs Macrophage Membrane Attack Complex • Tissue regeneration • Leukocyte recruitment and activation elamipretide (Stealth) • Inflammasome activation risuteganib (Allegro) Bacteria cell • Cell activation C8 C7 C6 • Killing and/or C9 photobiomodulation (LumiThera) Stem cells target damage Chemotatic or C9 C8 C7 brimonidine tartrate (Allergan) anaphylactic peptides C9 Human embryonic stem cells (hESCs) C8 C9 C9 (Lineage Cell Therapeutics) Convertases (Regenerative Patch Technologies) C7 C8 C9 Reduce toxic by-product accumulation Alternative pathway Umbilical stem cells (hUTCs) C6 C7 Human retinal progenitor cells (jCyte) Prevents Amyloid Aβ oligomer assembly Lectin pathway GAL-101 (Galimedix) ALZ-801 (Alzheon) Visual cycle modulation Classical pathways Reduce DHA peroxidation B:25.75" Any Cell RT011 (Retrotope) ALK-001 (Alkeus) T:25.5" B:4.25" T:4"

11454347_GNE_Retina_Today_Poster_M3FR.indd 1 PREPARED BY 11/9/20 2:41 PM 11454347 11454347 GNE Franchise Retina Today Pipeline Poster SPECSM3FR Job info Images Fonts Special Instructions Date: 11-9-2020 2:41 PM FRANCHISE_PIPELINE_POSTER (101620).ai None Long Horizontal PosterBleed: 25.75 x 4.25Trim: Client: GENENTECH, USA. (100%; 1.0MB), Genentech_tag_KO.eps (263%; 25.5 x 4Far right third of poster (8.5 x 4) will show Product: GENENTECH OPHTHALMOLOGY FRANCHISE 263KB) when folded and tipped. Client Code: M-US-00002046(v2.0) Additional Information WF Issue # 7556253 None Releasing as: Native Files Final Size: 25.5" x 4" Finishing: None Gutter: None Inks Additional Comments for Sizing Colors: 4CP Cyan, Magenta, Yellow, Black Bleed includes .125in bleed all around Team Producer: Cassandra Castillo AD: Serena Haahs AE: Beatrice Jean-Mary Scale: 1" = 1" QC: None Bleed 25.75" w x 4.25" h 25.75" w x 4.25" h Production: Frank Robinson Trim/Flat 25.5" w x 4" h 25.5" w x 4" h Digital Artist: studio Live/Safety 25.5" w x 4" h 25.5" w x 4" h FR Spellcheck: None

Path: PrePress:Genentech:OPHTHALMOLOGY_Franchise:11454347:11454347_GNE_Retina_Today_Poster_M3FR.indd PDFX1A _ PETER K. KAISER, MD | Medical Advisor, Retina Today; Cole Eye Institute, Cleveland Clinic; Cleveland, Ohio Keeping an eye on drug development in AMD is difficult. Therapeutic options move from one RETINA PIPELINE 2021 phase to the next at different times and at different rates, and drugs may start their path in one disease only to find success treating another. We hope you use this poster to understand A VIEW INTO ONGOING where we stand in clinical development for AMD treatment as we enter 2021. INNOVATION WET AMD

Other Pathways TIE2 Activation Pathways Integrin Pathways Tyrosine Kinase inhibitor (TKi) Pathways

CVX-51401 (CavtheRx) — Caveolin Modulator faricimab (Genentech/Roche) risuteganib (Allegro/Senju) volociximab (IVERIC bio) OTX-Tki/axitinib (Ocular Therapeutix) APX3330 (Ocuphire) — Ref-1 Inhibitor AG-73305 (Allgenesis Biotherapeutics) PAN THR-687 (Oxurion) OTT116 (OcuTerra) KPI-285 (Kala) AR-13503 (Aerie Pharmaceuticals) — Rho kinase (ROCK) inhibitor BI 836880 (Boehringer Ingelheim) AG-73305 (Allgenesis Biotherapeutics) GB-102/sunitinib (Graybug) EXN407 (Exonate) — SRPK1 Inhibitor AXT107 (AsclepiX Therapeutics) PAN 90806 (Panoptica) aganirsen (Gene Signal) — Inhibition of insulin receptor substrate 1 (IRS-1) SK-1011 (Sanwa Kagaku) Pericyte X-82/sunitinib (Tyrogenex) VEGF-R1 VEGF-R2 VEGF-R3 Integrin Receptors TIE2 Receptor PDGF Receptor axitinib (Clearside Biomedical) VEGF-A VEGF-A VEGF-C Ang1 PDGF-AA VEGF-B VEGF-C VEGF-D Ang2 PDGF-BB PLGF Ang3/4 PDGF-AB PDGF-CC Gene Therapy PDGF-DD DNA Genome RGX-314 (RegenxBio) ADVM-022 (Adverum)

Extracellular VEGF Pathways © 2019 by The Angiogenesis Foundation, Inc., All Rights Reserved VEGF PLGF D C B A pegaptanib (Valeant) FDA-APPROVED SHC AKT ranibizumab (Genentech/Roche) FDA-APPROVED GRB2 bevacizumab (Genentech/Roche) OFF-LABEL Therapeutic Protein brolucizumab (Novartis) FDA-APPROVED RAS abicipar pegol (Allergan) SOS RAS KSI-301 (Kodiak Sciences) ERK FYB201 (biosimilar) (Formycon/Bioeq) Tyrosine Kinase cascade PF582 (biosimilar) (Pfenex/Pfizer) RAF razumab (biosimilar) (Intas) CHS3551 (biosimilar) (Coherus Biosciences) MEK PROLIFERATION SB11 (biosimilar) (Samsung Bioepis) ONS-510 (biosimilar) (Outlook Therapeutics) DIFFERENTIATION Xlucane (biosimilar) (Xbrane) ERK PD807 (biosimilar) (Biopharm) SURVIVAL Therapeutic Gene SBS7001 (biosimilar) (Siam Bioscience) aflibercept (Regeneron/Bayer) FDA-APPROVED Nuclear Pore KNP-301 (Kanaph Therapeutics) conbercept (Kanghong Biotech) AG-73305 (Allgenesis Biotherapeutics) CHS-2020 (biosimilar) (Coherus Biosciences) Suprachoroidal injection: ranibizumab Port Delivery System (PDS) Polymer extended release: SOK583A1 (biosimilar) (Sandoz/Hexal) axitinib (Clearside Biomedical) RGX-314 (RegenxBio) OTX-TKI MYL1710 (biosimilar) (Mylan/Momenta) Clearside Biomedical (Ocular Therapeutix) GB-102 ALT-L9 (biosimilar) (Alteogen) (Graybug Vision) OPT-302 (Opthea) Extended KSI-301 (Kodiak Sciences) Duration AR-13503 Options Genentech (Aerie Pharmaceuticals) Kodiak Sciences Content guidance and source: Peter K. Kaiser, MD; *Editorially independent content supported by advertising from Genentech/Roche