retina pipeline *editorially independent content supported by...
TRANSCRIPT
Content guidance and source: Peter K . Kaiser, MD; *Editorially independent content supported by advertising from GenentechRETINA PIPELINE
A VIEW INTO ONGOING INNOVATION
November/December 2019
Tyrosine Kinase cascade
Therapeutic Protein
VEGF-R1
VEGF-AVEGF-BPLGF
VEGF-AVEGF-C
VEGF-CVEGF-D
VEGF-R2 VEGF-R3
Tyrosine Kinase inhibitor (TKi) Pathways
OTX-TKi (Ocular Therapeutix)RTKi-MPP (Kala)GB-102 (Graybug)PAN 90806 (Panoptica)SK 1011 (Sanwa Kagaku)sutent (x-82) (Tyrogenex)axitinib (Clearside Biomedical) AR-13503 (Aerie Pharmaceuticals) Caveolin subdomain downstream inhibitorCVX-51401 (CavtheRx)
W E T A M D
Gene Therapy
Extended Duration Options
RGX-314 (RegenxBio)ADVM-022 (Adverum)HMR59 (Hemera)
DNA Genome
Nuclear Pore
Therapeutic GeneSURVIVAL
DIFFERENTIATION
PROLIFERATION
SHCGRB2 AKT
RAS
ERKSOS
RAS
RAF
MEK
ERK
ranibizumab Port Delivery System (PDS)
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 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 where we stand in clinical development for AMD treatment as we enter 2020.
Ang1Ang2Ang 3/4
TIE2 Receptor
© 2019 by The Angiogenesis Foundation, Inc., All Rights Reserved
Integrin Receptors
TIE2 Activation Pathways
faricimab (Genentech/Roche)AXT107 (AsclepiX Therapeutics)
PDGF-AAPDGF-BBPDGF-ABPDGF-CCPDGF-DD
PDGF Receptor
Pericyte
Clearside Suprachoroidal injection
Clearside Biomedical
Genentech
Polymer Extended Release:
OTX-TKI (Ocular Therapeutix) GB-102 (Graybug Vision) KSI-301 (Kodiak Sciences) AR-13503 (Aerie Pharmaceuticals)
Kodiak Sciences
PLGF D C B AVEGF
Extracellular VEGF Pathways
pegaptanib (Valeant)ranibizumab (Genentech/Roche)bevacizumab (Genentech/Roche)brolucizumab (Novartis) abicipar pegol (Allergan)KSI-301 (Kodiak Sciences)FYB201 (biosimilar) (Formycon/Bioeq)PF582 (biosimilar) (Pfenex/Pfizer)razumab (biosimilar) (Intas)CHS3551 (biosimilar) (Coherus Biosciences)SB-11 (biosimilar) (Samsung Bioepis)FYB201 (biosimilar) (Formycon/Bioeq)ONS-510 (biosimilar) (Outlook Therapeutics)Xlucane (biosimilar) (Xbrane)CHS3551 (biosimilar) (Coherus Biosciences)PD807 (biosimilar) (Biopharm)SBS7001 (biosimilar) (Siam Bioscience)aflibercept (Regeneron/Bayer)conbercept (Kanghong Biotech)CHS-2020 (biosimilar) (Coherus Biosciences)SOK583A1 (biosimilar) (Sandoz/Hexal)MYL1710 (biosimilar) (Mylan/Momenta)ALT-L9 (biosimilar) (Alteogen)OPT-302 (Opthea)
Integrin Pathways
risuteganib (Allegro/Senju)THR-687 (Oxurion)
volociximab (IVERIC bio)SF0166 drop (SciFluor)AXT107 (AsclepiX Therapeutics)
PAN
axitinib (Clearside Biomedical)RGX-314 (RegenxBio)
FDA-APPROVED
FDA-APPROVED
OFF-LABEL
FDA-APPROVED
FDA-APPROVED
RETINA PIPELINE A VIEW INTO ONGOING INNOVATION
D RY A M D
Dry AMD Emerging Treatment Strategies
Prevent photoreceptor and RPE loss • Neuroprotection • Reduce toxic by-product accumulation • Visual cycle modulation • Stem CellsSuppress inflammationOther approaches
Other approaches
Inflammasome Inhibitionkamuvudine (Inflammasome Therapeutics) Xiflam (OcuNexus)Matrix Modulation HtrA1 inhibitordoxycycline (Oracea) FHTR2163 (Genentech/Roche)
Neuroprotection
Repair mitochondrial dysfunction/ oxidative stresselamipretide (Stealth)risuteganib (Allegro)photobiomodulation (LumiThera)brimonidine tartrate (Allergan)
NT-501 - ciliary neurotrophic factor (Neurotech)tandospirone (Alcon)OT-551 (Othera)FA
ILED
Stem Cells
Human embryonic stem cells (hESCs) (Lineage Cell Therapeutics)(Regenerative Patch Technologies)Umbilical stem cells (hUTCs) Human retinal progenitor cells ( jCyte)
Reduce toxic by-product accumulation
Prevents Amyloid Aβ oligomer assemblyGAL-101 (Galimedix) ALZ-801 (Alzheon)Reduce DHA peroxidationRT011 (Retrotope)
Glatiramer acetate (Copaxone, FDA approved, Teva)RN6G (Pfizer)GSK933776 (GSK)FA
ILED
Visual cycle modulation
ALK-001 (Alkeus) fenretinide (Sytera)emixustat (Acucela)OT-551 (Othera)FA
ILED
Content guidance and source: Peter K . Kaiser, MD; *Editorially independent content supported by advertising from Genentech
MBL
C4
C2
C3C3
C3
Factor B
Properdin
Factor D
C3b
C5C5b
MAC
C6
C7
C8
C9
C5a C5a
C3a
C3a
C3b or iC3b
Chemotatic or anaphylactic peptides
Convertases
Alternative pathway
Lectin pathway
Classical pathways
MAC proteins
C5 Convertase(C4b2a3b, C3bBbC3b)
C4b2aC3bBb
C1r + C1s
Host Cell
Host Cell(non-activating surface)
Host Cell
Host Cell
MASPs
C1qSuppress inflammation
PETER K. KAISER, MD• Medical Advisor, Retina Today• Cole Eye Institute, Cleveland Clinic• Cleveland, Ohio
Complement inhibition location and molecule ANX007 (Annexon) APL-2 (Apellis) CB2782 (Catalyst) Zimura (IVERIC bio) ALXN1720 (Alexion) HMR59 (Hemera) danicopan (Achillion) CR2-fH Ionis-FB-LRX (Ionis)
Alternative
Lectin Classical
• Opsonization, phagocytosis• IC solubilization• B cell activation (CR2 and C3dg)• Clearance of debris and apoptotic cells
• Activation of T Cells and APCs• Tissue regeneration• Leukocyte recruitment and activation• Inflammasome activation
• Cell activation• Killing and/or
target damage
• Activation of T cells and APCs
Amplification Loop
Modified by Dr. Kaiser from M Walport . Complement. First of two parts. NEJM. 2001;344(14):1058-1066 and other sources.
November/December 2019
t FA I L E D eculizumab (Alexion) tesidolumab (Novartis) lampalizumab (Genentech/Roche) CLG561 (Novartis)