Multifunctional Anti-VEGF for Retinal Disease

LNR 653.1

Products Providing Additive Benefit

To Current Anti-VEGF Market

Anti-VEGF Drugs

Anti-VEGF Drugs

2019 Market

Current Anti-VEGF Opportunity

Aflibercept is Considered the Gold Standard

Problem:

  1. Only 30% wet AMD patients gain superior vision of 3 lines; true gain is 4-6 letters
  2. 50% wet AMD patients result in GA over multiple injections
  3. Patients with both wet and dry symptoms ~ 40% of current wet AMD patients
  4. In DME, only 50% of patients fully resolve their macular edema with treatment

macular degeneration
The pathology of AMD is characterized by degeneration of photoreceptors and retinal pigment epithelial cells as well as by changes of choroidal capillaries in the macula

Does IL17A Pathway Play a Key Role in Inflammation of the RPE and Photoreceptor Degeneration and Improve Suboptimal Outcomes?

  • Proteins secreted by VEGF antibody-sensitive and resistant tumor models reveal that the most abundant protein secreted was IL17A
  • Increased serum levels of IL17 are found in patients with wet AMD compared to a healthy cohort. Another study replicated this finding and also increased circulating levels of IL1β, IL1α, IL4, IL5, IL10, and IL13
  • CD3+ CD4+ T cells extracted from peripheral blood mononuclear cells (PBMCs) actively produced IL-17 and C5a-mediated induction of IL17 upregulate the co-stimulatory proteins and secrete IL1β and IL6
  • A retinal toxic effect of IL17 occurs in the pathogenesis of AMD
    PBMCs extracted from AMD patients exhibit hypomethylation of the IL17RC promoter which coincides with enhanced expression levels of both IL17A and IL17RC in AMD maculae when compared with healthy maculae
  • IL17A blockade of IL17 signaling in an animal model significantly improves and reverses development of AMD-like lesions
  • Two IL17 polymorphisms, rs2275913 and rs3748067, have been associated with AMD
  • IL17A induces RPE cell death characterized by the accumulation of cytoplasmic lipids and autophagosomes and activation of pro-apoptotic Caspase-3 and Caspase-9
  • Intervention of IL17A blocking rescues RPE and photoreceptors in a MAPK-dependent apoptotic process.

LNR 653.1

Lanier’s Proprietary Approach to Designing Bi-functional Antibodies of Aflibercept and IL17A

  • Potency / VEGF binding comparable to aflibercept
  • Potency / IL17A binding comparable to secukinumab
  • Single multifunctional antibody

LNR 653.1

Lanier’s Proprietary Approach to Designing Bi-functional Antibodies of Aflibercept and IL17A

  • Potency / VEGF binding comparable to aflibercept
  • Potency / IL17A binding comparable to secukinumab
  • Single multifunctional antibody