July 2019
Volume 60, Issue 9
Free
ARVO Annual Meeting Abstract  |   July 2019
A bispecific aptamer targeting both VEGF and Angiopoietin-2 for treating retinal diseases
Author Affiliations & Notes
  • Scott Ferguson
    Aptitude Medical Systens, Inc., Santa Barbara, California, United States
  • DA LONG
    Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
  • Qin Yang
    Aptitude Medical Systens, Inc., Santa Barbara, California, United States
  • Hui Kang
    Aptitude Medical Systens, Inc., Santa Barbara, California, United States
  • Jingwen Yu
    Aptitude Medical Systens, Inc., Santa Barbara, California, United States
  • Wen-Chuan Chou
    Aptitude Medical Systens, Inc., Santa Barbara, California, United States
  • Matthew Vukovich
    Aptitude Medical Systens, Inc., Santa Barbara, California, United States
  • Raquel Formica
    Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
  • Zibran Hafiz
    Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
  • Peter A Campochiaro
    Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
  • Jinpeng Wang
    Aptitude Medical Systens, Inc., Santa Barbara, California, United States
  • Qiang Gong
    Aptitude Medical Systens, Inc., Santa Barbara, California, United States
  • Footnotes
    Commercial Relationships   Scott Ferguson, Aptitude Medical Systens, Inc. (E); DA LONG, None; Qin Yang, Aptitude Medical Systens, Inc. (E); Hui Kang, Aptitude Medical Systens, Inc. (E); Jingwen Yu, Aptitude Medical Systens, Inc. (E); Wen-Chuan Chou, Aptitude Medical Systens, Inc. (E); Matthew Vukovich, Aptitude Medical Systens, Inc. (E); Raquel Formica, None; Zibran Hafiz, None; Peter Campochiaro, None; Jinpeng Wang, Aptitude Medical Systens, Inc. (E); Qiang Gong, Aptitude Medical Systens, Inc. (E)
  • Footnotes
    Support  NIH grant EY027634
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 3665. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Scott Ferguson, DA LONG, Qin Yang, Hui Kang, Jingwen Yu, Wen-Chuan Chou, Matthew Vukovich, Raquel Formica, Zibran Hafiz, Peter A Campochiaro, Jinpeng Wang, Qiang Gong; A bispecific aptamer targeting both VEGF and Angiopoietin-2 for treating retinal diseases. Invest. Ophthalmol. Vis. Sci. 2019;60(9):3665.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract

Purpose : Despite the use of anti-VEGF agents, many patients of neovascular retinal diseases still fail to achieve meaningful vision gain. Combination therapy is a promising strategy to further improve efficacy, which combines VEGF inhibition with complementary mechanisms of action (MOA). Multi-specific targeting has the potential to inhibit multiple MOAs with a single drug, and thus is the preferred approach to develop combination therapy. However, few such programs are being developed due to the significant technical challenges. Nucleic acid aptamers are uniquely suited for multi-specific targeting given their modular composition and flexible chemical synthesis. To fully realize this potential, we invented a technology for discovering multi-specific aptamers, and developed a VEGF/Angiopoietin-2 (Ang2) bispecific aptamer as the initial program.

Methods : We developed Particle Display, which enables high-throughput screening of the affinity and specificity of individual aptamers and yields fully modified aptamers. First, we discovered aptamers targeting VEGF or Ang2 separately, and confirmed their in vivo efficacy in multiple models. We then synthesized multiple bispecific aptamers by connecting a VEGF aptamer and an Ang2 aptamer with different linkers, and identified the top sequence by comparing their binding properties with the parental aptamers.

Results : We discovered a VEGF aptamer (AMS0421) targets all isoforms of VEGF-A and possesses potent in vivo efficacy (reported separately). Moreover, we discovered an Ang2 aptamer (AMS0525) that cross-reacts with both mouse and human Ang2 but not human Ang1. Combining AMS0525 and Aflibercept achieved superior inhibition of both neovascularization and leakage than Aflibercept alone in the mouse oxygen-induced retinopathy (OIR) model. Finally, we developed a bispecific aptamer (AMSB103) that binds to both VEGF and Ang2 with pM affinity, comparable to the parental aptamers. AMSB103 can be formulated at 120 mg/ml, resulting in a ~10-fold higher molar dose than typically achieved with bispecific antibodies.

Conclusions : We demonstrated the capability of our platform by developing a potent VEGF/Ang2 bispecific aptamer (AMSB103). AMSB103 accommodates a much higher molar dose than antibodies, which has the potential to enable better efficacy. We are evaluating this aptamer in animal models, and also leveraging our platform to develop multi-specific aptamers for other MOA.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×