SBIR Phase II: Optimizing Manufacturing Efficiency of Bispecific Aptamer Therapeutics

The broader/commercial impact of this Small Business Innovation Research (SBIR) Phase II project is to reduce the impact of preventable vision loss caused by retinal diseases such as the wet form of advanced macular degeneration and diabetic macular edema. Vision loss has a significant impact on the lives of those who experience it as well as society as a whole. Not all patients respond effectively to the current standard of care and the treatment burden is high. The value proposition associated with the technology is enhanced efficacy by targeting multiple aspects of disease as well as reduced treatment burden compared to current standard of care. A differentiated product will create a competitive advantage and drive market adoption with the potential to generate billions in revenue. The global retinal disorder treatment market was estimated at USD 12.57 billion in 2022 and is expected to expand at a compound annual growth rate of 9.3% from 2023 to 2030. The business goal is to partner the program with a large pharmaceutical company with commercial experience in these indications. The proposed project is designed with the goal of identifying the best approach to manufacture the bispecific aptamer product and specifically to optimize the efficiency of the conjugation of polyethylene glycol to the bispecific aptamer therapeutic to confer improved pharmacokinetic properties. A wide range of reaction conditions will be tested and optimized as well the evaluation of numerous size and weight alternatives of polyethylene glycol. Once the manufacturing process has been optimized the resultant bispecific product will be evaluated for inhibitory activity, which will be compared with the individual aptamer components. The biophysical properties of the PEGylated compound will be assessed. These properties are key to establishing parameters for bispecific aptamer formulation and predicting intravitreal half-life. The best performing optimized PEGylated bispecific aptamer will be evaluated in vivo, to confirm its ability to engage its targets in an established animal model of retinal disease. What is learned in this proposal will enhance scientific and technological understanding as the findings will be applicable to other disease targets and indications. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.