Sbir phase II: antibody-drug conjugates (adcs) with high drug-antibody ratios (DAR) and molecularly targeted payloads

Federal Cooperative Agreement Summary

Window Therapeutics, Inc. received a $1.0 million Cooperative Agreement award from the National Science Foundation (NSF) under the Technology, Innovation, and Partnerships (TIP) program (CFDA 47.084) on July 15, 2025. The Small Business Innovation Research (SBIR) Phase II project, with a completion date of June 30, 2027, focuses on developing next-generation antibody-drug conjugates (ADCs) utilizing proprietary brush polymer technology. The core deliverable is the creation of ADCs with significantly elevated drug-to-antibody ratios (DAR) ranging from 30 to 90 drugs per antibody—substantially exceeding the current industry maximum of 8—enabling the incorporation of multiple novel, low-toxicity pharmaceutical payloads previously unsuitable for ADC formulations.

The project specifically targets a high-prevalence antigen expressed in approximately 75% of breast cancer patients and aims to evaluate a library of at least five distinct drugs with unique cancer-killing mechanisms that have never been incorporated into FDA-approved ADCs. By advancing ADC platform technology with enhanced drug loading capacity and improved targeting mechanisms, the research is designed to reduce chemotherapy-related side effects while broadening therapeutic applicability across metastatic cancer populations. This innovation directly addresses the substantial commercial opportunity in the breast cancer therapeutics market, valued at $17.13 billion as of 2021.

Abstract

The broader/commercial impact of this small business innovation research (sbir) phase II project is to significantly extend the life expectancy of the many americans who suffer from metastatic cancer by creating the next generation of antibody drug conjugates (adcs). Current FDA-approved adcs are advanced cancer therapies that use the targeted specificity of antibodies to deliver powerful cancer-killing drugs directly to cancer cells, minimizing damage to healthy cells and reducing side effects common with chemotherapies. However, current adcs have a low drug-to-antibody ratio where only a small number of drugs can be delivered per antibody, meaning only a select few of the most toxic drugs can be used in adcs. These drugs not only cause severe side effects, but also have mechanisms of killing that cancers quickly develop resistance to. A novel polymer technology can be used to increase the drug-to-antibody ratio for adcs by at least an order of magnitude. This ADC will specifically target an antigen expressed in 75% of breast cancer patients, utilizing high drug loading of a compound with a unique mechanism of action. In 2021, the global breast cancer market was valued at $17.13 billion and is expected to grow rapidly in the coming years. The proposed project aims to demonstrate that both increasing the drug-to-antibody ratio by over an order of magnitude and using drugs with unique mechanisms of killing can advance adcs to be more effective and broadly applicable to a larger population of metastatic cancer patients. To do so, proprietary brush polymers will be used to make adcs with drug-to-antibody ratios between 30 and 90 which is far above the maximum of 8 that is possible with current ADC technology. A library of these adcs with at least 5 different low toxicity drugs that have never before been used in FDA-approved adcs will be evaluated biologically in cell potency studies and mouse breast tumor efficacy models. Ideally from this large library of adcs, at least one will be identified that uses with a unique mechanism of killing and have superior preclinical efficacy compared to state-of-the art adcs that are currently used in the clinic. This ADC will also be evaluated for its distribution and elimination from the body. At least gram-scale manufacturing will be demonstrated for this ADC lead candidate 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.- subawards are not planned for this award.