SBIR-STTR Award

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) project will be a platform to identify new immunotherpeutics for the treatment of cancer. For a variety of human diseases, cancer in particular, several recently approved immunotherapeutics can effectively treat and, in some cases, cure several forms of cancer that were considered fatal. Unfortunately, there are only a handful of these treatments currently available, and the cost is high. This project aims to develop a new technology that may empower biopharma and biotech companies to discover next generation therapeutics in an expeditious and cost-effective manner with a much higher chance of success. Ultimately, the project aims to help bring more efficacious and more affordable choices for immunotherapeutics to benefit patients with unmet medical needs. This SBIR Phase I is a proposal to evaluate a cutting-edge single-cell-interaction platform technology for its potential to accelerate the discovery of immunotherapeutics, specifically, the bispecific T cell engagers (BiTEs), a clinically validated class of bispecific antibodies. BiTEs consist of two distinct domains that can simultaneously bind to a T cell target and a tumor target. BiTEs' unique ability to link T cells to tumor cells allows them to exhibit improved specificity and efficacy, in part through a novel mode of action, by activating T cells to kill tumor cells. However, the development process for BiTEs has been very slow, limiting their clinical availability for a broad range of devastating diseases. A recurring challenge in the field is the lack of a robust platform that is capable of rapid and efficient identification of lead BiTE candidates in a cost-effective manner. The current proposal aims to prove the technical and operational feasibility of the proposed microfluidic-based single-cell-interaction platform technology that can directly interrogate the functions of many individual BiTE variants in a compartmentalized assay format. 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.

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase II project is to accelerate development of immunotherapeutics and make them broadly available and affordable to patients in need. Immunotherapeutics, which work by engaging the immune system to tackle diseases, have demonstrated tremendous potential to cure, or improve quality-of-life of patients with cancer, autoimmunity, or other disorders. Unfortunately, only a handful of these treatments are currently available. Furthermore, immunotherapeutics are costly and unaffordable for the healthcare system and patients including the disadvantaged populations. These challenges can be attributed to the costly and inefficient therapeutic discovery processes with conventional drug screening platforms. This project aims to develop a high-throughput, single-cell based functional screening technology that can enable rapid discovery of many immunotherapeutics, specifically bispecific antibodies (“BsAbs”), to treat a broad range of debilitating diseases, and therefore can make significant and broad societal impact. Meanwhile, the BsAb market is in its early exponential growth phase and will reach $10 billion global sales in the next few years. The proposed technology will be quickly deployed to enable pharmaceutical and biotechnology clients to identify their therapeutic leads with unprecedentedly rapid turnaround and high success rate (commercial value).The proposed project aims to further develop, optimize and launch the first dedicated commercial platform for functional discovery of bispecific antibodies (“BsAbs”). The conventional trial-and-error approach, in which BsAbs are empirically designed and then must be evaluated individually for their functionality, is tedious, time-consuming, and expensive. The proposed technology represents a new paradigm in BsAb discovery by employing an ultra-high throughput, single cell-based functional screening, enabling efficient discovery of rare functional BsAbs with differentiable properties. The objectives of this project are to develop, optimize and quality control (QC) the entire platform workflow including upstream BsAb library and reporter cell preparations, midstream droplet assay and sorting, and downstream target validation and characterization. By the conclusion of this study, a robust and streamlined system will be ready for commercial launch, enabling pharmaceutical company partners to discover new BsAb immunotherapeutics. This project will result in new tools and methods in single-cell therapeutic discovery and make significant intellectual contributions including complex cell library construction, multiplexed reporters, and potentially new therapeutic candidates. Furthermore, the unique ability to interrogate many variables in a combinatory and high throughput fashion can lead to new insights of the modes of action and inform future design of immunotherapeutics.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.