R44AI174495

PROJECT SUMMARY / ABSTRACT WHO needs new, highly sensitive and ultra-specific lateral flow assays (LFA) to support its endeavors to eliminate onchocerciasis, a disease also known as river blindness affecting 18 million people, with another 218 million living at risk of contracting the disease. Onchocerciasis is fought by mass drug administration (MDA). WHO critically needs new diagnostic tests to support decisions to start and stop MDA programs and released in 2021 the corresponding desired target product profiles (TPPs). The most stringent TPP criterion is that the test must be extraordinarily specific (≥ 99.8%). Our non-profit sister company Drugs and Diagnostics for Tropical Diseases (DDTD) was hired in 2020 and 2021 by the Task Force for Global Health (TFGH) and the US Agency for International Development (USAID) to develop a new rapid diagnostic test for onchocerciasis. We succeeded in developing an assay composed of two novel O. volvulus antigens that are arranged as two distinct test lines on the assay strip. In an independent evaluation, the CDC found the test to be 89.6% sensitive (95% CI: 79.2-95.2%, N=58) and 100% specific (95% CI: 99.95-100%, N=194). This means that our biplex test meets the sensitivity and specificity requirements of both TPPs and, remarkably, its specificity is rt99.8% even at the lower bound 95% CI. In view of these data, USAID has already committed funding to evaluate the assay in the field on approximately 10,000 individuals, which will be conducted by the TFGH in early 2023. Given these exciting results, the massive relevance for public health, and the big momentum already garnered with key players (USAID, CDC, TFGH), we are now requesting Direct-to-Phase II funding from the NIH to swiftly progress the assay to manufacturing and commercialization. Phase II funding will be used to (1) optimize the biplex test in a reel-to-reel manufacturing-friendly mode, and to secure access to critical reagents, (2) establish a robust manufacturing process, with a focus on minimizing costs and maximizing speed, with SOPs and QC protocols validated for a manufacturing context, and data on lot-to-lot reproducibility data recorded in our QMS, and (3) produce 100’000 devices (in 5 lots of 20’000) that will be donated to the stakeholders (TFGH/USAID) to support further field testing and jump-start test adoption. It is noteworthy that said stakeholders have already sponsored our initial (“Phase I”) research, hence will have a vested interest in ensuring maximum return on their investment by facilitating all downstream activities necessary to provide a clear path to commercializing our test. We respectfully submit that a first-in-class tool, such as our new test, that will support the elimination of river blindness, a disease with 21 million active cases and 218 million at-risk individuals, will address an unmet need of paramount significance for global public health.