SBIR Phase I: Novel Peptide Immunomodulators for Treatment of Autoimmune and Inflammatory Disorders

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase I project is in developing a novel class of compounds capable of treating autoimmune and inflammatory conditions safely and effectively. With the constant threat of new COVID variants, influenza, and RSV, there is an unmet medical need for therapeutics that can effectively treat autoimmune diseases especially in pediatric patients without compromising the immune system to respond to infections.

This problem has been overcome with the discovery of novel compositions that demonstrate efficacy equal or superior to many of the first line therapies used to treat immune diseases. The improved safety, efficacy and lower cost of these therapeutics should provide a significant benefit to patients by overall contributing to their quality of life as compared to current medications, as well as marketing and partnering advantage in its commercialization efforts, which will focus on rare diseases, such as juvenile idiopathic arthritis-associated uveitis and pediatric Crohn’s disease among others.

In the era of socio-economic disparities, these affordable drugs will become available to the historically neglected low-income communities. If executed successfully, this proposal would validate the platform technology and demonstrate the feasibility of identifying candidates for further development into life-changing treatments.

This Small Business Innovation Research (SBIR) Phase I project will demonstrate the unique design of novel compounds to augment and re-program the immune responses from pro- to anti-inflammatory, based on the binding to MHC class II molecules that leads to immunomodulation. The technical complexities of understanding the effects of peptide sequences on the outcomes of cellular interactions present challenges related to selecting the appropriate amino acids both for the random and specific components of these compositions.

These hurdles will be addressed by design of several candidate compounds for each target condition, juvenile idiopathic arthritis-associated uveitis and pediatric Crohn’s disease, that will take into account the structure of autoantigenic peptides known to interact with both the MHC class II and T cell receptor (TCR). These candidate compounds will be initially tested in vitro in human macrophages to assess their potential to inhibit secretion of pro-inflammatory cytokines.

Of these compounds, the most efficient ones will be tested for activity in relevant animal models. This approach will allow identifying and selecting the best drug candidates for further development into therapies for pediatric conditions as outlined above.

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.