# A New Small-Molecule Kinase Inhibitor for Airway Disease > **NIH NIH R42** · NUPEAK THERAPEUTICS, INC. · 2024 · $1,018,383 ## Abstract Title A new small-molecule kinase inhibitor for airway disease Summary NuPeak Therapeutics Inc. is a biotechnology company (C corporation) designed to deliver a first-in-class small- molecule kinase inhibitor for therapeutic use in humans. The present project is aimed at the next steps to develop an inhibitor for treatment of respiratory airway disease especially due to asthma and COPD, which remain leading causes of morbidity and mortality in the U.S. and worldwide despite current therapeutic approaches. Moreover, there is growing recognition that these diseases are linked to airway inflammation and mucus production in response to respiratory viruses, allergens, or toxins. In that context, we identified a mitogen-activated protein kinase (MAPK) known as MAPK13 that drives the key features of respiratory airway disease in human cell and animal models. We also validated critical components of this pathway in asthma, COPD and long-term Covid- 19, suggesting the therapeutic benefit of a MAPK13 inhibitor in these patient populations. Further, this relatively orphan kinase was dismissed in favor of conventional inflammatory signals and was untargeted in previous kinase-inhibitor screens. Therefore, we used structure-based drug design to engineer proprietary small-molecule kinase inhibitors against MAPK13 and arrived at a lead candidate compound (NuP-4A) based on physical- chemical attributes, cell safety, enzyme inhibition, binding mechanism, interaction kinetics, kinome selectivity, pharmacokinetics, and animal safety. Consistent with these attributes, NuP-4A provides highly potent and safe correction in disease models. Notably, NuP-4A treatment corrects the basal-epithelial stem cell activation that drives the key disease phenotypes. This benefit is equivalent to Mapk13-deficiency or combined MAPK13-14 blockade in disease models. Initial toxicology studies suggest that NuP-4A will deliver a satisfactory safety margin in vivo. and provides a firm basis to move NuP-4A to the next stage of drug development. Smart delivery using intravenous and inhaled dosing will guide an effective, safe, and practical continuum of care for airway diseases. Here we concentrate on the next steps in our intravenous dosing program developed in concert with FDA recommendations. Thus, we propose a STTR Phase II program for NuPeak and Washington University to advance NuP-4A under the following Specific Aims: Aim 1 will optimize dosing and biomarkers in preclinical models to refine our clinical trial design; Aim 2 will complete the final non-GLP and GLP pharmacology and toxicology testing to obtain IND approval; Aim 3 will move our Chemistry, Manufacturing, and Control (CMC) process into a commercial facility to support clinical trials. The combined Aims will fully prepare the project for Phase 1 Clinical Trials in humans. NuPeak will operate with the entrepreneurial resources of BioGenerator and Harrington Discovery Institute and a license from Washington University under a ... ## Key facts - **NIH application ID:** 10805979 - **Project number:** 2R42HL149523-02 - **Recipient organization:** NUPEAK THERAPEUTICS, INC. - **Principal Investigator:** Kay O Broschat - **Activity code:** R42 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2024 - **Award amount:** $1,018,383 - **Award type:** 2 - **Project period:** 2019-08-07 → 2026-06-30 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/10805979 ## Citation > US National Institutes of Health, RePORTER application 10805979, A New Small-Molecule Kinase Inhibitor for Airway Disease (2R42HL149523-02). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10805979. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*