Accelerator for the rapid development of countermeasures targeting drug resistant fungal pathogens

Johns Hopkins University, Baltimore MD

Investigators

Abstract

SUMMARY Invasive fungal infections pose a significant medical challenge, particularly for individuals with compromised immune systems or other conditions due to HIV, cancer, organ transplantation, diabetes, chronic respiratory ailments, tuberculosis, COVID-19, and influenza. Prompt diagnosis and effective antifungal treatment are crucial for positive clinical outcomes. Current antifungal drugs are limited in number and efficacy, and their effectiveness has been compromised by the emergence of drug-resistant strains, notably Candida auris, Candida glabrata, and Aspergillus fumigatus. To combat this growing problem, there is an urgent need to develop new drugs capable of effectively treating invasive infections caused by drug-resistant fungal pathogens. Additionally, actionable point-of-care diagnostics for Candida bloodstream infections are essential for initiating timely and appropriate therapy, ultimately reducing overall mortality rates. While efforts from the biopharmaceutical industry have led to some expansion in the antifungal pipeline, more potent and targeted drugs are urgently required. In response to these pressing challenges, a Center of Excellence in Translational Research (CETR) focused on rapid drug and diagnostic development will be established. This Center harnesses expertise of leading academic and industry professionals, many of whom have a track record of successfully bringing FDA-approved products to market. The Projects selected encompass a wide range of new and established pharmacological drug targets, as well as a state-of-the-art diagnostic platform. Among the projects underway, collaborations with biopharmaceutical partners Prokaryotics and Scynexis are focused on the development of advanced small molecules targeting key enzymes involved in cell wall biogenesis. Additionally, efforts are underway to develop an antibody-based immunotherapy to combat drug-resistant infections. Finally, a Project dedicated to creating a novel point-of-care diagnostic capable of rapidly detecting Candida bloodstream infections in partnership with Cepheid Diagnostics on the GeneXpert platform, holds promise for revolutionizing the diagnosis and management of fungal infections. An integrated network of science cores staffed by experienced directors, facilitate efficient compound optimization and progression through clear ‘go, no-go’ metrics. While all programs prioritize high-threat drug-resistant Candida species, some drug candidates may also demonstrate efficacy against azole-resistant Aspergillus fumigatus. In summary, this CETR-based drug and diagnostic development accelerator represents a concerted effort to address the pressing need for novel treatments and diagnostics for invasive fungal infections. By leveraging the expertise of industry and world class translational academic partners, this initiative aims to rapidly advance innovative solutions to combat antifungal drug resistance and improve clinical outcomes for patients affected by these challenging fungal infections. The anticipated outcome of our successful efforts will be to create two IND-ready small molecule drug candidates, a lead optimized novel immunotherapy, and a 510(k) ready point-of-care diagnostic for bloodstream infections.