R01AI153145

A Preclinical Program for Targeting Mycobacterium Tuberculosis KASA - Abstract

We present herein a grant application focused on the late-stage development of preclinical candidate JSF-3285. Per our recently published research, we have disclosed the genesis of this program that led to the hit compound DG167 and identification of the essential SS-keto acyl synthase KASA as its target.

Building on this effort, our preliminary data detail the optimization to arrive at JSF-3285, which is efficacious in the acute and chronic models of M. tuberculosis infection in mice at doses as low as 5 mg/kg once-daily oral. This proposal seeks to build on this data by conducting the requisite drug combination and relapse studies to achieve clinical status and begin IND-enabling studies.

In addition, we propose a second-generation program based on preliminary data consisting of a structurally distinct amide series with promising in vitro efficacy, mouse PK, and X-ray structural data. The grant's second aim will evolve this series, leveraging our extensive X-ray structural data, SAR, and machine learning models, to produce at minimum novel early lead compounds if not compounds equal to or surpassing JSF-3285.

The sum total of the two aims, featuring JSF-3285 and second-generation candidate/s, will lend a high probability to a KASA inhibitor becoming clinically relevant in the next 5 years.

Rutgers The State University Of New Jersey

NOT APPLICABLE

93.855 - Allergy and Infectious Diseases Research

National Institute of Allergy and Infectious Diseases (NIAID) [HHS - NIH]

Newark, New Jersey 071073001 United States

Single Zip Code

NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed) (PA-20-185)

Amendment Since initial award the total obligations have increased 289% from $826,401 to $3,212,184.