Crestone, Inc. (Boulder) Secures CFF Funding for Preclinical Development of Novel Antibiotic to Treat NTM Infections
By: Colorado BioScience Association Date: 01/13/2020
Crestone, Inc. today announced an award from the Cystic Fibrosis Foundation (CFF) for the preclinical development of its antibiotic lead series to treat nontuberculous mycobacteria (NTM) infections, focusing on M. abscessus.
Pulmonary NTM disease is steadily increasing in the U.S., projected to be 180,000 cases and associated medical costs of $1.7 billion. Underlying lung conditions that lead to increased susceptibility include bronchiectasis, chronic obstructive pulmonary disease, and, in particular, cystic fibrosis (CF), where NTM infection occurs in about 14% of CF patients. This number is expected to increase. Treatment of NTM infections is difficult due to antimicrobial resistance and drug-related toxicities. M. abscessus is particularly recalcitrant to treatment.
Under this contract from CFF, efficacy of Crestone’s NTM drug candidate series will be tested at Colorado State University (CSU) and Johns Hopkins University (JHU), using different pre-clinical models to mimic established chronic infections that resemble NTM disease in humans. Further profiling of the lead compounds with collaborators at National Jewish Health will include resistance mechanisms and activity against a collection of CF M. abscessus isolates.
“Potent antibiotics with a novel mode of action and a good safety profile are sorely needed to augment the armamentarium of NTM drugs,” said Mary Ann DeGroote, MD, who is involved in Crestone’s NTM discovery efforts. “We are excited to advance our NTM program to the lead development stage where we plan to develop drug formulations for both oral and inhaled therapy. Our goal is to demonstrate a pharmacology, tolerability and efficacy profile that warrants the declaration of an IND candidate,” said Urs Ochsner, PhD, co-Founder and Vice President of R&D at Crestone.
Funding for this program will be provided in part by a two-year CFF Therapeutic Development Award, with the possibility of requesting further support for the continuation of pre-clinical studies and clinical assessment of new interventions, including safety and dose determination studies in CF patients.
About Crestone’s NTM inhibitors
Crestone’s lead candidates possess excellent in vitro potency and were identified in a medicinal chemistry campaign with SBIR funding from NIH. An earlier lead compound already demonstrated efficacy and tolerability in a proof-of-concept mouse study of M. abscessus infection with intrapulmonary delivery. The compounds selectively target MmpL3, a membrane transporter of trehalose monomycolate essential for cell wall synthesis. Since MmpL3 is unique to Mycobacteria, the inhibitors have a very narrow spectrum of activity that is limited to NTM and M. tuberculosis complex.
About Crestone, Inc.
Boulder, Colorado-based Crestone, Inc. is a clinical stage biopharmaceutical company focused on inventing and developing novel mechanism of action small molecule drugs for serious bacterial infections including Clostridioides difficile infection (CDI), resistant Gram-positive infections such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE), and chronic infections such as NTM disease.