Exotect Grant to Target New Therapies for Airway Mucous Secretion in CF, Other Diseases

The National Institutes of Health (NIH) has awarded Exotect a $224,576 Small Business Technology Transfer grant to develop small molecule therapies to treat cystic fibrosis and other diseases characterized by excessive airway mucous secretion.

These include chronic bronchitis, bronchiectasis, chronic obstructive pulmonary disease (COPD) and asthma.

Exotect, a preclinical early-stage Fannin Innovation Studio biopharma based in Houston, is working to develop a small molecule drug that targets the protein Syt2 (synaptotagmin 2), which plays a major role in the secretion of mucin from airway epithelial cells.

The program’s concept is based on research by Dr. Burton Dickey, chair of the Department of Pulmonary Medicine at the University of Texas MD Anderson Cancer Center.

In a 2009 study, Dickey and colleagues showed airway goblet cells needed Syt2 to secrete mucous. By targeting Syt2, such cells would not be able to produce high levels of mucous.

“The goal of our program is to identify drugs that prevent rapid mucin secretion that can block airways, while preserving baseline secretion that is required to keep airways clear,” Dickey said in a press release. “We were surprised to find that genetic modulation of Syt2 had such a profound effect on stimulated mucus secretion and are excited to develop small molecule inhibitors that target this protein.”

The NIH grant will be used to produce prototypes or derivatives of the drug candidate, which will then be tested for improved solubility, target affinity, pharmacodynamics and toxicity, in conjunction with the MD Anderson Cancer Center. This process will allow Exotect to determine the optimal molecule for clinical development.

“We’ve identified the target molecule; we need to find the right drug to hit it with,” said Dr. Dev Chatterjee, Exotect’s manager of research and development. “There are several parallel pathways to find the right drug. We have about nine compounds which we think are promising, so the next step is to push to one or two.”

Other collaborators for this research include Michael Tuvim, professor and director of laboratory research, and Dr. Roberto Adachi, associate professor.

The partnership involving Dickey, Tuvim, Adachi and Exotect will help the team select the best possible therapies to treat these airway diseases.

“We are excited by our discovery that small molecules targeting Syt2 may inhibit stimulated mucin release in the airway,” said Dr. Atul Varadhachary, the president of Exotect. “Our strong partnership with MD Anderson and approach to drug discovery and development are key to making this project a success.”