Calithera Biosciences Inc has dosed the first patients in its Phase 1b clinical trial of the arginase inhibitor CB-280 in adult patients with cystic fibrosis (CF) and chronic airway infection.

Research in CF patients has demonstrated that increased arginase activity correlates directly with worsened lung function, and reduced expiratory nitric oxide (NO) levels. Preclinical studies conducted by Calithera and collaborators have shown that arginase inhibition increases systemic arginine levels, decreases airway bacterial colonies, and improves lung function in CF mouse models of infection.

Inhibiting arginase may reduce infection and improve lung function in people with CF, according to Calithera Bio, which added that chronic polymicrobial infection remains a major area of unmet need in CF. 

The study will evaluate the safety and optimal dose range of CB-280 when added onto existing therapies for CF patients, including CFTR modulators. 

“We remain committed to advancing our arginase inhibitor clinical development program to fully explore the potential of this new class of therapeutics in a variety of conditions,” said Susan Molineaux, PhD, president and chief executive officer of Calithera. “Based on preclinical data and the unique pathology of this disease, we believe that CB-280’s mechanism of action represents an opportunity to further improve upon the current standard- of-care for CF patients, for whom there remains great unmet need despite recent therapeutic advancements.” 

The Phase 1b randomized, double blind, placebo-controlled, dose escalation trial will evaluate multiple ascending doses of CB-280 compared to placebo in 32 adult CF patients to determine a safe dose range for CB-280, dosed orally twice daily for 14 days. The study follows the completion of a Phase 1 trial that evaluated the safety, tolerability and pharmacokinetic profile of CB-280 in healthy volunteers, which was conducted under a United States Food and Drug Administration Investigational New Drug (IND) application. In October 2017, Calithera entered into a global collaboration agreement with Incyte, focused on research, development and commercialization of a first-in-class arginase inhibitor in hematology and oncology. As part of this agreement, Calithera retained the rights to develop additional arginase inhibitors in specific non-oncology indications, including CF. The molecule being evaluated in these clinical trials, CB-280, is wholly owned by Calithera.