C-Scape: our next clinical candidate, an oral antibacterial to potentially address the growing problem of antimicrobial resistance
C-Scape, an oral combination of ceftibuten, an approved third generation cephalosporin, and clavulanate, an approved beta-lactamase inhibitor, is currently being developed as an antibacterial candidate to address the growing problem of antimicrobial resistance. Achaogen initiated the C-Scape clinical development program in 2017 with the start of the Phase 1 clinical study and, in early 2018, Achaogen announced positive top-line results from this study. C-Scape was well tolerated across all doses studied in the Phase 1 trial, with no drug-drug interaction between the previously approved compounds when dosed in combination. The goal of the C-Scape clinical development program is to examine the effectiveness of C-Scape for treating patients suffering from complicated urinary tract infections (cUTI) who have lost effective oral treatment options due to multi-drug resistant pathogens such as Extended Spectrum Beta Lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae. Achaogen plans to meet with regulatory agencies in the first half of 2018 to seek agreement on the details of the C-Scape development plan that would include initiating a pivotal Phase 3 clinical trial in patients with cUTI in 2018.
Approximately 10 to 30 percent of clinical Enterobacteriaceae isolates in the United States and European Union produce ESBLs, rendering them resistant to all beta-lactam antibiotics except for carbapenems. Intravenous carbapenem therapy is considered a “last-line” option, creating an urgent need for a new oral antibiotic option. Preliminary non-clinical studies of C-Scape found potent in vitro microbiology activity against ESBL-producing Enterobacteriaceae and rapid bactericidal activity in time-kill experiments, which when combined with pharmacokinetic models based on clinical beta-lactam/beta-lactamase inhibitor data suggests the potential to achieve efficacious exposures with an oral three times daily dosing regimen.
In September 2017, Achaogen was awarded a BARDA contract with committed funding of $12 million over nine months and subsequent option periods that could bring the total value of the award to $18 million in non-dilutive funding to support clinical development of C-Scape. In January 2017, the FDA awarded C-Scape Qualified Infectious Disease Product (QIDP) status for the treatment of cUTI, including acute pyelonephritis. QIDP designation provides incentives for new antibiotics, including priority review and additional market exclusivity.