Findings Confirmed Superior Pharmacokinetic Profile Relative to Kalydeco

LEXINGTON, MA, USA I June 10, 2016 I Concert Pharmaceuticals, Inc. (NASDAQ: CNCE) today presented results from a Phase 1 multiple ascending dose trial of CTP-656, a next generation CFTR potentiator being developed for the treatment of cystic fibrosis. The Phase 1 healthy volunteer trial included a single dose tablet crossover comparison with Kalydeco®, the current standard of care for certain gating mutations of cystic fibrosis, showing that CTP-656 provided substantially superior key exposure parameters. The Phase 1 results support the development of CTP-656 as a once-daily potentiator for the treatment of cystic fibrosis. The results were presented by Concert during an oral presentation at the European Cystic Fibrosis Conference being held in Basel, Switzerland.

“We are impressed with the pharmacokinetic profile of CTP-656 that has emerged from our initial clinical evaluation. Importantly, we believe this profile supports simplified dosing, with the potential for improved efficacy,” said James Cassella, Ph.D., Chief Development Officer of Concert Pharmaceuticals. “We are committed to opening the Investigational New Drug Application by year-end and advancing CTP-656 into its Phase 2 efficacy study.”

The multiple ascending dose Phase 1 trial was conducted in two parts and enrolled 38 healthy volunteers to assess safety, tolerability and pharmacokinetics of CTP-656 in a tablet formulation. The first part assessed a single dose pharmacokinetic comparison of 150 mg of CTP-656 versus 150 mg of Kalydeco. The second part assessed three doses of CTP-656, 75 mg, 150 mg and 225 mg, dosed daily for seven days compared to placebo.

In part one, the results from the single dose crossover study demonstrated that 150 mg of CTP-656 provided a superior pharmacokinetic profile compared to 150 mg of Kalydeco. The key exposure parameters of C24 and AUC were approximately three-fold greater with CTP-656 compared to Kalydeco. In addition, a reduced rate of clearance with CTP-656 was observed. The half-life of 150 mg of CTP-656 was approximately 40% longer than 150 mg of Kalydeco. These results confirm the findings from Concert’s first direct comparison with Kalydeco in the previously reported Phase 1 single ascending dose trial.

In part two, at steady state, CTP-656 maintained its superior pharmacokinetic profile with greater exposure to the more potent parent drug than to less active metabolites. CTP-656 showed a dose-proportional increase in exposure with repeated dosing for the 150 mg dose relative to the 75 mg dose. Steady state with CTP-656 was achieved after 3 days of dosing. Results of the Phase 1 trial also showed that CTP-656 was well-tolerated and its safety profile was comparable to that of Kalydeco. No serious adverse events were reported.

A copy of the presentation is available online at:

Concert plans to conduct a single Phase 2 clinical trial with CTP-656 in cystic fibrosis patients with gating mutations. The Company expects to open an Investigational New Drug Application (IND) to support the Phase 2 trial in the fourth quarter of 2016. Topline results from the Phase 2 trial are expected in the second half of 2017.

About CTP-656 and Cystic Fibrosis
CTP-656 is a novel potentiator that may enable once-daily dosing that was developed by applying deuterium chemistry to modify ivacaftor. Concert is initially developing CTP-656 as a potential monotherapy treatment for cystic fibrosis due to gating mutations of the gene that encodes for cystic fibrosis transmembrane conductance regulator (CFTR), a protein, which regulates components of sweat, mucus clearance and digestion. Cystic fibrosis is a life-threatening, hereditary genetic disease that has systemic effects and can cause significantly reduced lung and digestive system function. According to the Cystic Fibrosis Foundation, an estimated 70,000 people worldwide have cystic fibrosis.

About Concert

Concert Pharmaceuticals is a clinical stage biopharmaceutical company focused on applying its DCE Platform® (deuterated chemical entity platform) to create novel small molecule drugs. This approach starts with approved drugs, advanced clinical candidates or previously studied compounds that have the potential to be improved with deuterium substitution to enhance clinical safety, tolerability and efficacy. The Company is developing a broad pipeline targeting genetic diseases, autoimmune disorders, CNS disorders and inflammatory diseases, among others. For more information, please visit

SOURCE: Concert Pharmaceuticals