Concert Pharmaceuticals Highlights CTP-656 Phase 1 Results at North American Cystic Fibrosis Conference

Concert Pharmaceuticals, Inc. (CNCE) today presented results from a Phase 1 single ascending dose trial of CTP-656, a next generation potentiator being developed for the treatment of cystic fibrosis.

In the Phase 1 healthy volunteer trial comparing CTP-656 to current standard of care Kalydeco®, CTP-656 provided a superior pharmacokinetic profile that supports once-daily dosing. CTP-656 is a new chemical entity designed by Concert to provide superior pharmacokinetic properties while leveraging the known safety and efficacy of Kalydeco. The results were presented during a poster session at the North American Cystic Fibrosis Conference in Phoenix, AZ.

“With CTP-656 we aim to develop another treatment option to meaningfully enhance patient care. In this Phase 1 trial, CTP-656 provided several advantages compared to Kalydeco including a reduced rate of clearance, longer half-life, substantially increased exposure and greater plasma levels at 12 and 24 hours. As a result, we plan to rapidly advance CTP-656 into a single Phase 2 clinical study to assess efficacy in patients with cystic fibrosis associated with gating or minimal function CFTR mutations following the completion of our multiple ascending dose phase 1 trial,” said James Cassella, Ph.D., Chief Development Officer of Concert Pharmaceuticals.

The single ascending dose Phase 1 clinical trial was conducted in 10 healthy volunteers and evaluated three doses (75, 150 and 300 mg) of CTP-656 as an aqueous suspension. The single ascending dose findings support once-daily administration of CTP-656 based on a half-life range of 14 – 17 hours. In the Phase 1 single ascending dose trial, CTP-656 demonstrated a linear dose response. In addition, the lowest dose studied (75 mg) of CTP-656 provided higher exposure (AUC) and higher plasma levels at 12 and 24 hours compared to commercially available 150 mg of Kalydeco. CTP-656 was well-tolerated across all dose groups. There were no serious adverse events reported in subjects who received CTP-656. Concert previously reported a single dose crossover comparison of an aqueous suspension of 150 mg of CTP-656 to a 150 mg solid dose of Kalydeco in nine subjects, whereby CTP-656 provided superior pharmacokinetic properties. An analysis of metabolites in plasma also showed that the overall exposure profile of CTP-656 differed from that of Kalydeco in that the majority of plasma exposure in the case of CTP-656 was due to parent drug, whereas with Kalydeco the majority of plasma exposure was due to a less-active metabolite and an approximately equivalent amount of an inactive metabolite was also observed.

While CTP-656 demonstrated an improved pharmacokinetic and metabolite profile compared to Kalydeco, the in vitro potentiation was found to be equivalent to ivacaftor in Fischer rat thyroid (FRT) cells transfected with CFTR (cystic fibrosis transmembrane conductance regulator) containing the G551D mutation and in human bronchial epithelial cells homozygous for the F508del mutation.

A subsequent Phase 1 trial evaluating multiple ascending doses of CTP-656 in healthy volunteers is expected to begin in the fourth quarter of 2015. That trial will include a single dose crossover comparison of a tablet formulation of CTP-656 compared to Kalydeco. Concert expects to report top-line results from this multiple ascending dose Phase 1 trial in the first half of 2016.

The U.S. Patent and Trademark Office has issued U.S. Patent No. 8,865,902 claiming CTP-656 and other deuterium-modified ivacaftor analogs as novel compositions of matter. About CTP-656 and Cystic Fibrosis CTP-656 is a novel potentiator that may enable once-daily dosing and was developed by applying deuterium chemistry to modify ivacaftor. Concert is initially developing CTP-656 as a potential treatment for cystic fibrosis as monotherapy in class III (gating) mutations (e.g. G551D) 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 CNS disorders, genetic diseases, renal disease, inflammatory diseases and cancer.