Early Clinical Findings Demonstrate Concert Pharmaceuticals’ CTP-656’s Potential as Once Daily Poten

Concert applies its proprietary deuterium chemistry approach to known drug compounds that it believes can be improved with deuterium substitution to enhance clinical safety, tolerability or efficacy. Its pipeline of product candidates includes CTP-656, a novel potentiator of the cystic fibrosis transmembrane conductance regulator (CFTR) protein for the treatment of cystic fibrosis. CTP-656 is being developed as a monotherapy or for use with other CFTR modulators. CTP-656 is a novel once daily dosed CFTR potentiator that was developed by applying deuterium chemistry to modify ivacaftor, known commercially as Kalydeco®.

Deuterium is essentially identical to hydrogen in size and shape, with the result that compounds containing deuterium are very similar to the hydrogen compounds in their pharmacological activity. However, deuterium differs from hydrogen in that it also contains a neutron. As a result, deuterium forms a more stable chemical bond with carbon than does hydrogen. The deuterium-carbon bond is typically six to nine times more stable than the hydrogen-carbon bond. This has important implications for drug development because drug metabolism often involves the breaking of hydrogen-carbon bonds. As a result, in select instances, compounds modified through selective replacement of hydrogen in place of deuterium can have different properties in the body than the unmodified compounds, such as a longer half-life or reduced formation of undesirable metabolites. Concert seeks to use its deuterium technology to create new drugs that offer clear clinical benefits over existing therapies.

Phase 1 clinical trial results demonstrated that CTP-656 is clearly differentiated from Vertex’s Kalydeco in that it lasts longer in the body and reaches the same blood levels with a smaller dose. While CTP-656 demonstrated an improved pharmacokinetic and metabolite profile compared to Kalydeco, it leverages the positive ivacaftor properties including similar safety and tolerability. The Phase 1 study was designed to assess single ascending doses of CTP-656 in nine healthy volunteers. These results were presented at the UK Trust’s UK CF conference and the North American Cystic Fibrosis Conference in the Fall of 2015. Additionally, a 150 mg dose of CTP-656 was compared to a 150 mg dose of Kalydeco. 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. This profile has the potential to provide greater therapeutic benefit and reduced drug-drug interactions. "CTP-656 has the potential to be an important new treatment, expanding therapeutic options for the cystic fibrosis community," said James Cassella, Ph.D., Chief Development Officer of Concert Pharmaceuticals. "We believe the development of CTP-656 as a once-daily treatment could benefit patients by simplifying dosing and potentially addressing adherence issues documented with the current standard of care.

The multiple ascending dose Phase 1 study is ongoing. It will be conducted in two parts and enroll 38 healthy volunteers to assess safety, tolerability and pharmacokinetics of CTP-656 in a tablet formulation. The first part will assess a single dose pharmacokinetic comparison of 150 mg of CTP-656 versus 150 mg of Kalydeco. The second part will assess three doses of CTP-656, starting at 75 mg and up to 300 mg once daily for seven days compared to placebo. Concert expects to report top-line results from the Phase 1 multiple ascending dose study in the first half of 2016. The Company intends to initiate a single Phase 2 trial in patients with cystic fibrosis associated with gating CFTR mutations in the second half of 2016.

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