CNV2197944

CNV2197944 is a novel, small molecule, state-dependent calcium channel blocker, designed to selectively inhibit highly active Cav2.2 channels. Preclinical studies demonstrated that CNV2197944 could have analgesic potential for a broad range of chronic pain conditions. Extensive safety and toxicology studies were conducted in support of the clinical development of CNV2197944, suggesting an excellent margin of safety and tolerability.

Phase I, placebo-controlled, single and multiple ascending dose clinical studies with orally administered CNV2197944, demonstrated that the drug was well tolerated in young and elderly subjects, with few adverse events reported at all doses tested to date. CNV2197944 was well absorbed following oral administration, with a pharmacokinetic profile that is predictable and consistent in both young and elderly subjects.

Two phase II proof of concept studies have been completed with CNV2197944. At the doses administered although well tolerated efficacy was not demonstrated. The company is considering alternative dosing regimens and investigating other therapeutic opportunities for this molecule.

Capitalising upon a rich and diverse patent estate of structurally and pharmacologically distinct preclinical cav2.2 molecules, Calchan are well positioned to utilise in house chemistry, pharmacology, translational biology and toxicology expertise to rapidly bring forward a new generation of cav2.2 blockers for the treatment of pain.

ASK1

The program is at a preclinical stage and utilizes a precedented biological pathway to selectively target the apoptosis signal-regulating kinase 1 (ASK1) which together with ASK2 is a member of the STE kinase family. ASK1 is downstream to the stress response and is a mitogen activated protein kinase, kinase, kinase (MAP3K) within the C-Jun N- terminal kinase (JNK) and P38 mitogen activated protein kinase pathways. The role of ASK1 in the stress response and in helping to mediate cytokine release has implicated this as a target in pain, inflammation, ischaemia, fibrosis, cancer and neurodegeneration.

The program has achieved structurally enabled medicinal chemistry, pharmacological proof of principal and is being rapidly progressed towards a ’first in man’ ready compound for oral delivery. ASK1 has received a competitive and peer reviewed grant of £2.4 million grant from Innovate UK.

ASK1 has been clinically validated as a target for the treatment of fibrotic liver disease (Nonalcoholic steatohepatitis: NASH). The ASK1 small molecule inhibitor Selonsertib demonstrated anti-fibrotic activity in NASH when administered over a 6 month treatment period (Presented at the American Association for the study of Liver Disease, Boston November 2017).