Ion Channels in Chronic Pain and Oncology
Our focus is on Ion Channel Biology and generation of new leads involved in Oncology and Chronic Neuropathic Pain.
Two major classes of Ion Channels are involved in driving the pathophysiology of chronic pain and as recently shown in driving stemness of certain solid tumors.
The Voltage Gated Calcium Channel (VGCC) and its auxiliary subunit CACNA2D1 are well known targets in Chronic Neuropathic Pain and in epilepsy. The CACNA2D1 is targeted in epilepsy by gabapentinoids (Gabapentin, Pregabalin) which was also shown to be a target in chronic pain after its usage in epilepsy.
The Voltage Gated Sodium Channels (VGSC) comprises a big family of targets with most prominent, because of its involvement in Pain, the Nav 1.7 channel.
Discovery pipeline
Pain
We have focused in creating novel ligands targeting the CACNA2D1 subunit aiming to generate assets which are peripherally restricted therefore bypassing the brain which has been a major source of serious adverse events using current therapeutics (Neurontin, Lyrica, Duloxetine). This is basically due to the fact that current therapies are not CNP-specific but anti-epileptics and anti-depressants shown to have an effect in CNP. Therefore, CNP as a highly unmet medical need indication requires novel leads to be discovered and brought to the clinic for efficacy and safety validation.
With regards to the VGSC Nav1.7 channel, currently there are a few assets brought to clinical testing in late phases of development however no such treatment has yet reached the market.
3A’s discovery pipeline includes small molecule and monoclonal antibody assets against CACNA2D1 and Nav1.7 targets
Oncology
Ion channels have been implicated in gaining a growth advantage of solid tumors with regards to the VGSC.
Recently, it has also been suggested that CACNA2D1 is driving the stemness of solid tumors such as Hepatocellular Carcinoma (HCC) mainly via a mechanism involving transcription factor activation this due to downregulation of miRNA families.
3A is currently pursuing a target validation program for VGSC and VGCC in solid tumors and after completion of this program will test the small molecule and mAbs created for therapeutic efficacy in cellular and animal models (Cell-derived and Patient-derived Xenografts, CDX/PDX) aiming to achieve PC-PoC.