AP-325, Algiax’s lead clinical candidate, is a small molecule that is being developed as an oral application for the treatment of neuropathic pain and as an injectable for the treatment of acute spinal cord injury. AP-325 has an orphan drug designation for the treatment of spinal cord injury.
AP-325 belongs to the chemical class of malononitrilamides (MNAs). MNAs were originally developed as low molecular weight immunosuppressive agents. AP-325 demonstrated a significant and long-lasting reduction of pain in several animal models of neuropathic pain, including peripheral and central neuropathy. The product targets the specific receptors in the superficial dorsal horn of the spinal cord and dorsal root ganglia (DRG).
AP-325 reversibly inhibits dihydro-orotate dehydrogenase (DHODH) which is a key cellular enzyme involved in the de novo pyrimidine synthesis. Due to the central role of pyrimidine nucleotides in immune cell function and inflammation, immune-mediated secondary injury following spinal trauma largely relies on the DHODH-dependent boost of de novo pyrimidine synthesis, and DHODH thus represents a key player in post-SCI secondary injury mechanisms.
New Chemical Entities (NCE’s) including AP-4 and AP-8
A selection of NCE’s (AP-2, AP-3, AP-4 and AP-8) binds to the GABAA -receptor at the picrotoxine binding-site with high affinity and are strong positive allosteric modulators of the GABAA -receptor. The functional activity of the selected NCE’s (AP-2, AP-3, AP-4 and AP-8) was confirmed in rodent models of neuropathic pain, which revealed long-lasting efficacy without adverse CNS side effects. In light of these facts, Algiax identified the NCE’s as preclinical follow-up of our clinical lead AP-325 and as a new treatment approach in Diabetes Type 1. Algiax is currently performing a preclinical program in collaboration with UCLA and JDRF to establish Proof-of-Concept in an animal model for Diabetes Type 1.
AP-61 is a novel imidazotriazinone with a potent inhibitory activity in human neutrophils against the high and low affinity rolipram binding sites. The compound shows an excellent selectivity for PDE4b vs. other PDE isoenzymes and is a potent inhibitor of human inflammatory cell function in-vitro. AP-61 is in preclinical development for the treatment of cognitive impairment.