Rationally Designed CID Master Key
AP1903 is a lipid permeable, synthetic organic compound used exclusively in conjunction with a CID therapy. It consists of two identical ligands joined by a chemical linker. Each ligand binds with high affinity to a CID Binding Domain. AP1903 thus cross-links two CID Binding Domains, bringing the CID Signaling Domains together in the correct protein-protein interaction to trigger the protein's natural downstream signal.
AP1903 consists of two identical ligands joined by a flexible linker, shown here in a bioactive conformation (derived from an FKBP12v36 protein-bound crystal structure).
The CID Binding Domain is based on the naturally occurring protein FKBP, modified to include a small extra pocket (FKBP12v36). A corresponding bump on AP1903 ensures that it binds very weakly to the naturally occurring FKBP protein (>1000x lower binding affinity). Its activity is therefore highly specific: it only activates cells expressing proteins containing the CID Binding Domain. This makes AP1903 very safe, with essentially no off target biological activity, and the CID protein sequence is close enough to native sequences to be minimally immunogenic.
AP1903 drug product is manufactured as a concentrated parenteral solution containing 5 mg drug/mL. It is diluted in saline and administered as a single dose (0.4 mg/kg) via IV infusion over 2 hours. It has been tested at single doses up to 1 mg/kg in a Phase I dose escalation clinical trial in healthy volunteers, where it was shown to be safe and well tolerated at all dose levels. It was tested in multiple 0.4 mg/kg doses administered every other week in the completed Phase I/II trial BP-PC-001, with no unexpected drug-related adverse events reported to date.