Smallpox

CMX001 is a lipid mimic of cidofovir formed by linking a lipid 3-hexadecyloxy-1-propanol, to the phosphonate group of cidofovir. CMX001 is designed to cross cellular membranes by passive diffusion (vida supra, Phospholipid Mimics Designed to Facilitate Uptake in the Small Intestine). Uptake by this mechanism should be more efficient and lead to a more rapid accumulation of cidofovir in the cytoplasm of the target cell. Once it has reached the cytoplasm, CDV is phosphorylated by host cell nucleoside kinases to form the active antiviral agent cidofovir diphosphate.

A broad spectrum antiviral agent
Initially, the antiviral activity of CMX001 was characterized in vitro in cell culture systems and in vivo in animal models. In cell culture assays, CMX001 is significantly more active than CDV against double-stranded DNA viruses including orthopoxviruses (variola, monkeypox, vaccinia, cowpox, and ectromelia), herpes viruses [cytomegalovirus (CMV), herpes simplex virus (HSV)-1, HSV-2, varicella zoster virus (VZV), Epstein-Barr virus (EBV), human herpes virus type 6, and human herpes virus type 8], and adenoviruses (AdV3, AdV5, AdV7, AdV8, and AdV31). Against variola major, CMX001 is approximately 250 fold more potent than CDV in inhibiting viral DNA replication.

Smallpox
In vivo, the antiviral activity of CMX001 has been characterized in mice infected with ectromelia, vaccinia, and cowpox viruses and in rabbits infected with rabbitpox. In each model, a dose of CMX001 was identified that provided protection against challenge with a lethal viral inoculum. In a pilot study in monkeypox infected cynomolgus monkeys, intermittent treatment with CMX001 over 12 days produced a statistically significant increase in time to death, but not a survival benefit.

Sale to the national stock piles for bio-defense is expected after successful completion of clinical development.