Broad-spectrum antivirals for treatment of adenovirus infection

Viral infections of the eye are caused by adenovirus (AdV), herpes simplex virus (HSV), and varicella zoster virus (VZV), with AdV being responsible for 80-90% of those infections. Human adenoviruses D and B (HAdV-D, HAdV-B) are causative agents of acute conjunctivitis, which occurs with a prevalence of up to 15 million annually in the US and an estimated >100 million worldwide. The disease is highly contagious and, while typically self-limiting in immunocompetent patients, it results in many days of school and work lost. Infections involving the cornea, such as epidemic keratoconjunctivitis (EKC), can persist chronically over weeks and months and result in significant morbidity with scarring, loss of eye movement, foreign body sensation, and partial loss of vision. Despite the prevalence and impact of HAdV eye infections, there are no approved drugs currently available as a specific therapy to inhibit viral replication and lower viral burden and transmission.

We have developed a novel antiviral nucleoside phosphonate (NPP-669), with the FDA-approved antiviral compound cidofovir (CDV) as its warhead. NPP-669 delivers the active CDV directly to the target tissues of viral infections, where it’s further phosphorylated to CDV-PP, while sparing other organs from potential toxic effects.  NPP-669 shows significantly increased potency over CDV against a broad-range of DNA viruses, including clinical HAdV isolates, proven preclinical efficacy in a hamster model if hAdV infection. Acute single-dose toxicity studies have demonstrated a superior safety profile compared to CDV and brincidofovir (BCV). We are developing NPP-669 as a topical ocular therapy for AdV conjunctivitis, with a focus on EKC.

The project has been supported by $3.6M in non-dilutive funding to date