Phase II year
2020
(last award dollars: 2023)
Phase II Amount
$1,297,811
Human cytomegalovirus (HCMV) transmission from mother to fetus is implicated in ~15% of stillbirths and~16,000 birth defects annually in the US. HCMV is also the major viral cause of medical complications associatedwith bone marrow and organ transplantation. Passive immunization using anti-HCMV enriched human immuneglobulin (HIG) has shown promising activity for both indications. HIG is a complex, variable product that maycause side effects from off-target antibody binding. A monoclonal antibody (mAb) offers qualitative advantagesover HIG including potency, safety, production efficiency and quality control. Trellis Bioscience has discovereda high affinity native human mAb (TRL345) against the most conserved site on the HCMV virion (gB AD-2 SiteI). TRL345 is a human IgG1kappa (G1m1,17 (z,a); Km3 allotype) monoclonal antibody cloned from human Blymphocytes. This mAb neutralized 15 out of 15 clinical isolates of all four major serotypes. It protected all of thespecialized cell types relevant to human pathology. It was also fully protective in a model of human placentalfragments grown as tissue explants ex vivo. This published work was completed under a Phase I/II SBIR grant.A Master Cell Bank has been developed that expresses TRL345 in CHO cells at a commercially useful level(1.74 g/L) at the 250L GMP scale. All IND-enabling analytical work has been completed, including GLP toxicologyin rats and tissue reactivity profiling. With SBIR CRP funding, the first clinical lot has been manufactured yieldingsufficient material for Phase 1 and 2 human clinical trials. We propose here to conduct a Phase 1 singleascending dose clinical trial in healthy volunteers.
Public Health Relevance Statement: Narrative
Women who are first infected with HCMV early during pregnancy have ~12% chance that their child will be born
with or later develop significant handicaps, primarily deafness but also varying degrees of cognitive and motor
function deficits. This population comprises ~120,000 women annually in the US with comparable incidence in
Europe and Japan. Reinfection or reactivation of latent infection also contributes to the risk of birth defects.
Although harder to detect, and thus less suitable for a clinical trial, the potential benefit of TRL345 likely extends
to the entire population of first trimester pregnancies. The economic impact of congenital HCMV, including the
costs of medical care and educational expenses, is estimated to be >$3 billion annually (US). HCMV is also the
leading viral cause of hospitalization for solid organ and bone marrow transplant patients, impacting close to
50,000 patients annually in the US at a cost of ~$5 billion.
Project Terms: <21+ years old><0-11 years old><1st trimester>| | |
