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9/26/2014  |   4:30 PM - 6:00 PM   |  

Native Human Antibody for HCMV Immunotherapy

TRL345 is a native human monoclonal antibody for use as passive immunotherapy for individuals at risk for HCMV-induced pathology. It binds with an affinity of 50 pM to a highly conserved epitope on the viral surface protein gB: AD-2 (site I). TRL345 neutralized 15 out of 15 clinical isolates tested, spanning a wide range of genotypes. It provided potent neutralization of VR1814 virus infection of HFF, HUVEC and ARPE-19 epithelial cells and of epithelial adapted strains of AD169, Towne and urine derived isolate UxcA. It further prevented syncytial spreading by an epithelial adapted Towne strain. A major indication of interest is to protect transplant recipients for whom HCMV is the most common serious infection causing poor outcomes. Viral polymerase inhibitors have shown efficacy in this indication, but are toxic and subject to emergence of drug resistance. To date, none of the multiple vaccine efforts have yielded a product with high efficacy, a frustrating result in light of clinical evidence suggesting efficacy for HCMV-specific gamma globulin. A monoclonal antibody offers substantial advantages over gamma globulin. Similarly, antibody treatment offers advantages over ex vivo priming of T cells as an alternative to vaccination. A second indication of interest is maternal transmission of virus to the developing fetus. TRL345 blocked HCMV infection of placental cell types central to virus transmission to the fetus, including differentiated cytotrophoblasts, trophoblast progenitor cells and placental fibroblasts. TRL345 was also effective for reducing infection in ex vivo human placental explants of anchoring villi. TRL345 has been expressed at 1.8 g/L in CHO cells. Scaled up manufacturing and formal toxicology are currently underway to support initiation of clinical trials in the transplant indication in 2015. Establishing safety and efficacy in this indication is expected to facilitate subsequent testing in pregnant women for prevention of congenital infection.

Lawrence M Kauvar (Point of Contact,Primary Presenter), lkauvar@trellisbio.com;
Larry Kauvar, PhD is a serial entrepreneur scientist who founded Trellis Bioscience where he serves as Senior VP, Chief Scientific Officer. He was previously the founder and Chief Scientific Officer of Telik, a public development stage small molecule drug company focused on oncology, and is a co-founder of Promedior, a private development stage biologics company focused on fibrotic diseases. He holds 60 US patents for drug discovery methods and tools as well as specific compounds. He is one of the inventors of CellSpot™, Trellis' core technology for discovery of native human monoclonal antibodies. Dr. Kauvar received his undergraduate degree in mathematics from Harvard in 1973, his PhD from Yale in Molecular Biophysics and Biochemistry in 1978, and conducted postdoctoral research at Caltech and UC San Francisco before founding Telik.

ASHA DISCLOSURE:

Financial - Receives Salary,Ownership interest for Employment,Management position,Board membership,Ownership from Trellis Bioscience.  

Nonfinancial - No relevant nonfinancial relationship exist.

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