Therapeutic Antibodies for Biofilm Infections

Period of Performance: 07/01/2016 - 06/30/2017

$1000K

Phase 2 SBIR

Recipient Firm

Trellis Bioscience, LLC
MENLO PARK, CA 94025
Principal Investigator

Abstract

Abstract About 65-80% of serious bacterial infections are biofilm-mediated. Not only do biofilms provide ananchor and physical protection from the immune system for bacterial cells, but the physiology and geneticprogramming of bacteria also shifts between the planktonic (free floating) and sessile (stationary) states.Most notably, antibiotic sensitivity differs substantially between the two states, with bacteria being orders ofmagnitude less sensitive to antibiotics in the sessile state. Biofilms are known to include a variety ofpolymers and proteins. One of these proteins has previously been shown to anchor the three dimensionalscaffolding of the polymers. Trellis has used its proprietary antibody discovery technology to clone a highaffinity antibody from human B lymphocytes, TRL1068, which binds the homologs of this protein from bothGram positive and Gram negative bacteria. In Phase I of this project, we used two rodent models ofbacterial infection to demonstrate that extraction of the protein from the biofilm by this antibody leads to thebiofilm dissolving in vivo as it does in vitro. Therapeutic benefit was seen for treatment of MRSA in bothmodels: a rat model of infective endocarditis and a mouse model of implant infection. In Phase II, we willconduct IND-enabling studies for FDA approval by establishing a manufacturing method under GMP andconducting toxicity testing of the therapeutic antibody. In parallel, we will continue preclinical research toexplore alternative indications and dosing regimens. This antibody offers potential clinical benefit against awide range of infections that are currently very difficult to treat. Infective endocarditis in particular is a anindication for which current therapy often fails, leading to expensive heart valve replacement surgery thathas a significant relapse rate (re-establishment of the biofilm protected infection) leading to death. Becausethe biofilm can be imaged directly (using trans-esophageal echocardiogram technology), efficacy definedby clinical endpoints can be correlated with the mechanism of action. Since the heart valve is readilyaccessible to antibody delivered intravenously, tissue penetration is not a significant variable for thisindication. The combination of high unmet medical need and favorable experimental features makes thisindication particularly useful for our initial clinical trials.