OPENING POSSIBILITIES FOR NOVEL THERAPIES
SOLVING SOME OF THE MOST DIFFICULT CHALLENGES IN AB DESIGN
Antibody based drugs represent a big market which is growing at significant rates, forecasted to reach 115B in 2022. The increasing need of pharma and biotech companies to differentiate their pipelines, by pursuing antibodies that can bind two (or more) targets, difficult targets that were considered not suitable for antibodies and using Abs with improved characteristics represent a significant opportunity for Biolojic’s unique capabilities.
1. DUAL SPECIFICITY
Design of a dual or triple-specific IgG Ab (with two identical heavy and two identical light chains)
Case Study: Modify an existing Ab against an oncology target (Erb2) so that it also binds another oncology target (VEGF).
Project outcome: Hi affinity binding to both targets, maintaining original epitope and profile (see figure below).
Project timeline: 2 months
Methodology: A. Identify epitope on the second target. B. Computationally identify positions that can be altered. C. Testing binding to new target while maintaining original binding.
2. DESIGNING AN AB FOR A CRYPTIC EPITOPE
(NOT AVAILABLE FOR BINDING IN THE NATIVE CONFORMATION)
A first-tier pharma company asked Biolojic to design an epitope specific antibody that will prevent an interaction between the target and its cognate receptor by binding to a cryptic epitope. Existing technologies are unlikely to discover an antibody against any epitope that is not exposed to solvent in the native conformation.
Biolojic delivered several such antibodies. Crystal structure confirmed that antibody binds exactly where we designed it to bind.
Project Outcome – novel Ab that binding at the desired cryptic site.
PROJECT DURATION: 9 MONTHS
i. Biological models of the disease have shown that the Biolojic’s Ab has an anti-inflammatory effect.
ii. This case was published: Computational design of epitope specific functional antibodies, Cell Reports, Nov 2019 (doi: 10.1016/j.celrep.2018.10.081
3. IMPROVING ANTIBODY CHARACTERISTICS
A first tier pharma company presented Biolojic with a functional Ab against an ion channel they tried to engineer for a few years. While the Ab was functional its affinity was very poor. Attempts to improve affinity either failed or led to loss of the function of the Ab.
Relying on its computational platform, within two months Biolojic introduced two mutations that improved affinity and activity 1000 folds.
In other projects Biolojic introduced very rapid improvement to existing Abs in different parameters: affinity (Kon and/or Koff), developability (improving TM, expression, yield, solubility) shown in the table below: