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TAU BIO-LOGIC Announces Humanization of Picomolar Affinity Monoclonal Antibody Targeting TauC3 Protein

April 19, 2019 By americanpharmaceuticalreview

TAU BIO-LOGIC in collaboration with LifeArc has successfully humanized a monoclonal antibody (TBL-100) that targets C-terminally truncated tau (tauC3). TAU BIO-LOGIC is developing TBL-100 for the treatment of Alzheimer's disease (AD) and Progressive Supranuclear Palsy (PSP). The humanized antibody has an affinity for tauC3 of 13pM (about 100-fold higher than most marketed therapeutic antibodies have for their targets) and a specificity that is 1000-fold greater than for full length tau (FLT). The high affinity and specificity of the antibody are expected to translate into improved efficacy and safety compared to other tau antibodies currently in development. TauC3 exists in lower abundance than FLT or N-terminally truncated tau but exerts disproportionately large pathological effects. This is due to tauC3 having the highest propensity to aggregate among all forms of tau and it’s also having the ability to recruit normal tau and nucleate pathological tau conformations. In AD, tauC3 is formed early in the disease course and levels correlate with cognitive decline. TauC3 causes intracellular neurotoxicity and is also believed to be the major driver of tau propagation. A study conducted by Professor Bradley Hyman at Harvard Medical School demonstrated TBL-100's potential to block tau propagation in the AD brain (Nicholls et al., 2017; PLoS ONE 12(5): e0177914). In PSP, tauC3 production and activity have been linked to a single polynuclear polymorphism (SNP) at rs1768208, a significant risk factor for the disease. Thus, TBL-100 could be beneficial for this condition as well.

The humanization of TBL-100 was conducted by LifeArc under a risk sharing agreement with TAU BIO-LOGIC, with terms that would see LifeArc receive a small royalty on future drug sales.

"We are delighted to have contributed to the development of TBL-100," said Dr. Justin Bryans, head of LifeArc's Centre for Therapeutic Discovery. "The collaboration has produced a lead candidate for further development and several good backup molecules offering a combination of excellent biophysical characteristics and thermostability properties, high affinity binding and high expression.

"Successful humanization marks an important milestone in the development of TBL-100, which we believe offers several advantages compared to other anti-tau antibodies and small molecule tau treatments in development, both in terms of safety and improved efficacy," said Daniel G. Chain, PhD, President and CEO of TAU BIO-LOGIC. "We aim to rapidly advance this promising disease-modifying therapeutic agent for patients suffering from AD and PSP since these conditions currently lack effective therapies.

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