Products and Development Programmes

ESBATech’s lead antibody fragment ESBA105 is a TNFα antagonist that is scheduled to enter clinical development later in 2008 in an ophthalmic indication. ESBA105 is designed to locally-neutralize TNFα, a clinically validated disease target. TNFα is a cytokine believed to be a primary cause of many inflammatory conditions. Overproduction of TNFα can cause the immune system to attack healthy tissue resulting in severe inflammation. Left untreated, this inflammation can cause permanent damage to cartilage, bones and tissue. In preclinical studies, ESBA105 has exhibited favorable pharmacokinetic properties such as a high potency, stability, selectivity and solubility with no aggregation and a low risk for immunogenicity.

In preclinical studies, ESBATech has achieved high concentrations of ESBA105 in all segments of the eye with topical delivery via eye drops. These data were confirmed in several independent preclinical in vivo tests. Anticipated therapeutic concentrations of ESBATech’s antibody fragments were observed in the anterior chamber (front of the eye) and in the posterior segments (back of the eye) including vitreous humour, retina, and choroid. The company believes that this highly stable and monomeric single-chain antibody fragment now meets the protein requirements that allow for sufficient delivery of immune binders into all segments of the eye via eye drops.

Local Delivery

ESBA105 will be delivered locally via eye drops. It is expected to exhibit high safety levels compared to systemically administered TNFα antagonist such as Remicade®, the gold standard in TNFα therapeutics. Systemic neutralization of TNFα can have serious side effects as evidenced by the series of FDA warnings for all the currently marketed TNFα antagonists. Remicade and Humira® now carry FDA “Black Box” label warnings due to severe adverse events associated with their systemic administration. ESBA105, delivered locally, has a half-life of 5 hours compared to Remicade’s 16 day half-life and therefore it is expected to be cleared from the body much faster and pose far less risk of serious side effects.

Mechanism of Actions

ESBA105 binds with high affinity and specificity to TNFα. It has a comparable IC50 value to Remicade in standard cell-culture assays and in animal proof-of-concept studies. Due to its small molecular size, ESBA105 should allow for increased penetration of the protein into tissues and therefore improve clinical effects as compared with full length monoclonal antibodies.

Intellectual Property

ESBATech’s products and technologies are patent protected. The company also has licensing agreements with Enzon and Micromet that secure freedom-to-operate in antibody fragment applications. Earlier investments in the technology platforms have created significant value in the form of validated IP and generated a number of novel compounds in the company’s pipeline.

Collaborations and sublicences

ESBATech has also established the expertise and know-how to apply this proprietary technology to the improvement of existing antibodies and can offer sublicenses to the scFv format under its licensing agreement with Micromet and Enzon.