A Therapeutic Antibody to Block Fibrosis

Background

Localized and systemic fibrosis encompasses many diseases whose common feature is excessive accumulation of collagen fibrils. These fibrils form tough scars that disrupt normal functions of affected tissues and organs, including skin, lung, liver, kidney, eye, peripheral nerve, joint capsules, and others. Although fibrotic diseases are highly progressive and cause a significant socioeconomic burden, there are no fully effective and safe medical interventions to limit them. To address this treatment gap, Thomas Jefferson University researchers have developed an antibody-based approach to reduce the excessive formation of fibrotic deposits. This new approach explicitly targets the extracellular process of formation of collagen fibrils, the main component of all fibrotic scars. Tests done in animal models of fibrotic diseases, including pulmonary fibrosis, keloid, arthrofibrosis, ocular fibrosis, and neurofibrosis, indicate the great utility of the antibody. They show that this technology is promising in reducing localized and systemic fibrotic lesions and the complications that can arise from such.

Technology Overview

Researchers at Jefferson have demonstrated that direct inhibition of aggregation of collagen molecules into fibrils reduces pathological organ fibrosis effectively and safely. The invention comprises an engineered collagen-specific monoclonal antibody that blocks the fibrotic process. Specifically, the research team’s approach is to block the interaction that drives the assembly of individual collagen molecules into insoluble fibrils, knowing that this interaction depends on a site-specific binding between the telopeptide region of one collagen molecule and the telopeptide-binding region of an interacting partner. This is achieved by targeting a core sequence of collagen telopeptide, an essential component that drives collagen fibril formation and excessive fibrosis. Extensive tests done in vivo and ex vivo indicate the remarkable efficacy of this antibody to limit the formation of unwanted collagen-rich deposits. Tests also showed that while the antibody targets the assembly of collagen fibrils formed de novo in response to tissue or organ injury, it does not alter any existing fibrils that form and maintain the normal architecture of tissues and organs. This patented new next-generation antibody and its fully humanized variant have great potential to block fibrotic scarring in all tissues and organs.

Stage of Development

• A fully humanized version is now available
• The antibody was also tested in the eye and peripheral nerves
• Extensive studies did not show any adverse effects of the antibody

Benefits

• This targeted approach is directed at disrupting an event that is crucial to the fibrotic disease process
• As the normal collagen turnover in healthy tissues is minimal, the proposed approach is unlikely to affect collagen homeostasis
• Prevents fibrosis related to scarring (de novo) but does not alter existing fibrotic matrices necessary for standard organ and tissue architecture
• Effective if delivered locally or by systemic administration
• No off-target effects

Opportunity

The technology is currently available for exclusive licensing and other partnerships.