Anti-Bin1 antibodies: new treatment for inflammatory bowel disease

Lead investigator: Sunil Thomas, PhD
Collaborators: James Mullin, PhD and George C. Prendergast, PhD

Unmet need

Inflammatory bowel disease (IBD), which includes ulcerative colitis and Crohn’s disease, is a debilitating autoimmune condition that can be clinically challenging to manage effectively. The CDC estimates that 1.3% of U.S. adults (about three million people) have been diagnosed with IBD.

Many IBD patients are diagnosed early in life, and as a result of chronic gut inflammation, experience higher risks of colorectal cancer. Presently, other than general suppression of immunity or inflammatory signals, there is little specific knowledge about how to limit or prevent IBD flare-ups.

Opportunity

The incidence of IBD in developed countries has been skyrocketing, and the disorder is now becoming a global disease, most especially in newly industrialized countries as societies become more Westernized in diet and other factors. The global market for gastrointestinal therapeutics is set to grow from US $51.9 billion in 2016 to US $65.1 billion by 2025, according to the business intelligence provider Grand View Research.

Unique attributes

Building on their expertise in tissue barrier functions of the gastrointestinal tract, LIMR scientists have developed an antibody-based therapy that inactivates Bin1, a membrane-associated molecule that facilitates gut inflammation in the setting of IBD. This therapeutic technology based on novel MOA tightens the poor gut-barrier function found in IBD patients, thereby attenuating multiple sources of inflammation that are associated with a leaky gut barrier.

The scaffold and signaling molecule Bin1 modifies stress and inflammatory responses of cells under stress. In genetic studies in mice, LIMR scientists discovered that Bin1 ablation dramatically attenuated colonic inflammation and risks of colon carcinogenesis.

In exploring therapeutic directions to mimic this effect, they discovered a cell-permeable anti-Bin1 antibody that is safe and effective when delivered systemically in preclinical models of IBD. Human colon tissue studies confirm observations that antibody uptake is sufficient to tighten barrier function, as measured physiologically or molecularly at the level of tight junction protein expression. Accordingly, anti-Bin1 acts to tighten colon barrier function, coordinately reducing mucosal lesions, crypt loss, lymphoid follicle rupture, and infiltration of neutrophils and lymphocytes into mucosal and submucosal areas of the colon.

Clinical applications

The LIMR mAb offers potential uses to treat multiple types of IBD.

Stage of development

Current work is at a preclinical stage of development, including ongoing mechanism studies and antibody humanization.

Intellectual property

Methods and compositions for the treatment of diseases and disorders. U.S. Patent No. 10,494,424 (issued December 3, 2019).

Collaboration opportunity

Refinement and humanization of murine anti-BIN1 mAb that preclinically alleviate IBD in vivo.

Relevant publications

Contacts

Institutional contact: George C. Prendergast, PhD, LIMR President and CEO, 484.476.8475, [email protected]

IP manager contact: Heather Rose, PhD, JD, VP of Technology Licensing and Startups, Thomas Jefferson University, 215.503.0770, [email protected]