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
- Chang MY, Boulden J, Valenzano MC, Soler AP, Muller AJ, Mullin JM and Prendergast GC (2012). Bin1 attenuation suppresses inflammatory colitis by enforcing intestinal barrier function. Dig Dis Sci 57:1813-21.
- Thomas S, Mercado JM, DuHadaway J, DiGuilio K, Mullin JM and Prendergast GC (2016). Novel colitis immunotherapy targets Bin1 and improves colon cell barrier function. Dig Dis Sci 61:423-32.
- Thomas S, Hoxha K, Alexander W, Gilligan J, Dilbarova R, Whittaker K, Kossenkov A, Prendergast GC and Mullin JM (2019). Intestinal barrier tightening by a cell penetrating antibody to Bin1, a candidate target for immunotherapy of ulcerative colitis. J Cell Biochem 120:4225-37.
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]