Overactive FXIIa — often caused by a mutation in the F12 gene — is the leading cause of HAE type 3, a rare form of angioedema. It triggers a biological process causing fluid to leak through blood vessel walls and into the surrounding tissues. This inflammation and swelling is characteristic of all HAE subtypes and becomes life-threatening when it affects the airways and lungs.
Rockefeller researchers Jan L. Breslow, MD, and Manish Ponda, MD, discovered that blocking FXIIa might guard against these attacks. They later identified several small molecules capable of inhibiting FXIIa.
“Our results indicate that inhibitors of FXIIa may show utility against HAE and potentially a variety of other inflammatory disorders,” Breslow said in a press release. “The possibility of developing new treatments to address such unmet medical needs continues to motivate our research efforts.”
The exclusive license agreement the university has now signed with Bridge allows the company to advance the researchers’ efforts toward creating viable new medicines. In recent years, there have been many therapeutic advances for patients with the classical types of HAE — types 1 and 2 – which are caused by mutations in the SERPING1 gene.
But therapies that specifically target HAE type 3 are limited.
Rockefeller joined several other universities, investment firms, and Takeda Pharmaceuticals in launching Bridge Medicines in 2016. The company’s operating model rests on moving early-stage research projects developed in academic institutions through pre-clinical and clinical development.
Bridge acts as an incubator of academic research with commercial potential. In contrast to common routes toward drug development, such as selling intellectual property to a pharmaceutical company for it to develop, or creating a new company around a single potential therapy, Bridge’s goal is to provide a space for new technologies to grow until they show success that will be needed to warrant human clinical trials.
Upon reaching that point, the potential new medicines would be spun off into new companies.
“We are thrilled to be working with Dr. Breslow on this highly innovative, and therapeutically promising project,” said William Polvino, MD, CEO of Bridge Medicines.
“Drs. Breslow and Ponda have already shown that the lead compounds are efficacious in disease models of immune mediated inflammatory disorders,” Polvino said. “We see this as an exciting opportunity to revolutionize treatment for these disorders with a new medicine.”
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