UConn, Biohaven Pharmaceuticals Ink Licensing Deal for Investigational Agent for Inflammatory and Autoimmune Diseases

Biohaven Pharmaceutical Holding Company Ltd. (NYSE: BHVN) announced today that it signed an exclusive, worldwide option and license agreement with the University of Connecticut for the development and commercialization rights to UC1MT, a therapeutic antibody targeting extracellular metallothionein (MT). Extracellular MT has been implicated in the pathogenesis of autoimmune and inflammatory diseases. Under this agreement, Biohaven has the option to acquire an exclusive, worldwide license to UC1MT and its underlying patents to develop and commercialize throughout the world in all human indications.

The antibody was discovered in the laboratory of Michael Lynes, PhD, head of the Department of Molecular & Cell Biology at the University of Connecticut Storrs. Lynes is a world leader in the study of metallothioneins and their role in disease. Biohaven and the University of Connecticut also signed a Sponsored Research Collaboration Agreement to support the ongoing exploration of the role of MT in human disease.

The new antibody, co-invented by the UConn researchers together with a team from Ghent University in Belgium, is designed to prevent the patient’s immune system from attacking its own body and potentially causing irreversible damage.

“We are very excited about this opportunity to potentially expand our portfolio with the addition of this novel antibody and assess its activity in a range of diseases, including neuro-inflammatory disorders,” says Dr. Vlad Coric, CEO of Biohaven. “The pre-clinical discovery work by Lynes at the University of Connecticut, and his collaborators at the Ghent University and Joslin Diabetes Center, an affiliate of Harvard Medical School, suggests that metallothionein can have dramatic influences on the modulation of both innate and adaptive immunity. We look forward to further evaluating this antibody and potentially advancing it into the clinic.”

The pre-clinical discovery work by Lynes at the University of Connecticut, and his collaborators […] suggests that metallothionein can have dramatic influences on the modulation of both innate and adaptive immunity. — Vlad Coric

“This agreement represents a critical next step for my research group, as it helps define the path for taking our basic research discoveries into the clinic. The expertise that Biohaven Pharmaceuticals brings to my research team has been invaluable in advancing this goal,” says Lynes. I believe we have an exciting opportunity to develop this new approach to the management of important inflammatory and autoimmune diseases where metallothionein plays a significant role.”

MTs are a family of low molecular weight, cysteine-rich, metal-binding proteins that have a wide range of functions in cellular homeostasis and immunity. MT has traditionally been considered to be an intracellular protein that can be found in both the cytoplasm and nucleus; however, MT also can be found in extracellular spaces, particularly in disease states involving chronic cellular stress where intracellular MT production is upregulated by inflammatory cytokines, and extracellular MT acts as a danger signal, attracting leukocytes and modulating the immune response. In pre-clinical studies, UC1MT has been observed to block this extracellular pool of MT and the resulting MT-mediated inflammation and immunomodulation.

“We are looking forward to this partnership as we see great potential for this novel mechanism in inflammation. We intend to capitalize on our strong development experience and the deep scientific expertise of Dr. Lynes’ team to rapidly advance innovative therapies to patients,” says Clifford Bechtold, chief operating officer and head of biologic development at Biohaven. Bechtold has previous pharmaceutical industry experience in optimizing biologics development and manufacturing capabilities.

This option builds upon Biohaven’s portfolio of innovative, clinical-stage product candidates for the treatment of neurodegenerative, neurologic and neuropsychiatric disease indications. Under the terms of the agreement, Biohaven paid an upfront option fee and, if Biohaven exercises its option to in-license the program, the University of Connecticut will receive additional license fees and will be entitled to low single-digit percentage royalties based on net sales of any commercialized products as well as milestone payments based on the achievement of development, regulatory and commercial milestones.

The Road to a New Antibody

More than a decade ago, Lynes, professor and head of the Department of Molecular and Cell Biology at UConn, and his research team discovered a novel and important role that a protein called metallothionein (MT) plays in influencing the body’s immune function. The body produces MT when cells are under stress, and extended periods of stress cause MT to be released from the cells that produced it, Lynes says. MT is an unusual protein that holds onto chemicals in the body – both those that are beneficial, such as zinc and copper, and those that are harmful – such as cadmium and mercury.

While studying MT, Lynes and his research team noticed that MT released from cells could mimic some of the signals that the immune system uses as cues to tell cells to go to one place or another in the body. Under normal circumstances, immune cells use these signals to guide them to local infections or other tissue damage. When cells are stressed over prolonged periods, this can mean that there is persistent inflammation accompanied by damage to nearby healthy tissue.

About 50 million people, or 20 percent of the U.S. population, suffer from some form of autoimmune disease or chronic inflammation, according to the American Autoimmune Related Diseases Association. More than 80 autoimmune diseases have been identified, and autoimmune diseases are becoming increasingly prevalent, for reasons unknown, according to the National Institute of Environmental Health Sciences. While causes of autoimmune diseases also remain largely unknown, scientific consensus is that autoimmune diseases are probably triggered by a combination of genetic and environmental factors.

A team of Belgium doctors and scientists studying Inflammatory Bowel Disease (IBD) had published a paper saying that their sickest patients were those whose bodies produced the most MT. The MT protein, which serves as a normal part of the cell’s internal machinery inside the cell, was getting outside the cell and causing damage. That paper by Dr. Martine DeVos, Debby Laukens, and Lindsey Devisscher led to a collaboration with Lynes.

Since the protein serves an essential purpose, researchers can’t shut it off all together; so they had to find a way to stop MT from prolonging inflammation and damaging healthy cells. Lynes and his team produced an antibody protein that basically attaches itself to MT when it is outside the cell and inactivates it – preventing the body from attacking its intestinal system. This approach dramatically reduced inflammation in mouse models of the human disease.

“We’ve recently extended that work with our colleagues You-Hua Tseng and Matthew D. Lynes at Joslin Diabetes Center of Harvard Medical School to show that UC1MT also shows therapeutic promise in a mouse model of Type 1 diabetes,” Lynes says.”

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