Heavy water keys collaboration between Bristol-Myers Squibb and KineMed

Companies to use stable isotope technology to identify biomarkers that can be used to treat Alzheimer\'s

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EMERYVILLE, Calif.—Using deuterium-labeled proteins to measure the transport time of protein down the molecular escalator of axons, KineMed Inc. will team with Bristol-Myers Squibb to facilitate development of promising new BMS drugs for the treatment of Alzheimer's disease.

The collaboration will apply KineMed's stable isotope technology to identify novel biomarkers that can be used to assess the extent and treatment of the disease. The length of the collaboration is specified to be two years and, when asked, Dr. Francis Cuss, senior vice president of discovery and exploratory clinical research at BMS, confirms that "We will be using KineMed markers for two years and hope to introduce something into the clinic by the end of that period."

Cuss notes that BMS is "constantly sweeping for outside opportunities. KineMed came up in such a sweep and we came to a quick agreement," he says.

KineMed is a privately held biotechnology company that specializes in translational and personalized medicine. Its proprietary technology uses the administration of stable (non-radioactive) isotopes to provide "high-definition" pharmacological measurements of disease activity and drug effects across a wide range of therapy areas, including diseases of the nervous system, metabolic and cardiovascular disease, cancer, inflammation and musculoskeletal diseases.

"Bristol-Myers Squibb is committed to helping patients prevail over serious diseases
through personalized medicine," Cuss notes, "and KineMed has a unique approach to identifying biomarkers for neurodegenerative diseases. We value KineMed's expertise in this area and look forward to working together in the fight against neurodegenerative diseases." By "personalized medicine," Cuss says, "at this stage we're really talking about 'stratified' medicine. The near-term opportunity is to identify strata of patients—responders, non-responders, those who demonstrate serious side effects. It's a way of providing more cost-effective medicine."

According to both Cuss and KineMed CEO Dr. Robert B. Stein, each company brings its own strengths. KineMed has pioneered the use of heavy water to study protein dynamics. Proteins are transported by axons. When labeled with heavy water, it is possible to measure the amount taken up and the rate of transport down the axon. A key to this process is that it's relatively non-invasive, and therefore a very reasonable alternative to radioisotopes.

In addition to its collaboration with BMS, KineMed is developing a small, high-quality pipeline of its own in-licensed compounds. Among these are a pair of drugs that stabilize the assembly and disassembly of the microtubular proteins that act as the escalator to ferry proteins from the cell body down the axon and thereby delay progression of disease and death.

Though applied to Alzheimer's disease in this case, the mechanism is thought to apply to Parkinson's disease as well, and KineMed has recently been awarded a grant from the Michael J. Fox Foundation to explore this possibility.

"We're quite advanced in the discovery and development process," Cuss adds, "in Phase II trials, with a compound that has shown activity in animal and humans at tolerable levels. This form of Alzheimer's disease involves breakdown products where gamma secretase enzyme snips the protein and forms plaques. Reduce this process, and you reduce breakdown products and thus, remove or prevent plaque formation. With neurofibular tangles—the other hallmark of Alzheimer's—we have a preclinical program."

"We are very enthusiastic about working with Bristol-Myers Squibb as we believe our
expertise and platform are most powerful when applied in the context of important drug R&D programs," Stein concludes.

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