Novel class of NAMPT activators for neurodegenerative disease discovered

This week, UT Southwestern researchers published a new paper about the molecular target of P7C3 compounds, a class that has been shown to help in various animal models of neurodegeneration. UT Southwestern previously licensed the P7C3 compounds to Dallas-based 2M Companies. 2M and Calico have now entered into a new license agreement under which Calico will take responsibility for developing and commercializing the compounds resulting from the research program. Under the agreement, Calico will fund research laboratories in the Dallas area and elsewhere to support the program.

The P7C3 Program and Today's Cell Paper

Death of nerve cells is the key mechanism in many devastating neurological diseases for which there are currently inadequate treatment options. UT Southwestern researchers Dr. Steven McKnight, Chairman of Biochemistry, Dr. Joseph Ready, Professor of Biochemistry, and Dr. Andrew Pieper, a former UT Southwestern faculty member who is now Associate Professor of Psychiatry and Neurology at the University of Iowa Carver College of Medicine, have collaborated since 2007 to find novel drugs that promote the growth of new nerve cells in the brain, a process known as "neurogenesis."

The P7C3 compounds discovered by the team have previously been shown to be effective in animal models of age-related neurocognitive impairment, Parkinson's disease, amyotrophic lateral sclerosis (ALS), and depression. New research published today in the journal Cell shows that these drugs activate a cellular enzyme involved in energy metabolism, known as NAMPT (short for nicotinamide phosphoribosyltransferase), which is critical to the proper functioning and survival of cells. A separate study published today in Cell Reports shows that the P7C3 compounds protect against brain dysfunction when given to rodents following traumatic injury.

Licensing of the P7C3 Program

In 2010, UT Southwestern entered a licensing agreement with 2M Companies for the P7C3 program. Today's agreement between 2M and Calico is an important further step in the process to commercialize these compounds. Under this agreement, 2M grants to Calico an exclusive worldwide license to the P7C3 program and other NAMPT modulators in exchange for an unspecified up-front fee, milestones, and royalty payments. Calico is the Google-backed life sciences company led by Arthur D. Levinson, former chairman and CEO of Genentech.

"Over the past decade Andrew Pieper, Joe Ready, and I have worked collaboratively to discover, characterize, and optimize the P7C3 class of neuroprotective chemicals. We are excited to join forces with Art Levinson, whom I have known and admired for over 25 years, and the Calico team to advance our scientific discoveries toward clinical and commercial objectives," said Dr. McKnight.

Melissa Krauth, head of life science investing at 2M and its affiliate Claria Bioscience, commented, "After many years of fruitful collaboration with UT Southwestern and the P7C3 inventors, we are delighted to place the P7C3 program in the very capable hands of the Calico team. This agreement validates our strategy of partnering with exceptional scientists and investing in early-stage, high-impact technologies to advance them toward the clinic."

Hal V. Barron, M.D., President of Research and Development at Calico, said, "This is an important collaboration for Calico. We look forward to working with the world-leading scientists who discovered the P7C3 class of molecules to learn whether the remarkable biological effects can be translated to the treatment of human disease."

Frank Grassler, Vice President for Technology Development at UT Southwestern, noted, "Unique among academic medical centers, our medicinal chemists build on UT Southwestern's world-renowned biomedical research to synthesize compounds that will become the therapies of the future. This collaboration and development agreement is a milestone for UT Southwestern and is a big boost for the Texas biomedical industry."