Turning T cells on … and off

Inovio Pharmaceuticals acquires early-stage DNA therapies to treat Alzheimer’s and multiple sclerosis

Lloyd Dunlap
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BLUE BELL, Pa.—In remarks positioning his company’s latest advances, Inovio Pharmaceuticals’ President and CEO Dr. J. Joseph Kim says, “Inovio is actually doing things one could only dream about a few years ago. The immune system protects us from infection, even trace cancer cells. Our DNA-based therapies modulate disease and fight off cancer. In effect, we are using killer T cells as our SWAT team.”
Kim stresses that its acquisition of worldwide rights (excluding China) for early preclinical therapies addressing Alzheimer’s disease and multiple sclerosis based on the academic research of Dr. Bin Wang is in the early stages of development. Wang, a professor at Fudan University’s Shanghai Medical College, is a pioneer in the field of DNA therapies, having worked closely with Dr. David Weiner at the University of Pennsylvania. Wang was the primary author on some of the earliest DNA vaccine papers and patents. In consideration for these rights, Inovio will make clinical and regulatory milestone payments to the university.
These newly licensed technologies are based on patent-protected and published discoveries from Wang and his collaborator, who found a novel way to generate inducible regulatory T cells, or iTreg. These iTreg cells are involved in shutting down immune responses after they have successfully eliminated invading organisms and in preventing autoimmunity or inflammatory diseases. In multiple published preclinical studies, this approach generated CD25-iTreg in an antigen-specific manner. These novel approaches could be used to develop therapies targeting major inflammatory diseases like multiple sclerosis and may be used to treat Alzheimer’s disease.
Kim adds that, “Acquiring these early-stage technologies is just another step in our ultimate goal of controlling the immune system to fight diseases in a more safe and effective manner using Inovio’s immune engineering platform. For most of our company’s development, our therapeutic cancer vaccines in the clinic are designed to properly activate and direct T cells to kill cancer cells, relentlessly, like Arnold in 'The Terminator.' These new candidates are designed to do the opposite—to control the troops— by shutting down unwanted and aberrant T-cell responses that cause autoimmune and inflammatory diseases. These new technologies give us the potential to go after these important disease targets.”
An estimated 5.2 million Americans have Alzheimer’s disease, including approximately 200,000 individuals younger than age 65. More than 500,000 seniors die each year from Alzheimer’s, the sixth leading cause of death in the United States. Because of the increasing number of people ages 65 and older in the United States, the annual number of new cases of Alzheimer’s is projected to double by 2050.
MS is a chronic inflammatory disorder of the central nervous system. It usually affects people beginning in their 20s or 30s and is one of the most common causes of non-traumatic disability among young and middle-aged people. MS affects more than 350,000 people in the United States and 2.5 million worldwide. MS-related healthcare costs are estimated to be more than $10 billion annually in the United States.
Inovio’s SynCon vaccines, in combination with its proprietary electroporation delivery, are generating best-in-class immune responses, with therapeutic T cell responses exceeding other technologies in terms of magnitude, breadth and response rate. “Electroporation,” Kim notes, “establishes a reversible channel that coaxes open the cell membrane and facilitates delivery of DNA-based therapies that provide the recognition code.” Human data to date have shown a favorable safety profile. Inovio’s lead vaccine, a therapeutic against HPV-caused pre-cancers and cancers, is in Phase 2. Other Phase 1 and preclinical programs target prostate, breast and lung cancers as well as HIV, influenza, malaria and hepatitis. Partners and collaborators include Roche, the University of Pennsylvania, the National Institutes of Health, HIV Vaccines Trial Network, National Cancer Institute, U.S. Military HIV Research Program, University of Southampton, U.S. Dept. of Homeland Security, University of Manitoba and PATH Malaria Vaccine Initiative.

Lloyd Dunlap

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