The Burrill Report

Calimmune, a young biotech that has garnered $20 million in grant money from the California Institute of Regenerative Medicine, said it is in discussions with regulators to begin a phase 1/2 trial of its experimental gene therapy that aims to alter key immune cells in patients to render them immune to HIV.

The four year old company, founded by several top scientists including Nobel Laureate David Baltimore, seeks to alter a patient's T-cells so they are without the protein CCR5, a co-receptor exploited by HIV to enter and hijack the immune cells. Baltimore more than ten years ago proposed gene therapy as a potential approach to treating the virus through the use of genetically-modified blood stem cells.

Though Calimmune’s approach is unique, it is not alone in trying to alter a patient’s T-cells to mimic the naturally occurring mutation, found in about 1 percent of Europeans and rendering them impervious to the virus. Among others seeking to apply gene therapy to this end is Sangamo Biosciences, which initiated an early-stage trial of its zinc finger protein technology in 2009.

The case of an HIV-positive leukemia patient in Berlin who needed a bone marrow transplant to treat his cancer has validated the potential of such approaches. In 2007, the man was given a transplant of a matching bone marrow donor who naturally has the mutation that leaves him unable to produce the CCR5 protein, the gateway used by the virus to enter the T-cell.

Such bone marrow transplants are viewed as too costly and risky to be a practical treatment, Nevertheless, it showed that a patient could be rid of the virus by giving rise to a population of T-cells that could not be invaded by the virus.

Calimmune’s approach involves taking the stem cells contained in the bone marrow—the hematopoietic stem cells that give rise to the blood and immune system—and using RNA interference in the lab to alter the cells so they don’t encode for the CCR5 protein. Those cells are then put back into the patient. The hope is that a single administration of the cells could provide lifetime protection to an HIV patient.

Though the company says it is too early to speculate on how such a therapy would be priced, it could provide not only a life-saving therapy, but one with a substantial economic impact. The company estimates the cost of antiretroviral therapy for an HIV patients costs $25,000 a year and close to $750,000 over the lifetime of the average patient.

CIRM has substantively increased its funding trajectory of the state’s biotech industry in the past two years,” say Ellen Feigal, vice president of research and development for CIRM. “The pairing of business and regulatory acumen with the scientific research is a key component of CIRM’s strategy to advance our translational programs into clinical trials in the next few years.”

“Our mission is to eradicate the ravages of HIV,” says Louis Breton, CEO of Calimmune. “We are focused on helping people gain greater freedom from medication, from high cost burdens, and from the longer-term toll of this formidable disease.”

July 01, 2011
http://www.burrillreport.com/article-gene_therapy_awaiting_fda_greenlight_to_begin_hiv_trial.html