In the annals of cancer medicine, radiation has a long and distinguished reputation as a potent weapon. But like all cancer treatments, radiation can cause side effects, because it attacks healthy cells, as well as diseased ones.
In 2000, New York physician David Sheinberg started a company, Actinium Pharmaceuticals, around an idea for making radiation a more potent and targeted therapy: He wanted to attach radioactive isotopes to specific antibodies—proteins that are programmed to target cancer cells—and turn them into drugs. But rather than using isotopes that produce gamma radiation, which is standard in cancer treatment, he chose ones that emit alpha particles instead.
Why alpha radiation? “These particles have tremendous killing power, but they travel short paths,” says Dragan Cicic, who joined Actinium as CEO in 2005. “If you bring them into the cell, they will just kill that cell. They won’t do anything to the surrounding tissue.”
Sounds simple enough, but it actually took Actinium nearly a dozen years to figure out how to make alpha-radiation-armed antibodies that are safe and effective, and most importantly, that have a long enough half-life to be able to be transported to treatment centers before they lose their cancer-killing power. Now Actinium is approaching mid-stage trials of its lead drug candidate, and its executives are so confident they’re on the right track they’re planning a public offering in the fourth quarter of this year.
The key to the company’s technology platform, says Cicic, is the method Sheinberg developed to attach radioactive isotopes to antibodies. What he came up with was a “chelator,” which is a linker that binds to the antibody on one side and the radioactive element on the other. “The antibody then brings the killing agent to the cancer cell,” Cicic explains. (The company is named after Actinium 225, one of the alpha-emitting isotopes used in the platform.)
Actinium’s lead product has been tried in about 60 patients with acute myeloid leukemia (AML) and has not produced significant side effects, Cicic says. Because of the drug’s targeting ability, “the amount of radiation that’s given is miniscule. We’re looking at a thousand times smaller dose of radiation” than what’s typically given with beta-emitting drugs, he says.
Actinium plans to initially develop the drug for AML patients who are over 60 and not strong enough to endure bone marrow transplant, which is one of the more commonly used treatments for the disease. “Among older patients, survival rates are very low, and only a small percentage are eligible for bone marrow transplants,” says co-founder Sheinberg, who is a professor of medicine at Memorial Sloan-Kettering Cancer Center and at Weill-Cornell University Medical College in New York. “There’s a huge need for tolerable treatments that prolong survival.”
Figuring out how to produce Actinium 225 at commercial quantities has not been easy. The company worked with a group of scientists in Germany to develop the manufacturing technology. One of the key collaborators was Cuban, which turned out to be a huge complication, Cicic says. “It took months to get him to a meeting here because there were issues with his visa,” Cicic says. “It took lots of intervention.” Eventually the visa issues were sorted out, and Actinium developed a manufacturing plan that it will put into place in time to meet demand, Cicic says. For now, though, the company only needs a small quantity of the isotope for clinical trials, which it is able to get from Oak Ridge National Laboratory in Tennessee.
On July 11, Actinium boosted its pipeline by licensing an antibody product developed at the Fred Hutchinson Cancer Research Center in Seattle. The drug is designed to destroy the bone marrow of patients with blood cancers, as a way of preparing them for bone marrow transplants. The antibody is currently linked to radioactive iodine, a gamma-emitting isotope, but Cicic says the plan is to ultimately transition it to Actinium’s alpha-emitting platform.
Actinium has raised about $60 million in several rounds of funding, says Sandeth Seth, senior managing director and head of healthcare investment banking at Laidlaw & Co., which managed the company’s $8 million Series E financing last year. Actinium initially raised seed funding from Organon, a Dutch company that’s now owned by Merck (NYSE: MRK), and from a billionaire philanthropist whom the company will not name.
Seth says Actinium will do a $20 million private placement after Labor Day and then consider an “alternative public offering,” which would likely involve merging it into a shell company that’s already publicly traded. “The cash needs as we transition from a platform company to a product company are getting to the point where the private markets can’t sustain it anymore,” Seth says.
Actinium may well generate some interest on Wall Street, where investors have been flocking to companies that are coming up with innovative ways to link cancer-killing agents to antibodies. Among the companies that have made strides with “antibody drug conjugates”—cancer-targeting antibodies linked to toxins—are Roche unit Genentech, Seattle Genetics (NASDAQ: SGEN), and Pfizer (NYSE: PFE).
Cicic hopes the idea that Sheinberg has been nurturing for so many years at Actinium will also catch on with investors. “This whole idea of arming antibodies with targeted payload therapies has been simmering for a while,” Cicic says. “People recognize it’s a very viable way to fight cancer.”
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