Micromet's Cancer Missiles Lure Boehringer, Sanofi

Micromet Inc., a 17-year-old biotechnology company with no medicines on the market, is attracting attention from product-hungry drugmakers. The lure: a technology for fighting cancer without using toxic chemicals.

What Micromet has developed is a way to activate T-cells, the elite troops of the immune system, to attack malignancies, including a rare leukemia that strikes children. It has signed partnerships with five of Europe’s largest drug companies: Bayer AG, Sanofi-Aventis SA, AstraZeneca Plc, Merck KGaA and Boehringer Ingelheim GmbH.

For years, companies like Micromet have struggled to perfect so-called immunotherapies that mobilize the body’s natural defenses against cancer. At the European Hematology Association’s meeting in Barcelona on Saturday, Micromet announced that its leukemia treatment led to remission in almost four-fifths of patients in a trial.

“With Micromet’s technology, you can give any T-cell the ability to recognize and kill the tumor,” said Michael Morse, an associate professor of medicine and tumor immunology specialist at Duke University School of Medicine in Durham, North Carolina. Although the technology is not fully tested, “there’s every reason to believe that this could work.”

The company’s most-advanced drug, blinatumomab, is derived from a common immune-system protein called an antibody that its scientists refashioned to carry out an unnatural task. One end of the protein attracts T cells; the other is engineered to latch onto specific types of cancer cells.

Replenishing Armies

When batches of these proteins, called BiTEs, for bispecific T-cell engager, are released into the bloodstream, they not only summon the immune cells to attack the cancer, they also stimulate the body to produce more of the cells, thus replenishing its armies.

“We’re leveraging the most potent arm of the patient’s immune system and directing it onto the tumor,” said Micromet chief executive officer Christian Itin in an interview.

Micromet shares rose 16 cents, or 2.4 percent, to $6.71 in Nasdaq Stock Market composite trading at 4 p.m. The drugmaker has gained 53 percent in the 12 months through today.

Immunotherapies got a boost on April 29 when the U.S. Food and Drug Administration approved Dendreon Corp.’s first-of-its- kind cancer vaccine for prostate tumors. The day of its approval, Dendreon’s stock soared as much as 38 percent, and the Nasdaq Biotech Index had its biggest one-day rise in six months.

It was a “landmark approval” that gave “positive momentum to the whole biotech space,” said Joseph Pantginis, an analyst at Roth Capital Partners LLC in Newport Beach, CA.

Changing Mindset

Like Micromet’s drug, Provenge primes the patient’s natural immune system. To make the vaccine, doctors extract white blood cells from a prostate-cancer patient, mix them with vaccine components and inject the combination back into the bloodstream. Provenge “opens a door and changes people’s mindset” about the immunotherapy approach, said Jeffrey Crawford, chief of medical oncology at Duke.

The disease blinatumomab is designed to treat, acute lymphocytic leukemia or ALL, isn’t common, but it is a high priority for some doctors. One reason is that two-thirds of the 5,400 new cases in the U.S. each year are children, many of whom only survive with painful chemotherapy that continues for years.

In adults the disease is harder to treat than in children; only 30 percent to 40 percent are cured with conventional chemotherapy.

Complete Remission

At the Barcelona hematology meeting, Micromet showed that blinatumomab can induce complete remission in patients who still had residual leukemia cells after multiple rounds of chemotherapy. About 80 percent of patients who stayed in the study were relapse-free at a median follow-up of 11 months.

“With older patients, it’s very difficult to rout out the last bit of leukemia,” said Peter Marks, director of leukemia services at Yale-New Haven Hospital. Immunologic methods such as Micromet’s “can be very powerful,” he said. “A treatment that could specifically kill leukemia without causing toxicity would certainly be in demand,” he said.

Micromet will begin the last phase of testing required for European approval of blinatumomab this June. Edward Tenthoff, an analyst with Piper Jaffray & Co. in New York, said it could be cleared for use in the U.S. by 2012, and within five years could see $1 billion in annual sales.

“There have been no improvements in ALL treatment in three decades,” said Mark Reisenauer, Micromet’s chief commercial officer. “The only comparably underserved disease is melanoma.”

Riddled With Cancer

Libby Johns is the kind of patient who inspires cancer researchers to try harder. She was diagnosed with ALL in June 2009, a month after her second birthday. When her parents noticed bruising all over her legs, they brought her to the hospital, where doctors found that 90 percent of her bone marrow was riddled with cancer cells.

Now three years old, Libby has had blood transfusions and continuous chemotherapy at the Hospital for Sick Children in Toronto, said her mother, Megan. The girl takes pills every day, has intravenous treatments once a month, and shots in the spine once every three months. This cycle, known as the “maintenance” phase of treatment, lasts 20 months. Libby must continue the regimen until August of next year.

In the course of treatment, Libby’s hair has fallen out three times, and Megan says it’s a struggle to keep the girl’s weight up. Fevers and low blood sugar have put her in and out of the hospital, and when she’s home, the drugs can leave her lethargic.

Few Options

“Some days she doesn’t have the energy to do much,” her mother said. “We just stay home, watch movies, have picnics in the house. I try to let her lead as normal a life as possible.”

While Libby is responding well to treatment, few options are available to children who are not cured with chemotherapy. For adults, who have a high relapse rate, an ineffective procedure called stem cell transplant is the only other line of defense, according to Yale’s Marks. Proven drugs are “very much needed,” he said.

Each of Micromet’s partnerships with large drugmakers is aimed at a different, hard-to-treat cancer. The collaboration with Boehringer, announced May 5, will take aim at multiple myeloma, a deadly disease that starts in the bone marrow and often fails to respond to chemotherapy.

Micromet’s Platform

Pantginis said drugmakers’ interest in the startup goes beyond a desire to license the small company’s drugs. They’re eyeing Micromet’s platform as a way to boost the effectiveness of cancer drugs they already sell, and also to extend the patent protection on those products, he said. If the companies can retool their older drugs using BiTE technology, they can stave off competition from generics in the future.

The concept of immunotherapy took a long time to bear fruit. In the early 1970s scientists started developing lab- grown proteins called monoclonal antibodies, designed either to block tumor growth or make tumors visible to other immune-system cells. They do this by homing in on specific molecules or “targets” on the surface of cancer cells.

The first commercial success came in 1997, when Genentech Inc. and Biogen Idec Inc. launched Rituxan, a drug for non- Hodgkin’s lymphoma. This was followed by best-selling drugs led by Roche Holding AG’s colon cancer drug Avastin, with almost $6 billion in global sales last year.

Second Generation

While these drugs are a big business for companies, most have shortcomings as medicines, said Steven Rosenberg, chief of surgery at the National Cancer Institute in Bethesda, Maryland. “We need to do better than prolonging survival by months,” Rosenberg said. Most of these drugs target just one of multiple drivers of tumor growth. In just a matter of months, tumors in many patients grow resistant to the drugs.

Scientists at Micromet and other biotech companies said that second-generation antibodies of the sort they are testing will be more effective. Companies like Bothell, Washington-based Seattle Genetics Inc. and Waltham, Massachusetts-based Immunogen Inc. employ what’s known as the “payload” technique.

The idea is to link a targeted antibody to a toxic drug that is unleashed once the medicine enters the tumor. One of these experimental drugs, T-DM1 for breast cancer, joins Roche’s best-selling Herceptin to a cancer-killing toxin using Immunogen’s technology and could be approved next year.

“The industry understands the limitations of traditional antibodies,” said Micromet CEO Itin. “We’re starting to see very interesting clinical candidates to enhance the activity of antibodies. We’re seeing an evolution.”

To contact the reporters on this story: Ellen Gibson in New York at egibson9@bloomberg.net;

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