IDM Building Cell Manufacturing Network For Phase III Cancer Trial

Immuno Designed Molecules is building a network of cell processing centers for local preparation of its ovarian cancer cell therapy, CEO Jean-Loup Romet-Lemonne told the Ernst & Young/Atlas Venture Eighth European Life Sciences Conference April 17 in Amsterdam.

"We are already building our first network...in order to prepare the cell drugs for the Phase III ovarian cancer trial. We already have all the major centers in Europe" as well as a center in Montreal and a few in the U.S., Romet-Lemonne said.

Paris-based IDM's lead product, MAK-BAb, began a 280-patient, 45-center Phase III trial in December for treatment of ovarian cancer.

"Our Phase III is involving 15 of these [cell processing centers] in 2000, and then we will expand this network of affiliates as a premarketing approach" as well as for clinical trials for other indications, Romet-Lemonne said. "Then we will extend this network of cell processing centers until the network is fully operational when our cell drugs reach the market."

"The portability of the cell processor will allow the company to implement its decentralized approach to manufacture and market cell drugs, which means that cell processing will be carried out in hospital laboratories close to the patient," he observed.

The company has two ways of producing cell drugs. "One way is the physician will sell the patient's monocytes to a huge manufacturing plant, where the cells will be processed and then sent back to the physician," Romet-Lemonne explained.

"The other way, the decentralized way, is where you transfer the technology through the cell processor, through the portable box" that can be kept in the lab.

Romet-Lemonne noted that university hospitals and cancer centers around the world "have fantastic facilities" that comply with good manufacturing practices "to produce bone marrow transplant cells, and that can be used now for cell preparation."

MAK-BAb is an ex-vivo cell therapy based on the patient's own monocytes. After being cultured with GM-CSF (Immunex' Leukine) for seven days to produce a macrophage, the monocyte-derived activated killer cells (MAK) are then combined with bispecific antibodies using Medarex' MDX-210. They are then injected back into the patient.

"The antibodies will guide the killer cells, the MAK cells, to the tumor cells expressing the antigen recognized by the antibody," Romet-Lemonne explained.

The antibodies target HER-2/neu overexpressing cells. "The contact with the bispecific antibody and the MAK cells will help the macrophage to engulf the tumor cell and destroy completely the tumor cell."

Two MAK therapies are in Phase II, one for bladder cancer and another for chronic lymphocytic leukemia. That trial also incorporates an anti-CD20 antibody licensed from Roche, to increase cancer cell killing.

IDM is building two families of cancer therapy cell drugs - "the first family to eliminate risk of all tumor cells," Romet-Lemonne said, referring to the MAK therapies.

The second family, he said, is a therapeutic vaccine that will "actively build an anti-cancer immune response to prevent cancer recurrence."

The second family, called dendritophages, includes two products in Phase II trials. One is completing a trial in prostate cancer, where it is used after prostatectomy to prevent subsequent metastases. Results from the 24-patient trial are expected by year's end. The other dendritophage is in a melanoma trial.

For dendritophages, monocytes are cultured with GM-CSF and interleukin-13 for seven days, and the resulting phage is incubated with fragments of the patient's tumor cells or purified antigens if one is known. The antigen is phagocytized by the dendritophage, and is injected subcutaneously to "get in touch with the lymph nodes, where the lymphocytes are," Romet-Lemonne elaborated.

Privately held IDM began in December 1993 and now has 52 employees, including operations in Marlborough, Mass. Its association with Medarex includes antibody licenses as well as use of the HuMAb-Mouse and CTLA-4 cancer vaccine technology. Medarex owns 6% of IDM, and will have 43% or a share in a partnership per the license agreement.