West Coast Editor

An asset-exchange deal with Medarex Inc. gives Genmab A/S full rights to the antibody HuMax-Inflam (also known as MDX-018), and Genmab plans a Phase I/II study with the drug in glioblastoma, with other trials likely in chronic obstructive pulmonary disease.

At the same time, Copenhagen, Denmark-based Genmab said the Danish Head and Neck Cancer Group, known by the rough acronym DAHANCA, is starting a Phase III, 600-patient trial to test another compound, HuMax-EGFr (zalutumumab), in previously untreated head and neck cancer patients.

Designed to examine whether HuMax-EGFr improves radiotherapy, the DAHANCA study could be confirmatory to the fast-track, pivotal trial Genmab already is conducting. That trial started a year ago, recruiting up to 273 patients with squamous cell carcinoma of the head and neck that is refractory or intolerant to platinum-based chemotherapy. About 90 percent of such patients have the epidermal growth factor on their tumors. (See BioWorld Today, Sept. 15, 2006.)

"We jointly owned with Medarex some oncology targets, as well as HuMax-Inflam, and we have spent quite a bit of time negotiating with them so that each party has sole ownership [of their respective compounds]," Lisa Drakeman, Genmab's CEO, told investors during a conference call.

"I don't think we owe anything further," she added, though financial terms were not disclosed. "Obviously, Medarex still has some equity, which gives them some value if this program goes well." Princeton, N.J.-based Medarex spun out Genmab in 1999 and retains an 11 percent equity stake in the company.

Claus Juan Møller-San Pedro, the firm's chief operating officer, noted that 2007 "has been a turnaround year" for Genmab, which in July disclosed it had regained full rights to HuMax-CD4 from partner Merck Serono SA, and is moving ahead with the compound against cutaneous T-cell lymphoma. (See BioWorld Today, July 2, 2007.)

A major part of the turnaround was the late 2006 deal with London-based GlaxoSmithKline plc, which signed a potential DKK12 billion (US$2.2 billion) agreement to get worldwide rights to the Phase III-stage HuMax-CD20, plus a stake of just more than 10 percent in Genmab. (See BioWorld Today, Dec. 20, 2006.)

The DAHANCA head and neck cancer trial marks the fifth Phase III trial for products in Genmab's portfolio, but much of the talk Thursday focused on HuMax-Inflam, which Genmab now completely owns, in exchange for multiple disease programs in oncology.

But the HuMax-Inflam compound could work in cancer, too, said Jan van de Winkel, chief scientific officer of Genmab. "The unique aspect of this antibody is that it binds to a site on the molecule that overlaps with a site on the receptor," he said, pointing out that the compound has been shown to block IL-8 in vivo as well, and seems important not only at the level of inflammatory cells but in cancer. "We will expect to talk at conferences about these studies in the coming months," he said.

Meanwhile, the glioblastoma Phase I/II study will be a two-part effort, involving safety measures through dose escalation as well as proof of concept. Since the patients involved suffer from "very malignant and very aggressively progressing" disease that represents a large unmet need, van de Winkel said, development could move along quickly.

Chronic obstructive pulmonary disease is another matter. Genmab said activity in that indication will not happen this year or next, though existing data seem promising.

"There is some strong clinical evidence that IL-8 is significantly up-regulated in the lungs of these patients," he said. "Whether blocking it with an antibody will work efficiently, of course, we don't know yet."

For COPD, no cure exists, though many drugs are approved for treating the condition, known more commonly as bronchitis. They include DuoNeb (albuterol and ipratropium, DEY LP), Brovana (arformoterol, Sepracor Inc.), and Perforomist (formoterol, DEY LP).

"The best thing the patients can do is stop smoking, but even if they stop smoking, they continue to deteriorate," van de Winkel said.

Last month, another compound with possible utility against COPD provided the seed of a deal worth up to $156 million for Parion Sciences Inc., of Durham, N.C., which licensed the preclinical epithelial sodium channel (ENaC) inhibitor P-680 to Foster City, Calif.-based Gilead Sciences Inc. The agreement brings $5 million up front, $5 million in an equity purchase and the rest in potential milestone payments. (See BioWorld Today, Aug. 17, 2007.)

Also last month, Montreal-based Topigen Pharmaceuticals Inc. raised C$26 million (US$25 million) in the first close of a Series C financing to fund Phase II trials with TPI 1020 for COPD. The compound is an inhaled, small-molecule, nitric-oxide formulation of the steroid budesonide, licensed from NicOx SA, of Sophia Antipolis, France. In preclinical models, TPI 1020 blocked neutrophil infiltration in the airways, as other steroids don't. (See BioWorld Today, Oct. 28, 2005.)