Human Genome Sciences Deal With Aegera Teams Complementary Oncologic Approaches

HGS also announces launch of Phase II trial for first-line lung cancer candidate.

Human Genome Sciences signed a three-year collaboration with Aegera Therapeutics that will combine HGS' TRAIL receptor antibodies with Aegera's developmental compounds to produce oncology drugs that spur cancer cell death in patients suffering from a variety of cancer types, HGS announced Dec. 20.

Based in Rockville, Md., HGS gains worldwide rights (excluding Japan) to develop and commercialize AEG40826 and related compounds through the agreement. Clinical oncology trials of the compound are slated to begin early next year.

HGS will pay a $15 million upfront licensing fee, make a CAD$5 million ($5.01 million) equity investment in Aegera, and provide about $10 million of spend for the joint effort in 2008, HGS Chief Commercial Officer Barry Labinger said during a same-day call to announce the deal.

In addition, Montreal-based Aegera will be entitled to as much as $295 million in milestone payments and low-double-digit royalties on net sales, Labinger explained. Alternatively, Aegera, prior to launch of one the compounds involved in the deal, could opt to pay 30 percent of expenses and receive 30 percent of profits in lieu of royalties. Aegera also will retain nononcologic rights to compounds not selected for development by HGS.

AEG40826, the lead compound, is a small molecule that inhibits proteins in cancer cells that resist apoptosis, or cell death. Inhibitor of apoptosis, or IAP, proteins can prevent cell death when they are over-expressed in cancer cells.

Activation of apoptosis is a key method of cancer treatment, HGS explained, and approaches developed by HGS could be enhanced by the Aegera IAP inhibitor. The firm plans trials to assess the effect of combining AEH40826 and related compounds with HGS' TRAIL 1 and 2 receptors.

"So now we have two different approaches targeting different points in the same pathway, each of which is able selectively to cause cancer cells to die by apoptosis," HGS Exec-VP R&D David Stump said during the call.

"Over the past few months, our own HGS scientists have conducted preclinical studies of AEG40826 in combination with the HGS TRAIL receptor antibodies," he added. "The results have demonstrated dramatic synergistic activity against a number of cancer types, including prostate, breast, esophageal, colorectal, [and] non-small cell lung cancers."

HGS will continue to study the antibodies and IAP inhibitors in tandem and separately as treatments for various cancers, Stump said.

The firm's goal is to build a "commercially-focused biopharmaceutical company," CEO Thomas Watkins said. HGS is accelerating development of a pipeline of novel, targeted oncology therapies, he said.

During the call, HGS also announced it has begun a Phase II clinical trial of HGS-ETR1 (mapatumumab) in combination with carboplatin and paclitaxel as a first-line therapy in patients with advanced non-small cell lung cancer. ETR1 is a human monoclonal antibody to TRAIL receptor 1. A Phase II trial in patients with advanced myeloma is ongoing.

For the new study, 105 patients will be randomized to three treatment groups: chemotherapy plus placebo, or chemo with ETR1 in a 10 mg/kg or a 30 mg/kg dose.

Stump noted HGS expects data in mid-2008 from the ongoing trial, in which ETR1 is being tested in combination with bortezomib (Millennium's Velcade ) in multiple myeloma patients.

Watkins also used the call to talk up HGS' pipeline, which includes a government contract to produce a drug to fight the effects of inhaled anthrax. Earlier this week, HGS reported that in a pivotal efficacy study in animals its ABthrax (raxibacumab) showed "dramatic and significant survival benefit in inhalation anthrax" even when administered after clinical symptoms were present.

Efficacy was demonstrated in tests involving two different animal species, Watkins explained, which is sufficient for efficacy under the Bioterrorism Act. Safety was demonstrated in two trials involving human participants, he added.

HGS is working to deliver 20,000 doses to the Strategic National Stockpile by late 2008. The company stands to earn $165 million from its deal with HHS, Watkins said, about 70 percent of which will be realized when delivery to the stockpile begins.

"We are hopeful that they will both want to expand the stockpile and replenish it," he added, noting that HGS also is seeking to sell ABthrax to other governments. "We are very interested in expanding that market, both within the United States and outside," Watkins stated.

HGS also has two drugs in Phase III - Albuferon (albinterferon alfa-2b), a collaboration with Novartis to treat chronic hepatitis C, and LymphoStat-B (belimumab), in development with GlaxoSmithKline as a therapy for lupus.

In August, HGS successfully completed a Phase IIb trial of Albuferon that showed efficacy comparable to Roche's Pegasys (peginterferon alpha-2a) but with significantly lower incidence of hematologic adverse events. These results triggered a $40 million milestone payment from development partner Novartis (¹ (Also see "Human Genome Sciences Achieves Milestone For Albuferon Phase II Completion" - Pink Sheet, 28 Aug, 2007.)).

-Joseph Haas ([email protected])