Betting on a totally mouse-free, "primatized" humanmonoclonal antibody, SmithKline Beecham (SKB) has upped itsante in Idec Pharmaceutical Corp. by another $20 million. Thislatest wager raises the pharmaceutical giant's stake in Idec'spotential therapy for autoimmune diseases to more than $50million.
Under the amended agreement, Idec (NASDAQ:IDPH) of La Jolla,Calif., announced Monday that besides the additional milestonepayments, SKB will pay the company royalties on sales of theanti-CD4 monoclonals.
The announcement follows by a fortnight disclosure in Europeof Idec's patent application covering "Recombinant Antibodiesfor Human Therapy." The company's proprietary nucleic acidsequences encode chimeric monoclonal antibodies consisting ofa human constant region (which performs the antibodymolecule's housekeeping functions) and a macaque monkey'svariable region (which recognizes and binds to the CD4receptors on helper T cells). These cells are major perpetratorsin turning the body's immune defenses against its own tissues.
Idec is in late-stage preclinical testing of a primatized anti-CD4monoclonal for treating autoimmune diseases, notablyrheumatoid arthritis, systemic lupus erythematosus (SLE),psoriasis and multiple sclerosis, said William H. Rastetter,president and chief executive officer.
By its agreement with SKB, Idec will handle preclinicaldevelopment, initial supplies of clinical-grade antibody andearly human trials. SKB will undertake subsequent large-scaleclinical studies, and obtaining regulatory approval. SKB alsonow has rights to the products in Japan and other Asiancountries. Idec and SKB share co-promotion rights in the U.S.and Canada.
Idec investigators Roland Newman and Nabil Hanna are listedas co-inventors on the patent application. Richard Krawiec, thecompany's director of investor relations and corporatecommunications, told BioWorld that a dash of serendipitycontributed to creation of "the world's first therapeuticmonoclonal antibody containing no mouse componentswhatsoever."
Most monoclonals include mouse amino-acid sequences, so theycannot be used for prolonged therapy of chronic diseases inhumans, who soon reject their murine molecules as foreign. Onthe whole, scientists searching for a sufficiently humanoidprimate that could replace rodents as a source of variable-region gene sequences without triggering a human immune-system backlash, have tended to dismiss macaques as being toogenetically similar to the human phenotype to respond to ahuman antigen.
But inventors Hanna and Newman, on a hunch, testedmacaques anyway, and found that they worked. "Thosemonkeys turned out to be genetically so close to humans,"Krawiec said, "that they produced antibodies structurallyindistinguishable from human ones in their variable regions,but distant enough to produce antibodies against humanantigens."
"The rationale for the use of primatized antibodies againsthuman cells involved in autoimmune diseases appears to be astrong one," concurred financial analyst David Webber of AlexBrown & Sons, who follows Idec's financial fortunes. Reacting toSKB's increased investment, he told BioWorld, "For Idec it'sextremely encouraging that after several months of familiaritywith this drug (the anti-CD4 primatized antibody), SKB wouldstep back up to the plate in such a handsome fashion."
In a triple-threat assault on the malignant B cells of non-Hodgkin's lymphoma, Idec is deploying a trio of othermonoclonal antibodies linked to tumor-killing payloads. Thecompany also announced Monday that it has filed with FDA fora Phase III clinical trial of its "Specifid" antibodies. The Specifidpanel of 15 antibodies targets specific cell-surface markerspresent on the malignant B cells of one-fourth of the patientpopulation.
FDA has cleared INDs for two newer therapeutic antibodysystems: a genetically engineered "pan-B" chimera forimmunotherapy, which has entered Phase I/II trials at theStanford University Medical Center, and a yttrium-conjugatedvariant for targeted radiation therapy, which will soon be inthe clinic. Pan-Bs, Krawiec explained, target and bind to a B-cellsurface marker present on the tumors of more than 90 percentof all lymphoma patients.
-- David N. Leff Science Editor
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