MONROVIA, Calif.—With an eye to reducing adverse events, biotherapeutics company Xencor announced it signed a non-exclusive licensing deal with Eli Lilly & Co. for Xencor's ImmunoFilter technology. Financial terms were not disclosed, but the multi-year deal will see the pharma giant gain access to immunogenicity data and software in exchange for annual fees.
As Dr. Bassil Dahiyat, Xencor CEO, explains, practically all protein and antibody therapeutics trigger an immunogenic response in humans, often with little or no detectable effect. In a few cases, however, this inherent immunogenicity can lead to reduced drug efficacy or even life-threatening autoimmune responses. "Because of the possibility of immunogenicity for all therapeutic proteins, and the possibility that adverse effects won't be observed until after drug approval, the issue has caused a great deal of concern and is now considered one of the primary issues in protein drug development," he says.
The ImmunoFilter platform relies on the correlation of protein/antibody sequence with specific versions of the major histocompatibility complex II (MHC II) of people receiving the biotherapeutic, which varies extensively among patient populations. By knowing what sequences trigger the worst reactions, scientists can use ImmunoFilter to either dictate changes to the sequence of the therapeutic or provide insight on possible patient stratification, much in the same way companies are using pharmacogenomic data.
The effectiveness of the ImmunoFilter platform was shown in a recent paper published in Clinical Immunology, where scientists at Xencor and City of Hope National Medical Center in
showed that specific MHC II genotypes were very prone to immunogenic reactions to Betaseron, an interferon-beta (IFN-β) therapeutic used to treat patients with multiple sclerosis. They found that patients who fall into these MHC II classes produce anti-IFN-β antibodies, thus limiting the treatment's efficacy. Duarte, California
"Ideally, however, you would use ImmunoFilter in the way that Lilly is planning: during lead optimization and selection to choose the lead that is least likely to create an immune response in the largest segment of the population," Dahiyat says. "In that way, ImmunoFilter could be a critical tool in enabling the rapidly growing efforts in protein and antibody engineering, and in allowing drug designers to preemptively design out highly immunogenic sequences."
The Lilly deal is an extension of earlier collaborative efforts between the two companies. Recently, Lilly exercised an option on a commercial license of a protein therapeutic candidate that was optimized using Xencor's Protein Design Automation (PDA) technology. The candidate is in early preclinical development.
As Dahiyat explains it, deals like these allow Xencor to focus its efforts on in-house drug discovery programs using PDA in areas such as autoimmune disease, cancer, and bone disorders. These efforts are expected to enter clinical trials later this year. "Because it doesn't require internal Xencor research to support the collaboration, ImmunoFilter licensing is a perfect example of how Xencor's collaboration model allows us to stay focused on our clinical development goals while maximizing the reach of our technology," he says.