Staff Writer

Xencor Inc. is partnering its protein-improving platform technology as part of a drug development collaboration.

The Monrovia, Calif.-based company agreed to use its Protein Design Automation (PDA) technology in partnership with Eli Lilly and Co. to optimize the physical and biochemical properties of an unspecified protein therapeutic. Xencor will use PDA to create variants of the therapeutic protein that meet specific criteria for clinical development.

"This is very validating for us because Lilly is a very sophisticated player," Xencor President and CEO Harry Stylli told BioWorld Today. "This is a protein that's important for them, but we have intellectual property on. We're making a more optimized molecule."

Indianapolis-based Lilly will have the option to develop resulting protein therapeutic candidates. Though Stylli declined to provide more specific details on the protein, he said it was clinically validated and that Xencor's technology would improve it in such a way to move beyond drawbacks associated with its class of molecules.

The privately held company's PDA technology combines computing with molecular biology processes and assays to create protein diversity. The technology takes advantage of the information embedded in protein structures to optimize key properties to yield therapeutic proteins with enhanced safety and efficacy in the clinic, the company said.

"It can map a protein sequence very efficiently and rapidly, screening thousands of sequences and reduce them down to a handful that are potentially important for a particular function of a protein," Stylli said, adding that the technology initially requires 50 percent to 60 percent of a target protein's crystal structure to derive refined proteins within hours. "We then test those, and then refine the selection process until we end up with the optimum properties for that particular protein. That computational process literally takes hours, while the experimental process can take days or weeks."

Xencor has used the process to modify more than 40 therapeutics, he added, improving properties such as stability, solubility, pharmacokinetics, selectivity and affinity.

Stylli declined to detail the agreement's specific financial structure, though he said it followed a typical model for a biopharmaceutical collaboration focused on success-driven reward. Such a partnership follows Xencor's business plan, allowing the 42-employee company to leverage and scale its technology to a variety of collaborative arrangements while also using it for internal discovery and development.

"We're going to identify biotherapeutics that are clinically and commercially validated, or have high potential, for which we can use our technology," Stylli said, "and they become the babies in our pipeline for forward integration."

Founded in 1997 by Bassil Dahiyat and Stephen Mayo, Xencor has raised $65 million to date. Its internal programs, all of which remain in preclinical stages of development, are focused on oncology, autoimmune diseases and transplantation.

Additional Xencor technology has led to another alliance - an antibody-based agreement with Protein Design Labs Inc. That multiyear collaboration allows Fremont, Calif.-based PDL to use Xencor's XmAb technology on a number of PDL's preclinical antibodies against its own targets in an effort to create more potent monoclonal antibodies. The XmAb technology is derived from the company's PDA technology.

"I regard this as the next killer application for antibodies - engineering the Fc region of the antibody," Stylli said, noting that the region is responsible for the killing power and half-life of antibodies. "We've got a very versatile plug-and-play technology that increases affinity for the antibody for a very important class of receptors - the Fc receptors."

He said 65 percent of the company's work is directed toward exploiting its antibody technology, with the remainder focused on protein improvement and immunogenicity issues. The latter is backed by a U.S. government grant to use Xencor's ImmunoPDA technology to develop non-immunogenic protein therapeutics for the broad population.