The University of Texas MD Anderson Cancer Center has emerged as one of the hot spots in the U.S. for cancer research, and GlaxoSmithKline (GSK) plc pounced on that potential with a research collaboration and license agreement for cancer immunotherapeutic antibodies that is structured more like a standard biotech deal.

Houston-based MD Anderson granted GSK exclusive worldwide rights to develop and commercialize the antibodies, which activate OX40 on the surface of T cells, in a deal potentially valued at more than $335 million. London-based GSK will make an undisclosed up-front license payment, fund research collaboration activities at MD Anderson's Institute for Applied Cancer Science (IACS) and provide payments for reaching development, regulatory and commercial milestones. MD Anderson also will be entitled to royalties from the commercial sales of products developed under the collaboration.

The technology was discovered by Yong-Jun Liu, former professor and chair of MD Anderson's department of immunology, and colleagues. Liu now serves as chief scientific officer and vice president of the Baylor Research Institute of the Baylor Health Care System in Dallas.

Although T cells are equipped with receptors that recognize and bind to antigens, which may include abnormal cells, T-cell recognition of a tumor antigen is not enough to activate the T cells against cancer cells, which require a secondary signal to launch an attack. OX40 represents one of these secondary or co-stimulatory receptor proteins that, when activated, enhance immune attack and block suppressors of immune response.

Under Liu's direction, MD Anderson scientists generated and screened hundreds of antibodies that could potentially act as on switches for OX40 by mimicking its natural activator, OX40L, a molecule that binds to OX40. Years of research narrowed the candidates to a handful of activators, or agonists, which were tested in mice and then altered for human use.

"Deals never happen too quickly, from our perspective," said Giulio Draetta, IACS director, who joined the Institute a year ago from the Dana-Farber Cancer Institute following tenure at Pharmacia (now part of Pfizer Inc., of New York) and Merck AG, where he served as vice president and global head of oncology drug discovery. He acknowledged the groundwork for "this very exciting opportunity" was laid at MD Anderson before he arrived.

Nevertheless, Draetta's experience in pharma and biotech – a decade ago, he also served as co-founder and vice president of research at former drug discovery firm Mitotix Inc. – provided the IACS with a seasoned leader who understood the "milestone-driven" pharma culture that keeps experts from both sides of the table working together until a preclinical compound has proven its mettle.

Driving Translational Medicine

"The IACS was formed to enable precisely such integration to expedite the accurate translation of great science into drugs," he said.

When Draetta arrived at IACS and "started to look around for opportunities to engage our nascent institute in driving translation," he discovered the wealth of scientific effort in therapeutic antibodies.

He contacted seven pharmaceutical companies about the potential commercial opportunities, and GSK emerged as the "most interested" suitor for the research and discovery deal.

GSK officials did not respond to interview requests.

The next challenge is to advance the cancer antibodies into a platform technology. Through IACS, veteran MD Anderson scientists will collaborate with GSK to conduct preclinical research on the antibodies, with the project overseen by a joint research committee. If successful, clinical trials will follow, with a commitment to use MD Anderson as a lead institution.

The academic partner's involvement at every step along the way helps to ensure the project won't easily be shelved if preclinical work hits a bump in the road or GSK takes a detour in strategic direction.

"The system is primed for us to be able to work together with GSK, and they have shown a lot of enthusiasm," Draetta said.

Although the deal is not the first for MD Anderson, which has a similar agreement with Merck and Co., it is by far the largest.

And MD Anderson is not alone. Last summer, the University of Pennsylvania inked a $20 million deal with Novartis AG to develop and commercialize personalized immunotherapy in a variety of cancers using Penn's chimeric antigen receptor (CAR) technologies. The partners plan to build the Center for Advanced Cellular Therapies on the Penn campus in Philadelphia to focus on the discovery, development and manufacturing of adoptive T-cell immunotherapies through a joint research and development program led by scientists from Penn, Novartis and the Novartis Institutes, with the pharma gaining an exclusive worldwide license to CAR-based therapies developed through the collaboration. (See BioWorld Today, Aug. 12, 2011, and Sept. 20, 2012.)

Still, the scope of the GSK-IACS deal is likely to raise the bar for research institutes negotiating with pharmas and biotechs.

"We're trying to do more of these [agreements]," Draetta acknowledged. "It's very important to have deals that commit to the next steps.

"Pharma is under incredible pressure to make ends meet," he added. "They're looking for critical path activity support. They want actionable knowledge."