BioWorld Today Contributing Writer
Privately held Theraclone Sciences Inc., of Seattle, has grabbed a tiger by the tail, inking a multiyear research and development collaboration with Pfizer Inc. for the company's in situ therapeutic antibody rescue (I-STAR) technology. The deal makes Theraclone eligible to receive up to $632 million in research funding and milestone payments upon the achievement of discovery, development, regulatory and commercialization milestones, plus undisclosed royalties on future sales.
New York-based Pfizer will be responsible for preclinical and clinical development of the antibodies.
The companies will use Theraclone's I-STAR technology to discover broadly protective monoclonal antibodies against up to two infectious disease targets and up to two cancer targets. Pfizer will receive an exclusive worldwide license to any therapeutic antibodies discovered under the collaboration.
The deal came together through Theraclone's acquaintance with Jose-Carlos Gutiérrez-Ramos, who joined Pfizer last January as senior vice president of worldwide biotherapeutics research and development. Gutiérrez-Ramos had learned of Theraclone's technology during his previous tenure as senior vice president and head of the Immunoinflammation Center for Drug Discovery at GlaxoSmithKline plc, of London. He introduced Theraclone executives to officials in Pfizer's oncology research program, who were equally intrigued with the technology, according to Steve Gillis, Theraclone's interim CEO and managing director of the investment firm ARCH Venture Partners.
In turn, Pfizer's oncology team introduced the I-STAR technology to members of the company's infectious disease group, who also wanted to apply it to targets of interest.
"In today's world, you always need to be talking to potential partners in the endless pursuit of nondilutive funding," Gillis told BioWorld Today. "The potential of getting two separate transactions was possible, as was the potential to roll everything into one transaction. At the end of the day, that's what we did."
Pfizer officials did not respond to requests for an interview, but Gutiérrez-Ramos said in a statement, "Theraclone's platform technology represents an important advancement in fully human therapeutic antibody discovery, which we believe has the potential to deliver a new generation of improved therapeutic antibodies more efficiently."
I-STAR technology uses memory B cells taken from blood samples of human donors with natural resistance to a disease of interest, Gillis explained. Each memory B cell has the potential to differentiate and make a unique antibody clone. The company cultures tens of thousands of memory B cells in microtiter wells at a density of one cell per well, then activates these cells to propagate and differentiate into antibody-producing cells. "Our technology wakes up those cells and interrogates them at the single cell level," Gillis said.
Antibodies that are secreted into the culture medium are harvested in sufficient quantity to enable screening for biological activity. Once an antibody with desired activity is found in the screen, the gene sequence for that antibody is obtained from the corresponding antibody-producing cells. The antibody genes then can be inserted into immortalized mammalian cells to enable production of unlimited quantities of that antibody clone for further study.
I-STAR technology enables Theraclone to test the function of tens of thousands of natural human antibodies rapidly and to find those with exceptional biologic activity.
"We've been fortunate in being able to incorporate early in the discovery screening [process] not just binding screens but functional screens and, therefore, we can get a head start on going after antibodies of interest," Gillis said.
Theraclone also signed a multiyear R&D agreement in October 2009 with Zenyaku Kogyo Co. Ltd., of Tokyo, to use the I-STAR technology to discover broadly protective monoclonal antibodies for pandemic influenza and severe seasonal influenza. Zenyaku holds an option to exclusive antibody rights in Asia, including certain Oceania countries, and retains an option in the territory to potential vaccine candidates stemming from the discovery research. In exchange, Theraclone received an up-front cash payment and is eligible for R&D milestones totaling more than $18 million through Phase I, plus additional milestones and royalties on future sales.
In June 2010, Theraclone researchers published data in Proceedings of the National Academy of Sciences indicating they had discovered a highly conserved molecular target on the influenza A virus and demonstrated in preclinical studies that antibodies against the target provide protection against seasonal and avian influenza. Theraclone researchers also participated in a study led by the International AIDS Vaccine Initiative that described two broadly neutralizing antibodies to HIV and a strategy to discover more of them. The results were published in the Sept 4, 2009, issue of Science. (See BioWorld Today, Sept. 4, 2009.)
In 2008, Theraclone was granted an award under IAVI's Innovation Fund to test its process for isolating from the blood of certain HIV-infected individuals potent monoclonal antibodies to HIV that are broadly neutralizing.
Unlike some other antibody discovery platforms, "we've demonstrated over the past couple of years the ability to generate antibodies," Gillis said. "Our publications in HIV and influenza have certainly helped validate the technology platform. We really believe we can interrogate every B cell in the human repertoire and, in doing so, find very rare antibodies that are broadly neutralizing and very, very potent. Therein lies the strength of the platform.
"We're taking an influenza antibody into the clinic in the middle of the year and hope to follow with a [cytomegalovirus] antibody at the end of the year," he added, noting that several other in-house discovery programs are under way.
Theraclone (formerly Spaltudaq Corp.) was founded in November 2004 as the third start-up of the biotech investment firm Accelerator Corp., of Seattle. Currently, the company has about 20 full-time employees, but head count will increase to meet the obligations of the Pfizer collaboration, according to Gillis.
The company's most recent financing a Series B that pulled in $29 million took place in 2007, co-led by ARCH Venture Partners, Canaan Partners and Healthcare Ventures, with participation from Amgen Ventures, MPM Capital and Alexandria Equities LLC. At this time, Theraclone has no plans to go public, Gillis said, noting that "the public markets certainly haven't shown themselves to be receptive to development-stage companies."