A picture-perfect focus
October 2012
by Kelsey Kaustinen  |  Email the author


LOS ANGELES—ImaginAb Inc. and Rockville, Md.-based MacroGenics Inc. have announced the signing of a collaboration and commercialization agreement for the development of in-vivo imaging agents for autoimmune diseases and cancer.
Per the terms of the agreement, ImaginAb will develop an anti-CD3 clinical imaging product, for which MacroGenics may be eligible for future milestones and royalties. The imaging strategy will be based on MacroGenics' anti-CD3 antibody as a patient selection tool for clinical programs, and ImaginAb will work to develop a high-performance CD3 binding fragment to be used in routine clinical imaging. ImaginAb will also support the development of companion imaging agents for MGA271, MacroGenics' anti-B7-H3 therapeutic candidate, as well as related applications for MacroGenics' CD3-based, Re-Directed T Cell Killing DART programs in cancer.  
"Collaborating with MacroGenics provides the opportunity to demonstrate the ways in which ImaginAb's antibody fragment-based imaging technology can be used at the clinical nexus between cancer and immunology," Dr. Christian Behrenbruch, CEO and co-founder of ImaginAb, said in a press release. "We are glad to partner on both the B7-H3 and CD3 imaging programs as they are high-potential targets for the treatment of cancer and autoimmune diseases. The recent clinical successes around key immune-directed targets in cancer, including those involving members of the B7 family of proteins, make these areas of research especially exciting. Our collaboration will augment ImaginAb's existing CD8 development program with an anti-CD3 imaging program."
The B7 class of targets, which includes B7H3 and B7H1, is highly sought after as a pharmaceutical target, Behrenbruch says, and the two are often described as "immuno-cloaking targets," what he refers to as "self-signaling cascades that are able to hide tumors from the immune system." One hypothesis, he notes, is that if you could target these and retrain the immune system to recognize cancer again, it could offer higher efficacy across multiple cancer types.  
MGA 271 is a first-in-class, humanized lgG1/kappa monoclonal antibody designed to recognize B7-H3, which is overexpressed in several kinds of solid tumors, such as ovarian, prostate, pancreatic, melanoma, colorectal, renal cell, bladder, gastric and non-small cell lung cancers. The compound is currently undergoing a multi-dose, dose-escalation Phase I study in patients with refractory B7-H3-expressing neoplasms.  
"Imaging immune function is the next frontier of diagnostic medicine and will have a major impact on how new therapeutics are developed for cancer and autoimmune diseases," said Dr. Scott Koenig, CEO of MacroGenics, in a statement. "Our collaboration with ImaginAb should benefit our internal development programs targeting CD3 and B7-H3."
MacroGenics did not respond to requests for additional comments on the agreement.
ImaginAb's approach, Behrenbruch notes, takes therapeutic drugs and re- engineers imaging agents directly from them. The imaging agents "have the same front-end targeting business as the therapeutic antibody does," but are inert and clear from the bloodstream rapidly so they can be used as imaging beacons. This makes "developing the imaging protocols and the relevancy of the imaging … very, very high in relation to the antibody drug."  
According to Behrenbruch, imaging such as this offers a significant advantage over biopsies in terms of patient selection, highlighting the recent failures of several late-stage compounds in the industry due to a perceived inability to effectively select patients for the therapies. He says there is no doubt that the market for molecular imaging products will continue to grow.
"I think this idea that diagnostic and therapeutic medicine together are going to play a much more entwined role, I think we're there. We see far more engagements than we did five years ago from pharma looking at novel ways of doing patient selection, novel ways of profiling a target in patients," says Behrenbruch. "And I think this idea, that diagnostic medicine can lower the cost of therapeutic development, I think is now starting to become something that people really believe and are committed to. And so the consequence of that is that all areas of diagnostic medicine are becoming more interesting, but I think imaging is really about to have its day.  
"Clinically, it's become a very standard part of care. The FDA is very positive about the role of imaging in clinical trials. I think molecular imaging has a lot of potential, and we feel that we have a solution in the molecular imaging state that's really ideally targeted at that high-growth segment, which is really the antibody space, so we're very excited about it," Behrenbruch says.
Code: E101215

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