A picture-perfect focus

MacroGenics, ImaginAb collaboration to develop clinical imaging agents

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LOS ANGELES—ImaginAb Inc. and Rockville, Md.-basedMacroGenics Inc. have announced the signing of a collaboration andcommercialization agreement for the development of in-vivo imaging agents for autoimmune diseases and cancer.
Per the terms of the agreement, ImaginAb will develop ananti-CD3 clinical imaging product, for which MacroGenics may be eligible forfuture milestones and royalties. The imaging strategy will be based onMacroGenics' anti-CD3 antibody as a patient selection tool for clinicalprograms, and ImaginAb will work to develop a high-performance CD3 bindingfragment to be used in routine clinical imaging. ImaginAb will also support thedevelopment of companion imaging agents for MGA271, MacroGenics' anti-B7-H3therapeutic 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 todemonstrate the ways in which ImaginAb's antibody fragment-based imagingtechnology 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 areglad to partner on both the B7-H3 and CD3 imaging programs as they arehigh-potential targets for the treatment of cancer and autoimmune diseases. Therecent clinical successes around key immune-directed targets in cancer,including those involving members of the B7 family of proteins, make theseareas of research especially exciting. Our collaboration will augmentImaginAb's existing CD8 development program with an anti-CD3 imaging program."
The B7 class of targets, which includes B7H3 and B7H1, ishighly sought after as a pharmaceutical target, Behrenbruch says, and the twoare 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 theimmune system to recognize cancer again, it could offer higher efficacy acrossmultiple cancer types.
MGA 271 is a first-in-class, humanized lgG1/kappa monoclonalantibody designed to recognize B7-H3, which is overexpressed in several kindsof solid tumors, such as ovarian, prostate, pancreatic, melanoma, colorectal,renal cell, bladder, gastric and non-small cell lung cancers. The compound iscurrently undergoing a multi-dose, dose-escalation Phase I study in patientswith refractory B7-H3-expressing neoplasms.
"Imaging immune function is the next frontier of diagnosticmedicine and will have a major impact on how new therapeutics are developed forcancer and autoimmune diseases," said Dr. Scott Koenig, CEO of MacroGenics, ina statement. "Our collaboration with ImaginAb should benefit our internaldevelopment programs targeting CD3 and B7-H3."
MacroGenics did not respond to requests for additionalcomments on the agreement.
ImaginAb's approach, Behrenbruch notes, takes therapeuticdrugs 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 asimaging beacons. This makes "developing the imaging protocols and the relevancyof the imaging … very, very high in relation to the antibody drug."
According to Behrenbruch, imaging such as this offers asignificant advantage over biopsies in terms of patient selection, highlightingthe recent failures of several late-stage compounds in the industry due to aperceived inability to effectively select patients for the therapies. He saysthere is no doubt that the market for molecular imaging products will continueto grow.
"I think this idea that diagnostic and therapeutic medicinetogether are going to play a much more entwined role, I think we're there. Wesee far more engagements than we did five years ago from pharma looking atnovel ways of doing patient selection, novel ways of profiling a target inpatients," says Behrenbruch. "And I think this idea, that diagnostic medicinecan lower the cost of therapeutic development, I think is now starting tobecome something that people really believe and are committed to. And so theconsequence of that is that all areas of diagnostic medicine are becoming moreinteresting, but I think imaging is really about to have its day.
"Clinically, it's become a very standard part of care. TheFDA is very positive about the role of imaging in clinical trials. I thinkmolecular imaging has a lot of potential, and we feel that we have a solutionin the molecular imaging state that's really ideally targeted at thathigh-growth segment, which is really the antibody space, so we're very excited aboutit," Behrenbruch says.

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