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Genmab exploring world of rabbits in Mab Discovery deal

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By Cormac Sheridan
Staff Writer

Genmab A/S has made an eye-catching move into rabbit-based antibody discovery by entering a multitarget deal with Mab Discovery GmbH, a company founded by a group of big pharma scientists.

Given Genmab’s deep roots in the use of transgenic mice for antibody discovery – the Copenhagen, Denmark-based company originally was spun out of Medarex Inc. (now part of New York-based Bristol-Myers Squibb Co.), which had previously acquired the pioneer in that area, San Jose, Calif.-based Genpharm International Inc. – the agreement is a significant validation not only for Mab Discovery but for the wider space of rabbit-based antibody discovery.

Several firms have emerged in recent years to declaim the advantages of rabbit-derived antibodies, which, they maintain, eliminate many of the headaches associated with optimizing molecules derived from more conventional routes such as transgenic mice or phage display. Those include Numab AG, of Wädenswil; Switzerland, Apexigen Inc., of Burlingame, Calif., which obtains its technology from sister firm Epitomics, Inc., also of Burlingame; and Therapeutic Human Polyclonals Inc., which Roche AG acquired in 2007. (See BioWorld Today, April 3, 2007, Aug. 27, 2010, and Oct. 30, 2013.)

“There is a general observation that technologies that have been in use for years get to their limits,” Stephan Fischer, CEO and co-founder of Neuried, Germany-based Mab Discovery, told BioWorld Today. The natural antibody repertoire of the rabbit is highly diverse, and rabbit species also have many other “developmentability” attributes. “They produce antibodies with a very high affinity and potency up front – there is no need to do in vitro lead optimization or any other engineering exercise that takes a lot of time and needs a lot of investment,” he said. “This is what you get in the rabbit B-cell supernatant right away.”

Fischer, previously head of biologicals R&D at Basel, Switzerland-based Roche, formed Mab Discovery in 2010, along with Andreas Tschirky, another Roche R&D veteran, with the help of $25 million investment from Wilmington N.C.-based CRO PPD Inc.

The company has used that cash to put in place a highly automated discovery platform, which employs fluorescence-activated cell sorting (FACS) to isolate antibody-producing B-cells from the serum of immunized rabbits. Between 25,000 and 50,000 B-cell clones are then grown in microtiter plates, using culture conditions designed to optimize antibody production, so that the resulting molecules can be evaluated in high-throughput cell-based assays and in silico. The lead candidates are humanized using standard approaches and fused to human Fc domains. The highly integrated system is based on know-how rather than on any single piece of proprietary technology. “There is no blocking IP,” Fischer said.

Although the process introduces a time saving of several months, its main value lies in the quality of the outcome, Fischer said. The Mab Discovery process yields between 50 and 150 hits, which can be further evaluated and optimized, whereas a more conventional process typically uncovers a handful of molecules. “This ,in our opinion, is a mechanism that translates into a better chance of success downstream,” he said.

Mab Discovery also has entered research collaborations with several large pharma companies, including Ingelheim, Germany-based Boehringer Ingelheim GmbH. “In all the cases we’ve tested so far, we’ve been very successful at finding active molecules in the end stage,” Fischer said.

Details of the Genmab deal have been kept under wraps, but given the Danish firm’s scientific strength in antibody-related technologies, the collaboration may be the strongest test yet of the thesis that rabbits can – immunologically speaking – go where mice cannot. “That is what they want to find out, if that is the case,” Fischer said.

Meanwhile, Genmab’s core antibody discovery and development business, based on the Ultimab platform that originated in Medarex, continues to make progress. On Thursday, the company logged a $22 million milestone from its partner Johnson & Johnson arising out of the progress of its anti-CD38 antibody daratumumab, in a phase II trial in multiple myeloma.