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Cross-linking Antibodies


By Allison Proffitt
Sept. 13, 2007 | BOSTON — At the recent DDT conference, InNexus Biotechnology announced its first product candidate — a monoclonal antibody DXL625 (CD20) — for the treatment of non-Hodgkin’s lymphoma.

Based in British Columbia, Canada, but boasting 18,000 square feet of lab space at the Mayo Clinic in Scottsdale, Arizona, InNexus has been a public company since a reverse merger in 2004. It’s been realizing revenue since its June 2007 agreement with Royalty Pharma, a New York-based company that  buys royalties. Royalty provides liquidity to royalty owners like InNexus, and assumes the associated future risks and rewards. Past successes include Humira and Rituxan.

In the case of DXL625 and the yet-to-be-announced second candidate that Royalty has optioned, InNexus received $2 million and the total purchase price may be increased to $30 million if certain conditions are fulfilled. “The Royalty agreement validates our model,” says InNexus president and CEO Jeff Morhet.

Interestingly, DXL625 targets the CD20 antigen, and is set to go “head to head with Rituxan,” Morhet says, putting Royalty in the interesting position of holding rights to both drugs.

Cross-link Key
The DXL625 antibody treatment relies on InNexus’ dynamic cross-linking (DXL) technology . The procedure attaches a custom homodimerizing peptide — or sticky loop — to the variable region of a monoclonal antibody, leaving the antibody itself undisturbed. The antibody docks at an antigen in the cell, and the peptide attracts other antibodies.

The key is that the peptide cross linking doesn’t occur until the antibody has found its target. In contrast to other methods of linking antibodies, DXL-linked antibodies are monomeric in solution, protecting against the possibility of antibodies bulking themselves into a mass too soon. 

“[There is] absolutely no change in the [antibody] binding affinity,” says Jur Strobos, InNexus’ CMO. The result, shown in mouse models, is a more potent therapeutic antibody. 

The mechanism works on a host of antibody types and therapies. “The advantage,” says Strobos, “is that you can obtain an approved antibody that’s already marketed for therapeutic use and just modify that compound.”

And that’s exactly the business plan: an antibody that InNexus buys (or develops) is paired with the DXL peptide. The two combined represent a new product — and patent rights — for InNexus.

“We want to file patents and go straight to pre-clinical and early clinical development,” says Jeff Morhet. “We want to hand off compounds by Phase III; keep our focus on early [development]... We’re looking for 24 months from announcement [of a new candidate] to IND,” he says. Once the candidate is ready for human trials, InNexus will pass it on to another company.

Morhet doesn’t mention specific target companies for the hand off, though the InNexus Website lists Genentech, Biogen Idec, Domantis, and Applied Molecular Evolution as both competition and potential partners. “The ‘for sale’ sign is out,” he says of DXL625.

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