December 2, 2015
By Mark Terry, BioSpace.com Breaking News Staff
CadheRx is working to develop therapeutic antibodies that target soluble E-cadherin (sEcad) for the treatment of solid tumors that are resistant to other treatments, especially Cetuximab and Herceptin-resistant epithelial cancers.
sEcad levels are increased in many epithelial cancers and cause increased tumor cell proliferation, migration, invasion and angiogenesis. In vitro and in vivo studies have shown that antibodies that target sEcad inhibit cell proliferation and promote cell death through apoptotic pathways in EGFR+/KRAS+ or BRAF+ Cetuximab resistant cell lines and tumors, as well as Her2+/Herceptin resistant cell lines and tumors.
The company was founded on intellectual property in-licensed from the laboratory of Sabine Brouxhon, clinical associate professor, department of emergency medicine in the School of Medicine at Stony Brook University.
Launched as a collaboration between Avalon Ventures and GlaxoSmithKline , CadheRx is located at COI Pharmaceuticals in San Diego, a community of innovation founded by Avalon to provide operational support, a fully equipped research-and-development facility and an experienced leadership team.
“CadheRx has been around a little longer than some of our other companies,” said Jay Lichter, Avalon’s president, chief executive officer and general manager in an exclusive interview with BioSpace . “We have some fantastic molecules that interact with soluble eCad in tumors cells and we’re able to prove that there’s profound cell killing in a variety of assays we have. We’re very excited about it. We’re moving ahead aggressively on it and expect to be hitting some milestones in the next year or so.”
Company Leadership
Jay Lichter—president and chief executive officer of COI Pharmaceuticals, and as such, is the chief executive officer of the biotech companies under its umbrella. He is also the managing director of Avalon Ventures, and has led investments in Carolus, Otonomy , Sova and Zacharon Pharmaceuticals. He is the inventor on over 260 patent and patent applications for six Avalon portfolio companies, including 78 issued patents. Lichter has been involved in licensing or merger and acquisition deals valued in excess of $1 billion.
Marc Nasoff—chief scientific officer. Nasoff is also the chief scientific officer of COI Pharmaceuticals. He was recently the director of biologics at GNF, a subsidiary of Novartis Pharma , where he worked closely with Novartis Biologics on developing human therapeutic antibodies.
Sanford Madigon—chief business officer. He has over 18 years of industry experience and is also the senior vice president, business development at COI Pharmaceuticals. He is also the president and chief operating officer of Sova Pharmaceuticals, an Avalon Ventures portfolio company. Prior to Sova, Madigon was co-founder and chief executive officer of Strategic Enzyme Applications, a San Diego-based clean technology company established, in part, as a strategic relationship with Monsanto.
Alessandra Blasina—principal scientist. Blasina is also principal investigator at COI Pharmaceuticals. Prior to joining COI and CadheRx, she was senior scientist, research process development at Shire Pharmaceuticals. Prior to Shire, she was a principal scientist at Pfizer .
Sabine Brouxhon—scientific founder. A clinical associate professor in the department of Emergency Medicine at Stony Brook University School of Medicine, she discovered the anti-cancer technology that was licensed to CadheRx. The technology uses an antibody-based cancer therapy that down-regulates several different pathways associated with therapy-resistance.
Company Financing
CadheRx was launched as one of several collaborations between Avalon Ventures and GSK. It received $10 million in a Series A financing round and research and development support from Avalon and GSK.
Pipeline
“One of the most significant drawbacks from current cancer treatments is that despite their initial effectiveness against solid tumors, patients often develop resistance to these treatments,” Brouxhon said in statement. “Our lab has discovered a novel antibody-based cancer therapy that acts through a completely different mechanism of action compared to existing drugs in industry. Notably, the antibody down-regulates multiple resistant pathways, thereby minimizing the cancer cells ability to recruit many interconnected oncogenes that are linked with resistant disease.”
Brouxhon and colleagues have successfully tested the antibody on cancer cell lines acquired from the National Cancer Institute (NCI). The studies have also indicated that the compound is selectively cytotoxic to cancer cells while not harming healthy cells or tissues.
Compared to several of the other companies launched as part of the Avalon-GSK collaboration, CadheRx is further along. Lichter indicated to BioSpace that they are very close to a lead, which should then turn into a clinical candidate. The next steps after that would be an application for an investigational new drug (IND), and then, if all goes well, an acquisition by GSK, which would run the clinical trials.
Market Competition
Although cancer therapy is a well-trod area, Lichter said, “It’s competitive in the sense that’s what’s interesting about soluble E-Cad is that it binds to a variety of known cancer targets that people are trying to inhibit with antibodies and functional antibodies. There are five or six of those that you can inhibit, and people have made individual inhibitors. Probably the most famous is Her2Neu from Genentech . But instead of going down that road, we made a soluble eCad, which binds to all these receptors. If we can make an antibody that forces internalization, we can shut down all five or six of these different known pro-oncolytic targets.”
What to Look For
Lichter seems particularly optimistic about this company’s path, with significant hopes that in the next couple years a promising lead molecule will be chosen with good backups, which will lead to a GSK acquisition and clinical testing.
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