Targeted Cancer Drugs With Punch: The Next Big Class of Antibodies

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in antibody-drug conjugates, doesn’t say much publicly about its efforts to amplify antibodies these days, but both Seattle Genetics and ImmunoGen list Bristol-Myers as a competitor in their annual reports filed with the Securities and Exchange Commission. Bristol-Myers has told investors that it is developing an antibody-drug conjugate against a target called CD70, which is still in early development. That would appear to put Bristol-Myers in competition with Seattle Genetics, which is also aiming an empowered antibody against the CD70 marker, for patients with renal cell carcinoma and non-Hodgkin’s lymphoma.

Pfizer (New York). The pharmaceutical giant (NYSE: PFE) used to sell an antibody-drug conjugate called gemtuzumab ozogamicin (Mylotarg) until it pulled it off the market in 2010 at the FDA’s request because of safety concerns. But that wasn’t the end of Pfizer’s work in the field. The company has a new product candidate, inotuzumab ozogamicin, in development for slow-growing “indolent” non-Hodgkin’s lymphoma and acute lymphocytic leukemia. That program is in mid-stage clinical development, according to Pfizer’s website. The drug is also being tested in combination with Roche’s rituximab (Rituxan) in a pivotal study for patients with relapsed/refractory aggressive non-Hodgkin’s lymphoma, the company says. [Updated to include information on pivotal study.]

Sutro Biopharma (South San Francisco). Sutro is built on technology from Stanford University for making antibody drugs through a faster and cheaper method that doesn’t require the standard incubation in living cells. The company, founded in 2003, has raised about $60 million in venture capital from a group that includes Skyline Ventures, Amgen Ventures, Lilly Ventures, and Alta Partners. Over the past year, it has turned increasing attention toward using its technology to make antibody-drug conjugates. The company is betting that one of its advantages will be in “site-specific” modifications, in which it can bind a toxin to the exact same spot on a Y-shaped antibody every time in its manufacturing process. Previous technologies have lacked that precision, CEO Bill Newell says, which could end up affecting the consistency of the final product. Sutro has had research partnerships with pharma companies before, including Pfizer, but part of its next challenge will be to find partners willing to license its ADC technology.

Ambrx (San Diego). This private San Diego company, co-founded by prominent chemist Peter Schultz, has raised more than $100 million since its founding to engineer various improvements into protein drugs. For the past several years, it has focused attention on making antibody-drug conjugates. It lists two antibody-drug conjugate programs in preclinical development on its website, one of which is part of a partnership with Pfizer. Former CEO Steve Kaldor said as far back as January 2010 that Genentech’s success with T-DM1 stirred a lot of interest among Big Pharma partners in new and interesting ways of linking antibodies to toxins. “It’s been amazing to see. T-DM1 is floating a lot of other boats,” Kaldor said at the time.

CytomX Therapeutics (South San Francisco). This company, founded with technology from UC Santa Barbara, secured $30 million in financing a couple years ago from Third Rock Ventures and Roche Venture Fund to engineer antibodies with enhanced properties. The company didn’t say much specifically at the time about what it planned to do with the money, but has now publicly stated its desire to make an antibody-drug conjugate against the EGF receptor. That molecular target has been well-validated as a good target for “naked” antibody drugs like Eli Lilly’s cetuximab (Erbitux). CytomX is betting it can make a targeted drug that’s more potent than cetuximab or Amgen’s panitumumab (Vectibix).

Fabrus (San Diego). This company has a geeky sense of humor, since its name is the shortened version of “Functional Antibodies R Us.” Fabrus, founded in 2007 at a Pfizer-supported incubator in San Diego, is more about creating diverse libraries of antibody drugs than about making ADCs, at least according to its website. But it formed a partnership in 2010 with … Next Page »

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