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

Xconomy National — 

[Updated: 11 am PT, 6/5/12] One of the big dreams in biotech over the past 35 years has been to make drugs that work like “smart bombs” by destroying tumors while minimizing collateral damage. Scientists have learned this is no easy thing, but now that a couple of these types of drugs have been shown to work, a new wave of companies is emerging to see if they can finally turn this vision into reality.

Targeted antibody drugs have been around for a long time, and have been shown to do a lot of good for patients. Some of the world’s best-selling medicines are designed to specifically hone in on cancer cells while mostly sparing healthy tissues. Yet it’s only been in the last several years that a couple of companies—Seattle Genetics and Genentech—have shown proof in clinical trials that they can go a step further than what’s been done with so-called “naked” antibodies. The concept is simple: Take a regular antibody, link it to a toxin, and design the combination so that it unleashes a killer payload on tumors. Done right, you ought to have a drug with more punch than traditional antibodies or chemotherapy.

The idea of making “empowered” or “armed” antibodies is known more formally in industry circles as the antibody-drug conjugate (ADC) business. Most previous attempts to amplify antibodies in the past failed because the toxins broke off and started floating around the bloodstream. That meant the drug never got to the right place, and the treatment caused similar side effects to standard chemotherapy. Seattle Genetics overcame that hurdle with the FDA approval last year of its lymphoma drug brentuximab vedotin (Adcetris). And Genentech is in late-stage trials of its souped-up version of Herceptin called trastuzumab emtansine (T-DM1). Both of these drugs have shown in clinical trials that they can be powerful anti-tumor weapons in very sick cancer patients. And not surprisingly, these successes have inspired a new group of genetic engineers to see what they can do to turn antibody-drug conjugates into mainstream cancer medicines.

“We as an industry now have a lot of experience with naked antibodies for cancer, and some of them are very good, but we know they aren’t perfect,” says Bill Newell, the CEO of South San Francisco-based Sutro Biopharma, a venture-backed startup. “They aren’t magic bullets. But I think as people recognize the valuable contribution antibodies have made to cancer, they naturally ask themselves, ‘how can we make them better?’ Essentially, antibodies are good, but antibodies with a payload may be even better.”

There is so much enthusiasm for the emerging antibody-drug conjugate movement that there’s even a World ADC Summit, now in its third year, scheduled for this October in San Francisco. Given the increasing interest among venture-backed companies that are seeking to come up with new antibody-drug conjugates, or provide new enabling technologies, I thought it would useful to put together a list of companies seeking to play a role. If I’ve overlooked a company you know of, please send me a note at [email protected] so I can update the list.

T-DM1. Image courtesy of Genentech

Genentech (South San Francisco). The biotech giant, part of Switzerland-based Roche, has the broadest and deepest experience with antibody-drug conjugates in the world. The company uses technology from Seattle Genetics and ImmunoGen in some cases to make ADCs, but it also has its own proprietary techniques which it doesn’t license outside the company. Genentech has had its most high-profile success with T-DM1, but that’s just one of 25 different antibody-drug conjugates in various stages of development, from discovery through late clinical trials. Nine of Genentech’s 38 cancer drugs in clinical trials—roughly one-fourth of the portfolio—belong to this new class of empowered antibodies. “We’ve really invested heavily in this technology and have the breadth and depth of our pipeline to show for it,” says Genentech spokeswoman Krysta Pellegrino. For a detailed rundown of Genentech’s ADC programs, click here.

Seattle Genetics (Bothell, WA). Seattle Genetics (NASDAQ: SGEN) is one of the two mainstays of the armed antibody field, along with Waltham, MA-based ImmunoGen (NASDAQ: IMGN). The company was founded in 1998 after Bristol-Myers Squibb closed down a Seattle research center that had been dedicated to developing antibody-drug conjugate technology. Besides its work on the new lymphoma drug Adcetris, the company lists six other empowered antibodies in clinical and preclinical development on its website. The company also licenses out its antibody-drug linking technology to other drug developers working on specific projects. The list of collaborators includes Genentech, Bayer, Celldex Therapeutics, Progenics Pharmaceuticals, Astellas Pharma, Daiichi Sankyo, Millennium:Takeda, GlaxoSmithKline, Genmab, Pfizer, and Abbott Laboratories.

ImmunoGen (Waltham, MA). ImmunoGen (NASDAQ: [[ticker:IMGN]) is the other stalwart of the empowered antibody world, having been founded way back in 1981. The company has never made a profit in all those years, and has had some very lean years, but it has been resurgent of late. That’s because it licensed its antibody-drug linking technology more than a decade ago to Genentech, which has used it to make T-DM1. That drug isn’t yet FDA approved, but it passed a pivotal clinical trial back in March, which was the last major milestone it needed to clear before seeking the regulatory green-light. ImmunoGen stands to collect a modest royalty on that product, and like Seattle Genetics, it seeks to use its antibody-drug conjugate technology for its own internal drug candidates, while also making some money by licensing it to other companies working on specific projects. Eli Lilly, Novartis, Amgen, Genentech, Biotest, Bayer, and Sanofi are among its collaborators.

Bristol-Myers Squibb (New York). The pharmaceutical company (NYSE: BMY), which once invested so heavily … Next Page »

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