TAP's Big Finish

After nearly 30 years, ImmunoGen's TAP antibody technology turns a corner

It has taken nearly three decades, but ImmunoGen Inc. is finally getting some traction with its TAP targeted antibody payload platform. The company has closed out 2010 with a rush of news, and now intends to get down to the business of developing its internal pipeline, which President and CEO Daniel Junius sees as the company's real growth driver.

In October, the company announced its largest deal yet for the TAP technology - with Novartis AG - as well as positive clinical data for its lead in-house candidate, lorvotuzumab mertansine (IMGN901).

These announcements came just days after partner Genentech Inc. announced positive data in a second breast cancer indication for the most advanced TAP compound - T-DM1, which consists of the big biotech's trastuzumab antibody against HER2 conjugated to ImmunoGen's DM1 toxin.

According to Junius, these successes were made possible by a series of lessons learned in the clinic, including failures of compounds designed using different iterations of the technology.

Now, having worked its way through three iterations of TAP that are differentiated mainly by improvements to the cytotoxic payload, ImmunoGen is looking to move beyond its heavily partnered business model.

This month, the company started a Phase I/II trial of lorvotuzumab in small cell lung cancer (SCLC) and anticipates making a decision by year end on whether to enter pivotal trials of the candidate in Merkel cell carcinoma (MCC).

By the end of 2011, ImmunoGen expects its internal pipeline plus its partnerships to account for about a dozen compounds in the clinic.

To advance its ambitions, the company had almost $95 million in its coffers at Sept. 30, bolstered by an $83 million follow-on in May. Including partnership income, it is guiding for its cash to grow to as much as $110 million by the end of its fiscal year next June 30.

Tweaking TAP

ImmunoGen has been using antibodies as targeting vehicles to deliver cytotoxic compounds since it was founded in 1981. It started with antibodies conjugated to traditional chemotherapeutics.

"The idea was that there was already something you knew would kill cancer cells," Junius told BioCentury. "The hope was that you could maintain the potency while targeting the chemotherapeutic to the tumor cells," thus sparing healthy cells.

But when it took these early antibody-drug conjugates (ADCs) into the clinic, ImmunoGen found the potency of the combination was lower than when the chemotherapeutic was given alone.

The next iteration of TAP used ricin as the payload. Ricin, a plant-derived class II ribosome-inactivating protein, was selected because it was more potent than traditional chemotherapeutics.

Oncolysin B, an immunotoxin consisting of a mAb linked to ricin, made it into a Phase III trial for lymphoma. But in that study, the company

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