ImmunoGen's leadership in the field of armed antibodies has strong support:

• ImmunoGen developed the payload technology used in the only armed antibody (trastuzumab-DM1) to have shown activity in patients whose cancer progressed on the same antibody (trastuzumab), unmodified; and
• More armed antibodies are in clinical testing with our technology than with that of any other company.

	Our experience - and that of our corporate collaborators - supports that an armed antibody has three key components:
		The cell-killing agent;
		the linker that holds it onto the antibody; and
		and the tumor-targeting antibody.

Our Cell-Killing Agents

We developed our proprietary cell-killing agents (CKAs) specifically to be delivered to cancer cells attached to antibodies. They are 1,000- to 10,000-fold more potent than the chemotherapy drugs traditionally given to patients. Such potency is necessary for efficacy with antibody-delivered agents and is difficult to achieve - one reason major companies have entered into collaborations with us.

The CKAs (DM1, DM4) used in the TAP compounds now in the clinic act by interfering with tubulin and kill the cancer cells when they try to divide. We have a commercial manufacturer in place for these agents to support our programs and those of our partners.

We've developed a separate family of CKAs that kill cancer cells by disrupting DNA instead of tubulin. Some cancers respond better to DNA-acting agents and some to tubulin-acting agents. We expect to unveil more information on our DNA-acting agents at a scientific conference later this year.

The Linker

This is the structure used to attach the CKA to the antibody.

Anticancer compounds developed using our TAP technology all contain linkers that keep our CKAs firmly attached to the antibody when the TAP compound is circulating in the bloodstream. Compounds made with our linkers can be administered at high doses - the highest in our field - and are not associated with the type of side effects that would be seen with meaningful CKA release in the blood.

The linker used plays a pivotal role in how a TAP compound is activated once it has bound to and entered a cancer cell. It's also central to other properties of a TAP compound, such as whether the compound can kill a neighboring cancer cell that doesn't express the target antigen.

We have developed a portfolio of linkers to enable selection of the best TAP compound design for the cancer target. We continue to expand our linker portfolio, and recently unveiled linkers that extend the utility of our TAP technology for cancers with multi-drug resistance or limited expression of the target antigen.

Needless to say, we use a modular approach - separate linkers and CKAs - as this lets us and our partners quickly and cost-effectively test our many linker/CKA combinations to achieve the best design.

The Antibody

The monoclonal antibody component of a TAP compound is the part that enables the compound to target cancer cells. Each TAP compound contains an antibody that binds specifically to an antigen found on cancer cells. The antibody component of a TAP compound determines which cancers potentially can be treated with the TAP compound. For example, the antibody component of IMGN901, which is huN901, targets the CD56 antigen found on small-cell carcinomas, ovarian cancers, and certain hematological malignancies including multiple myeloma.

While ImmunoGen is known for our TAP technology, we also have extensive antibody expertise. We are experienced in the evaluation of potential cancer targets and in the development of high-quality antibodies to these targets. We have proprietary humanization technology which enables us to modify non-human antibodies to avoid detection by a patient’s immune system. And we can develop cell lines capable of producing substantial quantities of an antibody in a manufacturing setting.

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