ImmunoGen 2004 Annual Report

Clinical data are essential for the validation of any novel therapeutic. The body of clinical data with TAP compounds is growing, and we expect this growth to accelerate in the future.

The first clinical data with a partner-developed TAP compound – MLN2704 – were reported at the American Society of Clinical Oncology (ASCO) 2004 annual meeting. MLN2704, developed by Millennium Pharmaceuticals, Inc., is composed of our DM1 payload and the Millennium MLN591 antibody. This antibody targets the prostate-specific membrane antigen (PSMA) expressed on virtually all prostate cancers. The findings reported were from a Phase I dose escalation study in patients with metastatic androgen-independent prostate cancer.

MLN2704 was found to be very well tolerated, even at doses as high as 343 mg/m2. Additionally, even though the study was designed to assess the safety of the compound, evidence of anticancer activity was reported. Among the nine patients that received either of the two highest dose levels studied, four had tumors that could be accurately measured. After receiving MLN2704, one of these patients had a sustained reduction in tumor size and two of these patients had stable disease. At the time of ASCO, the patient with the tumor shrinkage had received MLN2704 once every four weeks for 46 weeks and had no disease progression.

As a rise in PSA level is an indicator of prostate cancer progression, PSA blood levels were measured in all study patients. Among the nine “high dose” patients, two had their PSA levels stabilize and two additional patients had pronounced, sustained, reductions in PSA levels. One of these patients was the individual with marked tumor shrinkage.

ImmunoGen TAP Technology: Widely Applied
	Compound	Target	Tumors that Express Target

Clinical-Stage Proprietary Compounds	HuN901-DM1	CD56	Solid tumors: Small-cell lung cancer, other neuroendocrine cancers Liquid tumors: multiple myeloma, other
Clinical-Stage Proprietary Compounds	Cantuzumab mertansine	CanAg	Solid tumors: Colorectal, pancreatic, and other gastrointestinal cancers; non-small-cell lung cancers

Clinical-Stage Partner Compounds	MLN2704	PSMA	Solid tumors: Prostate cancers
Clinical-Stage Partner Compounds	Bivatuzumab mertansine	CD44v6	Solid tumors: Head and neck, breast

Preclinical Proprietary and Partner Compounds	Anti-CD33 TAP	CD33	Liquid tumors: Acute myeloid leukemia, other hematologic malignancies
	Compound for B-cell malignancies	Undisclosed	Liquid tumors: Non-Hodgkin’s lymphoma, other B-cell malignancies
	Trastuzumab-DM1	HER2	Solid tumors: Breast
	Others	Undisclosed	Undisclosed

Similar evidence of tolerability and activity have been reported with our wholly-owned TAP compounds. In Phase I clinical trials, cantuzumab mertansine was found to be well tolerated and evidence of anticancer activity was reported. For example, a patient with a large, diffuse, abdominal tumor had the signs of his disease all but disappear for more than a year with regular treatment with cantuzumab mertansine. A patient with treatment-resistant colon cancer had a marked reduction in the size of the tumors that had metastasized to her lungs. And a number of patients with treatment-resistant CanAg-positive cancer, including a patient with pancreatic cancer, experienced stable disease.

While less data have been reported to date with huN901-DM1, it, too, has been found to be well tolerated at doses that show evidence of anticancer activity. For example, a patient with a neuroendocrine cancer had a substantial, although transient, reduction in tumor size after receiving huN901-DM1, and additional patients experienced stable disease.

Looking forward, we expect the body of clinical data with TAP compounds to increase substantially through studies conducted by both us and our partners. On July 1, 2004, we assumed responsibility for the huN901-DM1 Phase I/II study underway in the US, and are working to expedite its completion. Patients with small-cell lung cancer (SCLC) are being enrolled in the Phase II leg of this study. Additionally, our former partner, Vernalis, is making progress with the Phase I study it initiated in SCLC in the United Kingdom.

We also plan to initiate our own clinical trial with huN901-DM1 in a hematologic malignancy, multiple myeloma. Preclinical work conducted at the Dana-Farber Cancer Institute confirms that a majority of multiple myeloma cases express CD56. The researchers also found that huN901-DM1 very effectively kills these multiple myeloma cells. We expect to begin our huN901-DM1 multiple myeloma clinical trial within the next six months. Demonstration of efficacy in such
a liquid tumor malignancy provides another possible route to marketing approval for huN901-DM1 that could be shorter than the one for SCLC.

Our other product candidate, cantuzumab mertansine, has undergone Phase I evaluation in studies completed by a former partner. We plan to initiate our own clinical program with this compound, and expect to test either cantuzumab mertansine, or a slightly modified version of it. We will provide details on our clinical study plans later in 2004.

While we are making progress with our clinical programs, our partners are also making progress with theirs. Millennium is now studying MLN2704 in Phase I/II trials. Outlicense partner Boehringer Ingelheim is studying its TAP compound, bivatuzumab mertansine, in multiple Phase I trials. Additionally, we expect Aventis, now a part of the Sanofi-Aventis group, to initiate clinical testing in the near future with the anti-CD33 TAP compound licensed from us.

We believe that the results from the studies we conduct with our own products, the results from the studies our technology outlicense partners conduct with their products, and the results from studies initiated by Aventis can all provide further validation for our technology.

Notice on Forward-Looking Statements