We created IMGN901 (formerly huN901-DM1) for the treatment of cancers that express the CD56 antigen. These include multiple myeloma and certain other hematologic malignancies, small-cell lung cancers (SCLC), and other cancers of neuroendocrine origin. We recently identified that this antigen is expressed on ovarian cancers, and presented these findings at the AACR annual meeting in April 2008. IMGN901 comprises our huN901 antibody – which targets CD56 – and our DM1 cell-killing agent. This TAP compound is wholly-owned by ImmunoGen.

Our highest priority IMGN901 study is our Phase I trial in multiple myeloma. We believe development of IMGN901 for multiple myeloma is a faster route to market for this compound than its development for SCLC. It is currently being evaluated in the clinic when used alone in the treatment of patients whose multiple myeloma has failed to respond to a number of prior therapies. The activity of IMGN901 has been shown to be markedly enhanced when used in combination with lenalidomide (Revlimid) or bortezomib (Velcade) in preclinical studies, as reported at the 2008 AACR annual meeting.

Phase I Trial in Multiple Myeloma

Interim findings from this study were reported at the ASH annual meeting in December 2007. To qualify for enrollment, patients must have CD56-positive multiple myeloma and must have undergone previous treatment for their disease. In this study, IMGN901 is administered weekly for two consecutive weeks in a three-week cycle.

Four dose levels had been evaluated in three patients each at the time of ASH 2007 – 40, 60, 75, and 90 mg/m2 – each given weekly for two weeks in a 3-week cycle, and evaluation of the 112 mg/m2 dose had begun. One of the three patients receiving the 60 mg/m2/day dose had an objective response by EBMT criteria that was maintained for 45 weeks. This patient previously had been treated with a number of Thalomid (thalidomide) regimens, with Revlimid (lenalidomide) and multiple other chemotherapy regimens, and with radiation therapy. One of the three patients treated with 90 mg/m2 also had an objective response, and stayed on IMGN901 for 12 weeks until she broke her leg and needed to withdraw from the study. This patient, too, previously had been treated with a number of agents, including Thalomid, Revlimid, and Velcade (bortezomib). Additional patients had stable disease.

Phase I Trial in CD56-Expressing Solid Tumors

This trial evaluates IMGN901 when administered daily for three consecutive days in a 21-day cycle to patients with CD56-expressing solid tumors, including SCLC. Interim findings were reported at the EORTC-NCI-AACR Conference in November 2006.

At the time of the Conference, dose levels ranging from 4 to 75 mg/m2/day (12 to 225 mg/m2 over three days) had been evaluated, and the maximum tolerated dose was not yet defined. Among the clinical responses reported are:

• A patient with recurrent, metastatic Merkel cell cancer has been in remission for over a year following treatment with IMGN901. This patient was diagnosed with Merkel cell cancer in late 2003 and underwent surgery, radiation therapy, and chemotherapy, but her cancer returned in late 2004. She qualified for enrollment in this study, had a complete response to treatment, and has remained in clinical remission for 21 months.
• A patient with relapsed SCLC had an unconfirmed partial response after treatment with IMGN901 at the 75 mg/m2/day dose level. Relapsed SCLC is a highly aggressive cancer that often fails to respond to subsequent treatments.
• 13 other patients had stable disease.

Phase II Trial in SCLC

This trial evaluates IMGN901 when administered weekly for four weeks in a six-week cycle to patients with relapsed SCLC/small-cell carcinoma. The dose level in this trial is well below the level already reached in the Phase I solid tumor study described above.

Interim findings were reported at the 43rd American Society of Clinical Oncology (ASCO) Annual Meeting in June 2007, including:

• A patient with relapsed SCLC had significant tumor regression that was sustained for 18 weeks.
• A patient with small-cell carcinoma of the cervix had a partial response in her first treatment cycle (the only cycle she received).
• Five patients had stable disease lasting for six to eighteen weeks.

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