- Novel antibody-drug conjugate (ADC) can kill Epidermal Growth Factor Receptor (EGFR)-overexpressing cancer cells via two mechanisms – EGFR-inhibition and direct cell-killing.
- In preclinical testing, IMGN289 was highly active against EGFR-overexpressing cancer cells, including those not dependent on EGFR signaling and those resistant to tyrosine kinase inhibitors (TKIs).
- ImmunoGen is on track to submit the IND for IMGN289 in mid-2013.
WALTHAM, MA, USA I April 11, 2013 I ImmunoGen, Inc. (IMGN), a biotechnology company that develops targeted anticancer therapeutics using its Targeted Antibody Payload (TAP) technology, disclosed for the first time today preclinical data for its EGFR-targeting ADC, IMGN289. The data are being presented at the American Association for Cancer Research (AACR) Annual Meeting 2013 in Washington, DC (abstracts# 5463, 5467, and 5483). ImmunoGen developed IMGN289 to treat EGFR–overexpressing cancers, which include many cases of squamous cell carcinoma of the head and neck (SCCHN) and non-small cell lung cancer (NSCLC), and expects to begin clinical testing of the compound later this year.
IMGN289 contains an EGFR-binding antibody that can achieve significant inhibition of EGFR-signaling, an important mechanism of action for EGFR–overexpressing cancers being fueled by EGFR. In studies reported today, the antibody in IMGN289 was shown to provide potency comparable to or better than cetuximab (Erbitux®) in preclinical models of SCCHN and NSCLC.
An ADC, IMGN289 also contains the Company’s potent DM1 cancer cell-killing agent, which is attached to the EGFR-binding antibody using ImmunoGen’s SMCC thioether linker. The linker/cell-killing agent format of IMGN289 is the same as that of ado-trastuzumab emtansine (Kadcyla™) and IMGN529 – other TAP compounds that also contain antibodies with anticancer properties.
The DM1 enables IMGN289 to kill EGFR–overexpressing cancers by a second method that is independent of the sensitivity of these cells to EGFR inhibition. In preclinical models of EGFR–overexpressing cancers reported today, IMGN289 was highly active against NSCLC not dependent on EGFR signaling and against NSCLC with acquired resistance to TKIs; in SCCHN models responsive to EGFR, IMGN289 was significantly more active than cetuximab.
“IMGN289 represents a highly promising new therapy for EGFR-overexpressing cancers,” commented John Lambert, Ph.D., Executive Vice President and Chief Scientific Officer. “Its dual mechanisms of action – ability to kill cancers through EGFR inhibition and through direct cell killing – should enable IMGN289 to be more effective than current EGFR-targeting agents against EGFR-overexpressing cancers, both those that are responsive to EGFR inhibition and those that are not.”
Dr. Lambert continued, “In developing IMGN289, our scientists identified a new class of EGFR-binding antibody – one that, in preclinical testing, achieves potent EGFR inhibition, but with less skin toxicity than marketed anti-EGFR antibodies. We expect IMGN289, comprising our TAP technology and this antibody, to provide significant efficacy benefits in the clinic with a favorable tolerability profile.”
IMGN289 is on track to become the Company’s fourth wholly owned clinical-stage compound. The Company is preparing to submit the IMGN289 IND in mid-2013 and to begin IMGN289 clinical testing later this year.
About Squamous Cell Carcinoma of the Head and Neck (SCCHN)
Approximately 52,000 people in the US were diagnosed with head and neck cancers last year.1 These cancers typically originate in the squamous cells of the mucosal linings of the (e.g., of the nose, mouth, or throat), and thus are categorized as squamous cell carcinomas of the head and neck.1 Research conducted at ImmunoGen has found that EGFR is overexpressed on virtually all cases of SCCHN, and that it is almost always highly overexpressed.2
About Non-Small Cell Lung Cancer (NSCLC)
In 2012, approximately 194,000 patients in the US were diagnosed with NSCLC, which accounts for about 85% of all lung cancer diagnoses.3 Research conducted at ImmunoGen has found that EGFR is highly overexpressed on many of the cases of the most common subtypes, adenocarcinoma, squamous cell carcinoma, and large cell carcinoma.4
About ImmunoGen, Inc.
ImmunoGen, Inc. develops targeted anticancer therapeutics. The Company’s TAP technology uses a tumor-targeting monoclonal antibody to deliver one of ImmunoGen’s highly potent cancer-cell killing agents specifically to tumor cells. Ten TAP compounds are now in the clinic, of which three are wholly owned by the Company. The most advanced compound using ImmunoGen’s TAP technology, Kadcyla™ (formerly T-DM1) has been approved for marketing in the US and is undergoing regulatory review in Europe and Japan; it is being commercialized in the US by Genentech, a member of the Roche Group. More information about ImmunoGen can be found at www.immunogen.com.
References
1 National Cancer Institute (version reviewed 2/1/2013), Fact Sheets: Head & Neck Cancers, http://www.cancer.gov/cancertopics/factsheet/Sites-Types/head-and-neck
2 Ponte et al., AACR 2013, abstract #5483
3 American Cancer Society (2013), Cancer Facts & Figures
4 Chittenden et al., AACR 2013, abstract #5467
SOURCE: ImmunoGen