Non-small-cell-lung cancer (NSCLC) is still a cancer with bad prognosis with treatment. Considering the fact that this cancer accounts for about 85% of all the diagnosed lung cancer, the ferocity of this cancer ends up tragically for most patients. Research conducted at ImmunoGen (IMGN) demonstrates that epidermal growth factor receptor (EGFR) is highly over-expressed on many of the cases of the most common subtypes, adenocarcinoma, squamous cell carcinoma, and large cell carcinoma.
Head and Neck cancers typically originate in the squamous cells of the mucosal linings of nose, mouth, throat etc., which made them categorize them squamous cell carcinomas of the head and neck.
The good news comes from ImmunoGen where scientists in the firm conducted research demonstrating that EGFR is expressed on virtually all cases of squamous cell carcinomas of the head and neck (SCCHN). This discovery should be excellent news in case there is a solution for the over-expression of EGFT and evidently, ImmunoGen offered the possibility of treatment. The firm has disclosed for the first time preclinical data for its EGFR-targeting antibody drug conjugate (ADC) dubbed IMGN289. ImmunoGen developed this drug uniquely to treat EGFR-over-expressing cancers, which include many cases of squamous cell carcinoma of the head and neck (SCCHN) and non-small cell lung cancer (NSCLC). ImmunoGen expects to begin clinical testing of the compound later this year.
The data were offered to physicians and researchers in the abstracts# 5463, 5467, and 5483 that was presented at the American Association for Cancer Research (AACR) Annual Meeting 2013 in Washington, DC.
The drug, IMGN289, contains an EGFR-binding antibody that can achieve significant inhibition of EGFR-signaling, an important mechanism of action for EGFR- over-expressing cancers being fueled by EGFR. The reported studies demonstrate that the antibody in IMGN289 was shown to provide potency comparable to or better than cetuximab (Erbitux®) in preclinical models of SCCHN and NSCLC. The TAP drug also contains the ImmunoGen'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™) that has been recently approved for HER2 breast cancer and in ImmunoGen's drug IMGN529 and in other TAP compounds that also contain antibodies with anticancer properties.
The DM1 enables IMGN289 to kill EGFR- over-expressing cancers by a second method that is independent of the sensitivity of these cells to the antibody, which inhibits EGFR.
In preclinical models of EGFR-over-expressing cancers, IMGN289 was highly active against NSCLC not dependent on EGFR signaling and against NSCLC with acquired resistance to Tyrosine kinases (TKIs); Good news for ImmunoGen and the oncology community is that in SCCHN models responsive to EGFR, IMGN289 was significantly more active than cetuximab.
"IMGN289 represents a highly promising new therapy for EGFR-over expressing 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-over-expressing 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, achieved 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 add to its product pipeline a 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.
Prohost Word: This firm has struggled for years to provide the safer and more effective monoclonal drug conjugates to the market when many other firms, small and giant, have given up on their attempts to develop the same. The first TAP drug has already been approved for a difficult-to treat HER2 breast cancer developed by its collaborator Roche/Genentech, which is expected to become a blockbuster, bringing more revenues than the monoclonal antibody Herceptin developed and marketed by Roche (RHHBF.PK) and generating over six billion dollars/year in sales revenues. ImmunoGen's pipeline is full of conjugated monoclonal antibodies for various cancers, some are being partnered and some are sub-licensed and four drugs remain the proprietary of ImmunoGen. It is up to investors to make the calculations.
We cannot mention the antibody drug conjugates successful production and development without mentioning Seattle Genetics (SGEN), which has also gotten its first product approved and has a rich product pipeline, part of it is partnered and part remains the proprietary of the firm.
Disclosure: We are long the firms mentioned in this article.
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