– Novel product candidate employs ImmunoGen’s TAP technology with an antibody that has marked anticancer activity – can kill cancer cells via multiple mechanisms
– On track for IND submission this summer
WALTHAM, MA, USA | April 4, 2011 | ImmunoGen, Inc. (Nasdaq:IMGN – News), a biotechnology company that develops targeted antibody-based anticancer products using its antibody expertise and Targeted Antibody Payload (TAP) technology, today disclosed the profile and first preclinical data for the Company’s novel IMGN529 product candidate for the treatment of B-cell malignancies including non-Hodgkin’s lymphoma (NHL) and chronic lymphocytic leukemia (CLL). This disclosure was made in conjunction with the 102nd Annual Meeting of the American Association for Cancer Research (AACR) taking place in Orlando, FL. IMGN529 consists of a CD37-targeting antibody that has notable anticancer activity with the Company’s potent cancer-cell killing agent, DM1, attached using its SMCC linker.
“IMGN529 has a unique profile that we anticipate will make it particularly effective for the treatment of NHL and other B-cell malignancies while also providing favorable tolerability,” commented John Lambert, Ph.D., Executive Vice President and Chief Scientific Officer. “IMGN529 is on track to be the first treatment for NHL that uses the tumor-killing power of our TAP with an antibody having meaningful anticancer activity of its own. This product candidate has demonstrated highly encouraging activity in preclinical testing and is on track for IND submission this summer.”
IMGN529 – Targeted Therapy with Multiple Mechanisms of Action
Currently, NHL is widely treated with the antibody product, rituximab (Rituxan®). A therapeutic or “functional” antibody, rituximab has anticancer activity and a favorable tolerability profile. To achieve better activity, however, rituximab often is used in combination with chemotherapy agents, which increases efficacy but can reduce tolerability. This has led a number of companies to try to develop more effective antibody therapies for the treatment of NHL that target CD20, like rituximab.
ImmunoGen scientists sought to identify an alternative target which is as widely expressed on malignant B cells as CD20 and offers other beneficial properties. One advantage of this approach is that it allows a resulting product candidate to potentially be used both instead of CD20-targeting therapies and with them. CD37 met these criteria; however, it was known to be difficult to develop humanized antibodies to this target that also have potent anticancer activity.
Numerous antibodies were successfully created by ImmunoGen scientists. These were then screened on multiple criteria, including intrinsic anticancer activity, to select the antibody used in IMGN529. The scientists also evaluated alternative ImmunoGen linkers and cancer-cell killing agents to select the SMCC-DM1 combination. This combination is best known for its use in trastuzumab-DM1 (T-DM1), which also contains a functional antibody.
Presentations being made by ImmunoGen scientists at AACR include data showing:
* The prevalence of CD37 is comparable to that of CD20 on key B-cell malignancy subtypes such as follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), Burkitt’s lymphoma (BL), and mantle cell lymphoma (MCL).1,2
* CD37 is also found on CLL.1,2
* The antibody component of IMGN529 has potent pro-apoptotic activity, complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC) in vitro, enabling it to kill cancer cells through multiple mechanisms of action.1,3
* Compared with rituximab, the antibody component of IMGN529 was found to have stronger pro-apoptotic activity and comparable ADCC in vitro, and exhibited comparable or greater cytotoxicity against human B-cell cancer lines.1,2,3
* IMGN529 retains these antibody-dependent anticancer activities, and also has the mechanism of action of a TAP compound: targeted delivery of the potent DM1 agent to the tumor cells. In preclinical testing, IMGN529 was found to have greater anticancer activity than its antibody component alone.1,2,3
* IMGN529 demonstrates potent efficacy in vivo against CLL and NHL human cell-line tumors, including those of the subtypes FL, DLBCL, and BL.1,2
“TAP compounds are able to be dosed in the clinic at levels where functional antibodies have activity,” noted Robert Lutz, Ph.D., Vice President, Translational Research and Development. “Thus, for appropriate targets, creating a TAP compound with a functional antibody has the potential to meaningfully enhance clinical efficacy. IMGN529 is the second compound, behind T-DM1, to use our technology with a functional antibody.”
About ImmunoGen’s Targeted Antibody Payload (TAP) Technology
ImmunoGen developed its TAP technology to achieve more effective, better tolerated anticancer drugs. A TAP compound consists of a tumor-targeting manufactured antibody with one of ImmunoGen’s proprietary, highly potent cancer-cell killing agents attached using one of the Company’s engineered linkers. The antibody serves to deliver the cancer-cell killing agent specifically to tumor cells, and the cell-killing agent serves to destroy these cells. Antibodies that have anticancer activity can be used with ImmunoGen’s technology and can further enhance efficacy.
The most advanced compound using ImmunoGen’s TAP technology, trastuzumab-DM1 (T-DM1), is in Phase III testing through the Company’s collaboration with Genentech, a member of the Roche Group.
About IMGN529
IMGN529 is a CD37-targeting TAP compound in development by ImmunoGen for the treatment of NHL and other B-cell malignancies. It consists of a CD37-targeting antibody that demonstrates pronounced anticancer activity with the Company’s proprietary DM1 cancer cell-killing agent attached using its SMCC linker. In preclinical testing, IMGN529 was more effective than rituximab against NHL and CLL human cell line tumors.
ImmunoGen plans to submit the IND for IMGN529 in mid-2011.
About ImmunoGen, Inc.
ImmunoGen, Inc. develops targeted anticancer therapeutics using the Company’s expertise in tumor biology, monoclonal antibodies and potent cancer-cell killing agents. The Company’s TAP technology uses monoclonal antibodies to deliver one of ImmunoGen’s proprietary cancer-cell killing agents specifically to tumor cells. There are currently seven TAP compounds in the clinic, with a wealth of clinical data reported with the technology. ImmunoGen’s collaborative partners include Amgen, Bayer HealthCare Pharmaceuticals, Biogen Idec, Biotest, Genentech (a member of the Roche Group), Novartis, and sanofi-aventis. The most advanced compound using ImmunoGen’s TAP technology, trastuzumab-DM1 (T-DM1), is in Phase III testing through the Company’s collaboration with Genentech. More information about ImmunoGen can be found at www.immunogen.com.
References
1 Park P. et al., AACR 2011, abstract #2830.
2 Mayo M. et al., AACR 2011, abstract #4581.
3 Deckert J. et al., AACR 2011, abstract #4565.
SOURCE: ImmunoGen, Inc.
Post Views: 53
– Novel product candidate employs ImmunoGen’s TAP technology with an antibody that has marked anticancer activity – can kill cancer cells via multiple mechanisms
– On track for IND submission this summer
WALTHAM, MA, USA | April 4, 2011 | ImmunoGen, Inc. (Nasdaq:IMGN – News), a biotechnology company that develops targeted antibody-based anticancer products using its antibody expertise and Targeted Antibody Payload (TAP) technology, today disclosed the profile and first preclinical data for the Company’s novel IMGN529 product candidate for the treatment of B-cell malignancies including non-Hodgkin’s lymphoma (NHL) and chronic lymphocytic leukemia (CLL). This disclosure was made in conjunction with the 102nd Annual Meeting of the American Association for Cancer Research (AACR) taking place in Orlando, FL. IMGN529 consists of a CD37-targeting antibody that has notable anticancer activity with the Company’s potent cancer-cell killing agent, DM1, attached using its SMCC linker.
“IMGN529 has a unique profile that we anticipate will make it particularly effective for the treatment of NHL and other B-cell malignancies while also providing favorable tolerability,” commented John Lambert, Ph.D., Executive Vice President and Chief Scientific Officer. “IMGN529 is on track to be the first treatment for NHL that uses the tumor-killing power of our TAP with an antibody having meaningful anticancer activity of its own. This product candidate has demonstrated highly encouraging activity in preclinical testing and is on track for IND submission this summer.”
IMGN529 – Targeted Therapy with Multiple Mechanisms of Action
Currently, NHL is widely treated with the antibody product, rituximab (Rituxan®). A therapeutic or “functional” antibody, rituximab has anticancer activity and a favorable tolerability profile. To achieve better activity, however, rituximab often is used in combination with chemotherapy agents, which increases efficacy but can reduce tolerability. This has led a number of companies to try to develop more effective antibody therapies for the treatment of NHL that target CD20, like rituximab.
ImmunoGen scientists sought to identify an alternative target which is as widely expressed on malignant B cells as CD20 and offers other beneficial properties. One advantage of this approach is that it allows a resulting product candidate to potentially be used both instead of CD20-targeting therapies and with them. CD37 met these criteria; however, it was known to be difficult to develop humanized antibodies to this target that also have potent anticancer activity.
Numerous antibodies were successfully created by ImmunoGen scientists. These were then screened on multiple criteria, including intrinsic anticancer activity, to select the antibody used in IMGN529. The scientists also evaluated alternative ImmunoGen linkers and cancer-cell killing agents to select the SMCC-DM1 combination. This combination is best known for its use in trastuzumab-DM1 (T-DM1), which also contains a functional antibody.
Presentations being made by ImmunoGen scientists at AACR include data showing:
* The prevalence of CD37 is comparable to that of CD20 on key B-cell malignancy subtypes such as follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), Burkitt’s lymphoma (BL), and mantle cell lymphoma (MCL).1,2
* CD37 is also found on CLL.1,2
* The antibody component of IMGN529 has potent pro-apoptotic activity, complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC) in vitro, enabling it to kill cancer cells through multiple mechanisms of action.1,3
* Compared with rituximab, the antibody component of IMGN529 was found to have stronger pro-apoptotic activity and comparable ADCC in vitro, and exhibited comparable or greater cytotoxicity against human B-cell cancer lines.1,2,3
* IMGN529 retains these antibody-dependent anticancer activities, and also has the mechanism of action of a TAP compound: targeted delivery of the potent DM1 agent to the tumor cells. In preclinical testing, IMGN529 was found to have greater anticancer activity than its antibody component alone.1,2,3
* IMGN529 demonstrates potent efficacy in vivo against CLL and NHL human cell-line tumors, including those of the subtypes FL, DLBCL, and BL.1,2
“TAP compounds are able to be dosed in the clinic at levels where functional antibodies have activity,” noted Robert Lutz, Ph.D., Vice President, Translational Research and Development. “Thus, for appropriate targets, creating a TAP compound with a functional antibody has the potential to meaningfully enhance clinical efficacy. IMGN529 is the second compound, behind T-DM1, to use our technology with a functional antibody.”
About ImmunoGen’s Targeted Antibody Payload (TAP) Technology
ImmunoGen developed its TAP technology to achieve more effective, better tolerated anticancer drugs. A TAP compound consists of a tumor-targeting manufactured antibody with one of ImmunoGen’s proprietary, highly potent cancer-cell killing agents attached using one of the Company’s engineered linkers. The antibody serves to deliver the cancer-cell killing agent specifically to tumor cells, and the cell-killing agent serves to destroy these cells. Antibodies that have anticancer activity can be used with ImmunoGen’s technology and can further enhance efficacy.
The most advanced compound using ImmunoGen’s TAP technology, trastuzumab-DM1 (T-DM1), is in Phase III testing through the Company’s collaboration with Genentech, a member of the Roche Group.
About IMGN529
IMGN529 is a CD37-targeting TAP compound in development by ImmunoGen for the treatment of NHL and other B-cell malignancies. It consists of a CD37-targeting antibody that demonstrates pronounced anticancer activity with the Company’s proprietary DM1 cancer cell-killing agent attached using its SMCC linker. In preclinical testing, IMGN529 was more effective than rituximab against NHL and CLL human cell line tumors.
ImmunoGen plans to submit the IND for IMGN529 in mid-2011.
About ImmunoGen, Inc.
ImmunoGen, Inc. develops targeted anticancer therapeutics using the Company’s expertise in tumor biology, monoclonal antibodies and potent cancer-cell killing agents. The Company’s TAP technology uses monoclonal antibodies to deliver one of ImmunoGen’s proprietary cancer-cell killing agents specifically to tumor cells. There are currently seven TAP compounds in the clinic, with a wealth of clinical data reported with the technology. ImmunoGen’s collaborative partners include Amgen, Bayer HealthCare Pharmaceuticals, Biogen Idec, Biotest, Genentech (a member of the Roche Group), Novartis, and sanofi-aventis. The most advanced compound using ImmunoGen’s TAP technology, trastuzumab-DM1 (T-DM1), is in Phase III testing through the Company’s collaboration with Genentech. More information about ImmunoGen can be found at www.immunogen.com.
References
1 Park P. et al., AACR 2011, abstract #2830.
2 Mayo M. et al., AACR 2011, abstract #4581.
3 Deckert J. et al., AACR 2011, abstract #4565.
SOURCE: ImmunoGen, Inc.
Post Views: 53
