On December 5, 2016 ImmunoGen, Inc. (Nasdaq: IMGN), a leader in the expanding field of antibody-drug conjugates (ADCs) for the treatment of cancer, reported that preclinical data on IMGN632, a novel CD123-targeting ADC, were presented today at the 58th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in San Diego, CA (Press release, ImmunoGen, DEC 5, 2016, View Source [SID1234516935]).

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CD123 is an attractive target due to its elevated expression in acute myeloid leukemia (AML). IMGN632 uses ImmunoGen’s new family of indolino-benzodiazepine cancer-killing agents, called IGNs. ImmunoGen designed IGNs to be highly potent and to alkylate DNA without crosslinking it. Specifically, IMGN632 uses the Company’s DGN549 payload and incorporates novel linker and conjugation technology.

"We developed our DNA-alkylating IGN payloads to meet the dual challenges of achieving high potency against target cells, while having a tolerability profile that enables continued patient treatment," said Richard Gregory, Ph.D., Executive Vice President and Chief Scientific Officer of ImmunoGen. "These preclinical data demonstrate that IMGN632 has the potential for broad and potent activity in patients with AML and an improved tolerability profile."

The data presented at ASH (Free ASH Whitepaper) (oral abstract #768) compared IMGN632, an ADC with an alkylating IGN, to a version of IMGN632 with a crosslinking payload. In vitro cytotoxic activity was compared in multiple AML cell lines. Both ADCs were found to be highly active against AML cells, including those with poor prognostic markers (FLT3-ITD, P53, MDR1), and were approximately 100-fold more active on AML patient samples than gemtuzumab ozogamicin.

Both ADCs exhibited similar efficacy in human AML xenograft models; however, the effects of the ADCs in toxicity studies were very different. While IMGN632, the alkylating ADC, was well tolerated at the dose tested, the crosslinking ADC showed persistent delayed toxicity (weight loss) at less than half the dose.

In addition, on normal bone marrow cells, IMGN632 was approximately 50-fold less toxic than the crosslinking ADC, while retaining high potency against AML cells.

These results show that IMGN632 has potent selective activity against AML cells with lower cytotoxicity to normal myeloid progenitor cells than an ADC designed to crosslink DNA activity. These data suggest IMGN632 has the potential to be a highly potent yet tolerable ADC for AML patients.

Supporting preclinical data were also presented at ASH (Free ASH Whitepaper) in which IMGN632 showed compelling activity in AML xenograft models (abstract #2832).

The Company plans to submit an IND application and initiate clinical testing of IMGN632 in 2017.

Preclinical data were also presented at ASH (Free ASH Whitepaper) on IMGN779, a potent CD33-targeting ADC using an IGN payload, (abstract #1645) from a combination study of IMGN779 with a PARP inhibitor (olaparib). The data demonstrated enhanced activity in several AML models including patient derived tumor cells and a disseminated AML xenograft model. IMGN779 is currently being evaluated in a Phase 1 study as a monotherapy in AML.

About Acute Myeloid Leukemia
Acute myeloid leukemia (AML) is a cancer of the bone marrow cells that produce white blood cells. It causes the marrow to increasingly generate abnormal immature white blood cells (blasts) that do not mature into effective infection-fighting cells. The blasts quickly fill the bone marrow, impacting the production of normal platelets and red blood cells. The resulting deficiencies in normal blood cells leave the patient vulnerable to infections, bleeding problems and anemia.

In 2016, it is estimated that nearly 20,000 new cases of AML will be diagnosed in the U.S. and more than 10,000 people will die from the disease.1