ImmunoGen Announces First Patient Dosed in Phase 1 Study of IMGN632 for Hematological Malignancies
Second ADC Using ImmunoGen’s Novel DNA-Alkylating Payloads to Enter the Clinic
IMGN632 uses ImmunoGen's novel indolino-benzodiazepine payload, DGN549, which alkylates DNA without crosslinking, as well as novel linker technology with a CD123-targeting antibody. In preclinical studies with IMGN632, ImmunoGen has reported potent and selective activity against AML cells with lower cytotoxicity to normal myeloid progenitor cells than an ADC designed to crosslink DNA.1 Supporting preclinical data for IMGN632 have also shown compelling activity in AML and acute lymphoblastic leukemia (ALL) models with single and multi-dose regimens.2,3 These data suggest that IMGN632 has the potential to be a highly effective, yet tolerable ADC.
“We continue to rapidly advance our novel IGN portfolio in a number of
hematological malignancies and are pleased to be moving our second IGN
ADC, IMGN632, into the clinic,” said
The Phase 1 trial in AML and BCPDN will follow a once every three week dosing schedule while in its dose-finding stage. The selected dose will then be used in expansion cohorts assessing IMGN632 in patients with BPDCN, AML, ALL, and other CD123-positive hematologic malignancies.
“We are excited to be leading off the clinical evaluation of IMGN632, a
potential new treatment option for patients with CD123-positive
hematologic malignancies,” said
presented at the
This is the second clinical trial using IGNs, a new class of cancer-killing agents developed by ImmunoGen for use in ADCs. ImmunoGen recently reported findings from the Company’s ongoing Phase 1 study of IMGN779 in patients with relapsed or refractory adult AML whose tumors express CD33.5 The data demonstrate that IMGN779 is well-tolerated with no dose-limiting toxicities, pharmacokinetic exposures and pharmacodynamic CD33 saturation increasing with dose, and anti-leukemia activity observed in patients with poor prognostic features.
IMGN632 is a humanized anti-CD123 ADC that is a potential treatment for AML, BPDCN, myelodysplastic syndrome, B-cell ALL and other CD123-positive malignancies. IMGN632 uses a novel IGN payload, linker and antibody technology, and has demonstrated potent and selective activity, with minimal cytotoxic effects, in preclinical models of AML and ALL.6,7
Indolino-benzodiazepine agents, or IGNs, are a new class of cancer-killing agent developed by ImmunoGen for use in ADCs. IGN payloads were designed to meet the dual challenges of achieving high potency against target cells, while having a tolerability profile that can enable continued patient treatment. These ultra-potent, DNA-acting IGNs alkylate DNA without crosslinking, which preclinically has resulted in potent anti-leukemia activity with relative sparing of healthy cells.8,9
About Acute Myeloid Leukemia (AML)
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.
It is estimated that, in the U.S. alone, 21,380 patients will be diagnosed with AML this year and 10,590 patients will die from the disease.10
About Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)
BPDCN is a disease of the bone marrow and blood that affects multiple organs, including the lymph nodes and the skin. It often presents as leukemia or lymphoma. There are little data about BPDCN and there is no established treatment. The average age at diagnosis is 60 to 70 years. There are more men than women who are diagnosed with BPDCN.11,12
ImmunoGen is a late-stage biotechnology company that develops targeted cancer therapeutics using its proprietary ADC technology. The Company’s lead product candidate, mirvetuximab soravtansine, is in a Phase 3 trial for FRα-positive platinum-resistant ovarian cancer, and is in a Phase 1b/2 trial in combination regimens for earlier-stage disease. ImmunoGen has three additional clinical-stage product candidates, two of which are being developed in collaboration with
Kadcyla® is a registered trademark of Genentech, a member of
1 Y. Kovtun et al, Abstract 768, Presented at
the American Society of Hematology, December 3-6, 2016.
2 S. Adams et al, Abstract 2832, Presented at the American Society of Hematology, December 3-6, 2016.
3 E. Angelova et al, Abstract 2718, Presented at the
4 Angelova, 2017.
5 J. Cortes et al, Abstract 1312, Presented at the
6 Kovtun, 2016.
7 Angelova, 2017.
8 Kovtun, 2016.
9 M. Miller et al. (2016) Mol Cancer Ther 15:1870-78.
11 Clinical Advances in Hematology & Oncology Volume 14, Issue
This press release includes forward-looking statements. For these
statements, ImmunoGen claims the protection of the safe harbor for
forward-looking statements provided by the Private Securities Litigation
Reform Act of 1995. It should be noted that there are risks and
uncertainties related to the development of novel anticancer products,
including IMGN632, including risks related to preclinical and clinical
studies, their timings and results. A review of these risks can be found
in ImmunoGen's Transition Report on Form 10-KT for the six-month
transition period ended
Sarah Kiely, 781-895-0600
Courtney O'Konek, 781-895-0600
FTI Consulting, Inc.
Robert Stanislaro, 212-850-5657