ImmunoGen, Inc., a biotechnology company that develops targeted anticancer therapeutics using its extensive ADC technology portfolio, announced the start of clinical testing of the company's IMGN779 product candidate for the treatment of acute myeloid leukemia (AML), a CD33-positive cancer.
IMGN779 contains a CD33-targeting antibody - enabling it to bind to AML cells - with a powerful cancer-killing agent attached to kill them. IMGN779 is the first ADC to utilise one of ImmunoGen's new family of indolino-benzodiazepine cancer-killing agents, which the company calls IGNs. DNA-alkylating IGNs have been designed to be ultra-potent, yet provide the tolerability necessary for ongoing retreatment.
"There is substantial need for new therapies for AML and considerable appeal to an ADC approach," said Ravi Chari, Ph.D., VP of chemistry and biochemistry. "A key challenge has been achieving the potency needed for clinical benefit with the tolerability required for continued patient retreatment. We developed our DNA-alkylating IGNs to meet these dual needs and believe this innovative new class can further extend the types of cancers that can be effectively treated with ADC therapeutics."
The IMGN779 phase 1 trial in CD33-positive AML will assess two alternative dosing schedules - weekly and biweekly administration - concurrently in its dose-finding stage. The selected dose and schedule will then be used in the two planned expansion cohorts: one assessing IMGN779 in patients with AML in first relapse and one assessing it in patients with relapsed/refractory AML.
"IMGN779 has the potential to make an important difference for patients with AML," said Anna Berkenblit, MD, VP and chief medical officer. "This phase 1 trial has been designed to efficiently inform the development pathway for IMGN779 by assessing alternative dosing schedules concurrently and then evaluating the selected schedule in specific under-served patient populations."
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 leaves the patient vulnerable to infections, bleeding problems and anemia.
It is estimated that, in the US alone, 20,000 patients will be diagnosed with AML this year and 10,000 patients will die from the disease.1 CD33 is expressed in virtually all cases of AML.
IMGN779 comprises a CD33-targeting antibody with a potent DNA-alkylating agent, the IGN DGN462, attached. The antibody serves to target the ADC to the CD33-positive AML cells which DGN462 can then kill. IMGN779 is wholly owned by ImmunoGen.
IGNs are a new class of cancer-killing agent developed by ImmunoGen for use in ADCs. Ultra-potent, these DNA-alkylating indolino-benzodiazepines are expected to extend the types of cancers able to be effectively treated with ADC therapies beyond those addressable with ImmunoGen's well-established tubulin-acting agents. Such cancers can include ones insensitive to tubulin-acting agents and/or with reduced antigen expression.