Initial Data for CD123-Targeting IMGN632 Demonstrate Encouraging
Anti-Leukemia Activity and Tolerable Safety Profile in Both AML and
BPDCN; Dose Exploration Continues
Maturing Data for CD33-Targeting IMGN779 Reflect Consistent
Activity and Tolerability Profile in AML; Dose Exploration
Continues
Preclinical Data on IMGN632 from Collaborators Further Support
the Potential in AML and BPDCN
ImmunoGen, Inc., (Nasdaq: IMGN), a leader in the expanding field
of antibody-drug conjugates (ADCs) for the treatment of cancer,
today announced that new data from the ongoing Phase 1 studies of
IMGN632 and IMGN779, next-generation CD123- and CD33-targeting
ADCs, respectively, in patients with relapsed or refractory adult
acute myeloid leukemia (AML) and blastic plasmacytoid dendritic
cell neoplasm (BPDCN) will be presented during an oral session at
the 60th American Society of Hematology (ASH) Annual Meeting in San
Diego. Preclinical data for IMGN632 as a monotherapy in BPDCN
patient-derived xenografts, as well as in combination with a PARP
inhibitor in AML models, will also be presented at the
conference.
The data presented at ASH demonstrate the potential of ADCs
generated from the company’s IGN platform to overcome the narrow
therapeutic window seen with previous generations of DNA-targeted
agents and offer new treatment options for AML and other
hematological malignancies.
“We designed our IGN payloads to alkylate one strand of DNA to
produce potent anti-leukemia activity, while reducing toxicity to
normal cells caused by the double-stranded damage associated with
earlier DNA-acting approaches,” said Anna Berkenblit, MD, Vice
President and Chief Medical Officer of ImmunoGen. “IMGN779 and
IMGN632 each incorporate an IGN payload and we are pleased to share
Phase I clinical results for both programs today at ASH.”
“With IMGN632, we are encouraged by both the tolerability and
responses seen thus far, including repeat dosing and complete
remissions in AML and BPDCN,” said Naval Daver, MD, Associate
Professor in the Department of Leukemia at MD Anderson Cancer
Center. “We look forward to continuing to enroll patients at
several dose levels to establish a recommended Phase 2 dose and
schedule for both indications.”
“With IMGN779, I am encouraged to see a significant decrease in
blasts in many patients with some achieving CRi,” said Jorge
Cortes, MD, Deputy Chair and Professor of Medicine in the
Department of Leukemia at MD Anderson Cancer Center. “The
anti-leukemia activity and tolerability seen with both the weekly
and the every two week schedule support continued enrollment to
identify a dose and schedule to enable further development of
IMGN779 as combination therapy in AML.”
Phase 1 Data on IMGN632 in AML and BPDCN
Key initial findings from the Phase 1 study of IMGN632 (Abstract
#27) include the following:
- IMGN632 was administered to 33 patients
over dose levels ranging from 0.015 to 0.45 mg/kg intravenously
every three weeks. IMGN632 displays a tolerable safety profile and
anti-leukemia activity at doses up to 0.3 mg/kg.
- Pharmacokinetic (PK) exposures and
pharmacodynamic (PD) CD123 saturation increase with dose.
- Reported adverse events (AEs) were
consistent with underlying disease, with no evidence of cumulative
toxicity following multiple doses (up to 6 doses).
- Single dose limiting toxicities (DLTs)
were seen at the three highest dose levels tested: one prolonged
neutropenia and two reversible cases of veno-occlusive
disease.
- Six of 23 evaluable AML patients (26%)
across multiple dose levels achieved an objective response,
including two complete remissions (CR) and four CRs with incomplete
recovery (CRi) in heavily pretreated patients, including over 60%
of patients with primary or relapsed refractory disease.
- Two of three evaluable BPDCN patients
achieved an objective response after a single dose of IMGN632, 1
CRi and 1 partial remission.
- Enrollment in expansion cohorts
continues to identify a recommended Phase 2 dose and schedule for
both AML and BPDCN.
Phase 1 Data on IMGN779 in AML
Key findings presented from the Phase 1 study of IMGN779
(Abstract #26) include the following:
- IMGN779 continues to display a
tolerable safety profile with repeat dosing across a wide range of
doses explored in 57 patients with relapsed AML. Patients across
both schedules (weekly and every two weeks) received a median of
four doses of IMGN779 (range, 1-40).
- Plasma IMGN779 concentrations indicate
consistent and sustained exposure through seven days at doses ≥0.39
mg/kg; the weekly schedule provides more consistent pharmacodynamic
CD33 saturation.
- Reported AEs were consistent with
underlying disease, and with no evidence of cumulative toxicity
following multiple doses (up to 40 doses).
- One DLT of veno-occlusive disease was
observed at the highest dose tested on the weekly schedule, 1.2
mg/kg.
- Anti-leukemia activity was seen at
doses ≥0.39 mg/kg in both schedules:
- 41% (12 of 29) of evaluable patients
showed a >30% reduction in bone marrow blasts with eight
patients (28%) having <8% residual blasts, and two having a CR
or CRi.
- Enrollment continues to identify the
recommended Phase 2 dose and schedule.
Oral Presentation Details
- Title: Maturing Clinical Profile
of IMGN779, a Next-Generation CD33-Targeting Antibody-Drug
Conjugate, in Patients with Relapsed or Refractory Acute Myeloid
Leukemia
- Presenter: Jorge Cortes, MD
Anderson Cancer Center
- Day/Time: Saturday, December 1,
2018, 7:45am PST (Oral session 613)
- Location: Manchester Grand Hyatt
San Diego, Seaport Ballroom F
- Abstract: 26
- Title: A Phase I, First-in-Human
Study Evaluating the Safety and Preliminary Antileukemia Activity
of IMGN632, a Novel CD123-Targeting Antibody-Drug Conjugate, in
Patients with Relapsed/Refractory Acute Myeloid Leukemia and Other
CD123-Positive Hematologic Malignancies
- Presenter: Naval Daver, MD
Anderson Cancer Center
- Senior Author: Hagop Kantarjian,
MD Anderson Cancer Center
- Day/Time: Saturday, December 1,
2018, 8:00am PST (Oral session 613)
- Location: Manchester Grand Hyatt
San Diego, Seaport Ballroom F
- Abstract: 27
Preclinical Poster Presentations on IMGN632 in AML and
BPDCN
Preclinical data on anti-leukemia activity for IMGN632 in
combination with a PARP inhibitor in AML, as well as a monotherapy
in BPDCN will also be presented.
Poster Presentation Details
- Title: Synergistic anti-leukemia
activity of PARP inhibition combined with IMGN632, an anti-CD123
antibody-drug conjugate in acute myeloid leukemia models
- Day/Time: Sunday, December 2,
2018, 6:00-8:00pm PST (Poster session 604)
- Senior author: Eunice Wang,
Roswell Park Cancer Institute
- Abstract: 2647
- Title: Pre-clinical efficacy of
CD123-targeting antibody-drug conjugate IMGN632 in Blastic
Plasmacytoid Dendritic Cell Neoplasm (BPDCN) models
- Day/Time: Monday, December 3,
2018, 6:00-8:00pm PST (Poster session 605)
- Senior author: Marina Konopleva,
MD Anderson Cancer Center
- Abstract: 3956
Additional information can be found at www.hematology.org,
including abstracts.
About IMGN779
IMGN779 is a novel ADC that combines a high-affinity, humanized
anti-CD33 antibody, a cleavable disulfide linker, and one of
ImmunoGen's novel indolino-benzodiazepine payloads, called IGNs,
which alkylate DNA without crosslinking, resulting in potent
preclinical anti-leukemia activity with relative sparing of normal
hematopoietic progenitor cells.1,2 IMGN779 is in Phase 1 clinical
testing for the treatment of AML.
About IMGN632
IMGN632 is a novel, anti-CD123 antibody-drug conjugate that is a
potential treatment for AML, BPDCN, and other CD123-positive
malignancies. IMGN632 uses a novel humanized anti-CD123 antibody
coupled via a peptide linker to a unique DNA-alkylating IGN
payload. In preclinical models, IMGN632 has exhibited potent
antitumor activity with a wide therapeutic index in AML, BPDCN, and
acute lymphoblastic leukemia (ALL). IMGN632 is in Phase 1 clinical
testing for the treatment of AML and BPDCN.
About IGNs
Indolino-benzodiazepine cancer-killing agents, or IGNs, are a
new class of cancer-killing agent developed by ImmunoGen for use in
ADCs. These ultra-potent, DNA-acting IGNs alkylate DNA without
crosslinking, which preclinically has resulted in potent
anti-leukemia activity with relative sparing of normal
hematopoietic progenitor cells.3.4 IMGN779, a CD33-targeting ADC in
Phase 1 testing for AML, was the first IGN ADC to enter clinical
testing. IMGN632, a CD123-targeting ADC entering Phase 1 testing
for AML and BPDCN, deploys a novel IGN payload.
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.5
ABOUT IMMUNOGEN
ImmunoGen is developing the next generation of antibody-drug
conjugates (ADCs) to improve outcomes for cancer patients. By
generating targeted therapies with enhanced anti-tumor activity and
favorable tolerability profiles, we aim to disrupt the progression
of cancer and offer our patients more good days. We call this our
commitment to “target a better now.” Our lead product candidate,
mirvetuximab soravtansine, is in Phase 3 study for folate receptor
alpha (FRα)-positive platinum-resistant ovarian cancer, and in
Phase 1b/2 testing in combination regimens. Our novel IGN
candidates for hematologic malignancies, IMGN779 and IMGN632, are
in Phase 1 studies.
Learn more about who we are, what we do, and how we do it
at www.immunogen.com.
1 Y. Kovtun et al. (2016) Blood 128:768.
2 M. Miller et al. (2016) Mol Cancer Ther 15:1870-78.
3 Y. Kovtun, 2016.
4 M. Miller, 2016.
5 American Cancer Society (2016), About Acute Myeloid
Leukemia.
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 IMGN779 and IMGN632, including
risks related to preclinical and clinical studies, their timings
and results. A review of these risks can be found in ImmunoGen's
Annual Report on Form 10-K for the year ended December 31, 2017 and
other reports filed with the Securities and Exchange
Commission.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20181201005016/en/
INVESTOR RELATIONS CONTACTTHRUST Strategic
CommunicationsChelcie Lister, 910-777-3049chelcie@thrustsc.com
MEDIA CONTACTCourtney O’Konek,
781-895-0600courtney.okonek@immunogen.comorFTI ConsultingRobert
Stanislaro, 212-850-5657robert.stanislaro@fticonsulting.com
ImmunoGen (NASDAQ:IMGN)
Historical Stock Chart
From Sep 2024 to Oct 2024
ImmunoGen (NASDAQ:IMGN)
Historical Stock Chart
From Oct 2023 to Oct 2024