CD33-Targeting IMGN779 Demonstrates Favorable
Safety Profile and Anti-Leukemia Activity in Ongoing Phase 1 Trial;
Dose Escalation Continues with Two Dosing Schedules
Preclinical Data Presentations on IMGN779 in
Combination and CD123-Targeting IMGN632 Highlight Breadth of
ImmunoGen Hematology Pipeline
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
Company’s ongoing Phase 1 study of IMGN779, a next-generation
CD33-targeting ADC, in patients with relapsed or refractory adult
acute myeloid leukemia (AML) were presented at the 59th American
Society of Hematology (ASH) Annual Meeting in Atlanta. Poster
presentations on preclinical data for IMGN779 in combination with
cytarabine and CD123-targeting IMGN632 in acute lymphoblastic
leukemia (ALL) are also being presented at the meeting.
The Phase 1 data presented at ASH demonstrate that IMGN779 was
well-tolerated with no dose-limiting toxicities (DLTs) observed in
patients with relapsed or refractory AML across nine dose levels
administered once every two weeks (Q2W) and one dose level
administered once a week (QW). In addition, anti-leukemia activity
was seen at doses ≥0.39 mg/kg in both schedules in patients with
poor prognostic features. The maximum tolerated dose has not been
reached and dose escalation continues. Data across the first seven
dose levels on the Q2W schedule were presented in June at the 22nd
Congress of the European Hematology Association (EHA).
“The data at ASH build on the initial safety and anti-leukemia
data presented earlier this year at EHA, and further support
continued dose escalation of IMGN779, a novel, next-generation
treatment for AML,” said Anna Berkenblit, M.D., vice president and
chief medical officer of ImmunoGen. “Given investigator enthusiasm
and high unmet need, the dosing cohorts have been rapidly enrolling
and we are very encouraged by the initial findings with IMGN779. We
are continuing to dose escalate on the every two week schedule and,
to evaluate the potential of continuous exposure, we have opened a
weekly dosing schedule in parallel. We look forward to establishing
the optimal dose and schedule, and quickly moving this compound
into later stages of development.”
Phase 1 Data on IMGN779 in AML
Key findings presented from the Phase 1 study of IMGN779 at ASH
(Abstract #1312) include the following:
- IMGN779 displays a tolerable safety
profile.
- No DLTs were observed on either
administration schedule at doses examined – up to 0.91 mg/kg Q2W
and 0.39 mg/kg QW.
- No increase in the nature, frequency,
or severity of any treatment-emergent adverse event was observed
with increasing dose.
- This profile has enabled repeat dosing,
with one patient showing a 93% reduction in bone marrow blasts with
extended treatment and who remains on therapy through Cycle
14.
- Pharmacokinetic (PK) exposures and
pharmacodynamic (PD) CD33 saturation continue to increase with
dose, and support further escalation and exploration of both the QW
and Q2W schedules.
- Anti-leukemia activity was seen at
doses ≥0.39 mg/kg in both schedules with:
- 16 of 17 patients showing a decrease in
peripheral blasts within 10 days after first dose with a median
maximal decrease of 71%; and
- Seven of 17 patients showing a 48%-96%
reduction in bone marrow blasts. These seven patients had poor
prognostic features (e.g., prior intense therapy, primary
refractory disease, RAS/TP53/FLT3/IDH mutations).
This ongoing Phase 1 trial is designed to establish the maximum
tolerated dose and determine the recommended Phase 2 dose for
IMGN779 administered as monotherapy. The trial is also intended to
evaluate safety and tolerability, and characterize PK, PD, and
preliminary anti-leukemia activity in relapsed or refractory
AML.
Preclinical Presentations on IMGN779 in Combination with
Cytarabine and IMGN632 in ALL
Supporting data evaluating the mechanism, anti-leukemia
efficacy, and tolerability of repeated dosing of IMGN779 in
combination with cytarabine using in vitro and in vivo human AML
preclinical models were also presented. Key findings from the
poster presentation (Abstract #1357) include:
- The combination of IMGN779 and
cytarabine increased DNA damage response, cell cycle arrest, and
apoptosis in vitro when compared to single agent treatment.
- The combination of IMGN779 and
cytarabine lead to increased survival and greater numbers of
complete responses in in vivo preclinical AML models.
- Use of cytarabine increased cell
surface CD33 levels on AML cells, suggesting a novel mechanism for
potentiating IMGN779 uptake.
Preclinical data (Abstract #2718) on IMGN632 reporting the
prevalence of CD123 expression in acute lymphoblastic leukemia
(ALL), and assessing the anti-leukemia activity of IMGN632 on ALL
cells will also be presented. Among the findings:
- CD123 expression is prevalent across
ALL subtypes including 90% of B-cell ALL (B-ALL) and nearly half of
T-cell ALL patient samples.
- IMGN632 demonstrates promising activity
against B-ALL cell lines and patient samples in vitro, including
the elimination of more than 90% of B-ALL blasts in 6 out of 8
patient samples. Normal cells were not affected by IMGN632 at
100-fold higher concentrations.
More information can be found at www.hematology.org, including
abstracts.
Poster Session Schedule and Details
- Title (Abstract #1312): "IMGN779, a
Next-Generation CD33-Targeting Antibody-Drug Conjugate (ADC)
Demonstrates Initial Antileukemia Activity in Patients with
Relapsed or Refractory Acute Myeloid Leukemia"
- Poster session #613: Saturday,
December 9, 5:30 - 7:30 PM ET.
- Title (Abstract #1357): "IMGN779, a
Next Generation CD33-Targeting ADC, Combines Effectively With
Cytarabine in Acute Myeloid Leukemia (AML) Preclinical Models,
Resulting in Increased DNA Damage Response, Cell Cycle Arrest and
Apoptosis In Vitro, and Prolonged Survival In Vivo"
- Poster session #616: Saturday,
December 9, 5:30 - 7:30 PM ET.
- Title (Abstract #2718): "CD123
Expression Patterns and Potential of IMGN632, a CD123-Targeted
Antibody Drug Conjugate, in Acute Lymphoblastic Leukemia"
- Poster session #618: Sunday,
December 10, 6:00 - 8:00 PM ET.
About IMGN779IMGN779 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 IMGN632IMGN632 is a humanized anti-CD123
antibody-drug conjugate that is a potential treatment for AML,
blastic plasmacytoid dendritic cell neoplasm (BPDCN),
myelodysplastic syndrome, B-cell acute lymphocytic leukemia, and
other CD123-positive malignancies. IMGN632 uses a novel IGN
payload, linker and antibody technology and in AML xenograft models
has demonstrated a large therapeutic index.3 ImmunoGen has filed an
investigational new drug (IND) application for IMGN632 and expects
to open a Phase I study before year end.
About IGNsIndolino-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.4,5 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.6
About ImmunoGen, Inc.ImmunoGen is a clinical-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
Jazz Pharmaceuticals. ImmunoGen's ADC technology is also used in
Roche's marketed product, Kadcyla®, and in programs in development
by Amgen, Bayer, Biotest, CytomX, Debiopharm, Lilly, Novartis,
Sanofi and Takeda. More information about the Company can be found
at www.immunogen.com.
Kadcyla® is a registered trademark of Genentech, a member of the
Roche Group.
1 Y. Kovtun et al. (2016) Blood 128:768.2 M.
Miller et al. (2016) Mol Cancer Ther 15:1870-78.3 S. Adams et
al, Abstract 2832, Presented at the American Society for Hematology
2016.4 Y. Kovtun, 2016.5 M. Miller, 2016.6 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
Transition Report on Form 10-KT for the six-month transition period
ended December 31, 2016 and other reports filed with the Securities
and Exchange Commission.
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For InvestorsImmunoGen, Inc.Sarah Kiely,
781-895-0600sarah.kiely@immunogen.comorFor MediaImmunoGen,
Inc.Courtney O'Konek,
781-895-0600courtney.okonek@immunogen.comorFTI Consulting,
Inc.Robert Stanislaro,
212-850-5657robert.stanislaro@fticonsulting.com
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