MacroGenics, Inc. (NASDAQ: MGNX), a clinical-stage
biopharmaceutical company focused on discovering and developing
innovative monoclonal antibody-based therapeutics for the treatment
of cancer, today announced clinical data from an ongoing Phase 1
study of flotetuzumab, MacroGenics’ CD123 x CD3 bispecific DART
molecule, in two oral and two poster presentations at the 60th
Annual Meeting of the American Society of Hematology (ASH), taking
place in San Diego, CA on December 1-4, 2018.
The Phase 1 dose expansion study of flotetuzumab in
relapsed/refractory patients with acute myeloid leukemia (AML)
enrolled 31 patients at the recommended Phase 2 dose of 500
ng/kg/day by continuous infusion with a lead-in dosing strategy.
The goal of the expansion cohort study was to evaluate the safety
and preliminary anti-leukemic activity of flotetuzumab, optimize
delivery and supportive care, including the management of cytokine
release syndrome (CRS), and to define the pharmacokinetic (PK) and
pharmacodynamic (PD) activity of flotetuzumab.
John DiPersio, M.D., Ph.D., Professor, Department of Medicine,
Division of Oncology at the Washington University School of
Medicine in St. Louis, presented “Phase 1 Cohort Expansion of
Flotetuzumab, a CD123 x CD3 Bispecific DART® Protein in Patients
with Relapsed/Refractory Acute Myeloid Leukemia.” In the
study, flotetuzumab demonstrated anti-leukemic activity in patients
with relapsed/refractory AML. In 27 response evaluable patients,
the overall response rate (ORR) was 26% (7/27), with a complete
response (CR) rate (a composite of both CR and CRi responses) of
19% (5/27). Notably, in primary refractory patients, an extremely
challenging population to treat, the ORR was 35% (6/17) with a CR
rate of 29% (5/17). The most common treatment-related adverse event
(TRAE) was infusion-related reaction/cytokine release syndrome
(IRR/CRS), and occurred in 93% (29/31) of patients. Grade 3 or
greater IRR/CRS was observed in 13% (4/31) of patients.
In a companion oral presentation, Sergio Rutella, M.D., Ph.D.,
Professor of Cancer Immunotherapy, John van Geest Cancer Research
Centre, Nottingham Trent University, United Kingdom, presented
“Adaptive Immune Gene Signatures Correlate with Response to
Flotetuzumab, a CD123 × CD3 Bispecific DART® Molecule, in Patients
with Relapsed/Refractory Acute Myeloid Leukemia.” Expression of
various immunomodulatory genes was evaluated in 38 patients with
AML. Notably, in this initial study, flotetuzumab enhanced bone
marrow expression of genes that mediate inflammation, antigen
presentation and IFN-γ signaling. Further, the IFN-γ signaling
signature was associated with response to flotetuzumab, suggesting
that this signature could be explored as a potential
biomarker-based approach to patient selection.
In addition to the oral presentations described above, two
posters relating to flotetuzumab were presented. The first poster
(#2738) was “Management of Cytokine Release Syndrome in AML
Patients Treated with Flotetuzumab, a CD123 × CD3 Bispecific
DART® Molecule for T-cell Redirected Therapy.” This poster provided
further characterization of the experience with IRR/CRS in patients
treated with flotetuzumab, approaches to management of IRR/CRS, and
evaluation of the association between various clinicopathologic
features, potential biomarkers and IRR/CRS. The use of multi-step
lead-in dosing as well as early intervention with tocilizumab
helped to ameliorate IRR/CRS, and initial translational studies
suggest that the frequency of CD4+ (but not CD8+) T cells at
baseline could potentially serve as a biomarker to help identify
patients who are at increased risk for developing more severe
IRR/CRS.
A second poster (#4065) titled “Bone Marrow T Cell Changes by
Multiplex IHC after Treatment with Flotetuzumab, a CD123 × CD3
Bispecific DART® Protein, in a Primary Refractory t-AML Patient”
presented a case study of an AML patient treated with flotetuzumab
in the Phase 1 study who experienced a complete response on
flotetuzumab therapy, as well as correlative translational studies.
The patient experienced a CR after one cycle of therapy, with an
associated increase in CD3+ and CD3+CD8+ T cells in the bone marrow
biopsy. After an additional cycle of therapy, the bone marrow
continued in CR. An increase in CD8+ T cells persisted beyond the
cessation of flotetuzumab dosing. The patient remained in CR with
no additional therapy for approximately 7 months.
“The oral presentations and posters related to the Phase 1
expansion cohort of flotetuzumab suggest that patients with
refractory AML, a population with very few therapeutic options, may
be more likely to respond to flotetuzumab within the cohort of
relapse/refractory patients. Further, initial translational studies
implicate an IFN-γ gene signature in the bone marrow as a potential
biomarker-based approach for patient selection,” said Scott Koenig,
M.D., Ph.D., President and CEO of MacroGenics. Overall, the results
presented at ASH have provided new insights and support the
continued study of flotetuzumab in AML patients, including those
with refractory AML. MacroGenics intends to initiate a combination
study of flotetuzumab and MGA012, an anti-PD-1 agent, in 2019,
guided by ongoing optimization of the monotherapy dosing
regimen.”
About Flotetuzumab
Flotetuzumab (also known as MGD006 and S80880) is a
clinical-stage molecule that recognizes both CD123 and CD3. CD123,
the interleukin-3 receptor alpha chain, has been reported to be
over-expressed on cancer cells in a wide range of hematological
malignancies, including AML and MDS. The primary mechanism of
action of flotetuzumab is believed to be its ability to redirect T
lymphocytes to kill CD123-expressing cells. To achieve this, the
DART molecule combines a portion of an antibody recognizing CD3, an
activating molecule expressed by T cells, with an arm that
recognizes CD123 on the target cancer cells.
Flotetuzumab is currently being evaluated in the U.S. and Europe
in a Phase 1 dose expansion study designed to assess the safety,
tolerability, and initial anti-leukemic activity of the molecule in
patients with relapse/refractory AML. MacroGenics retains full
development and commercialization rights to flotetuzumab in the
U.S., Canada, Mexico, Japan, South Korea and India. Servier
participates in the development of flotetuzumab and has rights to
this molecule in all other countries. The U.S. Food and Drug
Administration has granted orphan drug designation to flotetuzumab
for the treatment of AML.
About MacroGenics, Inc.
MacroGenics is a clinical-stage biopharmaceutical company
focused on discovering and developing innovative monoclonal
antibody-based therapeutics for the treatment of cancer. The
Company generates its pipeline of product candidates primarily from
its proprietary suite of next-generation antibody-based technology
platforms, which have applicability across broad therapeutic
domains. The combination of MacroGenics' technology platforms and
protein engineering expertise has allowed the Company to generate
promising product candidates and enter into several strategic
collaborations with global pharmaceutical and biotechnology
companies. For more information, please see the Company's website
at www.macrogenics.com. MacroGenics, the MacroGenics logo, DART and
TRIDENT are trademarks or registered trademarks of MacroGenics,
Inc.
Cautionary Note on Forward-Looking
Statements
Any statements in this press release about future expectations,
plans and prospects for the Company, including statements about the
Company's strategy, future operations, clinical development of the
Company's therapeutic candidates, milestone or opt-in payments from
the Company's collaborators, the Company's anticipated milestones
and future expectations and plans and prospects for the Company and
other statements containing the words "subject to", "believe",
"anticipate", "plan", "expect", "intend", "estimate", "project",
"may", "will", "should", "would", "could", "can", the negatives
thereof, variations thereon and similar expressions, or by
discussions of strategy constitute forward-looking statements
within the meaning of Section 27A of the Securities Act of 1933 and
Section 21E of the Securities Exchange Act of 1934. Actual results
may differ materially from those indicated by such forward-looking
statements as a result of various important factors, including: the
uncertainties inherent in the initiation and enrollment of future
clinical trials, expectations of expanding ongoing clinical trials,
availability and timing of data from ongoing clinical trials,
expectations for regulatory approvals, other matters that could
affect the availability or commercial potential of the Company's
product candidates and other risks described in the Company's
filings with the Securities and Exchange Commission. In addition,
the forward-looking statements included in this press release
represent the Company's views only as of the date hereof. The
Company anticipates that subsequent events and developments will
cause the Company's views to change. However, while the Company may
elect to update these forward-looking statements at some point in
the future, the Company specifically disclaims any obligation to do
so, except as may be required by law. These forward-looking
statements should not be relied upon as representing the Company's
views as of any date subsequent to the date hereof.
###
Contacts:
Jim Karrels, Senior Vice President, CFO
MacroGenics, Inc.
1-301-251-5172, info@macrogenics.com
Karen Sharma, Managing Director
MacDougall Biomedical Communications
1-781-235-3060, ksharma@macbiocom.com
MacroGenics (NASDAQ:MGNX)
Historical Stock Chart
From Mar 2024 to Apr 2024
MacroGenics (NASDAQ:MGNX)
Historical Stock Chart
From Apr 2023 to Apr 2024