MacroGenics Announces Publication in Science Translational Medicine Supporting Flotetuzumab Pivotal Study in Patients with Refractory Acute Myeloid Leukemia

Rhea-AI Summary

MacroGenics, Inc. (NASDAQ: MGNX) announced research in Science Translational Medicine revealing a gene expression signature in the tumor microenvironment of acute myeloid leukemia (AML) patients. This signature is linked to chemotherapy resistance and potential response to flotetuzumab, a bispecific DART molecule for patients with primary induction failure or early relapsed AML. The study emphasizes flotetuzumab's promise in addressing unmet medical needs in difficult AML patient populations, as highlighted by Chief Scientific Officer Ezio Bonvini.

Positive

• Identification of a predictive gene expression signature for flotetuzumab response in AML patients.
• Plans for a pivotal clinical study for flotetuzumab targeting difficult-to-treat AML patients.

Negative

• High percentage (40-50%) of AML patients fail to achieve complete remission with induction therapy.
• Limited options exist for patients without targetable mutations in AML.

Rockville, MD, June 03, 2020 (GLOBE NEWSWIRE) --

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 research published in the journal Science Translational Medicine that describes a gene expression signature of the tumor microenvironment in patients with acute myeloid leukemia (AML) that is associated with resistance to chemotherapy and response to flotetuzumab, an investigational, bispecific CD123 x CD3 DART® molecule currently in clinical development for the treatment of primary induction failure and early relapsed AML. The research was led by Sergio Rutella, M.D., Ph.D., FRCPath, Professor of Cancer Immunotherapy, John van Geest Cancer Research Centre at Nottingham Trent University in the UK.

The study analyzed several hundred primary bone marrow samples from independent cohorts of pediatric and adult AML patients to identify differences in immune gene expression in the bone marrow tumor microenvironment across age groups and molecular subtypes. The data indicated that an inflammatory signature related to INF-γ gene expression was predictive of resistance to chemotherapy and potential response to flotetuzumab immunotherapy in patients with primary refractory or early relapsed AML.

“Patients with AML who have failed primary induction therapy or relapsed early after an initial response represent a challenging patient population to treat,” said Ezio Bonvini, M.D., Senior Vice President and Chief Scientific Officer of MacroGenics. “These data provide a molecular basis to understand why AML patients who are refractory to chemotherapy may be responsive to immunotherapy with flotetuzumab and offer a rationale for further development of the molecule in a planned pivotal study in this patient population with unmet medical needs.”

About Acute Myeloid Leukemia

AML is a hematological malignancy characterized by differentiation arrest and uncontrolled clonal proliferation of neoplastic precursors that prevent normal bone marrow hematopoiesis. Nearly 20,000 new cases of AML are diagnosed in the U.S. each year, with a median age of 69 years at diagnosis. Approximately 40-50% of newly diagnosed patients fail to achieve a complete remission with intensive induction therapy (primary induction failure; PIF) or experience disease recurrence after a short remission duration (<6 months; early relapsed; ER). A very small number of these patients are expected to respond to salvage therapy. Although new targeted agents have been approved for the treatment of frontline or relapsed/refractory AML in recent years, approximately 50% of patients have no known targetable mutations. The discovery by the Rutella lab of an immunological gene signature in the AML tumor microenvironment forms the basis for a potential predictive biomarker for further clinical validation.

About Flotetuzumab

Flotetuzumab (also known as MGD006) is a clinical-stage bispecific DART molecule that recognizes both CD123 and CD3. CD123, the interleukin-3 receptor alpha chain, has been reported to be over-expressed on malignant cells in AML and other hematologic malignancies. 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 cells. Data from the Phase 1/2 clinical study of flotetuzumab in patients with PIF/ER AML were presented in December 2019 at the American Society of Hematology (ASH) Annual Meeting. MacroGenics plans a single-arm, registration-enabling clinical study to evaluate flotetuzumab in up to 200 patients with PIF/ER AML, with complete remission (CR) and CR with partial hematological recovery (CRh) as the primary endpoint. The study will be conducted as a continuation of the ongoing Phase 1/2 study (NCT02152956; to be updated). The FDA 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 and DART 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 the timing and steps required in the regulatory review process, expectations for regulatory approvals, the impact of competitive products, our ability to enter into agreements with strategic partners and other matters that could affect the availability or commercial potential of the Company's product candidates, business or economic disruptions due to catastrophes or other events, including natural disasters or public health crises such as the novel coronavirus (referred to as COVID-19), 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.

Anna Krassowska, Ph.D., Vice President, Investor Relations & Corporate Communications
Jim Karrels, Senior Vice President, CFO
1-301-251-5172, info@macrogenics.com

FAQ

What is the latest research from MacroGenics related to MGNX?

MacroGenics published research in Science Translational Medicine identifying a gene expression signature in AML linked to chemotherapy resistance and response to flotetuzumab.

What is flotetuzumab and how is it related to MGNX?

Flotetuzumab is a bispecific DART molecule currently in clinical development by MacroGenics for treating primary induction failure or early relapsed AML.

What are the implications of the new AML research for MacroGenics?

The research supports flotetuzumab's potential effectiveness in difficult-to-treat AML patients and the rationale for further clinical studies.

How does the gene expression signature affect AML treatment with flotetuzumab?

The gene expression signature may predict which AML patients are likely to respond to flotetuzumab, enhancing treatment strategies.

What challenges do AML patients face according to MacroGenics' press release?

AML patients face a high failure rate in achieving remission with current therapies, particularly those with primary induction failure or early relapsing disease.