Press Release

• Flotetuzumab demonstrated 29.4% complete response rate in evaluable primary refractory AML patients
• Translational studies suggest potential strategy for biomarker-based patient selection

ROCKVILLE, Md., Dec. 03, 2018 (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 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 60^th 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.

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Contacts:
Jim Karrels, Senior Vice President, CFO
MacroGenics, Inc.
1-301-251-5172, info@macrogenics.comKaren Sharma, Managing Director
MacDougall Biomedical Communications
1-781-235-3060, ksharma@macbiocom.com

Source: MacroGenics, Inc.