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Sep 23, 2020
MacroGenics Announces MGC018 Publication in Molecular Cancer Therapeutics
  • Manuscript describes preclinical development of MGC018
  • Phase 1 dose expansion trial evaluating MGC018 in patients with mCRPC, TNBC and NSCLC is currently recruiting patients

ROCKVILLE, MD, Sept. 23, 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 the publication of a manuscript in Molecular Cancer Therapeutics, a journal of the American Association for Cancer Research, highlighting the development of MGC018, the Company’s investigational antibody-drug conjugate (ADC) targeting B7-H3 for the treatment of solid tumors.

B7-H3 has been identified as a cell surface protein with limited expression on normal tissues but over-expressed on the epithelium and tumor-associated vasculature in solid tumors. Overexpression of this molecule has been shown to be associated with cancer disease severity, risk of recurrence and reduced survival. The Company’s early studies showed that ligation of B7-H3 by select monoclonal antibodies (mAbs) led to mAb internalization and antitumor activity toward B7-H3-expressing tumor cells when conjugated to a toxic payload. Based on these results, MacroGenics selected a lead candidate mAb and developed MGC018, an ADC targeting B7-H3 for the treatment of cancer.

As described in the paper “Preclinical Development of MGC018, a Duocarmycin-based Antibody-drug Conjugate Targeting B7-H3 for Solid Cancer,” the authors report on preclinical studies that showed that MGC018 mediated specific in vitro killing across a range of B7-H3-expressing solid tumor cell types. Furthermore, the preclinical studies showed that MGC018 mediated bystander in vitro killing of B7-H3-negative tumor cells in the presence of B7-H3-positive tumor cells.

MGC018 displayed potent antitumor activity in preclinical tumor xenograft models of breast, ovarian and lung cancer, as well as melanoma. Additionally, antitumor activity was observed toward patient-derived tumor xenograft models of breast, prostate and head and neck cancer displaying heterogeneous expression of B7-H3. Importantly, MGC018 exhibited an acceptable pharmacokinetic and safety profile in cynomolgus monkeys following repeat-dose administration.

“With its overexpression on a wide range of solid cancers but limited presence on normal tissues, B7-H3 is an attractive candidate for an ADC-targeting approach,” said Deryk Loo, Ph.D., Senior Director of Research at MacroGenics and the lead author of the paper. “The published preclinical antitumor activity data and safety profile provided evidence of a potentially favorable therapeutic index to support the development of MGC018 for the treatment of solid tumors.”

Scott Koenig, M.D., Ph.D., President and CEO of MacroGenics, further commented: “Encouraged by the MGC018 interim clinical dose escalation data presented at ASCO in May, we have recently initiated recruitment of patients with metastatic castration-resistant prostate, triple negative breast and non-small cell lung cancers in the dose expansion portion of the Phase 1 clinical study. We expect to provide an update on this study next year.”

About MGC018

MGC018 is comprised of an anti-B7-H3 humanized IgG1/kappa monoclonal antibody conjugated via a cleavable linker to the prodrug seco-DUocarmycin hydroxyBenzamide Azaindole (DUBA; licensed from Byondis, B.V.), with an average drug-to-antibody ratio (DAR) of ~2.7. DUBA is an alkylating agent that can damage DNA in both dividing and non-dividing cells, causing cell death. MGC018 is being evaluated in a Phase 1 study (NCT03729596). Preliminary clinical results from the dose escalation portion of this study were presented at the 2020 American Society for Clinical Oncology (ASCO) Scientific Program. MacroGenics retains full worldwide rights to MGC018.

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. For more information, please see the Company's website at www.macrogenics.com. MacroGenics and the MacroGenics logo 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.



Jim Karrels, Senior Vice President, CFO
MacroGenics, Inc.
1-301-251-5172, info@macrogenics.com


Source: MacroGenics, Inc.