MacroGenics Announces MGD019 Publication in Cell Reports Medicine

Rhea-AI Summary

MacroGenics, Inc. (NASDAQ: MGNX) announced positive preliminary results for its investigational drug MGD019, a PD-1 × CTLA-4 bispecific DART molecule, in a dose escalation clinical study. The findings were published in Cell Reports Medicine. MGD019 demonstrated an acceptable safety profile with no dose-limiting toxicities observed among 33 cancer patients, including some with advanced solid tumors previously unresponsive to checkpoint inhibitors. The study indicates potential for enhanced selectivity in immune checkpoint blockade, warranting further clinical investigation.

Positive

• MGD019 showed no dose-limiting toxicities (DLTs) in clinical trials.
• Demonstrated objective responses in patients typically unresponsive to conventional therapies.
• Pre-clinical and clinical data suggest enhanced blockade of PD-1 and CTLA-4.

Negative

• None.

PD-1 × CTLA-4 Bispecific DART® molecule is preliminarily well-tolerated in dose escalation clinical study

ROCKVILLE, MD, Dec. 22, 2020 (GLOBE NEWSWIRE) --  MacroGenics, Inc. (NASDAQ: MGNX), a biopharmaceutical company focused on developing and commercializing innovative monoclonal antibody-based therapeutics for the treatment of cancer, today announced the publication of a manuscript on MGD019, an investigational PD-1 × CTLA-4 bispecific DART molecule, in Cell Reports Medicine.  MacroGenics’ DART platform allows for the creation of bispecific antibody-based molecules with the ability to bind to two distinct targets in contrast to a single target as supported by traditional monoclonal antibodies. 

The publication, Development and Preliminary Clinical Activity of PD-1-Guided CTLA-4 Blocking Bispecific DART Molecule, highlights key findings from the ongoing Phase 1 trial of MGD019 first-in-human study of patients with advanced solid tumors (NCT03761017) as well as data from mechanistic studies. Findings in mechanistic studies demonstrated that cells co-expressing PD-1 and CTLA-4 are abundant in the tumor microenvironment (TME) compared to normal tissues, supporting PD-1 and CTLA-4 co-blockade in treating solid tumor cancers. This observation suggests that targeting dual PD-1/CTLA-4-expressing cells may also provide an opportunity for increased selectivity of checkpoint blockade in the TME, while relatively reducing effects in normal tissues.

In vitro studies demonstrated that MGD019 may provide complete blockade of PD-1 together with tunable inhibition of CTLA-4, with greatly enhanced blockade of CTLA-4 activity on dual-antigen expressing cells, a potential advantage over PD-1 or CTLA-4 blockade with individual monoclonal antibodies. In addition, MGD019 was well tolerated in non-human primates following repeated intravenous (IV) administrations (four weekly doses) of MGD019 at dose levels of 10, 40 and 100 mg/kg, well exceeding the highest non-severely toxic dose reported for the combination of nivolumab and ipilimumab in this species.

These mechanistic data formed the basis for the on-going, first-in-human study demonstrating clinical activity and correlated pharmacodynamics. At the cutoff date of April 1, 2020, 33 patients representing 21 different advanced solid tumor types were treated, including 13 patients (39.4%) who had previously received checkpoint inhibitor therapy.  Objective responses were reported in four patients (including one unconfirmed response) with tumor types typically unresponsive to conventional checkpoint inhibition.  MGD019 was generally well-tolerated up to the top predefined dose level of 10 mg/kg, with no dose limiting toxicities (DLTs) observed and a safety profile generally consistent with that of anti-PD-1 monotherapy.

“Treatment with PD-1 and CTLA-4 inhibitors such as nivolumab and ipilimumab has been effective in several cancer indications; however, the combination is associated with significant toxicity,” said Paul Moore, Ph.D., MacroGenics’ Vice President of Cell Biology and Immunology and the senior author on the paper. “The pre-clinical and clinical results published today demonstrated that MGD019 can mediate complete blockade of PD-1 with tunable blockade of CTLA-4, which is enhanced on dual-expressing cells, a potential advantage over blockade by combining individual monoclonal antibodies to PD-1 and CTLA-4. The early clinical data from the Phase 1 trial of MGD019 appear to indicate an acceptable safety profile and support further clinical investigation of MGD019 in cancer treatment.”

About MGD019

MGD019 is an investigational, bispecific DART molecule that was designed to enable blockade of two immune checkpoint molecules expressed on T cells, PD-1 and CTLA-4. Based upon the establishment of a recommended Phase 2 dose (RP2D) from a dose escalation study, MGD019 is initially being evaluated in a dose expansion study in microsatellite-stable colorectal cancer and non-small cell lung cancer. MacroGenics retains global rights to MGD019.

About MacroGenics, Inc.

MacroGenics is a biopharmaceutical company focused on developing and commercializing 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, the MacroGenics logo and DART are trademarks or registered trademarks of MacroGenics, Inc.

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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, commercial prospects of or product revenues from MARGENZA, milestone or opt-in payments from the Company's collaborators, the Company's anticipated milestones 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: risks that MARGENZA revenue, expenses and costs may not be as expected, risks relating to MARGENZA’s market acceptance, competition, reimbursement and regulatory actions, 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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FAQ

What are the latest results for MGNX's MGD019 clinical trial?

MGD019 showed no dose-limiting toxicities and objective responses in advanced solid tumors, indicating its potential efficacy.

When was MGNX's MGD019 study published?

The study was published on December 22, 2020, in Cell Reports Medicine.

What type of molecule is MGD019?

MGD019 is a PD-1 × CTLA-4 bispecific DART molecule designed to target two immune checkpoint molecules.

How many patients were treated in the MGNX study for MGD019?

33 patients were treated in the clinical study, representing 21 different advanced solid tumor types.