MacroGenics Announces Preliminary Clinical Results from Phase 1 Study of MGC018 to be Presented at ASCO Annual Meeting

• Dose escalation: anti-tumor activity observed in melanoma (including one confirmed partial response) and in mCRPC patients
• Cohort expansion in mCRPC: 11/22 (50%) patients have ≥ 50% PSA reduction; anti-tumor activity observed in four of seven patients evaluated (including one unconfirmed partial response)
• Conference call and webcast with external guest presenters on Friday, June 4, 2021 at 4:30 P.M. ET

ROCKVILLE, MD, May 19, 2021 (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 preliminary safety and anti-tumor activity data from the Company’s ongoing Phase 1 clinical trial of MGC018. This investigational antibody-drug conjugate (ADC) was designed to deliver a DNA alkylating duocarmycin payload to both dividing and non-dividing cells in a B7-H3-dependent manner. The dataset will be presented in a poster titled “Phase 1 Dose Escalation Study of MGC018, an anti-B7-H3 Antibody-Drug Conjugate (ADC), In Patients with Advanced Solid Tumors” (Abstract #2631) at the upcoming 2021 American Society of Clinical Oncology (ASCO) Annual Meeting to be held June 4-8, 2021.

Dose Escalation Results Update

The ASCO abstract included data as of January 21, 2021; updated data as of a May 3, 2021 cut-off are included below and will be presented at ASCO.

A total of 29 patients with advanced solid tumors were enrolled in five dose escalation cohorts with MGC018 at 0.5 to 4.0 mg/kg, administered intravenously every three weeks. This included six patients at the 4.0 mg/kg cohort enrolled subsequent to the 2020 ASCO poster presentation. A recommended Phase 2 dose (RP2D) was defined as 3.0 mg/kg every three weeks.

mCRPC. Preliminary evidence of anti-tumor activity by MGC018 has been observed, most notably in patients with advanced metastatic castration-resistant prostate cancer (mCRPC). Reductions in prostate-specific antigen (PSA) levels of ≥ 50% were observed in five of nine mCRPC patients treated in dose escalation, including one with substantial regression of bone disease. Of the nine patients with mCRPC, eight were evaluated for tumor response, all of whom demonstrated a best response of stable disease. Two of these eight patients had measurable disease; both had reductions in target lesions, including a 29% reduction in one patient. The nine mCRPC patients treated in dose escalation received a median of four therapies prior to MGC018, including taxane chemotherapy (eight patients) and next generation hormonal agents (all patients had previously received abiraterone, enzalutamide or both). All nine mCRPC patients in dose escalation are off therapy.  Of the five patients who had ≥ 50% PSA reduction, one withdrew consent (without disease progression) at 4 months, one had new bone lesions at 6 months, one initiated subsequent therapy at 6 months, and two had no progression at 7 months.

Melanoma. During dose escalation, three melanoma patients were administered MGC018 at 4.0 mg/kg (the highest dose administered). All had previously received three different checkpoint inhibitor agents. The best responses in target lesion sum reductions for these patients after being treated with MGC018 were 24%, 28% and 36% (confirmed partial response), with this last patient remaining on MGC018 therapy for more than 6 months as of the data cut-off. Based on these data, MacroGenics recently initiated a melanoma expansion cohort (N=approximately 20).

Safety. Adverse events for the dose escalation cohorts of 0.5 mg/kg to 4.0 mg/kg as of the May 3, 2021 data cut-off were generally consistent with those previously reported at ASCO 2020. MGC018-related toxicities included hematologic and skin toxicities that have been clinically manageable. In dose escalation overall, at least one treatment-related adverse event was experienced by 27 of 29 patients (93%). At 4.0 mg/kg, one patient developed a dose-limiting toxicity manifested by Grade 3 fatigue that lasted for more than 72 hours and as previously reported, a Grade 4 neutropenia occurred in a patient in the 2.0 mg/kg cohort.

Preliminary Results for mCRPC Cohort Expansion

As of the May 3, 2021 data cut-off, 28 of the 40 patients in the mCRPC cohort expansion had been enrolled, with disease classification available for 20 of these patients: seven had bone only, nine had mixed soft tissue and bone, and four had soft tissue only. Of the 28 mCRPC patients in cohort expansion, 22 had received at least one dose of MGC018 and had a post-baseline PSA. Eleven of these 22 patients (50%) had a PSA reduction of 50% or greater. All but three of these 22 patients were still on therapy as of the data cut-off. Of 13 patients who had measurable disease, six were not yet evaluable and seven had their first 9-week imaging, of which four had reductions in target lesion sums of 13%, 21%, 27% and 35% (unconfirmed partial response). Twelve of these 13 patients were still ongoing on MGC018.

“We continue to be very encouraged by evolving data from our ongoing Phase 1 study of MGC018. To date, we have observed preliminary signals of anti-tumor effects, including PSA reductions of 50% or more in 16 of 31 (52%) patients with late-stage castration-resistant prostate cancer across dose escalation and dose expansion,” said Scott Koenig, M.D., Ph.D., President and CEO. “We are very pleased to report decreases in target lesion sums, including an unconfirmed partial response, in mCRPC patients with measurable disease. Finally, we are encouraged to see anti-tumor activity, including a confirmed partial response, in post-checkpoint melanoma patients who have received MGC018. We look forward to sharing the full data at ASCO and providing further updates on our ongoing dose expansion cohorts, including patients with mCRPC, non-small cell lung cancer, triple negative breast cancer, melanoma and squamous cell carcinoma of the head and neck, at subsequent scientific conferences.”

Conference Call

MacroGenics’ management will host a conference call and webcast with external guest presenters to discuss the preliminary MGC018 results on Friday, June 4, 2021 at 4:30 P.M. ET. To participate in the conference call, please dial (877) 303-6253 (domestic) or (973) 409-9610 (international) ten minutes prior to the start of the call and provide the Conference ID: 1583522. The listen-only audio and slide webcast of the conference call can be accessed under "Events & Presentations" in the Investor Relations section of the Company's website at http://ir.macrogenics.com/events.cfm. A replay of the webcast will be available shortly after the conclusion of the call and archived on the Company's website for 30 days.

ASCO Presentation

The abstract for MacroGenics’ MGC018 poster presentation was submitted to ASCO in February 2021 and is available on the ASCO website at https://conferences.asco.org/am/abstracts. The poster will be available for on-demand viewing on the ASCO website and on the Events & Presentations page on MacroGenics’ website at http://ir.macrogenics.com/events.cfm on or around June 4, 2021.

About MGC018

MGC018 is an ADC 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. B7-H3 is a molecule highly expressed on many solid tumors and associated with a poor clinical outcome. MGC018 is being evaluated in a Phase 1 study (NCT03729596). MacroGenics retains worldwide rights to MGC018.

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