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Nov 9, 2018
MacroGenics Reports Presentation of Clinical Data at 33rd Annual SITC Meeting
  • Enoblituzumab + pembrolizumab combination study data reported: ORRs in anti-PD-1/PD-L1 naïve SCCHN and NSCLC cohorts benchmarked favorably vs. approved anti-PD-1 agents
  • Interim data from Phase 1 dose expansion study of MGA012 (anti-PD-1): objective responses in NSCLC, cervical cancer, endometrial cancer and soft tissue sarcoma
  • Interim data from study of enoblituzumab in neoadjuvant prostate cancer: enoblituzumab localization in prostate cancer tissues with increased CD8+ infiltrate


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 presentation of clinical data in oral and poster presentation sessions at the Society for Immunotherapy of Cancer’s (SITC) 33rd Annual Meeting in Washington, D.C.

Enoblituzumab + Pembrolizumab Combination Phase 1 Study Data to be Presented

Charu Aggarwal, M.D., M.P.H., Assistant Professor of Medicine at the Hospital of the University of Pennsylvania, will present "A Phase 1, Open-Label, Dose Escalation Study of Enoblituzumab in Combination with Pembrolizumab in Patients with Select Solid Tumors" on Sunday, November 11, 2018, at 9:35 AM ET. A poster (O24) related to this presentation was made available at the meeting today.

A Phase 1 clinical study of the combination of enoblituzumab, an Fc-optimized monoclonal antibody (mAb) that targets B7-H3, and pembrolizumab, an anti-PD-1 mAb, was conducted to evaluate the safety of this combination when administered to patients with B7-H3-expressing melanoma, squamous cell carcinoma of the head and neck (SCCHN), non-small cell lung cancer (NSCLC) and urothelial cancer. The study also evaluated potential anti-tumor activity, pharmacokinetics and pharmacodynamics of this combination. A total of 133 patients were treated in the study and the data cut-off date was October 12, 2018.

The combination of enoblituzumab and pembrolizumab demonstrated acceptable tolerability in patients treated to date, with any adverse event ≥ Grade 3 occurring in 27.1% of patients. The rate of immune-related adverse events experienced in the study was comparable to that observed in patients who receive anti-PD-1 as monotherapy.

In the SCCHN dose expansion cohort, of the response-evaluable patients who had not previously received anti-PD-1 or anti-PD-L1 therapy, 6 of 18 (33.3%) had confirmed partial responses (PRs). For the subset of patients with B7-H3 tumor expression ≥10%, 6 of 15 (40.0%) had confirmed PRs. Objective response rates ranging from 13% to 16% have previously been reported in SCCHN patients treated with anti-PD-1 alone.

In the NSCLC dose expansion cohort, of the response-evaluable patients who had not previously received anti-PD-1 or anti-PD-L1 therapy and who were PD-L1 negative (i.e., PD-L1<1%), 5 of 14 (35.7%) had confirmed PRs. Objective response rates ranging from 8% to 17% have previously been reported in PD-L1 negative NSCLC patients treated with anti-PD-1 alone.

Based on these results, MacroGenics intends to commence follow-on studies of enoblituzumab in combination with MGA012, an anti-PD-1 mAb, in patients with SCCHN and NSCLC beginning in the second half of 2019.

"We are very encouraged by the tolerability and initial anti-tumor activity of enoblituzumab in combination with anti-PD-1. Once again, as we’ve recently seen when combining margetuximab with anti-PD-1 in gastric cancer, the leveraging of an Fc-optimized molecule with checkpoint blockade appears to coordinately engage both innate and adaptive immunity, resulting in antitumor activity," said Scott Koenig, M.D., Ph.D., President and CEO of MacroGenics. "Further investigation of enoblituzumab in combination with anti-PD-1 is warranted in patients with SCCHN and NSCLC, including in combination with chemotherapy. And given the expression levels of B7-H3 across several other tumor types, we believe further investigation of enoblituzumab in combination with anti-PD-1 is warranted in other indications, including both checkpoint-naïve and experienced populations.”

MGA012 Interim Phase 1 Dose Expansion Cohort Data Presented by Incyte

MacroGenics’ collaborator, Incyte, today presented a poster titled “First-in-Human Phase 1 Study of INCMGA00012 in Patients With Advanced Solid Tumors: Interim Results of the Cohort Expansion Phase” (P669) at SITC 2018. MacroGenics licensed MGA012 (also known as INCMGA00012) to Incyte in 2017.

In the cohort expansion portion of this Phase 1 study, MGA012 has been generally well tolerated in both weight-based and flat dosing schedules. The immune-related AE profile is acceptable and as expected for a PD-1/PD-L1 inhibitor. In addition, the interim analysis shows confirmed response evaluation criteria in solid tumors (RECIST) responses in all tumor-specific expansion cohorts, including NSCLC, cervical cancer, endometrial cancer and soft tissue sarcoma.

Incyte has indicated that it is expanding this study to evaluate safety of the 500mg Q4W dose in a larger cohort of MSI-h or dMMR endometrial cancer patients as well as a Q3W flat dosing regimen in a tumor-agnostic population. MGA012 is being investigated as monotherapy and in combination with other treatment modalities in clinical trials, five of which are also presented at SITC 2018 (P336, P313, P304, P305, P306).

Interim Results from Enoblituzumab in Neoadjuvant Prostate Cancer Study Presented

Also related to enoblituzumab, MacroGenics’ academic collaborators and study sponsors at Johns Hopkins University presented a poster titled “Phase II Neoadjuvant and Immunologic Study of B7-H3 Targeting with Enoblituzumab in Localized Intermediate-and High-Risk Prostate Cancer” (P338). The aim of this ongoing investigator-sponsored study is to understand the impact of B7-H3 targeting/blockade on prostate-specific antigen (PSA) recurrence following prostatectomy, the impact on the prostate gland tumor microenvironment (TME) and assess whether B7-H3 immunohistochemistry staining can be used to predict response or resistance to B7-H3–targeted therapies.

The interim results presented indicate that enoblituzumab binds B7-H3 to malignant glands with high affinity and specificity.  In addition, CD8+ T cell quantitation in the enoblituzumab-treated prostatectomy samples indicate a statistically significant increase in infiltrate compared to age-and stage-matched untreated prostatectomy controls.

MacroGenics and its collaborators’ posters at the SITC 2018 Annual Meeting are available for download from the Events & Presentations page on MacroGenics' website at http://ir.macrogenics.com/events.cfm. Slides from Dr. Aggarwal’s oral presentation will be made available on the same website page at the time of her presentation.

About MacroGenics' B7-H3 Franchise

MacroGenics is pursuing therapeutic product candidates utilizing three different and complementary mechanisms of action targeting B7-H3, an immunomodulatory molecule expressed in a broad range of tumor types with limited expression in normal tissue. The most advanced clinical candidate, enoblituzumab, is an Fc-optimized monoclonal antibody directed against B7-H3. The second program, orlotamab, also in clinical testing, is a bispecific DART® molecule designed to target tumors expressing B7-H3 by recruiting and expanding T cells at the tumor site via CD3 engagement. The third B7-H3-directed product candidate, MGC018, is an antibody-drug conjugate (ADC) directed against solid tumors expressing B7-H3 and is in Phase 1 clinical study initiation. MacroGenics is testing orlotamab and intends to test MGC018 in combination with checkpoint blockade (using MGA012) in clinical studies. MacroGenics retains worldwide development and commercialization rights to all three B7-H3 product candidates.

About MacroGenics' PD-1 Franchise

MacroGenics is advancing multiple PD-1-directed programs to provide further differentiation from existing PD-1-based treatment options and enable a broad set of combination opportunities across the Company’s portfolio: (1) MGA012 is an anti-PD-1 mAb licensed to Incyte, but which MacroGenics retains the rights to develop in combination with its pipeline assets. Incyte has announced its intention to pursue monotherapy development through registration-directed studies with initial data anticipated in 2020. (2) MGD013 is a first-in-class bispecific DART molecule designed to provide coordinate blockade of two immune checkpoint molecules expressed on T cells, PD-1 and LAG-3, for the potential treatment of a range of solid tumors and hematological malignancies. MacroGenics recently established the dose and schedule for MGD013 administration and has initiated dose expansion in up to nine tumor types in a Phase 1 study. (3) MGD019 is a DART molecule designed to provide co-blockade of both PD-1 and CTLA-4, two immune checkpoint inhibitors, on T cells. MacroGenics’ Investigational New Drug (IND) application for MGD019 was cleared by the FDA and the Company is currently engaged in Phase 1 study startup.

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 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.


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

Source: MacroGenics, Inc.