OncoMed Announces Early Clinical Data for anti-TIGIT Antibody

Phase 1a Dose-Escalation Data Demonstrates a Favorable Safety Profile and Signals of Immune Cell Modulation in Patients with Late Stage Solid Tumors

REDWOOD CITY, Calif. and WASHINGTON, Nov. 09, 2018 (GLOBE NEWSWIRE) -- OncoMed Pharmaceuticals, Inc. (NASDAQ: OMED), a clinical-stage biopharmaceutical company focused on discovering and developing novel anti-cancer therapeutics, today announced initial results from the Phase 1a dose escalation portion of a Phase 1a/b trial of etigilimab, the company’s anti-TIGIT antibody. TIGIT (T-cell immunoreceptor with Ig and ITIM domains) is a next generation checkpoint receptor shown to block T-cell activation and the body’s natural anti-cancer immune response. OncoMed’s anti-TIGIT checkpoint inhibitor candidate is an IgG1 monoclonal antibody which binds to the human TIGIT receptor on T-cells with a goal of improving the activation and effectiveness of T-cell and NK cell tumor-killing activity. The data were presented today at the Society for Immunotherapy of Cancer meeting taking place in Washington, D.C.

The initial results from the Phase 1a dose escalation portion of the Phase 1a/b trial included data from 18 patients with a variety of late stage metastatic cancers including colorectal, endometrial, pancreatic, among others, who were treated with etigilimab at doses ranging from 0.3 to 20 mg/kg every other week. There were no dose-limiting toxicities through the 20 mg/kg every other week dose.  In this “all comers” difficult-to-treat patient population, stable disease was observed in 7 (38.9%) patients with prolonged disease control seen in some patients with the longest durations of stable disease being 205 and 225 days.  Of the remaining 11 patients in the study, ten patients had progressive disease, and one patient did not meet criteria to be evaluated for efficacy. The most frequent treatment-related adverse events were rash (27.8%), fatigue (16.7%), nausea (16.7%), pruritus (16.7%), and cough (11.1%). Immune-related adverse events, signaling immune activation included rash (27.8%), pruritus (16.7%), autoimmune hepatitis (5.6%) and stomatitis (5.6%). Grade 3 or higher treatment-related AEs included rash (16.7%), and abdominal pain, embolism, hypertension, and pulmonary embolism (11.1% each).

Biomarker analysis demonstrated a significant reduction of peripheral T regulatory cells (Tregs), most significant at doses ≥ 10 mg/kg, and signals of immune activation.  These results are consistent with preclinical studies with a surrogate anti-TIGIT antibody and suggest select immune cell depletion and activation of T cell signaling in patients treated with the drug.

“These data indicate that etigilimab was well-tolerated by patients and showed modulation of specific subsets of peripheral T cells,” said John Lewicki, Ph.D., President and Chief Executive Officer of OncoMed. “The decrease in peripheral Tregs and observations of stable disease in certain patients are consistent with the expected mechanisms of our IgG1 anti-TIGIT antibody.”

The company is currently enrolling a single agent Phase 1a expansion cohort in select tumor types. Concurrently, the company is also enrolling the phase 1b portion of the trial where escalating doses of etigilimab are given in combination with nivolumab in the treatment of patients with solid tumors who have progressed after treatment with anti-PD1 or anti-PD-L1. The trial will define a dosing regimen that could provide the basis for expanded studies of etigilimab in combination with anti-PD1.

TIGIT and its ligands, PVR and PVR-L2 comprise a novel immune checkpoint which blocks T-cells from attacking tumor cells and is similar in structure and function to the inhibitory protein PD-1. OncoMed's anti-TIGIT antibody (etigilimab) is intended to activate the immune system through multiple mechanisms and to enable anti-tumor activity. At the 2018 AACR Annual Meeting, OncoMed presented preclinical data (Abstract 5627) which demonstrated that anti-TIGIT treatment reduced the abundance of Tregs within tumors in animal models. Mechanistic studies demonstrated an important contribution of effector function for anti-tumor efficacy. Using a surrogate anti-TIGIT antibody, potent single-agent dose-dependent anti-tumor efficacy was demonstrated on large established CT26 WT  tumors and in other models. Anti-TIGIT efficacy was shown to require effector function for tumor growth inhibition and biomarker analysis demonstrated reduction of Treg frequency and activation of T-cells and NK cells as part of the mechanism of action of anti-TIGIT. Additionally in a human tissue study, TIGIT expression on Tregs was found to be considerably higher than on CD8+ T-cells in multiplexed IHC panels across a panel of multiple solid tumors types. This program is part of OncoMed's collaboration with Celgene.

About OncoMed Pharmaceuticals
OncoMed Pharmaceuticals is a clinical-stage biopharmaceutical company focused on discovering and developing novel anti-cancer therapeutics. OncoMed has internally discovered a broad pipeline of investigational drugs intended to address the fundamental biology driving cancer's growth, resistance, recurrence and metastasis. Product candidates in OncoMed’s portfolio include navicixizumab (anti-DLL4/VEGF bispecific, OMP-305B83), etigilimab (anti-TIGIT, OMP-313M32), and GITRL-Fc (OMP-336B11). OncoMed also continues to pursue new drug discovery research. For further information about OncoMed Pharmaceuticals, please see www.oncomed.com.

Forward Looking Statements
To the extent that statements contained in this press release are not descriptions of historical facts regarding OncoMed Pharmaceuticals, they are forward-looking statements reflecting the current beliefs and expectations of management made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, including, without limitation, OncoMed’s intentions and expectations regarding the anti-tumor and immune-modulating activity of etigilimab; the ability of etigilimab to improve the activation and effectiveness of T-cell and NK cell tumor-killing activity; the safety and tolerability of etigilimab; and the continued clinical investigation of etigilimab, including the continued enrollment of patients in the current etigilimab clinical trial and the potential for expanded studies of etigilimab in combination with anti-PD1. Such forward-looking statements involve substantial risks and uncertainties that could cause OncoMed's clinical development programs, future results, performance or achievements to differ significantly from those expressed or implied by the forward-looking statements. Such risks and uncertainties include, among others, the uncertainties inherent in the preclinical and clinical development process; OncoMed's ability to raise additional capital to support the development of its unpartnered programs; and OncoMed's dependence on its key executives. OncoMed undertakes no obligation to update or revise any forward-looking statements. For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to OncoMed's business in general, see OncoMed's Annual Report on Form 10-K filed with the U.S. Securities and Exchange Commission (SEC) on March 9, 2018, OncoMed’s Quarterly Report on Form 10-Q filed with the SEC on November 1, 2018, and OncoMed's other current and periodic reports filed with the SEC.


Sylvia Wheeler

Alex Santos