On January 13, 2021 Jounce Therapeutics, Inc. (NASDAQ: JNCE), a clinical-stage company focused on the discovery and development of novel cancer immunotherapies and predictive biomarkers, reported the initiation of patient enrollment in the INNATE Phase 1 clinical study of its lead macrophage program JTX-8064 as a monotherapy and in combination with either JTX-4014, its internal PD-1 inhibitor, or pembrolizumab in patients with advanced solid tumors (Press release, Jounce Therapeutics, JAN 13, 2021, View Source [SID1234573951]). JTX-8064, the first tumor-associated macrophage candidate developed from Jounce’s Translational Science Platform, is a humanized IgG4 monoclonal antibody designed to specifically bind to the macrophage receptor Leukocyte Immunoglobulin Like Receptor B2 (LILRB2/ILT4), inhibiting LILRB2 binding with its ligands and reprogramming immune-suppressive macrophages to enhance anti-tumor immunity.

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"We are pleased to announce we have dosed the first patient in our INNATE Phase 1 study which is designed to progress quickly through dose escalation and demonstrate proof of concept in tumor specific expansion cohorts," said Beth Trehu, M.D., chief medical officer at Jounce Therapeutics. "Expansion cohorts in INNATE will address multiple different patient populations, including PD-(L)1 inhibitor naïve patients with both PD-(L)1 inhibitor sensitive and resistant tumor types, and PD-(L)1 inhibitor experienced patients whose tumors were resistant to PD-(L)1 inhibitors. Patients with PD-(L)1 inhibitor resistant tumors represent a large and growing unmet medical need. We believe LILRB2 may function as an immune checkpoint for macrophages and JTX-8064 may have the potential to restore PD-(L)1 inhibitor activity in otherwise resistant settings. INNATE will also assess pharmacodynamic and potential predictive biomarkers to guide future development, aligning with Jounce’s philosophy of developing the right immunotherapies for the right patients."

The Phase 1 INNATE study will consist of 4 parts:

JTX-8064 monotherapy dose escalation in solid tumors
JTX-8064 dose escalation in combination with Jounce’s PD-1 inhibitor, JTX-4014, and also with pembrolizumab in solid tumors
JTX-8064 monotherapy in indication-specific expansion cohorts
JTX-8064 in combination with JTX-4014 or pembrolizumab in indication-specific expansion cohorts
ClinicalTrials.gov identifier: NCT04669899

About JTX-8064
JTX-8064 is a humanized IgG4 monoclonal antibody designed to specifically bind to Leukocyte Immunoglobulin Like Receptor B2 (LILRB2/ILT4) and block interactions with its ligands. JTX-8064 is the first tumor-associated macrophage candidate developed from Jounce’s Translational Science Platform. Preclinical data presented at the 2020 Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s Annual Meeting and the 2019 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting support the development of JTX-8064 as a novel immunotherapy to reprogram immune-suppressive macrophages and enhance anti-tumor immunity. A Phase 1 clinical study named INNATE (NCT04669899), for JTX-8064 as a monotherapy and in combination with JTX-4014 or pembrolizumab, is currently enrolling patients with advanced solid tumors.

About JTX-4014
JTX-4014 is a well-characterized fully human IgG4 monoclonal antibody designed to block binding to PD-L1 and PD-L2. JTX-4014 demonstrated a 17% durable overall response rate in a Phase 1 trial of 18 heavily pre-treated PD-(L)1 inhibitor naïve patients, which excluded all tumor types for which PD-(L)1 inhibitors were approved. In this Phase 1 trial, JTX-4014 was shown to have an acceptable safety profile. JTX-4014 is currently being assessed in the INNATE Phase 1 trial (NCT04669899) in combination with JTX-8064, a LILRB2 (ILT4) inhibitor. JTX-4014 is also being assessed in the SELECT Phase 2 clinical trial (NCT04549025) in combination with vopratelimab, a clinical-stage monoclonal antibody that binds to and activates ICOS, the Inducible T cell CO-Stimulator, a protein on the surface of certain T cells commonly found in many solid tumors. The SELECT trial compares vopratelimab plus JTX-4014 to JTX-4014 alone in immunotherapy naïve NSCLC patients who have been pre-selected with the TISvopra predictive biomarker, an 18 gene RNA tumor inflammation signature which predicted the emergence of ICOS hi CD4 T cells and clinical benefit in the ICONIC trial of vopratelimab alone and in combination with a PD-1 inhibitor.