On April 10, 2021 Jounce Therapeutics, Inc. (NASDAQ: JNCE), a clinical-stage company focused on the discovery and development of novel cancer immunotherapies and predictive biomarkers, reported new preclinical data on JTX-8064, the first tumor-associated macrophage program from their Translational Science Platform, at the 2021 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Virtual Annual Meeting being held April 10-15, 2021 (Press release, Jounce Therapeutics, APR 10, 2021, View Source [SID1234577840]). The poster presentation includes data showing a high Leukocyte Immunoglobulin Like Receptor B2 (LILRB2) to interferon gamma (IFNγ) ratio is associated with resistance to PD-(L)1 inhibitor treatment in humans, JTX-8064’s ability to bridge innate and adaptive immunity, and how Jounce’s Translational Science Platform informed indication selection for the Phase 1 INNATE trial.
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"The translational analyses presented at AACR (Free AACR Whitepaper) link JTX-8064’s mechanism to tumor types that may respond better to LILRB2 inhibition," said Elizabeth Trehu, M.D., chief medical officer of Jounce Therapeutics. "The Phase 1 INNATE trial is designed to move as quickly as possible to proof of concept and this new data enabled the prioritization of tumor-specific expansion cohorts, which are on track to start enrolling in the second half of 2021. Furthermore, the negative prognostic implications of a high LILRB2 to IFNγ ratio support the role of LILRB2 in resistance to PD-(L)1 inhibitors and highlight the potential for JTX-8064 to reverse this resistance."
In a poster titled "Tumor associated macrophages and resistance to immune checkpoint blockade: Consideration of cancer indications for the clinical development of JTX-8064, an anti-LILRB2/ILT4 monoclonal antibody" Jounce demonstrated:
JTX-8064 can induce T cell activation in co-culture with macrophages, demonstrating its potential to bridge the gap between innate and adaptive immune responses;
CD163+ M2 macrophages co-localize with T cells in the tumor microenvironment, and patients with high levels of LILRB2 or a proprietary tumor-associated macrophage (TAM) signature score relative to an IFNγ signature score are less responsive to PD-(L)1 inhibitors, providing evidence that LILRB2+ macrophages may be involved in mechanisms of primary resistance to PD-(L)1 inhibitors; and
Expression profiles of LILRB2 mRNA, TAM signatures, and other inflammatory cell signatures were used to identify tumor types that may benefit most from JTX-8064 treatment and used to inform indication selection for expansion cohorts of the Phase 1 INNATE trial.
The poster is available on the "Our Pipeline" section of the Jounce Therapeutics website at www.jouncetx.com.
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 and 2021 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meetings support the development of JTX-8064 as a novel immunotherapy to reprogram immune-suppressive macrophages and enhance anti-tumor immunity. A Phase 1 clinical trial named INNATE (NCT04669899), of JTX-8064 as a monotherapy and in combination with either JTX-4014, or pembrolizumab, is currently enrolling patients with advanced solid tumors.