On June 22, 2020 Jounce Therapeutics, Inc. (NASDAQ: JNCE), a clinical-stage company focused on the discovery and development of novel cancer immunotherapies and predictive biomarkers, reported the presentation of new preclinical data from its JTX-1811 program and translational data from its ongoing vopratelimab program at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Virtual Annual Meeting (Press release, Jounce Therapeutics, JUN 22, 2020, View Source [SID1234561284]).
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"The progress we have made to date with both JTX-1811, our anti-CCR8 antibody, and vopratelimab, our ICOS agonist, represent the strength of our Translational Science Platform as we continue to gain new insights about the tumor microenvironment from preclinical studies through clinical development. We are excited to share the first results from our anti-CCR8 program, demonstrating JTX-1811’s ability to deplete immunosuppressive tumor infiltrating T regs and to provide synergistic activity with PD-1 inhibitors in otherwise PD-1 inhibitor resistant tumor models," said Elizabeth Trehu, M.D., chief medical officer of Jounce Therapeutics. "Additionally, analyses of the vopratelimab-associated ICOS hi CD4 T cells from long-term responders in the ICONIC trial provide more insight into the potential contribution of these cells to durable clinical benefit. Both presentations represent our commitment to translational science and deep understanding of the tumor immune microenvironment as we strive to provide meaningful clinical benefit to patients with cancer."
Key highlights from the poster titled, "Preclinical evaluation of JTX-1811, an anti-CCR8 antibody with enhanced ADCC activity, for preferential depletion of tumor-infiltrating regulatory T cells" include:
Tumor-infiltrating T-regulatory (TITR) cells suppress anti-tumor immunity in the tumor microenvironment.
CCR8 may be a superior target for TITR cells because it is expressed at high densities on the cell surface of tumor T-regulatory cells.
A surrogate antibody specific for mouse CCR8 showed single agent and synergistic combination activity with PD-1 inhibitors in anti-PD-1 resistant murine tumor models.
An antibody with enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) may optimize the window for depletion of human TITR cells.
Based on these preclinical data, JTX-1811, a high affinity CCR8-specific humanized monoclonal antibody with enhanced ADCC activity, is being developed for the selective depletion of TITR cells.
Key highlights from the poster titled, "ICOS hi CD4 T cells emerging on vopratelimab treatment have Th1, central memory, and Tfh characteristics that may contribute to durability of clinical responses" include:
The emergence of a peripheral blood ICOS hi CD4 T cell population is associated with durable responses to vopratelimab alone and in combination with nivolumab.
The ICOS hi phenotype is induced in an antigen-specific manner through stimulation of the T cell receptor, and vopratelimab is only active on primed ICOS hi CD4 T cells.
The ICOS hi CD4 T cell population within peripheral blood of ICONIC responders is comprised of Th1, T central memory (Tcm) and T follicular helper (Tfh) subsets, which may be critical for direct anti-tumor effects as well as durability of clinical responses.
Retrospective flow analysis of publicly available mass cytometry data demonstrated ipilimumab or ipilimumab in combination with nivolumab induced enrichment of a robust Th1 but not Tcm or Tfh phenotypes within peripheral blood.
In a hCTLA-4 knock-in mouse model, preliminary assessment of anti-tumor efficacy demonstrated added activity when scheduled dosing of an ICOS agonist included administration following ICOS hi induction by ipilimumab.
In the ongoing EMERGE study, Jounce is testing the hypothesis that the addition of an ICOS agonist following ipilimumab-induction of ICOS hi CD4 T cells may enhance clinical benefit.
Both posters and audio presentations are available under "Publications" in the "Our Pipeline" section of the Jounce Therapeutics website at www.jouncetx.com.
About JTX-1811
JTX-1811 is a monoclonal antibody designed to selectively deplete immunosuppressive tumor-infiltrating T regulatory (TITR) cells. The target of JTX-1811 is CCR8, a chemokine receptor enriched on TITR cells. When JTX-1811 binds to CCR8, it targets TITR cells for depletion by enhanced antibody-dependent cellular cytotoxicity mechanism. Jounce expects to file an Investigational New Drug (IND) application in the first half of 2021.
About Vopratelimab
Jounce’s lead product candidate, vopratelimab, is 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 found in many solid tumors. Vopratelimab was previously assessed in the Phase 1/2 ICONIC trial and was found to have an acceptable safety profile and be well-tolerated, alone and in combination with each of the anti-PD-1 antibodies nivolumab and pembrolizumab, and ipilimumab, an antibody that binds to CTLA-4. Vopratelimab is currently being assessed in the Phase 2 EMERGE clinical trial in a sequenced combination with ipilimumab in patients with non-small cell lung cancer (NSCLC) who have progressed on or after both a platinum-based regimen and a PD-1 or PD-L1 inhibitor. Jounce is also planning to initiate the Phase 2 SELECT clinical trial of vopratelimab with its investigational PD-1 inhibitor, JTX-4014, in TISvopra biomarker-selected patients who are PD-1 inhibitor naïve in second line NSCLC.