Jounce Therapeutics Presents First Preclinical Data on Anti-CCR8 Antibody JTX-1811 and Vopratelimab Translational Data at The American Association for Cancer Research Virtual Annual Meeting
- Preclinical data supports the development of JTX-1811, targeting CCR8, as a novel immunotherapy for the selective depletion of immunosuppressive tumor-infiltrating T-regulatory cells -
- Translational data expand on scientific rationale for both ongoing EMERGE Phase 2 trial and upcoming SELECT trial -
“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
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
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.
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.
Cautionary Note Regarding Forward-Looking Statements
Various statements in this release concerning Jounce’s future expectations, plans and prospects, including without limitation, Jounce’s expectations regarding the timing, progress and results of the EMERGE and SELECT clinical trials may constitute forward-looking statements for the purposes of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995 and other federal securities laws and are subject to substantial risks, uncertainties and assumptions. You should not place reliance on these forward-looking statements, which often include words such as “expects,” “plan,” “potential” or similar terms, variations of such terms or the negative of those terms. Although Jounce believes that the expectations reflected in the forward-looking statements are reasonable, Jounce cannot guarantee such outcomes. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including, without limitation, Jounce’s ability to successfully demonstrate the efficacy and safety of its product candidates; the clinical results for its product candidates, which may not support further development and marketing approval; Jounce’s ability to enroll patients in its clinical trials; the potential advantages of Jounce’s product candidates; the development plans of its product candidates and any companion or complementary diagnostics; actions of regulatory agencies, which may affect the initiation, timing and progress of preclinical studies and clinical trials of Jounce’s product candidates; and those risks more fully discussed in the section entitled “Risk Factors” in Jounce’s most recent Annual Report on Form 10-K filed with the
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