On November 10, 2018 Jounce Therapeutics, Inc. (NASDAQ: JNCE), a clinical-stage company focused on the discovery and development of novel cancer immunotherapies and predictive biomarkers, reported that reverse translational and biomarker data derived from its ICONIC (ICOS AgONist Antibody for Immunotherapy in Cancer Patients) trial of JTX-2011 and preclinical data from the ICOS (Inducible T cell CO-Stimulator) program were presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 33rd Annual Meeting, being held November 9-11, 2018 in Washington, D.C (Press release, Jounce Therapeutics, NOV 10, 2018, View Source;p=RssLanding&cat=news&id=2376614 [SID1234531232]).
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"The data presented at SITC (Free SITC Whitepaper)’s 33rd Annual Meeting demonstrate the role of JTX-2011 in the emergence and agonism of ICOS hi CD4 T effector cells and provide further evidence in support of the biological and clinical activity of JTX-2011. The regimens we are advancing, including ongoing combinations with ipilimumab, are grounded in these important scientific findings," said Elizabeth Trehu, M.D., chief medical officer of Jounce Therapeutics. "New insights from our Translational Science Platform continue to inform JTX-2011 clinical development. We believe our science-based approach is necessary to develop new immunotherapies to benefit cancer patients."
Data presented from ICONIC patients demonstrate the agonistic properties of JTX-2011. These data are in addition to the subset analysis data presented at ASCO (Free ASCO Whitepaper) 2018 demonstrating the emergence of ICOS hi CD4 T cells in the bloodstream in all patients with ≥30% target lesion tumor reductions, both in patients treated with JTX-2011 monotherapy and in combination with nivolumab. The ICOS hi CD4 T cells were not observed in patients with primary progressive disease.
"Through additional reverse translational studies presented today, we established two key insights that provide the scientific foundation for the next stage of development of JTX-2011," said Richard Murray, Ph.D., chief executive officer and president of Jounce Therapeutics. "First, the emergence of these ICOS hi CD4 T cells was related to JTX-2011, as it has not been detected in a separate study we conducted of responding and non-responding patients that received PD-1/L1 inhibitor monotherapy treatment; and second, in vitro experimental data showed that JTX-2011 only activates CD4 T cells if they already express high levels of ICOS. Additionally, new preclinical tumor model data presented in a separate poster, strengthens our belief that agents that induce ICOS hi CD4 T cells detectable in the bloodstream, such as anti-CTLA-4, may be attractive combination partners for JTX-2011."
In a poster titled "Emergence of an ICOS hi CD4 T cell subset correlates with tumor reductions in subjects treated with the ICOS agonist antibody JTX-2011," Jounce researchers describe the reverse translational efforts ongoing in the ICONIC trial including:
Follow-up on the initial observation of the emergence of ICOS hi CD4 T cells. Emergence of this cell population, which correlated with clinical benefit in patients treated with both JTX-2011 monotherapy and in combination with nivolumab, was presented at ASCO (Free ASCO Whitepaper) in June 2018. These data build upon the initial observation and provides further characterization of the emerging cell population as T effector and not T regulatory cells and includes evidence that the cells do not emerge in patients responding to PD-1 monotherapy.
Additional in vitro data presented demonstrate that JTX-2011 alone induces a cytokine response from CD4 T cells, only if the T cells have pre-existing ICOS hi characteristics.
CTLA-4 inhibition has been shown to induce a population of ICOS hi cells in the bloodstream, while PD-1 inhibitors do not, and these observations further support the biological rationale for the ongoing clinical development of JTX-2011 in combination with ipilimumab.
In a poster titled "Inducible T cell Co-stimulator (ICOS) is upregulated on lymphocytes following radiation of tumors and ICOS agonism in combination with radiation results in enhanced tumor control," Jounce collaborators at the Earle A. Chile’s Research Institute, Providence Portland Medical Center, highlight the benefit of upregulation of ICOS in circulating and intra-tumoral T cells by radiation and its role in effective combination treatment with an ICOS agonist antibody to mediate tumor reduction. The data presented demonstrate:
The combination of radiation therapy and treatment with an ICOS agonist antibody led to increased anti-tumor response in an immunogenic mouse tumor model.
In a less immunogenic tumor model, response required the combination of ICOS agonist and PD-1 antagonist with radiation, suggesting again that ICOS agonism in combination with modalities that upregulate ICOS, such as with radiation, may represent an attractive regimen for combination immunotherapy of anti-PD-1 resistant tumors.
Both posters are available on the Investors and Media section of the Jounce Therapeutics website under "Presentations & Publications" at www.jouncetx.com.
About JTX-2011
Jounce’s lead product candidate, JTX-2011, is a monoclonal antibody that binds to and activates ICOS, a protein on the surface of certain T cells. Preclinical data support that JTX-2011 may have a dual mechanism of action that stimulates anti-tumor T effector cells, and also reduces the immunosuppressive T regulatory cells in the tumor microenvironment. The company is developing JTX-2011 to treat solid tumors as a single agent and in combination with other therapies.