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By integrating clinical insights into each aspect of the drug development process, Jounce is discovering and developing immunotherapy programs that target multiple immune cell types.

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ICOS Agonist Program – Vopratelimab

Our lead product candidate, vopratelimab, is a monoclonal antibody that binds to and activates the Inducible T cell COStimulator (ICOS), a protein on the surface of certain T cells that we believe can stimulate an immune response against cancerous cells. The development of vopratelimab stems from insights generated by our founders, Drs. Jim Allison and Padmanee (Pam) Sharma, that showed that induction of ICOS hi CD4 T cells is correlated with positive clinical outcomes in patients treated with ipilimumab. Based on these insights and additional preclinical evidence, we have accomplished the following to date:

  • Discovered an agonist monoclonal antibody clinical candidate, vopratelimab;
  • Demonstrated an acceptable safety profile of vopratelimab alone and in combination with each of nivolumab, pembrolizumab and ipilimumab;
  • Identified an on-mechanism, treatment emergent, pharmacodynamic biomarker, ICOS hi CD4 T cells in the peripheral blood, that is associated with clinical benefit in patients treated with vopratelimab monotherapy and in combination with nivolumab;
  • Demonstrated that ICOS hi CD4 T cell emergence is caused by vopratelimab and not PD-1/PD-L1 inhibition;
  • Identified a baseline RNA signature that is a potential predictive biomarker for both ICOS hi CD4 T cell emergence and clinical benefit; and
  • Gained important insights into optimal dose and sequencing schedule for our immune agonist.


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Vopratelimab is intended to treat solid tumors as a single agent and in combination with other therapies.

Based on extensive reverse translational analysis from our Phase 1/2 ICONIC trial, we are focusing on two development paths for the vopratelimab program. Both development paths are focused on fully realizing the biology of the ICOS hi CD4 T cells and their proliferation and sustained activation by vopratelimab.

EMERGE: The first development path focuses on induction of ICOS hi CD4 T cells prior to administration of vopratelimab. Based on this biology, we initiated the Phase 2 EMERGE trial of vopratelimab in combination with ipilimumab in June 2019. The EMERGE trial is an open-label, multi-center study to evaluate the efficacy of vopratelimab in combination with ipilimumab in patients with non-small cell lung carcinoma (NSCLC) and urothelial cancer and applies a unique dosing and sequencing schedule of the vopratelimab and ipilimumab combination.

Patients and physicians interested in the Phase 2 EMERGE trial can contact EMERGE@jouncetx.com. For more information on this trial, please visit https://clinicaltrials.gov (Identifier: NCT03989362).

SELECT: The second development path focuses on the use of a predictive biomarker for patient selection. In the analysis of ICONIC patients, we identified a biomarker that is an RNA signature from baseline tumor samples that correlated with the emergence of ICOS hi CD4 T cells, overall response rate (ORR), and overall survival (OS), in patients treated with vopratelimab alone or in combination with nivolumab. In 2020, we plan to initiate the new Phase 2 predictive biomarker trial, called SELECT, which will study vopratelimab in combination with our investigational PD-1 inhibitor, JTX-4014 in RNA signature selected patients.

Vopratelimab was also assessed in our ICONIC trial and was found to be safe and well-tolerated, both alone and in combination with nivolumab, an anti-PD-1 antibody. In a subset analysis, patients in the ICONIC trial with emergence of ICOS hi CD4 T cells demonstrated improved response rate, progression free survival (PFS) and overall survival (OS) compared to patients with ICOS lo CD4 T cells. The Phase 1 portion of ICONIC also established the safety of vopratelimab in combination with nivolumab, in combination with ipilimumab and in combination with pembrolizumab.


JTX-4014, our PD-1 inhibitor, is a Phase 2 ready asset to be used in combination with our current and future development candidates. The first Phase 2 trial with JTX-4014 is the SELECT trial in combination with vopratelimab in biomarker-selected patients. JTX-4014 is a well-characterized, fully human IgG4 monoclonal antibody designed to block binding to PD-L1 and PD-L2.


The next development candidate to emerge from our Translational Science Platform is JTX-1811, a monoclonal antibody designed to deplete T regulatory cells (T regs) in the TME. Targeting T regs may play an important role in addressing the growing unmet need in cancer patients as T regs diminish productive immune responses. Given the profile of the target and related preclinical data in a PD-1 inhibitor resistant setting, we believe this program may have the potential to benefit patients not currently being served by today’s immunotherapies. JTX-1811 is currently in IND-enabling activities and we anticipate filing an IND and initiating a Phase 1 clinical trial for JTX-1811 in 2021.


Currently approved immunotherapy treatments have primarily focused on activating T cells within tumors, an approach that has successfully led to therapies that are making a difference in patients’ lives. However, many patients still do not respond to these treatments.

We believe that the ability to target different cell types in the TME, such as innate immune cells and stromal cells, may allow us to pursue tumor types not currently served by therapies which target adaptive immune cells, as well as potentially convert the TME from an immunosuppressive environment to an immune-activating environment. We believe our differentiated approach to understanding and interrogating these other immune cell types favorably positions us to exploit the promise of immunotherapy in cancer.

Based on our translational approach, we have characterized a large number of human tumors in which the innate immune or stromal mechanisms may be suppressing or repelling the immune system within the TME. With this hypothesis, we have strived to create a broad pipeline consisting of assets focused on multiple immune cell types including T regs, macrophages and stromal cells, in order to optimize the use of the immune system, coupled with patient selection strategies.


license agreement with celgene

In July 2019 we entered into an exclusive license agreement with Celgene. Under the terms of this agreement, Celgene has licensed the worldwide rights to JTX-8064, a highly-selective, potential first-in-class antibody that targets the LILRB2 receptor on immunosuppressive macrophages. JTX-8064 was discovered and developed using our Translational Science Platform. This out-license validates our approach and demonstrates our ability to efficiently and effectively discover targets and advance them toward development.

Jounce Therapeutics Announces Update on Strategic Collaboration with Celgene Corporation