PIPELINE

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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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Publications

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.

CLINICAL PROGRAMS AND PROGRESS

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VOPRATELIMAB

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 fully realizing the biology of the ICOS hi CD4 T cells and their proliferation and sustained activation by vopratelimab.

SELECT: The trial 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 October 2020, we initiated the new Phase 2 predictive biomarker trial, called SELECT, which studies vopratelimab in combination with our investigational PD-1 inhibitor, JTX-4014 in RNA signature selected patients.

Patients and physicans interested in the Phase 2 SELECT trial can contact SELECT@jouncetx.com.  For more information on this trial, please visit https://clinicaltrials.gov (Identifier: NCT04549025).

Vopratelimab was also assessed in our ICONIC and EMERGE trials and was found to be safe and well-tolerated, both alone and in combination with nivolumab, an anti-PD-1 inhibitor or ipilimumab, an anti-CTLA-4 inhibitor. 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

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.

JTX-8064

JTX-8064 is an anti-Leukocyte Immunoglobulin Like Receptor B2 (LILRB2)/ILT4 antibody and is the first tumor-associated macrophage candidate to emerge from Jounce’s Translational Science Platform. Preclinical data presented at the 2019 American Association for Cancer Research (AACR) Annual Meeting supports the development of JTX-8064 as a novel immunotherapy to reprogram immune-suppressive macrophages and enhance anti-tumor immunity.

JTX-1811

The next development candidate to emerge from our Translational Science Platform is JTX-1811, a monoclonal antibody designed to selectively deplete immuno-suppressive tumor-infiltrating T regulatory (TITR) cells. Targeting T regs may play an important role in addressing the growing unmet need in cancer patients as T regs diminish productive immune responses. 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.

In October 2020, Gilead Sciences and Jounce Therapeutics closed the transaction, including an exclusive license agreement for our novel immunotherapy program, JTX-1811. “Gilead’s investment in Jounce and, specifically, JTX-1811 reinforces the value of our Translational Science Platform and differentiated and sustainable approach to novel immuno-oncology programs, focused on patients with cancer who have yet to benefit from immunotherapy. We look forward to seeing JTX-1811 progress to the clinic,” said Richard Murray, PhD, Chief Executive Officer and President of Jounce Therapeutics. “Our mission to deliver the right immunotherapy to the right patient population for meaningful and long-lasting benefit remains at the core of our discovery and clinical development work. Our JTX-1811 program is a prime example of these efforts.”

INNOVATIVE AND SUSTAINABLE DISCOVERY PIPELINE

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.