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.
Amanda Hanson, Kutlu Elpek, Ellen Duong, Lindsey Shallberg, Martin Fan, Calvin Johnson, Matthew Wallace, George R. Mabry, Stephen Sazinsky, Lauren Pepper, Chengyi J. Shu, Sriram Sathyanarayanan, Sarah Zuerndorfer, Tyler Simpson, Monica Gostissa, Michael Briskin, Deborah Law, Jennifer Michaelson, Christopher J. Harvey. ICOS agonism by JTX-2011 (vopratelimab) requires initial T cell priming and Fc crosslinking for optimal T cell activation and antitumor immunity in preclinical models. Published PLOS ONE (September 2020).
Amanda Hanson, B.A., et. al. ICOS hi CD4 T cells emerging on vopratelimab treatment have Th1, central memory, and Tfh characteristics that may contribute to durability of clinical responses. Presented at AACR Virtual Annual Meeting, June 22, 2020.
Fabien Dépis, Ph.D., et. al. Preclinical evaluation of JTX-1811, an anti-CCR8 antibody with enhanced ADCC activity, for preferential depletion of tumor-infiltrating regulatory T cells. Presented at AACR Virtual Annual Meeting, June 22, 2020.
Timothy Anthony Yap, M.D., et. al. Association of a Predictive RNA Signature (RS) With Emergence of ICOS hi CD4 T Cells and Efficacy Outcomes for the ICOS Agonist Vopratelimab (vopra) and Nivolumab (nivo) in Patients (pts) on the ICONIC Trial. Presented at ASCO-SITC Clinical Immuno-Oncology Symposium, February 6, 2020.
Russell K. Pachynski, M.D., et al. Phase 2 Multicenter Trial of ICOS Agonist Vopratelimab and a CTLA-4 Inhibitor in PD-1/PD-L1 Inhibitor Experienced Adult Subjects with Non-Small Cell Lung Cancer or Urothelial Cancer (EMERGE). Presented at SITC Annual Meeting, November 9, 2019.
Kyriakos P. Papadopoulos, M.D., et al. Phase 1 First in Human Study of Programmed Cell Death Receptor-1(PD-1) Inhibitor Monoclonal Antibody (mAb) JTX-4014 in Adult Subjects with Advanced Refractory Solid Tumor Malignancies. Presented at SITC Annual Meeting, November 8, 2019.
Chang-Ai Xu, Andrew Z. Feng, Charan K. Ramineni, Matthew R. Wallace, Elizabeth K. Culyba, Kevin P. Guay, Kinjal Mehta, Robert Mabry, Stephen Farrand, Jin Xu & Jianwen Feng. L445P mutation on heavy chain stabilizes IgG4 under acidic conditions. Published in mAbs (June 2019).
Timothy A. Yap, MBBS, PhD, MRCP, BS., et al. Improved Progression-Free and Overall Survival (PFS/OS) in Patients (pts) with Emergence of JTX-2011 (vopratelimab) Associated Biomarker (ICOS high CD4 T cells) on the ICONIC Trial. Presented at AACR Annual Meeting, April 2, 2019.
Christopher Harvey Ph.D., et al. Genetic and Molecular Profiling of ICOS hi CD4 T Cells Demonstrates Clonal Expansion of Th1 Effector Cells Following Vopratelimab (JTX-2011) Treatment in Subjects With Solid Tumors. Presented at AACR Annual Meeting, April 2, 2019.
Elizabeth Trehu, M.D., FACP. Lessons Learned from a Clinical Trial Targeting ICOS. Presented at the Keystone Symposia on Cancer Immunotherapy: Mechanistic Insights to Improve Clinical Benefit, March 12, 2019.
Amanda Hanson, et al. Emergence of an ICOS hi CD4 T cell subset correlates with tumor reductions in subjects treated with the ICOS agonist antibody JTX-2011. Presented at SITC Annual Meeting, November 10, 2018.
Michael J. Gough Ph.D. 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. Presented at SITC Annual Meeting, November 9, 2018.
Timothy A. Yap, MBBS, PhD, MRCP, BS. ICONIC: Biologic and clinical activity of first in class ICOS agonist antibody JTX-2011 +/- nivolumab (nivo) in patients (pts) with advanced cancers. Presented at ASCO Annual Meeting, June 2, 2018.
Heather A. Hirsch, Ph.D., et al. Integrated genomics and histology based studies of triple negative breast cancer identify ICOS as potential target for therapeutic intervention. Presented at AACR Annual Meeting, April 16, 2018.
Spencer C. Wei, Jacob H. Levine, Alexandria P. Cogdill, Yang Zhao, Nana-Ama A.S. Anang, Miles C. Andrews, Padmanee Sharma, Jing Wang, Jennifer A. Wargo, Dana Pe’er, and James P. Allison. Distinct Cellular Mechanisms Underlie Anti-CTLA-4 and Anti-PD-1 Checkpoint Blockade. Published in Cell (August 2017).
Howard A. Burris, MD. Phase 1 Safety of ICOS Agonist Antibody JTX-2011 Alone and with Nivolumab (nivo) in Advanced Solid Tumors; Predicted vs Observed Pharmacokinetics (PK) in ICONIC. Presented at the ASCO Annual Meeting, June 5, 2017.
Our lead product candidate, vopratelimab, is a monoclonal antibody that binds to and activates the Inducible T cell CO–Stimulator (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:
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 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.
JTX-8064 is an anti-Leukocyte Immunoglobulin Like Receptor B2 (LILRB2) 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.
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. 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.
On September 1, 2020, Gilead Sciences and Jounce Therapeutics announced 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.”
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.