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.
Kyriakos P. Papadopoulos, MD, et al. Phase 1, First-in-Human trial of JTX-8064, an anti-LILRB2/ILT4 monoclonal antibody, as monotherapy and in combination with anti-PD-1 in adult patients with advanced solid (INNATE). Presented at the ASCO Annual Meeting, June 2021.
Oleh Kobziev, MD, et al. Phase 2 Study of PD-1 Inhibitor JTX-4014 (Pimivalimab) Alone and in Combination with Vopratelimab, an ICOS Agonist, in Biomarker-selected Subjects with Metastatic NSCLC After One Prior Platinum-containing Regimen (SELECT). Presented at the ASCO Annual Meeting, June 2021.
Lara McGrath, Ph.D., et. al. Tumor Associated Macrophages and Resistance to Immune Checkpoint Blockade: Consideration of Cancer Indications for the Clinical Development of JTX-8064, an anti-LILRB2/ILT4 Monoclonal Antibody. Presented at the AACR Annual Meeting, April 2021.
Yasmin Hashambhoy-Ramsay, Ph.D., et. al. Evaluating Biomarkers of JTX 8064 (anti LILRB2/ILT4 monoclonal antibody) in an Ex Vivo Human Tumor Histoculture System to Inform Clinical Development. Presented at the SITC Annual Meeting, November 2020.
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.
JTX-8064, our highest priority and lead macrophage program, 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. JTX-8064 aims to convert immunosuppressive macrophages to an anti-tumor state and to create a bridge between the innate and T cell arm of the immune system.
INNATE: The Phase 1/2 trial is designed to rapidly demonstrate proof of concept for JTX-8064 as a monotherapy and in combination with pimivalimab (Jounce’s proprietary PD-1 inhibitor) in patients with advanced refractory solid tumors. Trial initiation began January 2021 with monotherapy dose escalation which completed in July followed by an ovarian cancer monotherapy expansion cohort initiation in August 2021. JTX-8064 in combination with Pimivalimab (Jounce’s proprietary PD(L)-1i) dose escalation study completed in October followed by the initiation of 7 tumor specific combination expansion cohorts. These tumor-specific expansion cohorts were identified based on biology, unmet need, differentiation from other LILRB2 inhibitors and consideration of PD-1 or PD-(L)1 inhibitor sensitivity and resistance.
Pimivalimab, our PD-1 inhibitor, is a Phase 2 asset to be used in combination with our current and future development candidates. The first Phase 2 trial with pimivalimab is the SELECT trial in combination with vopratelimab in biomarker-selected patients, and pimivalimab is also being used in the INNATE Phase 1/2 trial in combination with JTX-8064. Pimivalimab is a well-characterized, fully human IgG4 monoclonal antibody designed to block binding to PD-L1 and PD-L2.
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 that showed that induction of ICOS hi CD4 T cells is correlated with positive clinical outcomes in patients treated with ipilimumab. 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 SELECT 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, pimivalimab in RNA signature selected patients.
In October 2020, Gilead Sciences and Jounce established an exclusive license agreement for our novel immunotherapy program, GS-1811, formerly known as JTX-1811. GS-1811 is a monoclonal antibody designed to selectively deplete immuno-suppressive tumor-infiltrating T regulatory (TITR) cells. The target of GS-1811 is CCR8, a chemokine receptor enriched on TITR cells. When GS-1811 binds to CCR8, it targets TITR cells for depletion by enhanced antibody-dependent cellular cytotoxicity. Jounce managed development of GS-1811 through IND clearance, and it is now being solely developed by Gilead.
Jounce Therapeutics, Inc. does not currently accept or grant requests for expanded access to any of its investigational therapies outside of clinical trials. To learn more about our ongoing clinical trials, please see the “Clinical Programs and Progress” section under “Our Pipeline” on our website.
This Expanded Access Policy applies generally to all investigational therapies manufactured or distributed by Jounce for use in the treatment of cancer or any other serious disease or condition.
21st Century Cures Act:
The 21st Century Cures Act asks manufacturers of investigational therapies, like Jounce, to publicly post our policy on evaluating and responding to requests submitted for expanded access under section 561(b) of the US Federal Food, Drug, and Cosmetic Act.
At such time as Jounce begins to make expanded access to any of our investigational therapies available, this website and policy will be updated to notify the public of the procedures for making expanded access requests and our criteria for evaluating such requests.
Additional questions may be directed to (857) 320-2558 Jounce typically responds to inquiries about our Expanded Access Policy within two (2) working days.
JTX-1484 is an anti-Leukocyte Immunoglobulin Like Receptor B4 (LILRB4)/ILT3 antibody and is the first myeloid candidate to emerge from Jounce’s Translational Science Platform. LILRB4 is expressed on immunosuppressive myeloid cells in the tumor micro-environment, or TME. We believe JTX-1484 is potent and specific blocker of human LILRB4 with potentially favorable PK and pre-clinical safety profile. Blocking LILRB4 in the TME may lead to reduced immune suppression and enhancement of T cell functionality, either as monotherapy or in combination with T cell checkpoint inhibitors.
Jounce’s Translational Science Platform creates sustained value through a robust discovery engine. 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. Our discovery engine aims to match the right therapy to the right patients through a biomarker driven approach.
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.