-Translational analysis of patients that do not respond to PD-(L)1 inhibitors show high pretreatment intratumoral LILRB2 expression relative to an IFNγ gene signature-
- JTX-8064’s mechanism of action to reprogram macrophages can bridge innate immune cell activity to T cell adaptive immunity in preclinical models-
CAMBRIDGE, Mass., April 10, 2021 (GLOBE NEWSWIRE) -- Jounce Therapeutics, Inc. (NASDAQ: JNCE), a clinical-stage company focused on the discovery and development of novel cancer immunotherapies and predictive biomarkers, today reported new preclinical data on JTX-8064, the first tumor-associated macrophage program from their Translational Science Platform, at the 2021 American Association for Cancer Research (AACR) Virtual Annual Meeting being held April 10-15, 2021. The poster presentation includes data showing a high Leukocyte Immunoglobulin Like Receptor B2 (LILRB2) to interferon gamma (IFNγ) ratio is associated with resistance to PD-(L)1 inhibitor treatment in humans, JTX-8064’s ability to bridge innate and adaptive immunity, and how Jounce’s Translational Science Platform informed indication selection for the Phase 1 INNATE trial.
“The translational analyses presented at AACR link JTX-8064’s mechanism to tumor types that may respond better to LILRB2 inhibition,” said Elizabeth Trehu, M.D., chief medical officer of Jounce Therapeutics. “The Phase 1 INNATE trial is designed to move as quickly as possible to proof of concept and this new data enabled the prioritization of tumor-specific expansion cohorts, which are on track to start enrolling in the second half of 2021. Furthermore, the negative prognostic implications of a high LILRB2 to IFNγ ratio support the role of LILRB2 in resistance to PD-(L)1 inhibitors and highlight the potential for JTX-8064 to reverse this resistance.”
In a poster titled “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” Jounce demonstrated:
- JTX-8064 can induce T cell activation in co-culture with macrophages, demonstrating its potential to bridge the gap between innate and adaptive immune responses;
- CD163+ M2 macrophages co-localize with T cells in the tumor microenvironment, and patients with high levels of LILRB2 or a proprietary tumor-associated macrophage (TAM) signature score relative to an IFNγ signature score are less responsive to PD-(L)1 inhibitors, providing evidence that LILRB2+ macrophages may be involved in mechanisms of primary resistance to PD-(L)1 inhibitors; and
- Expression profiles of LILRB2 mRNA, TAM signatures, and other inflammatory cell signatures were used to identify tumor types that may benefit most from JTX-8064 treatment and used to inform indication selection for expansion cohorts of the Phase 1 INNATE trial.
The poster is available on the “Our Pipeline” section of the Jounce Therapeutics website at www.jouncetx.com.
JTX-8064 is a humanized IgG4 monoclonal antibody designed to specifically bind to Leukocyte Immunoglobulin Like Receptor B2 (LILRB2/ILT4) and block interactions with its ligands. JTX-8064 is the first tumor-associated macrophage candidate developed from Jounce’s Translational Science Platform. Preclinical data presented at the 2020 Society for Immunotherapy of Cancer’s Annual Meeting and the 2019 and 2021 American Association for Cancer Research Annual Meetings support the development of JTX-8064 as a novel immunotherapy to reprogram immune-suppressive macrophages and enhance anti-tumor immunity. A Phase 1 clinical trial named INNATE (NCT04669899), of JTX-8064 as a monotherapy and in combination with either JTX-4014, or pembrolizumab, is currently enrolling patients with advanced solid tumors.
About Jounce Therapeutics
Jounce Therapeutics, Inc. is a clinical-stage immunotherapy company dedicated to transforming the treatment of cancer by developing therapies that enable the immune system to attack tumors and provide long-lasting benefits to patients through a biomarker-driven approach. Jounce currently has multiple development stage programs ongoing while simultaneously advancing additional early-stage assets from its robust discovery engine based on its Translational Science Platform. Jounce’s highest priority program, JTX-8064, is a LILRB2 (ILT4) receptor antagonist shown to reprogram immune-suppressive tumor associated macrophages to an anti-tumor state in preclinical studies. A Phase 1 clinical trial, named INNATE, of JTX-8064 as a monotherapy and in combination with JTX-4014, Jounce’s internal PD-1 inhibitor, or pembrolizumab is currently enrolling patients with advanced solid tumors. Jounce’s most advanced product candidate, vopratelimab, is a monoclonal antibody that binds to and activates ICOS, and is currently being studied in the SELECT Phase 2 trial. JTX-4014 is a PD-1 inhibitor intended for combination use in the INNATE and SELECT trials and with Jounce’s broader pipeline. Additionally, Jounce exclusively licensed worldwide rights to JTX-1811, a monoclonal antibody targeting CCR8 and designed to selectively deplete T regulatory cells in the tumor microenvironment, to Gilead Sciences, Inc. For more information, please visit www.jouncetx.com.
Cautionary Note Regarding Forward-Looking Statements:
Various statements in this release concerning Jounce’s future expectations, plans and prospects, including without limitation, Jounce’s expectations regarding the timing, progress and results of preclinical studies and clinical trials of JTX-8064; commencement of indication-specific expansion cohorts of Jounce’s INNATE clinical trial; the use of JTX-4014 in combination with Jounce’s other product candidates; may constitute forward-looking statements for the purposes of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995 and other federal securities laws and are subject to substantial risks, uncertainties and assumptions. You should not place reliance on these forward-looking statements, which often include words such as “expect,” “plan,” “potential,” “will” or similar terms, variations of such terms or the negative of those terms. Although Jounce believes that the expectations reflected in the forward-looking statements are reasonable, Jounce cannot guarantee such outcomes. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including, without limitation, risks that the COVID-19 pandemic may disrupt Jounce’s business and/or the global healthcare system more severely than anticipated, which may have the effect of delaying enrollment and completion of Jounce’s clinical trials, or delaying timelines and regulatory submissions for its product candidates; Jounce’s ability to successfully demonstrate the efficacy and safety of its product candidates and future product candidates; the preclinical and clinical results for its product candidates, which may not support further development and marketing approval; the potential advantages of Jounce’s product candidates; Jounce’s ability to successfully manage its clinical trials; the development plans of its product candidates and any companion or complementary diagnostics; actions of regulatory agencies, which may affect the initiation, timing and progress of preclinical studies and clinical trials of Jounce’s product candidates; Jounce’s ability to obtain, maintain and protect its intellectual property; Jounce’s ability to manage operating expenses and capital expenditures; and those risks more fully discussed in the section entitled “Risk Factors” in Jounce’s most recent Annual Report on Form 10-K filed with the Securities and Exchange Commission as well as discussions of potential risks, uncertainties, and other important factors in Jounce’s subsequent filings with the Securities and Exchange Commission. All such statements speak only as of the date made, and Jounce undertakes no obligation to update or revise publicly any forward-looking statements, whether as a result of new information, future events or otherwise.
Investor and Media Contacts:
Jounce Therapeutics, Inc.
Jounce Therapeutics, Inc.