Jounce Therapeutics Presents INNATE Phase 1 and SELECT Clinical Trial data at the European Society of Medical Oncology Immuno-Oncology (ESMO - IO) Annual Congress

Jounce Therapeutics, Inc.
Jounce Therapeutics, Inc.

- INNATE trial Phase 1 dose escalation data showed JTX-8064 was well-tolerated as a single agent and in combination with pimivalimab (pimi) -

- Patient with advanced biliary tract cancer who failed multiple lines of prior treatment including a PD-1 inhibitor showed a durable partial response with combination treatment -

- SELECT randomized Phase 2 trial data showed encouraging trends in the low dose vopratelimab (vopra) arm in combination with pimi compared to pimi alone -

- Shorter duration of target engagement with vopra 0.03 mg/kg may avoid T cell exhaustion from agonist stimulation, leading to clinical benefit -

CAMBRIDGE, Mass., Dec. 08, 2022 (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 clinical data from the INNATE trial with JTX-8064 and pimi and the SELECT trial with vopra and pimi in two poster presentations at the ESMO-IO 2022 Annual Congress being held in Geneva, Switzerland.

JTX-8064 is a highly selective and potent inhibitor of myeloid-specific Leukocyte Immunoglobulin Like Receptor B2 (LILRB2, also known as ILT4) with the potential to reverse PD-(L)1 inhibitor resistance. JTX-8064 is being studied in the INNATE trial (NCT04669899), a Phase 1/2 dose escalation/expansion trial of two investigational agents, JTX-8064 monotherapy (mono) and combination (combo) with pimi, Jounce’s investigational PD-1 inhibitor. Vopra is an inducible T cell costimulator (ICOS) agonist monoclonal antibody that stimulates CD4 T cells and may amplify anti-tumor activity. The SELECT trial is a randomized Phase 2 trial of vopra combined with pimi versus pimi monotherapy in TISvopra biomarker selected, immunotherapy naïve, 2nd line non-small cell lung cancer (NSCLC) patients.

In the poster titled “Phase 1 Study of JTX-8064, a LILRB2 (ILT4) inhibitor, as monotherapy and combination with pimivalimab (pimi), a PD-1 inhibitor (PD-1i), in patients (pts) with advanced solid tumors” Phase 1 data defining the recommended Phase 2 dose (RP2D) were presented. Patients with advanced solid tumors who progressed after all available therapy were treated at seven dose levels of JTX-8064 mono and two dose levels of JTX-8064 plus pimi 500 mg q3w using a Bayesian design. The study’s primary objectives are safety and determination of the RP2D. Secondary objectives are pharmacokinetics (PK), receptor occupancy (RO), and immunogenicity, and exploratory objectives include evaluation of anti-tumor activity including objective response rate (ORR) by RECIST 1.1 criteria.

Thirty-one patients were treated in dose escalation, 22 JTX-8064 mono, and nine JTX-8064 plus pimi. There were no dose limiting toxicities and maximum tolerated dose was not reached. Eleven monotherapy patients (50%) and six combination patients (66.7%) had treatment-related adverse events (TRAE), most of which were Grade 1 or 2, and there was only one serious TRAE, a tumor flare in the 1200 mg mono cohort. PK was linear. Full RO through 21 days was achieved at ≥ 300 mg resulting in selection of an RP2D of 700 mg q3w for JTX-8064 +/- pimi. Phase 1 efficacy data in the mono cohort (n=22): zero partial response (PR), seven (35%) stable disease (SD) including two durable SD (appendiceal cancer 8.3, ovarian cancer 12.2 months). Phase 1 efficacy data in the combo cohort (n=9): one confirmed PR (6.2 months) at 700 mg in a PD-1i resistant cholangiocarcinoma patient (PD-L1 score of 0) and resolution of both bone pain and cachexia, three (33%) SD with one durable SD of 6 months (PD-1i resistant NSCLC). Enrollment into multiple expansion cohorts is ongoing.

A poster titled “SELECT: A phase II randomized trial evaluating 2 doses of vopratelimab (V) + pimivalimab (P) vs P in TISvopra selected patients (pts)” of the vopra plus pimi SELECT trial included an update to data previously announced on clinical endpoints, including additional durability data for patients who remain on study. SELECT is a randomized Phase 2 trial (NCT04549025) evaluating vopra, Jounce’s ICOS agonist, in combination with pimi versus pimi alone in 69 immunotherapy naïve, second line, non-small cell lung cancer patients. Two hypotheses were tested in the study. First, two different doses were examined, both intended to result in different levels of pulsatile target engagement, which may optimize the dose of an agonist by reducing T cell exhaustion. Second, all patients in the study were selected by TISvopra, an 18 gene RNA tumor inflammation signature, previously associated with improved clinical outcomes in patients treated with vopra +/- nivolumab. Sixty nine (n=69) TISvopra positive patients with metastatic NSCLC after one prior platinum-containing regimen were randomized 2:1:1 to pimi monotherapy 1000 mg (n=36), vopra 0.1 mg/kg (n=18) plus pimi or vopra 0.03 mg/kg (n=15) q6w plus pimi.

Both doses of vopra demonstrated distinct patterns of pulsatile target engagement while vopra 0.03 mg/kg achieved a shorter duration of target engagement and a meaningful rest period from receptor saturation and signaling was observed. The low dose vopra combination trended favorably for the primary endpoint (percent change from baseline of all measurable lesions averaged over 9 and 18 weeks), ORR, and progression free survival (PFS). ORR was 40% (95% confidence intervals [CI]16.34, 67.71) for low dose vopra combination cohort, 27.8% (CI 14.20, 45.19) for pimi alone, and 16.7% (CI 3.58, 41.42) for high dose vopra combination cohort. Six month landmark PFS was 80% (CI 50, 93) for low dose vopra combination, 36% (CI 20, 53) for pimi monotherapy, and 31% (CI 11, 52) for high dose vopra combination. Benchmarks for approved PD-1 inhibitors in second line IO naïve NSCLC are ORR 18-20% and 6 month landmark PFS 30-38%. PD-L1 was evenly distributed across TISvopra patients and not associated with efficacy, suggesting TISvopra may select for patients who respond independent of PD-L1. Study treatment was well tolerated with 7.2% of patients reporting Grade ≥3 TRAEs. Most common TRAEs were Grade 1/2 hyperthyroidism and hypothyroidism.

Preclinical data demonstrating that a shorter period of target engagement with vopra in vitro stimulates T cells without the exhaustion seen with longer treatment was also summarized in the poster. This data provides a scientific rationale that clinical outcomes obtained with lower doses of vopra may be improved relative to doses that result in continuous target engagement, as the SELECT clinical data suggests. Jounce plans to pursue a partnership to enable further development of vopra 0.03 mg/kg in combination with a PD-1 inhibitor.

The posters will be available on the “Our Pipeline” section of the Jounce Therapeutics website after presentation at www.jouncetx.com.

About JTX-8064

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 1/2 clinical trial named INNATE (NCT04669899) of JTX-8064 as a monotherapy and in combination with Jounce’s internal anti-PD-1 inhibitor, pimivalimab (formerly JTX-4014) is currently enrolling patients with advanced solid tumors.

About Vopratelimab

Vopratelimab is a clinical-stage monoclonal antibody that binds to and activates ICOS, the Inducible T cell CO-Stimulator, a protein on the surface of certain T cells commonly found in many solid tumors. Vopratelimab is being assessed in the SELECT Phase 2 clinical trial (NCT04549025) in combination with Jounce’s internal investigational PD-1 inhibitor, pimivalimab (formerly JTX-4014), compared to pimivalimab alone. The SELECT trial completed enrollment of 69 immunotherapy naïve NSCLC patients who have been pre-selected with the TISvopra predictive biomarker, an 18 gene RNA tumor inflammation signature which predicted the emergence of ICOS hi CD4 T cells and clinical benefit in the ICONIC trial of vopratelimab alone and in combination with a PD-1 inhibitor.

About Pimivalimab

Pimivalimab (formerly JTX-4014) is a well-characterized fully human IgG4 monoclonal antibody designed to block binding to PD-L1 and PD-L2. Pimivalimab demonstrated a 17% durable overall response rate in a Phase 1 trial of 18 heavily pre-treated PD-(L)1 inhibitor naïve patients, which excluded all tumor types for which PD-(L)1 inhibitors were approved. In this Phase 1 trial, pimivalimab was shown to have an acceptable safety profile. Pimivalimab is currently being assessed in the INNATE Phase 1/2 trial (NCT04669899) in combination with JTX-8064, a LILRB2 (ILT4) inhibitor. Pimivalimab is also being assessed in the SELECT Phase 2 clinical trial (NCT04549025) in combination with vopratelimab.

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 may 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. JTX-8064 is currently being investigated alone and in combination with pimivalimab (formerly JTX-4014), Jounce’s internal PD-1 inhibitor, in one monotherapy and eight indication-specific combination therapy cohorts in the Phase 1/2 INNATE trial and is currently enrolling patients with advanced solid tumors in the Phase 2 portion of the study. 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. Pimivalimab 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 GS-1811 (formerly 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 plans to pursue a partnership to enable further development of vopratelimab in combination with a PD-1 inhibitor 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,” 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, Jounce’s ability to successfully demonstrate the efficacy and safety of its product candidates the preclinical and clinical results for its product candidates, which may not support further development and marketing approval; whether interim results or past results from a clinical trial will be predictive of the final results of the trial or the results of future trials; the potential advantages of Jounce’s product candidates; Jounce’s ability to establish and maintain a partnership on favorable terms, if at all and the success of any such partnership that Jounce enters into; 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 Contact:
Eric Laub
Jounce Therapeutics, Inc.
+1-857-259-3853
elaub@jouncetx.com