vopratelimab (JTX-2011) / Concentra Biosci - LARVOL DELTA

CD28 and ICOS in immune regulation: Structural insights and therapeutic targeting. (PubMed, Bioorg Med Chem Lett) - "Key therapeutic approaches include CTLA-4-Ig fusion proteins (abatacept, belatacept) for autoimmune diseases, ICOS agonists (feladilimab, vopratelimab) to enhance anti-tumor immunity, and bispecific CD28-engaging antibodies (CD28xCD3, CD28xPSMA) for cancer immunotherapy. By integrating structural insights with translational drug development, this review provides a framework for optimizing CD28- and ICOS-targeted therapies. Further advancements in biologics, peptide-based inhibitors, and immune checkpoint modulation will enhance the precision and efficacy of immunotherapeutic strategies."

Journal • Review • Immunology • Oncology • CTLA4 • ICOS

Vopratelimab (JTX-2011) Alone and in Combination With Anti-Programmed Cell Death Protein 1 (PD-1) or Anti-Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) in Subjects With Advanced and/or Refractory Solid Tumors (clinicaltrials.gov) - P1/2 | N=4 | Terminated | Sponsor: Jounce Therapeutics, Inc. | Completed ➔ Terminated; Sponsor decision to discontinue providing study drug to patients who have been on study treatment for more than two years

Combination therapy • Metastases • Trial termination • Oncology • Solid Tumor

Study of PD-1 Inhibitor JTX-4014 Alone and in Combination With Vopratelimab in Biomarker-selected Subjects With Metastatic NSCLC After One Prior Platinum-containing Regimen (clinicaltrials.gov) - P2 | N=69 | Terminated | Sponsor: Jounce Therapeutics, Inc. | Active, not recruiting ➔ Terminated; The Sponsor decided to discontinue development of pimivalimab prior to the planned study completion. At the time of the decision to discontinue development, enrollment in the study had been completed.

Trial termination • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

ICOS Agonist Vopratelimab Modulates Follicular Helper T Cells andImproves B Cell Function in Common Variable Immunodeficiency (CIS 2024) - "Our datademonstrate the potential of TFH modulation in restoring TFH andenhancing B cell maturation in CVID. The effects of an ICOS agonist inprimary antibody defects warrants further investigation; this biologic mayalso be of therapeutic interest in other clinical settings of antibodydeficiency."

IO biomarker • Late-breaking abstract • Primary Immunodeficiency • CD27 • CD4 • ICOS • IL10 • IL21 • IL4

ICOS agonist vopratelimab modulates follicular helper T cells and improves B cell function in common variable immunodeficiency. (PubMed, Clin Immunol) - "The effects of an ICOS agonist in antibody defects warrants further investigation. This biologic may also be of therapeutic interest in other clinical settings of antibody deficiency."

IO biomarker • Journal • Primary Immunodeficiency • CD27 • CD4 • ICOS • IL10 • IL21 • IL4

Study of PD-1 Inhibitor JTX-4014 Alone and in Combination With Vopratelimab in Biomarker-selected Subjects With Metastatic NSCLC After One Prior Platinum-containing Regimen (clinicaltrials.gov) - P2 | N=69 | Active, not recruiting | Sponsor: Jounce Therapeutics, Inc. | Trial primary completion date: Sep 2022 ➔ May 2024

Biomarker • Combination therapy • IO biomarker • Metastases • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Analysis and Regulatory Mechanisms of Platelet-Related Genes in Patients with Ischemic Stroke. (PubMed, Cell Mol Neurobiol) - "In addition, Caffeine, Carboplatin, and Vopratelimab were the targeted drugs of these key genes. This study identified four platelet-related key genes of IS, which might help to deepen the understanding of the role of platelet-related genes in the molecular mechanism of IS."

IO biomarker • Journal • Cardiovascular • Hematological Disorders • Ischemic stroke • Thrombosis • DOCK8 • ICOS • MIR17 • MIR193A • MIR423

Study of PD-1 Inhibitor JTX-4014 Alone and in Combination With Vopratelimab in Biomarker-selected Subjects With Metastatic NSCLC After One Prior Platinum-containing Regimen (clinicaltrials.gov) - P2 | N=69 | Active, not recruiting | Sponsor: Jounce Therapeutics, Inc. | Trial completion date: Mar 2023 ➔ May 2024

Biomarker • Combination therapy • IO biomarker • Metastases • Trial completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Vopratelimab (JTX-2011) Alone and in Combination With Anti-PD-1 or Anti-CTLA-4 in Subjects With Advanced and/or Refractory Solid Tumors (clinicaltrials.gov) - P1/2 | N=4 | Completed | Sponsor: Jounce Therapeutics, Inc. | Active, not recruiting ➔ Completed | Trial completion date: Jul 2024 ➔ Jan 2023 | Trial primary completion date: Apr 2024 ➔ Jan 2023

Combination therapy • Metastases • Trial completion • Trial completion date • Trial primary completion date • Oncology • Solid Tumor

Concentra Biosciences to Acquire Jounce Therapeutics (Precision Oncology News) - "Jounce Therapeutics...said it will be acquired by Concentra Biosciences and lay off 84 percent of its workforce. Concentra will acquire Jounce for $1.85 in cash per share plus a non-tradeable contingent value right (CVR). The CVR will provide Jounce shareholders the right to receive 80 percent of the net proceeds from any license or disposition of Jounce's programs effected within two years of closing and 100 percent of the potential aggregate value of certain specified potential cost savings. The acquisition is projected to close in the second quarter of 2023....According to the company, the remaining Jounce employees will work to ensure that patients on the SELECT and INNATE trials have the opportunity to continue receiving therapy with vopratelimab, JTX-8064, and pimivalimab, along with completing the acquisition and conducting activities to maximize the value of the CVR."

M&A • Biliary Cancer • Biliary Tract Cancer • Bladder Cancer • Breast Cancer • Clear Cell Renal Cell Carcinoma • Endometrial Cancer • Gastric Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Gynecologic Cancers • Head and Neck Cancer • Kidney Cancer • Liposarcoma • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Renal Cell Carcinoma • Sarcoma • Skin Cancer • Soft Tissue Sarcoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Squamous Cell Skin Cancer • Thoracic Cancer • Triple Negative Breast Cancer • Undifferentiated Pleomorphic Sarcoma • Urothelial Cancer • Uterine Cancer

Association of an 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. (ASCO-SITC 2020) - P1/2; "Background: ICOS is a costimulatory molecule upregulated on activated T cells. In this retrospective subset analysis, the RS score, but not PD-L1, in baseline tumor biopsies was predictive of emergence of an ICOS hi CD4 T cell population and improved RECIST response, PFS, and OS in patients treated with vopra alone and in combination with nivo. Clinical evaluation of vopra and investigational PD-1 inhibitor JTX-4014 in cancer patients with RS selection is planned. Research Funding: Jounce Therapeutics."

Clinical • IO Biomarker • Oncology • Solid Tumor • GS • PD-L1

[VIRTUAL] ICOS hi CD4 T cells emerging on vopratelimab treatment have Th1 central memory characteristics and may contribute to durability of clinical responses (AACR-II 2020) - P1/2, P2 | "Vopra is currently being tested as a sequenced combination with ipilimumab (ipi) in the Phase 2 EMERGE trial (NCT03989362). Assessment of phenotype and function of ICOS hi CD4 T cells was conducted using serial collections of peripheral blood mononuclear cells (PBMCs) from a subset of evaluable subjects in the ICONIC trial. Emergence of a peripheral ICOS hi CD4 T cell population correlates with response to vopra treatment and occurs independent of anti-PD-1 activity. Transcriptional profiling of ICOS hi CD4 T cells further defined the phenotype as Tcm cells that express cytotoxic effector molecules, which may contribute to observed clinical benefit. Treatment with ipi in combination with an ICOS agonist resulted in enhanced efficacy in mice, and follow-up studies exploring sequential dosing are ongoing."

Clinical • IO Biomarker • Oncology

ICONIC: Phase 1/2 trial of ICOS agonist JTX-2011 alone and in combination with nivolumab (nivo) (AACR 2017) - "Abstract embargoed at this time."

Clinical • P1/2 data • Biosimilar • Oncology

SELECT: A phase 2 randomized trial evaluating 2 doses of vopratelimab (V) + pimivalimab (P) vs P in TISvopra selected patients (pts) (ESMO-IO 2022) - P2 | "Tumor inflammation signature (TIS) at and above a designated cut-off, termed TISvopra, was previously associated with improved clinical outcomes in patients treated with V +/- nivolumab. P is active and continues to be used in combination trials. Shorter TE duration of V 0.03 mg/kg may contribute to clinical activity."

Clinical • P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ICOS • PD-L1

Jounce Therapeutics Announces Restructuring (Market Screener) - "Jounce Therapeutics, Inc...announced today that it is reducing its workforce by approximately 57 percent. The decision to reduce its workforce was made as Jounce believes advancement of its clinical programs, JTX-8064 and vopratelimab, requires funding and a scope that the Company cannot pursue on its own and will be seeking business development opportunities for both programs....Jounce expects to incur a non-recurring charge of approximately $11.2i million in the first quarter of 2023 related to the restructuring announced today. The workforce reduction will be substantially completed by March 31, 2023."

Commercial • Licensing / partnership • Oncology • Solid Tumor

Jounce Therapeutics Presents INNATE Phase 1 and SELECT Clinical Trial data at the European Society of Medical Oncology Immuno-Oncology (ESMO - IO) Annual Congress (GlobeNewswire) - P1 | N=281 | INNATE (NCT04669899) | Sponsor: Jounce Therapeutics, Inc. | "Jounce Therapeutics...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....Thirty-one patients were treated in dose escalation, 22 JTX-8064 mono, and nine JTX-8064 plus 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."

P1 data • Head and Neck Cancer • Oncology • Squamous Cell Carcinoma of Head and Neck

Jounce Therapeutics Presents INNATE Phase 1 and SELECT Clinical Trial data at the European Society of Medical Oncology Immuno-Oncology (ESMO - IO) Annual Congress (PRNewswire) - P2 | N=75 | SELECT (NCT04549025) | Sponsor: Jounce Therapeutics, Inc. | "'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....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."

P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Jounce Therapeutics Reports Third Quarter 2022 Financial Results (GlobeNewswire) - P2 | N=75 | SELECT (NCT04549025) | Sponsor: Jounce Therapeutics, Inc. | "Vopratelimab (ICOS) and Pimivalimab (PD-1): SELECT Phase 2 data to be presented at ESMO-IO Annual Congress 2022...SELECT is a randomized Phase 2 trial evaluating vopratelimab (vopra), Jounce’s inducible T cell costimulator (ICOS) agonist, in combination with pimi versus pimi alone in immunotherapy naïve, TISvopra biomarker-selected, second line non-small cell lung cancer patients....As previously reported, vopra 0.03 mg/kg in combination with pimi resulted in a 40% response rate and an 80% six month landmark progression-free survival (PFS) by independent central radiology review. These continue to compare favorably to updated results for pimi monotherapy, with a 27.8% response rate and 36% six month landmark PFS, as will be reported at ESMO-IO. Jounce plans to pursue a partnership to enable further development of vopra 0.03 mg/kg in combination with a PD-1 inhibitor."

P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

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. (ASCO 2017) - P1/2; "JTX-2011 has been well tolerated up to 0.1 mg/kg and with nivo at .01 mg/kg IV q 21 days. Greater than linear exposure increase was observed and TE may be higher than QSP model prediction."

Adverse events • P1 data • Biosimilar • Colorectal Cancer • Melanoma • Pain • Triple Negative Breast Cancer

Jounce Therapeutics to Present Multiple Posters at the Society for Immunotherapy of Cancer’s (SITC) 37th Annual Meeting and the European Society of Medical Oncology Immuno-Oncology (ESMO-IO) Annual Congress (GlobeNewswire) - "Two clinical poster presentations will be made at the ESMO-IO 2022 Annual Congress being held in Geneva, December 7-9. The submitted abstract for the JTX-8064 INNATE trial contains Phase 1 data, including safety, PK, and tumor response data. Jounce continues to expect to report preliminary clinical data on at least 80 Phase 2 patients from the INNATE trial by end of year 2022. The submitted abstract for the vopratelimab/pimivalimab SELECT trial includes all data previously announced on clinical endpoints. Additional durability data for patients who remain on study will also be reported."

P1 data • P2 data • Oncology • Solid Tumor

Vopratelimab (JTX-2011) Alone and in Combination With Anti-PD-1 or Anti-CTLA-4 in Subjects With Advanced and/or Refractory Solid Tumors (clinicaltrials.gov) - P1/2 | N=4 | Active, not recruiting | Sponsor: Jounce Therapeutics, Inc. | Recruiting ➔ Active, not recruiting | N=20 ➔ 4

Combination therapy • Enrollment change • Enrollment closed • Oncology • Solid Tumor

EMERGE: Vopratelimab and a CTLA-4 Inhibitor in PD-1/PD-L1 Inhibitor Experienced Subjects With NSCLC or Urothelial Cancer (clinicaltrials.gov) - P2 | N=61 | Completed | Sponsor: Jounce Therapeutics, Inc. | Active, not recruiting ➔ Completed | N=452 ➔ 61 | Trial completion date: Jul 2022 ➔ Mar 2022

Enrollment change • Trial completion • Trial completion date • Genito-urinary Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Urothelial Cancer

"The sun sets on #Icos (via @JacobPlieth) https://t.co/w4C44YkWk5 #vopratelimab #Izuralimab $JNCE $XNCR $AZN $BMY $GSK" (@evaluatevantage)

ICOS

Jounce Therapeutics Reports Results from Phase 2 Randomized SELECT Trial Testing 2 Different Doses of Vopratelimab in TISvopra Biomarker-Selected Patients (GlobeNewswire) - P2 | N=75 | SELECT (NCT04549025) | Sponsor: Jounce Therapeutics, Inc. | "As the study was powered to detect a 20% absolute difference of the pooled combo doses compared to pimi monotherapy, and the actual difference was 7%, SELECT did not meet its primary endpoint. In the combination dose cohort with the lowest dose of vopra (0.03mg/kg), interesting trends were observed in both the primary endpoint, with an absolute mean change of 15%, and in the prespecified secondary endpoints of overall response rate (ORR), which was 40% compared to 25% in pimi alone, and landmark six month progression free survival (PFS) of 80% compared to 33% with pimi alone....We plan to submit a clinical abstract to present the entire SELECT study, including more mature data, at the ESMO Immuno-Oncology Congress in December 2022."

P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer

Jounce Therapeutics Reports Second Quarter 2022 Financial Results (GlobeNewswire) - "Vopratelimab (ICOS) and Pimivalimab (PD-1): On track to report clinical data before year end. Jounce plans to submit a clinical data abstract on the SELECT trial, including additional single agent data for pimivalimab, to the ESMO Immuno-Oncology Congress 2022....JTX-1484 (LILRB4/ILT3): Jounce has submitted a preclinical abstract on JTX-1484 for consideration at this year’s annual Society for Immunotherapy of Cancer (SITC) meeting being held from November 9-11 in Boston, MA."

P2 data • Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology