ZH9 intravesical / Prokarium - LARVOL DELTA

Prokarium Reports Positive Interim Data from Phase 1/1b PARADIGM-1 trial of ZH9 in NMIBC patients, Demonstrating Excellent Safety and Encouraging Early Efficacy (Businesswire) - "Of 22 patients that received at least 1 dose of ZH9, 6 patients (27%) experienced an Adverse Event related to treatment with ZH9 all of which were mild or moderate and transient. No grade 3 or higher toxicities, dose-limiting toxicities, or drug related serious adverse events were observed. ZH9 demonstrated 91% freedom-from-relapse at 12 months in the heavily pretreated study population (10/11 patients at 12m, per protocol completion)."

P1 data • Bladder Cancer

Live attenuated Salmonella ZH9 as novel microbial immunotherapy for the treatment of bladder cancer (AACR 2024) - "To explore the durability of protection, surviving intravesical ZH9 treated animals were rechallenged, demonstrating protection from both bladder and subcutaneous MB49 tumors suggestive of lasting local and systemic anti-tumor immunity...The investigation includes thorough translational and biomarker studies to delve into the mechanism of action of ZH9 and explore patient stratification approaches. By easing the treatment burden on patients, lowering healthcare costs, and featuring a scalable manufacturing process, ZH9 has the potential to revolutionize the treatment paradigm in NMIBC and reshape the patient journey."

IO biomarker • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • CD4 • CD8

Advancing bladder cancer treatment with live attenuated salmonella ZH9: from monotherapy to combination strategies (AACR 2025) - "Intravesical ZH9 monotherapy following orthotopic MB49 tumor inoculation demonstrated significant survival benefit compared to both vehicle control and BCG treatments...These data support Salmonella ZH9 as an effective first-line monotherapy and checkpoint inhibitor combination therapy for bladder cancer, with potential to reduce treatment burden on patients, lower associated healthcare costs and to ease microbial therapy supply constraints due to a scalable manufacturing process. Clinical evaluation of ZH9 in a Phase 1b study evaluating safety, pharmacology, and early efficacy in NMIBC is ongoing."

Monotherapy • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • PTEN

Redefining bladder cancer treatment with ZH9 – from monotherapy to combination strategies (SITC 2025) - P1 | "Immune responses were characterised by flow cytometry and histology analyses of bladder tissue.Results Intravesical ZH9 monotherapy following orthotopic MB49 tumour inoculation demonstrated significant survival benefit compared to both vehicle control and BCG treatments...Combination of local ZH9 treatment with regimens of checkpoint inhibitor antibodies anti-PD-L1 (MB49 model) and anti-PD-1 (GEMM model) that were otherwise ineffective, led to significant efficacy, demonstrating true synergy of local ZH9 treatment with systemic immunotherapies.Conclusions These data support ZH9 as a superior first-line monotherapy and a potent combination partner for checkpoint inhibitors in bladder cancer, demonstrating enhanced efficacy and the potential to reduce patient treatment burden, lower healthcare costs, and overcome supply challenges through scalable manufacturing. Clinical evaluation of ZH9 in a Phase 1b study evaluating safety, pharmacology, and early efficacy in NMIBC..."

Monotherapy • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • PTEN

PARADIGM-1: A Phase 1/1b Study of ZH9 Treatment in Patients With Non-Muscle Invasive Bladder Cancer (clinicaltrials.gov) - P1 | N=22 | Active, not recruiting | Sponsor: Prokarium Ltd | Recruiting ➔ Active, not recruiting

Enrollment closed • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

PARADIGM-1: A Phase 1/1b Study of ZH9 Treatment in Patients With Non-Muscle Invasive Bladder Cancer (clinicaltrials.gov) - P1 | N=24 | Recruiting | Sponsor: Prokarium Ltd | Trial primary completion date: Feb 2025 ➔ Jun 2025

Trial primary completion date • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

Exploring the potential of urine-based immune profiling: evaluating sample quality and feasibility (CIMT 2024) - P1 | "Taken together these findings suggest that urine biomarker analysis is feasible even in decentralized or multicentred clinical trials, addressing logistical challenges in transporting samples from trial sites to analytical laboratories, thus supporting broader implementation in clinical research. This biomarker strategy is implemented in the ongoing PARADIGM-1 clinical trial (NCT06181266) investigating ZH9, a novel live attenuated bacterial immunotherapy, aiming to redesign the treatment paradigm in NMIBC with a single induction dose therapy."

IO biomarker • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urology • CD14 • PTPRC

Prokarium Achieves Milestone with First Patient Dosing in PARADIGM-1 Non-Muscle Invasive Bladder Cancer Clinical Trial (Businesswire) - "Prokarium...announces the dosing of the first patient in their PARADIGM-1 Phase I/Ib clinical trial in non-muscle invasive bladder cancer (NMIBC) patients (NCT06181266). The study is being conducted at multiple clinical sites across the United States and will initially evaluate the safety of a single intravesical administration of their investigational immunotherapy, ZH9, in NMIBC patients. The study will further investigate and characterize clinical efficacy of the ZH9 treatment regimen in pre-planned expansion cohorts under the same IND."

Trial status • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

PARADIGM-1: A Phase 1/1b Study of ZH9 Treatment in Patients With Non-Muscle Invasive Bladder Cancer (clinicaltrials.gov) - P1 | N=24 | Recruiting | Sponsor: Prokarium Ltd | Not yet recruiting ➔ Recruiting

Enrollment open • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

PARADIGM-1: A Phase 1/1b Study of ZH9 Treatment in Patients With Non-Muscle Invasive Bladder Cancer (clinicaltrials.gov) - P1 | N=24 | Not yet recruiting | Sponsor: Prokarium Ltd

New P1 trial • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

SalmonellaTyphi ZH9 as a novel microbial immunotherapy for bladder cancer (CIMT 2022) - "Our preclinical data show that a single intravesical ZH9 installation, but not BCG, results in significantly improved survival and also protects cured animals from repeated tumor engraftment, both locally and distally, in the murine orthotopic MB49 tumor model...In addition to the primary objective of determining the safety and tolerability of ZH9 administered intravesically following oral priming with ZH9 in patients with NMIBC, we will conduct an extensive translational and biomarker investigational package to explore the mechanism of action of ZH9 and the type and magnitude of local and systemic immune responses. The translational strategy will refer to the lessons learnt from BCG treatment and inform us on both local and systemic immune responses, by analysing urine and blood, respectively, as non-invasive liquid biopsies."

IO biomarker • Bladder Cancer • Genito-urinary Cancer • Immunology • Oncology • Solid Tumor • Urothelial Cancer