Clinical Trials Program Update

Clinical evidence fundamentally underpins commercial success in healthcare and consequently is one of the key pillars of our investment program. High-quality clinical evidence is needed by clinicians to make the decision to adopt Cxbladder in clinical practice and by healthcare payors to make decisions to cover and reimburse a Cxbladder test. The guidelines committees of professional medical societies, including the American Urological Association (AUA), the National Comprehensive Cancer Network (NCCN) and the European Association of Urology (EAU), also rely on this evidence to support embedding Cxbladder as a standard of care.

Status of Studies Within Our Clinical Trials Program

Last updated: 22nd Jan, 2025

Ongoing Study Program	Goal	Population and Use	Status
STRATA Safe Testing of Risk for AsymptomaTic MicrohematuriA	CU for Triage CV/CU for Triage Plus (retrospective)	Microhematuria (MH) Risk stratification	Recruitment closed with 555 patients including 223 low risk patients (test and control) with interim analysis results published in Journal of Urology Monitoring for final analysis completed mid-Aug, some re-work needed. Database lock March 2025 and final Clinical Study Report (CSR) expected Sep 2025
DRIVE Detection and RIsk Stratification in VEterans Presenting with Hematuria	CV for Triage Plus for a Veterans’ cohort Data for MH pooled analysis	MH and gross hematuria (GH) Risk stratification	Enrolment closed with 710 patients enrolled including 48 tumor confirmed patients (target was 45) from across 10 US VA sites Database lock completed and publication submission expected by March 2025
microDRIVE Detection and RIsk Stratification in VEterans Presenting with MicroHematuria	CV of Triage Plus Data for MH pooled analysis	MH Detection	Currently a decentralised study across all VAMCs coordinated through a single US VA Medical Center. Protocol amendment provides for addition of 4 more sites to increase enrolment 447 patients have consented for the study with 224 samples received to date The target is 1000 patients with 35 tumor confirmed patients Last patient in is now projected to be Q3-2025
AUSSIE Australian Urologic Risk Stratification of PatientS wIth HEmaturia	CV of Triage Plus (Australian cohort) Data for pooled analysis	MH and GH Risk stratification	The target is 35 UC confirmed patients including a minimum of 10 MH patients Currently 456 subjects enrolled with 29 UC confirmed including 5 MH patients Last patient in projected to be Q2-2025
Pooled Analysis	CV of Triage Plus	MH and GH Risk stratification	MH (and separately GH patient data where available) from DRIVE, AUSSIE and microDRIVE will be pooled and performance determined Paper submission is one quarter after publication of DRIVE, microDRIVE and AUSSIE
LOBSTER LOngitudinal Bladder Cancer Study for Tumor Recurrence	CV of Monitor/ Monitor Plus	Surveillance Risk stratification	Enrolment will be complete when 75 UC recurrences are observed across 10–15 sites Enrolment is 413 subjects providing 810 samples with 48 UC recurrences observed to date and expected completion is Q3-2026
CREDIBLE Cystoscopic REDuction In BLadder Evaluations for microhematuria	CU of Triage Plus	MH Risk stratification	Protocol IRB approved for 14 and contracts finalized for 6 of expected 15 sites Interim analysis will occur at 600 to determine if incidence is <5% and if so will continue until 1000 are enrolled Enrolment due to commence February 2025

* Dates are calendar years, not financial years
** Pacific Edge's IRB-approved clinical trials are listed at clinicaltrials.gov

The Strategic Rationale For Each Study

Our clinical studies are principally aimed at delivering two types of evidence: clinical validity (CV) evidence (evidence that Cxbladder accurately identifies a patient’s clinical status in an independent patient cohort) and clinical utility (CU) evidence (evidence that Cxbladder is clinically useful for patients and physicians in a defined population and indication). We are also undertaking studies to deliver analytical validity (AV) evidence (evidence that a test result is reproducible in laboratory conditions).

STRATA: Demonstrate the clinical utility (CU) of Cxbladder Triage using a prospective, two-arm randomized design to risk-stratify patients and rule out from cystoscopy

Establish CU for Cxbladder Triage in microhematuria populations to identify patients at low risk of bladder cancer that can safely avoid cystoscopy.
Retrospective analysis with Cxbladder Triage Plus to show theoretical CU for the second-generation test in microhematuria populations with the improved performance characteristics.
CU evidence supports AUA/NCCN guidelines inclusion using Cxbladder Triage and sets the stage for Cxbladder Triage Plus to risk stratify microhematuria populations.

DRIVE: Prospective recruitment of patients to a single-arm observational study to demonstrate the CV of Cxbladder Detect and Triage Plus test in risk stratifying Veterans presenting with hematuria

Demonstrate CV of Cxbladder Detect and Triage Plus within a Veterans cohort supporting AUA/NCCN Guidelines inclusion in microhematuria & gross hematuria patients.
Contribute data to pooled-analysis to establish CV for Triage Plus in microhematuria patients.
CV evidence for Cxbladder Triage in microhematuria & gross hematuria patients supplementing NZ studies.

microDRIVE:

Demonstrate the clinical validity of Cxbladder Triage Plus  in detecting urothelial cancer in patients presenting with microhematuria.
MicroDRIVE will compare the performance of Triage Plus against the current gold-standard for the detection of urothelial cancer, diagnostic cystoscopy and pathology.
Contribute data to pooled-analysis to establish CV for Triage Plus in microhematuria patients.

AUSSIE: Prospective recruitment of patients to a single-arm observational study to demonstrate CV in an Australian healthcare setting for patients presenting with hematuria

Demonstrate CV of Cxbladder Triage Plus with an Australian cohort.
Demonstrate accurate risk stratification of hematuria patients to intensify or de-intensify evaluation.
Contribute data to meta-analysis to establish CV for Triage Plus in microhematuria patients.

Microhematuria Pooled Analysis: Pooled-analysis of Cxbladder Triage Plus performance from multiple studies involving prospectively recruited patients from single-arm observational studies including eligible microhematuria patients

CV of Cxbladder Triage Plus with microhematuria patients.
Combines data from DRIVE, AUSSIE, and MicroDRIVE. CV evidence supports AUA/NCCN guidelines inclusion using Cxbladder Triage Plus to risk stratify microhematuria populations.

LOBSTER: Prospective recruitment of patients to a single-arm observational study to evaluate the clinical validity of Cxbladder Monitor/Monitor Plus.

To safely risk stratify patients under surveillance for recurrence of urothelial cancer (UC).
To demonstrate that it is safe to alternate Cxbladder Monitor with cystoscopy for intermediate and high-risk patients under surveillance for recurrence of UC.
Targeting AUA/NCCN guidelines inclusion for biomarkers as an alternative to cystoscopy in a surveillance setting.

CREDIBLE: Demonstrate the clinical utility (CU) of Triage Plus using a randomized controlled study design prospectively enrolling microhematuria patients scheduled for evaluation of said hematuria

Will compare cystoscopy use for patients in the control arm risk stratified by AUA Standard of Care guidelines into high, intermediate and low risk with patients in the test arm risk stratified by Cxbladder Detect and managed as AUA high risk (Triage Pluspositive) and AUA low risk (Triage Plusnegative).

Analytical Validity (AV): Develop a test that is repeatable in the lab for a given indication and population.
Clinical Validity (CV): Make sure the test works in the same way on an independent eligible population for the given indication.
Clinical Utility (CU): Put the test in the hands of a physician to establish that it can usefully change patient management within the context of care for the defined population and indication.