# Development of Ciclopirox Prodrug as a Novel Systemic Treatment for High-Risk Non-Muscle Invasive Bladder Cancer

> **NIH NIH R44** · CICLOMED, LLC · 2020 · $936,240

## Abstract

Project Summary
The American Cancer Society estimates ~80,470 patients will be diagnosed with bladder cancer
(BCa) and ~17,670 will die of the disease in the US this year (www.cancer.org). BCa exists as two
diseases, non-muscle invasive bladder cancer (NMIBC) and muscle invasive bladder cancer
(MIBC). Approaches to treating NMIBC and MIBC, as well as treatment outcomes, are quite
different. Despite endoscopic resection followed by intravesical administration of immunotherapy or
chemotherapy agents, 60-70% of NMIBC will recur with 20-30% of patients progressing to MIBC,
where the gold standard treatment is neoadjuvant cisplatin-based chemotherapy followed by radical
cystectomy. CicloMed LLC is developing Ciclopirox Prodrug (CPX-POM) for the treatment of
bladder cancer. CPX-POM is rapidly and completely metabolized to ciclopirox (CPX), the active
metabolite and undergoes renal elimination resulting in urine concentrations that exceed in vitro
IC50's several-fold following intravenous (IV) administration. In vitro activity of CPX was
demonstrated in several high-grade human urothelial bladder cancer cell lines. In vivo preclinical
proof of principle for CPX-POM has been thoroughly demonstrated in a validated, chemical
carcinogen mouse model of bladder cancer. Following submission of an investigational new drug
application to the US Food and Drug Administration (FDA), CicloMed LLC conducted a US
multicenter, First-in-Human, Phase 1, open-label, dose escalation study in patients with advanced
solid tumors (NCT03348514). Nineteen patients were enrolled in the Phase 1 trial. Based on safety
and dose tolerance, the Recommended Phase 2 Dose (RP2D) for IV CPX-POM is defined as 900
mg/m2. The goals of this Direct to Phase II SBIR application are to characterize the clinical
pharmacology of the IV CPX-POM RP2D in a window of opportunity study of 12 newly diagnosed or
recurrent BCa patients undergoing transurethral resection (TURBT), and based pharmacologic
activity demonstrated bladder tumor tissues obtained in these patients, interrogate urothelial cancer
patient biospecimens for altered regulation of cell signaling pathways inhibited by CPX-POM
administration. Single cell sequencing will be employed as an unbiased approach to characterizing
pharmacologic activity and potential mechanisms of action in the window of opportunity study
patients. Immunohistochemistry (IHC) analyses will determine effects of CPX-POM treatment on cell
proliferation, Notch signaling pathway expression, and CD8+ tumor lymphocyte infiltration. Single
cell sequencint will inform additional IHC analyses. The proposed window of opportunity trial in
NMIBC patients and molecular/genetic interrogation of urothelial cancer biorepository are critical
data needed to design and conduct the planned Phase 2 clinical proof of concept trial in 30-40
evaluable high-risk NMIBC patients.

## Key facts

- **NIH application ID:** 10077649
- **Project number:** 1R44CA246997-01A1
- **Recipient organization:** CICLOMED, LLC
- **Principal Investigator:** WILLIAM MC CULLOCH
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $936,240
- **Award type:** 1
- **Project period:** 2020-09-09 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10077649

## Citation

> US National Institutes of Health, RePORTER application 10077649, Development of Ciclopirox Prodrug as a Novel Systemic Treatment for High-Risk Non-Muscle Invasive Bladder Cancer (1R44CA246997-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10077649. Licensed CC0.

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