fosciclopirox (CPX-POM) / BioNovus, University of Kansas Medical Center - LARVOL DELTA

Notable Advances Volasertib Phase 2 Program Utilizing Proprietary Predictive Precision Medicine Platform-Guided Enrollment (GlobeNewswire) - "Notable Labs, Ltd...announced the advancement of its volasertib Phase 2 program utilizing PPMP to enrich the study population for clinical responders...'PPMP’s recently reported, 100% accurate prediction of fosciclopirox’s clinical trial outcome has allowed us to eliminate an entire 30-patient cohort from the planned volasertib program, and further validated our PPMP-guided development strategy.'....'We in-licensed volasertib because of its robust clinical experience in Boehringer Ingelheim’s expansive Phases 1-3 program and our PPMP data that distinguished predicted volasertib-responders from predicted non-responders based on samples from patients with AML. We therefore believe that PPMP will focus volasertib’s development on clinically responding patients, boost its clinical response rate and enhance patient outcomes.'"

Pipeline update • Trial status • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Safety, Dose Tolerance, Pharmacokinetics, and Pharmacodynamics Study of CPX-POM in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=9 | Completed | Sponsor: CicloMed LLC | Trial completion date: Dec 2022 ➔ Apr 2023 | Trial primary completion date: Dec 2022 ➔ Apr 2023

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

CPX-POM-003: Study of Fosciclopirox in Patients With Relapsed/Refractory Acute Myeloid Leukemia (clinicaltrials.gov) - P1/2 | N=18 | Terminated | Sponsor: CicloMed LLC | Phase classification: P1b/2a ➔ P1/2 | N=28 ➔ 18 | Recruiting ➔ Terminated; Discontinued

Combination therapy • Enrollment change • Phase classification • Trial termination • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Safety, Dose Tolerance, Pharmacokinetics, Pharmacodynamics of CPX-POM in Patients With Newly Diagnosed or Recurrent Bladder Tumors (clinicaltrials.gov) - P2 | N=12 | Completed | Sponsor: CicloMed LLC | Active, not recruiting ➔ Completed

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

Notable Reports Predictive Precision Medicine Platform (PPMP) Accurately Predicted Fosciclopirox Trial Outcome (GlobeNewswire) - P2a | N=28 | NCT04956042 | Sponsor: CicloMed LLC | "Notable Labs, Ltd...and CicloMed, LLC...today announced initial safety and efficacy data of fosciclopirox and the performance of PPMP, Notable’s Predictive Precision Medicines Platform, from the Phase 2a trial in adult patients with relapsed/refractory acute myeloid leukemia, R/R AML (NCT04956042). Fosciclopirox is sponsored by CicloMed and co-developed by both companies. In the Phase 2a trial, PPMP-predicted patient responses were confirmed by the actual responses to treatment....Eighteen heavily pre-treated patients were enrolled in the trial with nine patients evaluable for response assessment per-protocol. Fosciclopirox, administered at the Recommended Phase 2 Dose, was well-tolerated. However, none of the nine evaluable patients achieved a complete response. Stable disease, over four months, was observed in two evaluable patients."

P2a data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Phase 1B/2A safety, pharmacokinetics and pharmacodynamics study of fosciclopirox alone and in combination with cytarabine in patients with relapsed/refractory acute myeloid leukemia. (ASCO 2023) - P1b/2a | "The trial is currently open at two sites with 14 patients enrolled and 8 evaluable for the primary endpoint. Clinical trial information: NCT04956042."

Clinical • Combination therapy • P1/2 data • PK/PD data • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Graft versus Host Disease • Hematological Malignancies • Immunology • Leukemia • Oncology • Transplantation • CASP3 • CASP7

Window of opportunity trial to characterize the safety, pharmacokinetics, and pharmacodynamics of fosciclopirox (CPX-POM) in cisplatin-ineligible muscle invasive bladder cancer patients. (ASCO-GU 2020) - P1; "Clinical trial information: NCT03348514. Research Funding: CicloMed LLC."

Clinical • PK/PD data • CD8 • NOTCH1 • PCNA

Safety, dose tolerance, pharmacokinetics, and pharmacodynamics of fosciclopirox (CPX-POM) in patients with advanced solid tumors. (ASCO-GU 2020) - P1; "IV CPX-POM was well tolerated with treatment-related AEs primarily CNS-related. At MTD, systemic and urinary CPX exposures exceeding in vitro IC50 values by several-fold. The 900 mg/m2 dose is currently being evaluated in an expansion cohort study in cisplatin-ineligible muscle invasive bladder cancer patients scheduled for cystectomy."

Clinical • PK/PD data • CXCL8 • IL6 • NOTCH1

Window of opportunity trial to characterize the safety, pharmacokinetics, and pharmacodynamics of fosciclopirox (CPX-POM) in cisplatin-ineligible muscle invasive bladder cancer patients. (ASCO-GU 2020) - P1; "Clinical trial information: NCT03348514. Research Funding: CicloMed LLC."

Clinical • PK/PD data • CD8 • NOTCH1 • PCNA

Phase 1B/2A safety, pharmacokinetics, and pharmacodynamics study of fosciclopirox alone and in combination with cytarabine in patients with relapsed/refractory acute myeloid leukemia. (ASCO 2022) - P1b/2a | "The steady-state plasma pharmacokinetics of F are being characterized during C1. Enrollment began in October 2022 with four patients enrolled to date."

Clinical • Combination therapy • P1/2 data • PK/PD data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • HES1 • NOTCH1 • NOTCH2

Fosciclopirox clinical proof of concept in patients with nonmuscle invasive and muscle-invasive bladder cancer. (ASCO 2022) - P1, P2 | "In NCT04608045, neoadjuvant F was administered as monotherapy in cisplatin-ineligible (C-I) MIBC patients and in combination with gemcitabine + cisplatin in chemotherapy-eligible (C-E) MIBC patients. To date, fosciclopirox is well tolerated and achieves sufficient systemic, tumor, and urine CPX exposure at the RP2D. Evidence of target inhibition was demonstrated in NMIBC tumors and preliminary signs of clinical activity observed in MIBC patients. Safety and efficacy trials are planned to confirm and expand findings in NMIBC and MIBC patients."

Clinical • Bladder Cancer • Constipation • Fatigue • Gastroenterology • Gastrointestinal Disorder • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer • BIRC5 • MYC • NOTCH1 • NOTCH2

[VIRTUAL] Fosciclopirox suppresses growth of high-grade urothelial cancer by targeting Notch signaling (AACR-II 2020) - P1 | "An expansion cohort study in 12 cisplatin-ineligible MIBC patients receiving two treatment cycles of CPX-POM prior to radical cystectomy (RC) is underway. Evidence of pharmacologic activity is being characterized in bladder tumor tissues obtained at RC."

Bladder Cancer • Genito-urinary Cancer • Hematological Malignancies • Oncology • Solid Tumor • Urothelial Cancer • NOTCH1

Safety, Dose Tolerance, Pharmacokinetics, and Pharmacodynamics Study of CPX-POM in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=9 | Completed | Sponsor: CicloMed LLC | Recruiting ➔ Completed | Trial completion date: Sep 2022 ➔ Dec 2022 | Trial primary completion date: Sep 2022 ➔ Dec 2022

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

Safety, Dose Tolerance, Pharmacokinetics, Pharmacodynamics of CPX-POM in Patients With Newly Diagnosed or Recurrent Bladder Tumors (clinicaltrials.gov) - P2 | N=12 | Active, not recruiting | Sponsor: CicloMed LLC | Recruiting ➔ Active, not recruiting | Trial completion date: Sep 2022 ➔ Jun 2023 | Trial primary completion date: Sep 2022 ➔ Jun 2023

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

Safety, Dose Tolerance, Pharmacokinetics, Pharmacodynamics of CPX-POM in Patients With Newly Diagnosed or Recurrent Bladder Tumors (clinicaltrials.gov) - P2 | N=12 | Recruiting | Sponsor: CicloMed LLC | Trial completion date: Mar 2022 ➔ Sep 2022 | Trial primary completion date: Mar 2022 ➔ Sep 2022

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

Safety, Dose Tolerance, Pharmacokinetics, and Pharmacodynamics Study of CPX-POM in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=12 | Recruiting | Sponsor: CicloMed LLC | Trial completion date: May 2022 ➔ Sep 2022 | Trial primary completion date: May 2022 ➔ Sep 2022

Trial completion date • Trial primary completion date • Oncology • Solid Tumor

Safety, Dose Tolerance, Pharmacokinetics, and Pharmacodynamics Study of CPX-POM in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=12 | Recruiting | Sponsor: CicloMed LLC | Trial completion date: Nov 2021 ➔ May 2022 | Trial primary completion date: Nov 2021 ➔ May 2022

Trial completion date • Trial primary completion date • Oncology • Solid Tumor

Safety, Dose Tolerance, Pharmacokinetics, Pharmacodynamics of CPX-POM in Patients With Newly Diagnosed or Recurrent Bladder Tumors (clinicaltrials.gov) - P2; N=12; Recruiting; Sponsor: CicloMed LLC; Trial completion date: Nov 2021 ➔ Mar 2022; Trial primary completion date: Nov 2021 ➔ Mar 2022

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

Notable and CicloMed Initiate Phase 1B/2A Clinical Trial of Fosciclopirox in Acute Myelogenous Leukemia Under Co-Development Agreement (Businesswire) - "Notable Labs, Inc...and CicloMed LLC...have initiated a Phase 1B/2A clinical trial of fosciclopirox in patients with refractory acute myelogenous leukemia (AML) under the terms of a co-development agreement. In the ongoing open-label, Phase 1B/2A trial currently underway at The University of Kansas Cancer Center, Notable is applying its high-fidelity predictive precision medicines platform with the goal of assessing patient responsiveness to fosciclopirox....Under the terms of the co-development agreement, CicloMed holds the primary responsibility for executing clinical trial operations while Notable is primarily focused on optimizing Notable’s predictive precision medicine platform. Both parties will be responsible for the costs associated with the on-going clinical trial."

Licensing / partnership • Trial status • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Safety, Dose Tolerance, Pharmacokinetics, and Pharmacodynamics Study of CPX-POM in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1; N=19; Completed; Sponsor: CicloMed LLC; Recruiting ➔ Completed

Clinical • Trial completion • Oncology • Solid Tumor

Safety, Dose Tolerance, Pharmacokinetics, and Pharmacodynamics Study of CPX-POM in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1; N=12; Recruiting; Sponsor: CicloMed LLC; Trial completion date: May 2021 ➔ Nov 2021; Trial primary completion date: May 2021 ➔ Nov 2021

Clinical • Trial completion date • Trial primary completion date • Oncology • Solid Tumor

CPX-POM-003: Study of Fosciclopirox in Patients With Relapsed/Refractory Acute Myeloid Leukemia (clinicaltrials.gov) - P1b/2a; N=28; Recruiting; Sponsor: CicloMed LLC; Not yet recruiting ➔ Recruiting

Clinical • Combination therapy • Enrollment open • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Safety, dose tolerance, pharmacokinetics, and pharmacodynamics of fosciclopirox (CPX-POM) in patients with advanced solid tumors. (ASCO-GU 2020) - P1; "IV CPX-POM was well tolerated with treatment-related AEs primarily CNS-related. At MTD, systemic and urinary CPX exposures exceeding in vitro IC50 values by several-fold. The 900 mg/m2 dose is currently being evaluated in an expansion cohort study in cisplatin-ineligible muscle invasive bladder cancer patients scheduled for cystectomy."

Clinical • PK/PD data • CXCL8 • IL6 • NOTCH1

CicloMed Announces Initiation of Phase 1B Trial of Fosciclopirox in Newly Diagnosed and Recurrent Urothelial Cancer Patients (GlobeNewswire) - “CicloMed LLC…announced that the Phase 1B clinical trial of fosciclopirox for the treatment of bladder cancer is now open…In addition, the company announced at that time it had opened a Phase 1 expansion cohort study (NCT04608045) at three US sites evaluating fosciclopirox in a neoadjuvant setting in muscle-invasive bladder cancer patients scheduled for cystectomy. The Phase 1 expansion cohort study is expected to complete enrollment by September 2021.”

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

Fosciclopirox suppresses growth of high-grade urothelial cancer by targeting the γ-secretase complex. (PubMed, Cell Death Dis) - P1, P2 | "Additionally, there was a reduction in Presenilin 1 and Hes-1 expression in the bladder tissues of CPX-POM treated animals. Following the completion of the first-in-human Phase 1 trial (NCT03348514), the pharmacologic activity of fosciclopirox is currently being characterized in a Phase 1 expansion cohort study of muscle-invasive bladder cancer patients scheduled for cystectomy (NCT04608045) as well as a Phase 2 trial of newly diagnosed and recurrent urothelial cancer patients scheduled for transurethral resection of bladder tumors (NCT04525131)."

Journal • Bladder Cancer • Gastrointestinal Disorder • Genito-urinary Cancer • Hematological Disorders • Hematological Malignancies • Oncology • Oral Cancer • Solid Tumor • Urothelial Cancer • HES1