RP7214 / Rhizen - LARVOL DELTA

Study to Evaluate the Safety, Pharmacokinetics and Clinical Activity of RP7214 in Combination With Azacitidine in Patients With Myelodysplastic Syndrome, Chronic Myelomonocytic Leukemia and Acute Myeloid Leukemia (clinicaltrials.gov) - P1/2 | N=0 | Withdrawn | Sponsor: Rhizen Pharmaceuticals SA | N=36 ➔ 0 | Not yet recruiting ➔ Withdrawn

Combination therapy • Enrollment change • Trial withdrawal • Acute Myelogenous Leukemia • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

A First in man study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of RP7214, a Dihydroorotate Dehydrogenase (DHODH) inhibitor in Healthy Subjects. (PubMed, Br J Clin Pharmacol) - P1 | "Inhibition of DHODH, as evidenced by increased DHO levels was observed, confirming target engagement. The high systemic exposure with a favourable safety profile shows potential for the development of RP7214 in SARS-CoV-2 and acute myeloid leukemia (NCT04680429)."

Clinical • Journal • PK/PD data • Acute Myelogenous Leukemia • Hematological Malignancies • Infectious Disease • Leukemia • Novel Coronavirus Disease • Oncology • Respiratory Diseases

Study to Evaluate the Safety, Pharmacokinetics and Clinical Activity of RP7214 in Combination With Azacitidine in Patients With Myelodysplastic Syndrome, Chronic Myelomonocytic Leukemia and Acute Myeloid Leukemia (clinicaltrials.gov) - P1/2 | N=36 | Not yet recruiting | Sponsor: Rhizen Pharmaceuticals SA | Initiation date: Apr 2022 ➔ Jan 2023

Combination therapy • Trial initiation date • Acute Myelogenous Leukemia • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

Study to Evaluate the Efficacy and Safety of Oral RP7214, a DHODH Inhibitor, in Patients With Symptomatic Mild COVID-19 Infection. (clinicaltrials.gov) - P2 | N=163 | Completed | Sponsor: Rhizen Pharmaceuticals SA | Recruiting ➔ Completed

Trial completion • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • CD8 • CRP • IL6

Activity of RP7214, a novel, selective, and potent small molecule inhibitor of DHODH, in AML (AACR 2022) - "Herein, we describe the efficacy of RP7214 as a single agent and in combination with standard of care drugs in preclinical models of AML Cell viability of AML cell lines (U937, HL-60, THP-1, and KG-1) following incubation with RP7214 as a single agent or in combination with Azacytidine or Venetolcax for 72 h was determined in an MTT-based assay...Similarly, combination of 3 µM-RP7214 with 3 nM Venetoclax demonstrated 15% (P < 0.05) inhibition of cell growth compared to single agents in MV-4-11 cell line. Results demonstrate the utility of RP7214 as a single agent and in combination with standard of care drugs in inducing apoptosis and promoting differentiation to fully mature cells in AML. A Phase 2a trial in AML patients is planned."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • ITGAM

Rhizen Pharmaceuticals AG Presents Data on Its Differentiated PARP and DHODH Inhibitor Programs at AACR 2022 (Businesswire) - "Rhizen Pharmaceuticals AG...announced the release of data on its differentiated next-generation clinical-stage PARP (Poly ADP-Ribose Polymerase) and DHODH (DiHydro Orotate DeHydrogenase) inhibitor programs at the American Association for Cancer Research (AACR) 2022 Annual Meeting. Rhizen’s poster presentations describe the preclinical characterization and differentiated features of its novel PARP inhibitor (RP12146) and preclinical data supporting the broad positioning of its DHODH inhibitor (RP7214) in AML."

Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • Solid Tumor

Study to Evaluate the Safety, Pharmacokinetics and Clinical Activity of RP7214 in Combination With Azacitidine in Patients With Myelodysplastic Syndrome, Chronic Myelomonocytic Leukemia and Acute Myeloid Leukemia (clinicaltrials.gov) - P1/2 | N=36 | Not yet recruiting | Sponsor: Rhizen Pharmaceuticals SA

Combination therapy • New P1/2 trial • Acute Myelogenous Leukemia • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

Study to Evaluate the Efficacy and Safety of Oral RP7214, a DHODH Inhibitor, in Patients With Symptomatic Mild COVID-19 Infection. (clinicaltrials.gov) - P2; N=204; Recruiting; Sponsor: Rhizen Pharmaceuticals SA; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • CD8 • CRP • IL6 • PCR

A Single and Multiple Ascending and Food Effect Study of RP7214, a DHODH Inhibitor in Healthy Adult Subjects (clinicaltrials.gov) - P1; N=42; Completed; Sponsor: Rhizen Pharmaceuticals SA; Active, not recruiting ➔ Completed

Trial completion

Study to Evaluate the Efficacy and Safety of Oral RP7214, a DHODH Inhibitor, in Patients With Symptomatic Mild SARS-CoV-2 Infection. (clinicaltrials.gov) - P2; N=204; Not yet recruiting; Sponsor: Rhizen Pharmaceuticals SA

New P2 trial • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • PCR

A Single and Multiple Ascending and Food Effect Study of RP7214, a DHODH Inhibitor in Healthy Adult Subjects (clinicaltrials.gov) - P1; N=42; Active, not recruiting; Sponsor: Rhizen Pharmaceuticals SA; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed

A Single and Multiple Ascending and Food Effect Study of RP7214, a DHODH Inhibitor in Healthy Adult Subjects (clinicaltrials.gov) - P1; N=42; Recruiting; Sponsor: Rhizen Pharmaceuticals SA; N=18 ➔ 42; Trial primary completion date: Mar 2021 ➔ Jun 2021

Clinical • Enrollment change • Trial primary completion date

A Single Oral Dose Study of RP7214, a DHODH Inhibitor in Healthy Adult Subjects (clinicaltrials.gov) - P1; N=18; Recruiting; Sponsor: Rhizen Pharmaceuticals SA; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open

A Single Oral Dose Study of RP7214, a DHODH Inhibitor in Healthy Adult Subjects (clinicaltrials.gov) - P1; N=18; Not yet recruiting; Sponsor: Rhizen Pharmaceuticals SA

Clinical • New P1 trial

Rhizen Pharmaceuticals Announces US FDA Acceptance of its IND Application for RP7214 in SARS-CoV-2 Infection, Phase 1 Clinical Trial of RP7214 Set to Begin Early December 2020 (Equitybulls) - "Rhizen Pharmaceuticals...today announced the approval of its Investigational New Drug (IND) application by the U.S. Food and Drug Administration (FDA) to study its oral DHODH inhibitor for SARS-CoV-2 infection. The company announced that initial study shall evaluate single ascending doses of RP7214 in healthy volunteers and that dosing is expected to commence in early December 2020. The company also announces positive feedback from the FDA during its pre-IND discussion on its plans to follow-up this study with a multiple-ascending dose study in Covid-19 patients....Further, the IND-enabling preclinical studies have shown RP7214 to be orally available, safe and tolerable with predictable dose-linear pharmacokinetics."

IND • New P1 trial • Preclinical • Novel Coronavirus Disease