RP12146 / Rhizen - LARVOL DELTA

Safety, Pharmacokinetics and Anti-tumor Activity of RP12146, in Patients With Solid Tumors (clinicaltrials.gov) - P1 | N=23 | Completed | Sponsor: Rhizen Pharmaceuticals SA | Active, not recruiting ➔ Completed

Metastases • Trial completion • Breast Cancer • Endometrial Cancer • Fallopian Tube Cancer • Lung Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Small Cell Lung Cancer • Solid Tumor • HRD

Safety, Pharmacokinetics and Anti-tumor Activity of RP12146, in Patients With Solid Tumors (clinicaltrials.gov) - P1 | N=23 | Active, not recruiting | Sponsor: Rhizen Pharmaceuticals SA | Trial primary completion date: Dec 2023 ➔ Mar 2024

Metastases • Trial primary completion date • Breast Cancer • Endometrial Cancer • Fallopian Tube Cancer • Lung Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Small Cell Lung Cancer • Solid Tumor • HRD

Anti-tumor activity of RP12146, a PARP1/2 inhibitor, in patients with metastatic castration-resistant prostate cancer. (ASCO-GU 2024) - P1 | "In combination with abiraterone, RP12146 synergistically inhibited cell growth in both androgen-dependent (VCAP, LNCaP) and androgen-independent (C4-2) metastatic prostate cancer cell lines, signifying the role of RP12146 in this indication. RP12146 has shown a differentiated safety profile so far in patients with mCRPC, with limited hematological toxicities as compared to the first-generation PARP inhibitors. Encouraging activity was seen in mCRPC patients with BRCA2 mutation. Updated safety and efficacy data will be provided at the time of presentation."

Clinical • Metastases • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor • BRCA • BRCA2 • CDK12 • CHEK2 • PARP2

Safety, pharmacokinetics and anti-tumor activity of RP12146, a PARP1/2 inhibitor, in patients with locally advanced or metastatic solid tumors. (ASCO 2023) - P1 | "RP12146 showed a differentiated safety profile so far with limited hematological toxicities reported as compared to the first-generation PARP inhibitors. Updated safety and efficacy data will be provided at the time of presentation. Clinical trial information: NCT05002868."

Clinical • Metastases • PK/PD data • Anemia • Breast Cancer • Genito-urinary Cancer • Hematological Disorders • Oncology • Ovarian Cancer • Prostate Cancer • Solid Tumor • BRCA • BRCA2 • CDK12 • CHEK2 • DRD • PARP2 • RAD51C

Safety, Pharmacokinetics and Anti-tumor Activity of RP12146, a PARP Inhibitor, in Patients With Locally Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=23 | Active, not recruiting | Sponsor: Rhizen Pharmaceuticals SA | Recruiting ➔ Active, not recruiting | N=60 ➔ 23 | Trial completion date: Aug 2023 ➔ Feb 2024 | Trial primary completion date: May 2023 ➔ Dec 2023

Enrollment change • Enrollment closed • Metastases • Trial completion date • Trial primary completion date • Breast Cancer • Endometrial Cancer • Fallopian Tube Cancer • Lung Cancer • Neuroendocrine Tumor • Oncology • Ovarian Cancer • Peritoneal Cancer • Small Cell Lung Cancer • Solid Tumor • HRD

RP12146, a novel, selective, and potent small molecule inhibitor ofPARP 1/2, synergizes with SOC therapy in preclinical models of solidtumors (AACR-NCI-EORTC 2022) - P1 | "Combination of RP12146 withTemozolomide, SN-38, Topotecan, and Lurbinectedin demonstrated eitheradditive or synergistic effects manifested by an inhibition in growth, inductionof apoptosis and cell cycle arrest in Breast, Gastric, Glioma, Lung Cancer,and Ovarian cancer cell lines. Data demonstrate the therapeutic potential of RP12146 assingle agent and in combination in solid tumors. RP12146 is currently beingevaluated in Phase 1 clinical trials in patients with locally advanced ormetastatic solid tumors (NCT05002868)."

Preclinical • Brain Cancer • CNS Tumor • Gastric Cancer • Gastrointestinal Cancer • Glioma • Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Solid Tumor • ANXA5 • BRCA • PARP2

Activity of RP12146, a novel, selective, and potent small molecule inhibitor of PARP 1/2, in solid tumors (AACR 2022) - P1 | "Combination of RP12146 with Temozolomide, Topotecan, Lurbinectedin, and Abemaciclib demonstrated either additive or synergistic effects manifested by an inhibition in growth of solid tumor cell lines. Data demonstrate the therapeutic potential of RP12146 as single agent and in combination in solid tumors. RP12146 is currently being evaluated in Phase 1 clinical trials in patients with locally advanced or metastatic solid tumors (NCT05002868)."

Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor • BRCA • PARP2

Pre-clinical and early clinical assessment of the safety and anti-tumor activity of RP12146, a PARP1/2 inhibitor in solid tumors (ESMO 2022) - P1 | "Results RP12146 exhibited anti-tumor potential with TGI of 28% as a single agent and 95.19% with gemcitabine combination in the OVCAR-3 xenograft model. In the on-going clinical study, RP12146 has been well-tolerated in the first two cohorts and further evaluation at higher doses in dose escalation is underway. Updated safety and preliminary efficacy data will be provided at the time of presentation."

Preclinical • Breast Cancer • Genito-urinary Cancer • Oncology • Ovarian Cancer • Prostate Cancer • Solid Tumor • CDK12 • DRD • PARP2

Rhizen Pharmaceuticals AG Announces Upcoming Data Presentations at ESMO 2022 for Its Clinical Stage Assets; Tenalisib in Locally Advanced/ Metastatic Breast Cancer and RP12146 in Multiple Solid Tumors (Businesswire) - "P1/1b | N=60 | NCT05002868 | Sponsor: Rhizen Pharmaceuticals SA | "Dose escalation of a Phase -I/Ib trial of RP12146, a next generation PARP 1/2 inhibitor designed to overcome the safety liabilities associated with first generation PARP inhibitors, was successfully completed and is enrolling at the RP2D dose for the expansion phase. RP12146 showed dose related exposures with robust target engagement and notable absence of haematological toxicities viz anaemia and cytopenia."

P1 data • Preclinical • Oncology • Solid Tumor

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

Rhizen Pharmaceuticals AG Announces First Patient Dosing in a Phase I/Ib Study of Its Novel PARP Inhibitor (RP12146) in Patients With Advanced Solid Tumors (Businesswire) - "Rhizen Pharmaceuticals AG (Rhizen)...announced today that it has commenced dosing in a multi-center, phase I/Ib trial to evaluate its novel poly (ADP-ribose) polymerase (PARP) inhibitor (RP12146) in patients with advanced solid tumors. This two-part multi-center phase I/Ib study is being conducted in Europe and has been designed to initially determine safety, tolerability, maximum tolerated dose (MTD), and/or recommended phase II dose (RP2D) of RP12146 and to subsequently assess its anti-tumor activity in expansion cohorts with HRR mutation-enriched ES-SCLC, ovarian and breast cancer patients."

Trial status • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Safety, Pharmacokinetics and Anti-tumor Activity of RP12146, a PARP Inhibitor, in Patients With Locally Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1; N=60; Recruiting; Sponsor: Rhizen Pharmaceuticals SA; Not yet recruiting ➔ Recruiting

Enrollment open • Breast Cancer • Endometrial Cancer • Fallopian Tube Cancer • Lung Cancer • Neuroendocrine Tumor • Oncology • Ovarian Cancer • Peritoneal Cancer • Small Cell Lung Cancer • Solid Tumor • HRD • MRI

An Open-label Study to Assess the Safety, Pharmacokinetics and Anti-tumor Activity of RP12146, a PARP Inhibitor, in Patients With Locally Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1; N=60; Not yet recruiting; Sponsor: Rhizen Pharmaceuticals SA

New P1 trial • Breast Cancer • Endometrial Cancer • Fallopian Tube Cancer • Lung Cancer • Neuroendocrine Tumor • Oncology • Ovarian Cancer • Peritoneal Cancer • Small Cell Lung Cancer • Solid Tumor • HRD • MRI

[VIRTUAL] Preclinical profile of RP12146, a novel, selective, and potent small molecule inhibitor of PARP1/2 (AACR 2021) - "Efficay was superior compared to Olaparib tested at an equivalent dose. Data demonstrate the therapeutic potential of RP12146 in BRCA mutant tumors. Testing in patients is planned in H1 2021."

Preclinical • Oncology • BRCA • BRCA1 • PARP2