RP4010 / Rhizen - LARVOL DELTA

Efficacy of RP4010, a calcium release-activated calcium (CRAC) channel inhibitor, in preclinical models of gastrointestinal cancers (AACR 2019) - P1; "RP4010 synergized with gemcitabine and nab-paclitaxel in PDAC; nab-paclitaxel and docetaxel in GC (CI<1), and significantly enhanced the activity of everolimus in PNETs. Our studies indicate that RP4010, a novel CRAC channel inhibitor could be a viable therapeutic option in GI cancers that need further clinical evaluation. A multi-center Phase I/IB dose-escalation trial evaluating the safety and efficacy of RP4010, a CRAC channel inhibitor in patients with relapsed or refractory Lymphomas is currently ongoing in USA (ClinicalTrials.gov Identifier: NCT03119467)."

Preclinical • Gastric Cancer • Gastrointestinal Cancer • Hematological Malignancies • Lymphoma • Neuroendocrine Tumor • Oncology • Pancreatic Cancer

Developing a Mathematical Model of Intracellular Calcium Dynamics for Evaluating Combined Anticancer Effects of Afatinib and RP4010 in Esophageal Cancer. (PubMed, Int J Mol Sci) - "Guided by simulation, we were able to identify a proper ratio of afatinib and RP4010 for combined treatment, and such a combination presented synergistic anticancer-effect evidence by experimental measurement of intracellular Ca and cell proliferation. This intracellular Ca dynamic-based mathematical simulation approach could be useful for a rapid and cost-effective evaluation of combined targeting therapy drugs."

Journal • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastrointestinal Cancer • Oncology • Squamous Cell Carcinoma

Store-operated calcium signaling is an effective therapeutic target in AML (AACR 2018) - P1; "...Standard 7 + 3 chemotherapy consisting of cytarabine in combination with an anthracycline such as daunorubicin has been used for more than four decades...Importantly, RP4010 efficacy is not altered in the presence of stromal cell support...A Phase 1/1b study in R/R Non-Hodgkin Lymphoma (NHL) patients is currently underway in the US, and our data would support expansion to other hematological malignancies as well, particularly AML. Senior authors J. C. B and E. H contributed equally to this work."

Acute Myelogenous Leukemia • Non-Hodgkin’s Lymphoma

Calcium Release-Activated Calcium (CRAC) Channel Inhibition Suppresses Pancreatic Ductal Adenocarcinoma Cell Proliferation and Patient-Derived Tumor Growth. (PubMed, Cancers (Basel)) - "Anti-tumor activity of RP4010 was enhanced in the presence of gemcitabine/nab-paclitaxel in a PDAC PDx model. Our study indicates that targeting CRAC channel could be a viable therapeutic option in PDAC that warrants further clinical evaluation."

Clinical • Journal • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor

Safety and Efficacy Study of RP4010, in Patients With Relapsed or Refractory Lymphomas (clinicaltrials.gov) - P1; N=21; Terminated; Sponsor: Rhizen Pharmaceuticals SA; N=60 ➔ 21; Trial completion date: May 2020 ➔ Dec 2019; Recruiting ➔ Terminated; Study has been stopped after reviewing PK and safety results

Clinical • Enrollment change • Trial completion date • Trial termination

RP4010, a small molecule inhibitor of Store-Operated Calcium Entry (SOCE), potentiates activity of Gilteritinib and Cytarabine in preclinical models of AML (AACR-NCI-EORTC 2019) - "Findings provide a rationale for use of this molecule in clinical trials involving naïve or relapsed/refractory AML patients. RP4010 is currently being evaluated in a Phase-1 dose-escalation study in patients with relapsed/refractory lymphomas."

Preclinical

Rhizen Pharmaceuticals S.A. announces poster presentation of RP4010, a novel first-in-class store-operated calcium entry (SOCE) inhibitor in preclinical models of Acute Myeloid Leukemia (AML) at the 2019 AACR-NCI-EORTC Conference in Boston (GlobeNewswire, Rhizen Pharmaceuticals SA) - “Rhizen Pharmaceuticals S.A. announces poster presentation of RP4010, a novel first-in-class SOCE inhibitor in preclinical models of Acute Myeloid Leukemia (AML). Highlights from the poster include: RP4010 demonstrated single-agent activity and remarkable potentiation in activity of standard of care/approved drugs for treating AML. RP4010 potentiated the activity of gilteritinib (XOSPATA) in reducing cell growth, induction of apoptosis, cell cycle arrest, regulation of expression of genes involved in myeloid differentiation and modulation of downstream markers. RP4010 when combined with cytarabine (ARA-C), demonstrated significant anti-tumor activity in an MV-4-11 xenograft model.”

Preclinical

Targeting Orai1-mediated store-operated calcium entry by RP4010 for anti-tumor activity in esophagus squamous cell carcinoma. (PubMed, Cancer Lett) - "Treatment with RP4010 resulted in reduction of intracellular Ca oscillations, caused cell cycle arrest at G0/G1 phase in vitro, decreased nuclear translocation of nuclear factor kappa B (NF-κB) in vivo and in vitro, and inhibited tumor growth in vivo. Taken together, data demonstrated the therapeutic potential of RP4010 in EC patients via inhibition of SOCE-mediated intracellular Ca signaling."

Journal

Rhizen Pharmaceuticals S.A. announces poster presentation of RP4010, a calcium release-activated calcium (CRAC) channel inhibitor in preclinical models of Gastrointestinal (GI) Cancers at the 2019 AACR Annual Meeting (GlobeNewswire, Rhizen Pharmaceuticals SA) - Rhizen Pharmaceuticals S.A. announces poster presentation of RP4010, a novel first-in-class CRAC channel inhibitor in preclinical models of Gastrointestinal (GI) cancers. Treatment of GI cancer cell lines with single-agent RP4010 decreased cell growth . RP4010 synergized with gemcitabine and nab-paclitaxel in Pancreatic Ductal Adenocarcinoma (PDAC). RP4010 synergized with nab-paclitaxel in Gastric Cancer (GC). RP4010 significantly enhanced the activity of everolimus in Pancreatic Neuroendocrine Tumors (PNETs).

Preclinical

Safety and Efficacy Study of RP4010, in Patients With Relapsed or Refractory Lymphomas (clinicaltrials.gov) - P1; N=60; Recruiting; Sponsor: Rhizen Pharmaceuticals SA; Trial completion date: Dec 2019 ➔ May 2020; Trial primary completion date: Dec 2018 ➔ Dec 2019

Clinical • Trial completion date • Trial primary completion date