FHND6091 / Sino Biopharm - LARVOL DELTA

Proteasome inhibitor FHND6091: A potent therapeutic candidate forPTEN-deficient cholangiocarcinoma (AACR 2024) - "In a PDX xenograft model with PTEN deficiency, gavage administration of FHND6091 BIW at 1.0 mg/kg (first week) / 1.5 mg/kg (subsequent two weeks) exhibited advanced anti-tumor activity (TGI = 52.32%) compared to intraperitoneal administration of Bortezomib at 0.5 mg/kg BIW (TGI = 31.88%). FHND6091, characterized by its irreversibility, high potency and oral bioavailability, emerges as a promising proteasome inhibitor for the treatment of both hematologic and solid tumors. These findings strongly support FHND6091 as a potential candidate for the treatment of CCA in clinical settings. Furthermore, the regulating of sensitivity to proteasome inhibitors by the PTEN status extends beyond cholangiocarcinoma to encompass various human cancers, such as ovarian, prostate, and digestive system malignancies."

First-in-human • Biliary Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Multiple Myeloma • Oncology • Solid Tumor • PTEN

Proteasome inhibitors FHND6091 enhance the ability of NK cells to kill tumor cells through multiple mechanisms. (PubMed, Eur J Pharmacol) - "Subsequently, upon engaging with the surface activation receptors of NK cells, these ligands triggered NK cell activation, leading to the subsequent elimination of tumor cells. Thus, our findings elucidated the mechanism whereby FHND6091 exerted its immunotherapeutic activity as a STING agonist, enhancing the killing ability of NK cells against tumor cells."

Journal • Tumor cell • Hematological Malignancies • Multiple Myeloma • Oncology • CALR • STING • ULBP2

A Study Evaluating Safety, Tolerability and Clinical Activity of FHND6091 in Patients With Multiple Myeloma (clinicaltrials.gov) - P1 | N=40 | Recruiting | Sponsor: Jiangsu Chia Tai Fenghai Pharmaceutical Co., Ltd. | Trial completion date: Dec 2023 ➔ Dec 2024 | Trial primary completion date: Dec 2022 ➔ Dec 2023

Trial completion date • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology

Preclinical Pharmacokinetics, Tissue Distribution and in vitro Metabolism of FHND6091, a Novel Oral Proteasome Inhibitor. (PubMed, Drug Des Devel Ther) - "Moreover, only a small fraction of the parent compound was excreted via feces and urine and oxidative metabolites were detected in feces and plasma. The overall preclinical pharmacokinetic profile supported the selection and development of FHND6091 as a clinical candidate."

Journal • PK/PD data • Preclinical • Hematological Malignancies • Multiple Myeloma • Oncology • Targeted Protein Degradation