Shanghai: Tuesday, August 29, 2017: Hutchison MediPharma Limited (“HMP”) has initiated a Phase I clinical trial of HMPL‑689 in China. HMPL-689 is a novel, highly selective and potent small molecule inhibitor targeting phosphoinositide-3 kinase delta isoform (“PI3Kδ”), a key component in the B-cell receptor (“BCR”) signaling pathway.
This Phase I study is a multi‑center, open‑label, two‑stage study to evaluate safety, tolerability, pharmacokinetics (“PK”) and preliminary efficacy of HMPL-689 monotherapy in relapsed and/or refractory non-Hodgkin lymphoma patients. During the initial dose-escalation stage, the primary objective is to determine the maximum tolerated dose (MTD) or the recommended Phase II dose (“RP2D”). Safety, tolerability and preliminary efficacy of HMPL-689 at the RP2D will be further studied in a subsequent dose-expansion stage in which several subtypes of lymphoma patients will be evaluated. Additional details about this study can be found at clinicaltrials.gov, using identifier NCT03128164.
PI3K signaling is mediated by four different catalytic isoforms (p110α, β, ɣ, δ). The δ (delta) isoform is the most critical isoform and a proven target in the BCR signaling pathway. This isoform is restricted to hematopoietic cells and is highly expressed in lymphoid cells.
HMPL-689 is a novel, potential best-in-class, highly selective and potent small molecule inhibitor targeting the isoform PI3Kδ. HMPL-689 was designed for superior PI3Kδ isoform selectivity, in particular to not inhibit PI3Kɣ (gamma), to minimize the risk of serious infection caused by immune suppression. In preclinical PK studies, HMPL-689’s PK properties have been found to be favorable with expected good oral absorption, moderate tissue distribution and low clearance. HMPL-689 is also expected to have low risk of drug accumulation and drug-to-drug interaction and is highly potent, particularly at the whole blood level.
A Phase I, first-in-human, dose escalation study in healthy adult volunteers in Australia to evaluate the pharmacokinetic and safety profile following single oral dosing HMPL-689 was completed in 2016. Results were as expected with linear PK properties and good safety profile. Additional details about this study can be found at clinicaltrials.gov, using identifier NCT02631642.