On October 11, 2022 Pacylex reported that the US Department of Defense (DOD) awarded The University of Texas MD Anderson Cancer Center $1.4 million to treat Acute Myeloid Leukemia (AML) patients with PCLX-001, a first-in-class N-myristoylation inhibitor in clinical development by Pacylex (Press release, Greenfire, OCT 11, 2022, View Source [SID1234624499]). PCLX-001 is being studied in non-Hodgkin lymphoma (NHL) and solid tumor cancer patients at 4 clinical sites in Canada. This investigation will be the first of an N-myristoyl transferase (NMT) inhibitor, PCLX-001, in AML patients.
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This clinical study is being undertaken because PCLX-001 showed promise in preclinical testing in AML cell lines and patient blast cells where it induced apoptosis at concentrations that spared a majority of normal, healthy peripheral blood lymphocytes and monocytes and PCLX-001 monotherapy had dose-dependent anticancer activity in AML MV-4-11 cell line derived xenografts (CDXs) and AML patient derived xenografts (PDXs) and produced complete remissions in subcutaneous AML CDX. In tail-vein injected PDX models, PCLX-001 treatment resulted in up to 95% reduction of human CD45+ cells in peripheral blood and bone marrow.
"This clinical study is the culmination of work we have been doing in AML models for several years," said Luc Berthiaume, CSO of Pacylex. "It combines insights on the role myristoylation may play in cancer with an NMT inhibitor Pacylex licensed for exclusive development".
Dr. Naveen Pemaraju will be the principal investigator for the AML clinical study at MD Anderson. It will enroll AML patients whose disease has progressed despite other cancer therapies. "We look forward to seeing PCLX-001 tested in AML patients given how responsive this cancer is in other non-clinical studies", said Dr. John Mackey, CMO of Pacylex. "In our ongoing dose-escalation clinical study, 16 patients have received PCLX-001 without observing dose limiting toxicities and the drug levels delivered are in the range we think can help AML patients."
Four clinical sites are involved in the ongoing clinical study in NHL and solid tumor patients in Canada; the University of Alberta Cross Cancer Institute, Princess Margaret Hospital in Toronto, Centre Hospitalier de l’Université de Montréal (CHUM) and the BC Cancer Agency in Vancouver. That study has dosed 16 patients and will include approximately 15-20 more in the initial phase and is registered at ClinicalTrials.gov Identifier: NCT04836195.
PCLX-001
PCLX-001 (aka DDD86481) is a first-in-class, small molecule NMT inhibitor originally developed by the University of Dundee Drug Discovery Unit as part of a program to treat African sleeping sickness, funded by Welcome Trust. Pacylex is developing PCLX-001 in the form of a once-a-day pill initially to treat leukemia and lymphoma. PCLX-001 has also been shown to inhibit the growth of lung and breast cancer tumors in animal models. In leukemia, lymphoma and breast cancer patients, the levels of NMT2 is correlated with survival, suggesting an important biological role in these cancers. In tests using cultured cancer cells in vitro, PCLX-001 is at least ten times as potent as ibrutinib (Imbruvica) and dasatinib (Sprycel), two clinically approved drugs currently used to treat hematologic malignancies.