Edmonton, Alberta, Canada May 24, 2024. Pacylex Pharmaceuticals Inc. (Pacylex) is a clinical-stage pharmaceutical company developing N-myristoyltransferase (NMT) inhibitors as targeted therapies for the treatment of hematologic cancers and solid tumors. Today Pacylex announced that complete Phase 1 clinical study results for zelenirstat, a proprietary, potent, NMTi, will be presented at the American Society of Clinical Oncology (ASCO) Annual Meeting from May 31 to June 4, 2024, at McCormick Place in Chicago, Illinois.
The Phase 1 dose escalation safety and tolerability study was conducted in 29 patients with refractory/relapsed (r/r) lymphoma and refractory solid tumors who averaged 4 lines of prior therapy. Zelenirstat, administered as a once daily oral medication, was well-tolerated in Phase 1 patients up to the recommended Phase 2 dose (RP2D) with no dose limiting toxicities observed in 6 dose levels. The most common treatment related adverse events were mild to moderate gastrointestinal side effects which were self-limiting and occurred in a minority of patients.
The 7 patients receiving the recommended Phase 2 dose had significantly better progression free and overall survival than the 17 treated at lower doses; 57% had stable disease or better for six months or longer, despite having 5 different types of cancer. Prolonged Stable Disease was observed in a person with colorectal cancer that had only short-term benefit from any of the 6 prior lines of therapy; this participant continues to receive the RP2D more than a year after starting therapy and had reductions of approximately 50% in CEA (carcinoembryonic antigen) and tumor volumes.
Zelenirstat appears to work in different cancers by inhibiting the myristoylation required for assembly, translocation, and/or function of validated targets like B-cell receptor, EGFR, and VEGFR. Zelenirstat also blocks Complex I formation in mitochondria of cancer cells which shuts down oxidative phosphorylation, especially critical for metastasis and cancer stem cells.
A poster will present the complete safety results and efficacy signals from the Company’s Phase 1 study of zelenirstat, as well as evidence for mechanisms of action relevant to anticancer activity in different cancer types. The Company’s CMO, Dr. John Mackey, and CEO, Dr. Michael Weickert, will be available during the poster session and for one-on-one meetings. The details of the poster are below and available HERE:
“The safety of zelenirstat in Phase 1 was superior to many other systemic therapies, and even though the phase I population had exhausted standard options and were not selected for their potential to respond to an NMT inhibitor, zelenirstat therapy produced prolonged stable disease or better in 57% of the patients receiving the recommended Phase 2 dose,” said Dr. John Mackey, CMO of Pacylex Pharmaceuticals.
“Our emerging understanding is zelenirstat simultaneously undermines many mechanisms critical to cancer signaling, tumor blood supply, and energy production by disrupting myristoylation upon which these processes depend”, said Dr. Michael Weickert, CEO of Pacylex. “This means zelenirstat has exciting potential as an important therapeutic option across many different cancers.”
Zelenirstat is currently being dosed in patients in two Phase 2a studies, in refractory and relapsed B-cell non-Hodgkin’s lymphoma and in advanced refractory colorectal cancer patients, at 4 clinical sites in Canada.
For additional information, please visit www.pacylex.com.
For more information:
Pacylex Pharmaceuticals Contact: Michael J. Weickert
CEO, Pacylex Pharmaceuticals, Inc.
E: michael.weickert@pacylex.com
P: 650-218-1840
Twitter @Pacylex (https://twitter.com/pacylex)
LinkedIn (www.linkedin.com/company/pacylex-pharma)
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About zelenirstat (PCLX-001)
Zelenirstat (formerly identified as PCLX-001) is a first-in-class, oral, small molecule NMTi being developed to treat patients with leukemia, lymphoma, and solid tumors. Zelenirstat selectively killed cancer cells in vitro and in animal models has been shown to regress hematologic malignancies and inhibit the growth of lung and breast cancer tumors. In AML models, zelenirstat preferentially killed leukemic stem enriched cell populations and reduction of the leukemic burden directly in the bone marrow.
About zelenirstat Phase 1 and 2 studies
Pacylex completed the dose escalation phase of a Phase 1 multiple ascending dose safety, tolerability, and pharmacokinetics study on zelenirstat in people with relapsed/refractory lymphoma and refractory solid tumors (NCT04836195). A recommended Phase 2 dose was determined. Zelenirstat demonstrated an acceptable safety and tolerability profile, pharmacokinetics consistent with once daily oral dosing, and early signs of efficacy.
Zelenirstat is currently being studied in a Phase 2a open-label study designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and clinical activity of zelenirstat in patients with relapsed/refractory B-cell non-Hodgkin Lymphoma (NHL) and a separate Phase 2a cohort in patients with refractory metastatic colorectal cancer that has progressed despite all available standard therapies.
About Pacylex Pharmaceuticals
Pacylex is a clinical-stage pharmaceutical company headquartered in Edmonton, Alberta, Canada, targeting hematologic and solid cancers with orally bioavailable NMT inhibitors. Zelenirstat is the lead drug in a new class of NMT inhibitors, enabling Pacylex to exploit NMTs as new clinical targets for cancer treatment. Pacylex is conducting two multi-center Phase 2a studies in Canada in patients with relapsed/refractory NHL and refractory metastatic colorectal cancer. The IND for a Phase 1 multiple ascending dose study in acute myeloid leukemia (AML) has been cleared and the FDA has granted zelenirstat both Orphan Drug Designation and Fast Track Designation for AML. The US Department of Defense is supporting the initial clinical investigation of zelenirstat in patients with AML. The Cure Cancer Foundation supported initial clinical studies through its World’s Longest Games.
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