Pacylex Pharmaceuticals Announces First Patient Dosed in a Phase 2a Study of zelenirstat in Patients with Refractory Metastatic Colorectal Cancer

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Key Takeaways

  • Pacylex initiates a Phase 2a study in colorectal cancer with the first patient dosed with the recommended Phase 2 dose (RP2D)
  • Prolonged Stable Disease of 6 months or longer was observed in 57% (4/7) of the solid tumor patients receiving RP2D in the Phase 1 study
  • A person with metastatic colorectal cancer who had progressive disease after each of six lines of drug therapy continues full dose zelenirstat in his 13th month on the Phase 1 study, with ongoing reductions of approximately 50% in CEA and tumor volumes. This is longer disease control than was achieved with any prior line of treatment.

April 18, 2024. Edmonton, Alberta, Canada. Pacylex Pharmaceuticals Inc. (Pacylex) is a clinical-stage pharmaceutical company focused on the development of a new class of targeted therapies, N-myristoyltransferase inhibitors (NMTi) for the treatment of hematologic and solid tumor cancers. Today Pacylex announced the first patient has been dosed in a Phase 2a expansion study in patients with refractory metastatic colorectal cancer. 

The Phase 1 dose escalation safety and tolerability study was conducted in 29 heavily pre-treated solid tumor and lymphoma patients who averaged 4 lines of prior drug therapy on which they relapsed or were refractory. Eight colorectal cancer patients were among those included in the study. The most common treatment related adverse events identified in the trial were mild to moderate gastrointestinal side effects which were self-limiting and occurred in a minority of patients. A recommended Phase 2 dose (RP2D) for expansion studies was established. Zelenirstat prolonged progression free and overall survival in Phase 1 solid tumor patients receiving the RP2D, compared to those receiving lower doses. Prolonged Stable Disease of 6 months or longer was observed in 57% (4/7) of the patients receiving RP2D, including a patient with metastatic colorectal cancer continuing on treatment for more than 1 year with reductions of approximately 50% in CEA (carcinoembryonic antigen) and tumor volumes. 

“Given the patient benefits and excellent tolerability seen in our Phase 1 study, and particularly in our sentinel colorectal cancer patient, we are eager to see if other colorectal cancer patients receiving our Phase 2 dose will also benefit,” said Dr. John Mackey, CMO of Pacylex. “People with refractory colorectal cancer desperately need new treatment options, and we are investigating whether zelenirstat can provide that.”

“Adding colorectal cancer as our first solid tumor indication explores the broad potential for zelenirstat, a first-in-class oral cancer therapy, in both hematologic cancers and solid tumors,” said Pacylex CEO Dr. Michael Weickert. “The importance of myristoylation to many cancer processes is underappreciated, and Pacylex is way ahead in developing this novel therapeutic class, NMT inhibitors, to treat cancer refractory to available treatments.”

The Company has an ongoing Phase 2a study of patients with B-cell non-Hodgkin lymphoma. This colorectal cancer Phase 2a expansion study will enroll up to 20 subjects to assess the preliminary clinical activity and confirm the safety of zelenirstat in refractory colorectal cancer.

For additional information, please visit www.pacylex.com.

Pacylex Pharmaceuticals Contact: Michael J. WeickertCEO, Pacylex Pharmaceuticals, Inc.

E: michael.weickert@pacylex.com

P: 650-218-1840


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 killed leukemic stem enriched cell populations and allowed the regeneration and growth of normal bone marrow cells.

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 relapsed/refractory lymphoma and solid tumor patients (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.



Key Takeaways

  • Pacylex initiates a Phase 2a study in colorectal cancer with the first patient dosed with the recommended Phase 2 dose (RP2D)
  • Prolonged Stable Disease of 6 months or longer was observed in 57% (4/7) of the solid tumor patients receiving RP2D in the Phase 1 study
  • A person with metastatic colorectal cancer who had progressive disease after each of six lines of drug therapy continues full dose zelenirstat in his 13th month on the Phase 1 study, with ongoing reductions of approximately 50% in CEA and tumor volumes. This is longer disease control than was achieved with any prior line of treatment.
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Adding colorectal cancer as our first solid tumor indication explores the broad potential for zelenirstat, a first-in-class oral cancer therapy, in...
Michael Weickert — CEO

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