Repurposed drug shows potential as leukaemia treatment

A drug developed at the University of Dundee for a neglected tropical disease could be repurposed to treat leukaemia following Fast Track Designation by the U.S. Food and Drug Administration (FDA).

The drug, originally known as DDD86481 and now named PCLX-001, will be trialled in adult patients with relapsed or refractory acute myeloid leukaemia (AML). Fast Track Designation facilitates drug development and expedites the review of new therapies intended to treat or prevent serious conditions and address unmet medical needs.

PCLX-001 was originally developed by Dundee’s Drug Discovery Unit as part of a program to treat African sleeping sickness. The compound is an analogue of DDD85646, which inhibited an essential function (myristoylation) in the parasite that causes sleeping sickness but was not suitable to treat the latter stages of the disease that affect the brain.

During this research, the Dundee team discovered the compound could also kill some human cancer cells by the same process, but they could not identify which cancers were appropriate for clinical trials.

The entire family of related NMT-inhibiting compounds was then licensed by Canadian pharmaceutical company Pacylex Pharmaceuticals, Inc., who are developing PCLX-001 as a once-a-day oral pill initially to treat leukaemia and lymphoma. It has also since been shown to inhibit the growth of lung and breast cancer tumours in animal models.

Professor David Gray, Head of Biology at the Drug Discovery Unit, said, “This is an exciting development that demonstrates how complementary scientific research can have tremendous impact at the global level.

“We were frustrated in our efforts to develop DDD85646 as a drug to use against African sleeping sickness. At the same time, Dr Luc Berthiaume, from the University of Alberta, had a deep understanding of cancers he believed such compounds could work against, but did not have the compounds to prove his theories.

“It was therefore serendipitous that Luc was introduced to PCLX-001, then known as DDD86481, at a seminar he gave at Dundee and more fully at a subsequent conference he invited me to speak at. Everyone at the DDU is delighted to hear that PCLX-001 has received Fast Track Designation. This is another important step towards delivering real benefits to cancer patients.”

In 2020, more than 474,500 new cases of leukaemia were reported globally with more than 311,500 deaths. AML is one of the most common types of leukaemia in adults.

Pacylex is a clinical-stage company that was spun out of Dr Berthiaume’s lab and develops first-in-class therapies for leukaemia, lymphoma, and solid tumour cancers.

The FDA’s decision was informed by the results of Pacylex’s nonclinical studies and an ongoing Phase 1/2 clinical study of PCLX-001 in non-Hodgkin Lymphoma (NHL) and solid tumour patients, which showed the treatment to have a favourable safety and tolerability profile. 

The FDA also recently approved PCLX-001 for Phase 1 clinical study to start in AML patients in the coming months and granted it Orphan Drug Designation. PCLX-001 is currently being studied in cancer patients at several research institutes in Canada and is the first and only NMT inhibitor in clinical studies.

Pacylex CMO John Mackey MD said, “Acute myeloid leukaemia is a rapidly progressing, difficult-to-treat blood cancer with a poor prognosis. Because Pacylex’s nonclinical data with PCLX-001 suggest that AML may be the cancer type most sensitive to NMT inhibitors, we have been eager to advance PCLX-001 into clinical studies in AML patients in the near future.”

PCLX-001 is the fourth molecule developed at DDU to enter clinical trials.