Pacylex Pharmaceuticals Inc. and Heidelberg Pharma AG announced today the presentation of positive data from their collaboration on antibody drug conjugates (ADCs) incorporating zelenirstat and PCLX-002 at the 16th Annual World ADC conference in San Diego, California. The data, presented in a poster session on November 4, 2025, demonstrate that zelenirstat, a first-in-class N-myristoyltransferase inhibitor (NMTi), shows enhanced potency when used as a payload in ADCs targeting breast and prostate cancer cell lines.
Zelenirstat is currently under clinical investigation as an oral therapy for hematologic cancers, but this new research highlights its potential as a targeted therapy for solid tumors. The study tested multiple ADCs with different targeting molecules and linkers, showing that zelenirstat ADCs were 20-fold to more than 1,000-fold more potent than zelenirstat alone against cancer cell lines. This significant increase in potency underscores the value of ADC technology in delivering cytotoxic agents directly to cancer cells while sparing healthy tissue.
“We have shown that zelenirstat is not only active as an oral heme cancer drug, but by deploying it as payload on an ADC, we markedly improve its potency against solid tumor cells,” said Dr. Michael Weickert, CEO of Pacylex. “Given zelenirstat’s novel mechanism of action and clinical safety, we will aggressively explore it, and our other Pacylex molecules, as targeted ADC payloads.”
The need for new ADC payloads is critical, as only a limited number have entered clinical practice. NMT inhibitors offer a unique mechanism of action that targets multiple processes essential for cancer cell growth and survival. Pacylex has developed a family of 28 NMTis with single-digit nanomolar IC50s against human NMT1, which may serve as effective ADC payloads.
Zelenirstat has already demonstrated an acceptable safety and tolerability profile in a Phase 1 study in patients with relapsed/refractory lymphoma and refractory solid tumors (NCT04836195). It has received Orphan Drug Designation and Fast Track Designation from the FDA for acute myeloid leukemia (AML). A clinical study in relapsed/refractory AML patients is currently accruing (NCT06613217).
Heidelberg Pharma brings its expertise in ADC technology, including its proprietary ATAC technology based on the toxin Amanitin. The collaboration aims to leverage zelenirstat’s clinical safety and novel mechanism to develop next-generation ADCs for solid tumors. More information about the companies can be found at www.pacylex.com and www.heidelberg-pharma.com.
