Pacylex Pharmaceuticals Inc. and Heidelberg Pharma AG announced positive data from their collaboration testing zelenirstat and PCLX-002 in antibody drug conjugates (ADCs) at the 16th Annual World ADC meeting in San Diego, California. The poster presentation, held on November 4, 2025, demonstrated that zelenirstat, a first-in-class N-myristoyltransferase inhibitor (NMTi), is a potent payload in ADCs targeting breast and prostate cancer cell lines, with potency improvements ranging from 20-fold to over 1,000-fold compared to zelenirstat alone.
Zelenirstat, also known as PCLX-001, is currently in clinical development as an oral therapy for hematologic cancers, including relapsed/refractory lymphoma and acute myeloid leukemia (AML). The drug has shown an acceptable safety profile in Phase 1 studies and has received Orphan Drug Designation and Fast Track Designation from the FDA for AML. The new data suggest that deploying zelenirstat as an ADC payload could significantly enhance its efficacy against solid tumors, addressing a critical need for new ADC payloads.
Dr. Michael Weickert, CEO of Pacylex, stated, “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. 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 study evaluated multiple ADCs with different targeting molecules and linkers, all incorporating zelenirstat as the payload. The results underscore the versatility of NMT inhibitors as ADC payloads, with Pacylex’s family of NMTis including 28 compounds with single-digit nanomolar IC50s against human NMT1. This mechanism targets multiple processes critical to cancer cell growth and survival, offering a unique approach compared to existing ADC payloads.
Heidelberg Pharma, known for its ATAC technology using amanitin from the death cap mushroom, brings expertise in ADC development. The collaboration aims to leverage zelenirstat’s clinical safety and novel mechanism to create effective treatments for solid tumors.
Pacylex is headquartered in Edmonton, Alberta, Canada, with an office in the San Francisco Bay area. The company is conducting a clinical study in relapsed/refractory AML patients (NCT06613217). Heidelberg Pharma is based in Ladenburg, Germany, and listed on the Frankfurt Stock Exchange (www.heidelberg-pharma.com).
The implications of these findings are significant for the ADC field, which currently relies on a limited number of payloads. Zelenirstat’s unique mechanism and clinical safety profile could provide a new therapeutic option for patients with solid tumors, potentially improving outcomes in breast and prostate cancers where ADCs have shown promise.
