Edmonton, Alberta, Canada October 14, 2024. Pacylex Pharmaceuticals Inc. (Pacylex) is a clinical-stage pharmaceutical company and world leader in developing N-myristoyltransferase inhibitors (NMTis) as targeted therapies for the treatment of hematologic cancers and as payloads for antibody drug conjugates (ADCs) for treatment of solid tumor cancers. Today, Pacylex announced that CEO, Michael Weickert will present progress in clinical development of oral zelenirstat, the first in class NMTi for heme cancers, and initial analysis of zelenirstat and other NMTis as ADC payloads, at the BIO Investor Forum, October 15-16, 2024, at the Fairmont Hotel, in San Francisco, CA, United States.
Details for the presentation are below. Dr. Weickert will also be available during the conference for one-on-one meetings.
Pacylex Pharmaceuticals has the only clinically validated NMTi, zelenirstat. A Phase 1 dose escalation safety and tolerability study in 29 heavily pre-treated (median of 4 prior lines of drug therapy) solid tumor and lymphoma patients showed treatment related, self-limited, mild to moderate gastrointestinal adverse events in a minority of patients with no does limiting toxicity observed below a daily dose of 280mg. Zelenirstat prolonged progression free and overall survival in 57% of Phase 1 solid tumor patients receiving the recommended Phase 2 dose (210mg), compared to those receiving lower doses. One colorectal patient and one DLBCL (Diffuse large B-cell lymphoma) patient have each received zelenirstat 210mg/day for a year or more with benefit, the DLBCL patient having achieved objective partial tumor volume and metabolic responses.
ADCs are a major category of cancer therapeutics but in recent years, the need for new payloads has increased. Five attributes make zelenirstat an attractive payload candidate: 1) clinical validation of safety, 2) clinical validation of anti-cancer activity, 3) multiple mechanisms of anti-cancer activity that disrupt novel cancer signaling and survival pathways as well as metabolism, 4) activity in models of drug-resistant cancer, 5) limited acquired resistance despite long-term drug exposure. Pacylex has exclusive license to 503 NMTis, 27 of which have single-digit nM IC50s against human NMT1.
“We look forward to accelerating the development of our extensive NMTi portfolio as ADC payloads with the participation of partners and investors” said Dr. Michael Weickert, CEO of Pacylex. “We will continue to develop oral zelenirstat in parallel for heme cancers and several other cancer and non-cancer indications.”
Pacylex Pharmaceuticals Contact: Michael J. Weickert
CEO, Pacylex Pharmaceuticals, Inc.
P: 650-218-1840
About zelenirstat (aka PCLX-001 or DDD86481)
Zelenirstat (formerly identified as PCLX-001 or DDD86481) is a first-in-class, oral, small-molecule NMTi being developed to treat patients with leukemia, lymphoma, and for the treatment of solid tumors when used as a payload for ADCs. Zelenirstat selectively kills cancer cells in vitro and has been shown to regress hematologic malignancies and inhibit the growth of lung and breast cancer tumors in animal models.
Pacylex completed and published a
Phase 1 multiple ascending dose safety, tolerability, and pharmacokinetics study on zelenirstat in patients with relapsed/refractory lymphoma and refractory solid tumors (
NCT04836195). 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 in patients with relapsed/refractory B-cell non-Hodgkin Lymphoma (NHL) and in a separate Phase 1 / 2 study in AML patients is about to start.
About NMTis as ADC payloads
The effect of NMTis on cancer cells is pleiotropic. Across multiple cancer types, NMTis interfere with pathways essential to proliferation and survival including: Receptor tyrosine kinases (e.g. EGFR and VEGFR)/SFK pathways, Wnt pathway, PI3K/AKT/mTOR signaling pathway, Notch signaling, TLR4 inflammatory responses, B-cell and T-cell receptor signaling pathway, Flt3/c-Kit signaling, ferroptosis, ER-Golgi trafficking via ADP-ribosylation factors (Arfs), AMPK signaling, autophagy and mitochondrial respiratory complex 1 assembly and function. NMTis induce ER stress and apoptosis in cancer cells. The preferential toxicity of NMTis towards cancer cells makes them an exciting new class of ADC payload. In animal models, NMTi-ADCs have regressed solid cancer tumors.
Pacylex has exclusive rights to 503 small molecules NMTis, including 27 high potency compounds (IC50 <10nM) against human NMT1. Zelenirstat has advantages as an NMTi-ADC payload: 1) clinical validation of safety, 2) clinical validation of anti-cancer activity, 3) multiple mechanisms of anti-cancer activity that disrupt novel cancer signaling and survival pathways as well as metabolism, 4) activity in models of drug-resistant cancer, 5) limited acquired resistance despite long-term drug exposure. The investigation of the potential of zelenirstat and its analogs as ADC payloads has begun.
About Pacylex Pharmaceuticals
Pacylex is a clinical-stage pharmaceutical company headquartered in Edmonton, Alberta, Canada, which targets hematologic cancers with orally bioavailable NMTi zelenirstat and solid tumor cancers with NMTis used as ADC payloads. Zelenirstat is the lead drug in a new class of NMTis, enabling Pacylex to exploit NMTs as new clinical targets for cancer treatment and a new class of ADC payloads. Pacylex is conducting a multi-center Phase 2a studies in Canada in patients with relapsed/refractory NHL and the IND for a Phase 1 multiple ascending dose study in 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 AML patients. The Cure Cancer Foundation, Alberta Cancer Foundation, and Alberta Innovates supported the initial clinical studies. For additional information, please visit
www.pacylex.com.
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