On September 3, 2024 Pacylex Pharmaceuticals Inc. (Pacylex) reported that it is seeking partners to develop its large family of NMT inhibitors as a new class of Antibody Drug Conjugate (ADC) payloads (Press release, Pacylex Pharmaceuticals, SEP 3, 2024, View Source [SID1234646334]). To introduce its ADC payload molecules, Pacylex will participate in the upcoming ADC & Radiopharmaceuticals Pharma & Biotech Partnering Summit on September 9-10 at the Revere Hotel Boston Common, Boston, Massachusetts, and the 15th World ADC Summit, November 4-7 at the Town & Country Resort in San Diego, California.
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
ADCs have emerged as a major category of therapeutics, particularly in the field of oncology. Despite this, only a very limited number of ADC payloads have been used to kill cancer cells. This new class of payload, NMT inhibitors, simultaneously affect multiple processes critical to cancer cell growth and survival and have been shown to regress solid tumor cancers in animal models when coupled with ADCs. Pacylex has exclusive license to 503 NMTis, 27 of which have single-digit nM IC50s against human NMT1. The lead molecule in Pacylex’s NMTi collection, zelenirstat, a first-in-class myristoylation inhibitor, has been shown to inhibit the myristoylation required for assembly, translocation, and/or function of validated targets, such as B-cell receptor, Flt3-cKit complex, EGFR, and VEGFR. Zelenirstat also blocks respiratory Complex I formation in the mitochondria of cancer cells, thereby shutting down oxidative phosphorylation, which is critical for metastasis and cancer stem cells.
Zelenistat is the only clinically validated NMTi; it is well tolerated in Phase 1 patients with refractory/relapsed (r/r) lymphoma and refractory solid tumors. Phase 1 safety, PK, and drug exposure results with oral zelenirstat in 24 heavily pretreated NHL and solid tumor patients showed no dose-limiting toxicities. Patients receiving the recommended Phase 2 dose (RP2D) had significantly better progression-free and overall survival than those treated at lower doses; 57% had stable disease or better for six months or longer, despite cancers originating in 5 different organs. A patient with colorectal cancer who only achieved short-term benefits from the 5 prior lines of therapy, received the RP2D of zelenirstat for 475 days with reductions of approximately 50% in carcinoembryonic antigen (CEA) and tumor volumes. A Phase 2a patient with DLBCL has achieved a partial response and is on their 13th 28-day cycle of zelenirstat.
"The ability of NMTis to interrupt many critical cancer processes simultaneously makes them exciting drug candidates but also excellent potential ADC payloads", said Dr. Michael Weickert, CEO of Pacylex. "Our collection of potent NMTis is one of only two families of molecules shown independently to be potent and on target, and zelenirstat is the only clinically validated NMTi. We want to establish ourselves as a partner of choice for those seeking novel and effective payloads for their ADC programs."