On January 16, 2024 Cellectar Biosciences, Inc. (NASDAQ: CLRB), a late-stage clinical biopharmaceutical company focused on the discovery, development and commercialization of drugs for the treatment of cancer, reported promising preclinical data for its proprietary novel alpha-emitting phospholipid radiotherapeutic conjugate, CLR 121225 (225Ac-CLR 121225) an actinium-labeled phospholipid ether (PLE), in pancreatic cancer models (Press release, Cellectar Biosciences, JAN 16, 2024, View Source [SID1234643477]). The development of this compound will expand the company’s clinical pipeline of PLE cancer targeting compounds to include targeted alpha therapies (TATs), complementing its beta-emitting phospholipid radiotherapeutic conjugate, iopofosine I 131, which achieved its primary endpoint in the CLOVER WaM pivotal study in highly refractory Waldenstrom’s macroglobulinemia patients.

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Cellectar’s PLE platform may provide unique advantages which overcome the issues experienced by existing TAT delivery platforms. While current TAT platforms, such as antibodies and peptides, possess the potential to be effective for treating cancers with low tumor volume, they are challenged to treat higher volume or bulky tumors due to insufficient penetration and the need for high quantities of the target epitope. Cellectar’s PLE’s possess biochemical properties that enable penetration of the TAT payload deep into the tumor mass and the abundance of lipid rafts on tumor cells provides near universal delivery and enhanced outcomes.

"The advancement of our TAT program is part of our overall strategy to develop a comprehensive portfolio of first- and best-in-class radiotherapeutics designed to treat both blood cancers and solid tumors that now includes both alpha and beta-emitting radiotherapeutics," commented James Caruso, president and CEO of Cellectar. "Our promising preclinical data with actinium-225 highlights the potential utility of our PLE platform to provide targeted delivery to nearly any isotope resulting in compounds with excellent activity and tolerability. Our novel TAT compounds, including actinium-225, lead-212 and others, have demonstrated this potential in pancreatic cancer, triple-negative breast cancer and other types of tumor models which allows us to deliver the optimal radioisotope based on tumor biology to maximize outcomes. These data provide further evidence supporting the continued development of CLR 121225, which is expected to enter a Phase 1 first-in-human study later this year or early next year."

In preclinical studies, CLR 121225 demonstrated potent anti-tumor activity in refractory pancreatic cancer mouse xenograft models. A single administration at each dose level (100nCi, 250nCi and 500nCi) resulted in tumor volume reduction in a dose dependent manner with the highest dose providing near complete eradication of the tumor. Additionally, it was shown that CLR 121225 demonstrated excellent biodistribution; approximately 15 – 20% of the infused drug accumulated in the tumor within four hours and continued to accumulate over 72 – 96 hours. The mice had no end organ toxicities demonstrating good tolerability. The data are consistent with experiments using other alpha emitters conjugated to the company’s proprietary PLE targeted delivery platform.