Cellectar Biosciences Broadens Pipeline with Targeted Alpha Therapy (TAT) for Solid Tumors and Releases Promising Preclinical Data

Rhea-AI Summary

Cellectar Biosciences, Inc. announced promising preclinical data for its proprietary novel alpha-emitting phospholipid radiotherapeutic conjugate, CLR 121225, in pancreatic cancer models. The compound demonstrated potent anti-tumor activity in refractory pancreatic cancer mouse xenograft models, with a single administration resulting in tumor volume reduction in a dose-dependent manner. The data also showed excellent biodistribution and good tolerability, supporting the continued development of CLR 121225 for a Phase 1 first-in-human study.

Oncology Doctor

The preclinical findings for Cellectar Biosciences' novel alpha-emitting phospholipid radiotherapeutic conjugate, CLR 121225, suggest a significant advancement in the treatment of resistant pancreatic cancer. Pancreatic cancer is known for its poor prognosis and limited treatment options, partly due to its typically late diagnosis and resistance to conventional therapies. The utilization of targeted alpha therapies (TATs) represents a shift towards precision oncology, where treatments are designed to minimize damage to healthy tissues while maximizing tumor cell destruction.

CLR 121225's ability to achieve tumor volume reduction in a dose-dependent manner, with the highest dose leading to near-complete eradication of the tumor in preclinical models, is noteworthy. The compound's excellent biodistribution, with significant accumulation in the tumor and lack of end organ toxicities, indicate a favorable therapeutic index. This could potentially translate into improved patient outcomes with fewer side effects compared to existing treatments. However, it is imperative to approach these results with cautious optimism until clinical trials in humans confirm safety and efficacy.

Medical Research Analyst

The transition of Cellectar Biosciences' CLR 121225 from preclinical studies to Investigational New Drug (IND)-enabling studies is a critical step towards clinical application. The reported preclinical efficacy in xenograft models of refractory pancreatic cancer provides a strong rationale for further development. In the context of drug development, alpha-emitting compounds like 225Ac-CLR 121225 have attracted attention due to their high linear energy transfer (LET), which leads to potent cytotoxic effects with limited penetration, reducing collateral damage to surrounding healthy tissue.

The PLE platform's apparent ability to overcome limitations of current TAT delivery platforms, such as insufficient penetration in bulky tumors, could represent a significant technological advancement. This versatility in delivering a variety of radioisotopes based on tumor biology could enable personalized treatment regimens. However, it's crucial to monitor how these preclinical results translate into human studies, as the complexity of human biology often presents unforeseen challenges.

Financial Analyst

The announcement by Cellectar Biosciences regarding their proprietary TAT compound's preclinical success potentially positions the company favorably within the competitive landscape of cancer therapeutics. From an investment perspective, advancements in Cellectar's clinical pipeline could have positive implications for the company's valuation, contingent upon successful progression through clinical trials and eventual regulatory approval. The market for pancreatic cancer treatments is particularly lucrative given the high unmet medical need.

Investors will likely monitor the IND-enabling studies and subsequent Phase 1 clinical trial closely, as these milestones are critical for validating the compound's therapeutic potential and safety profile. The company's strategic focus on developing both alpha and beta-emitting radiotherapeutics could diversify its portfolio and reduce risk. Nevertheless, the inherent risks of drug development, including the possibility of adverse outcomes in clinical trials or regulatory setbacks, should be considered when evaluating the company's future prospects.

Proprietary TAT Phospholipid Conjugate Demonstrates Potent Activity in Resistant Pancreatic Cancer

Initiating IND-enabling Studies for First-in-Human Phase I Clinical Study

FLORHAM PARK, N.J., Jan. 16, 2024 (GLOBE NEWSWIRE) -- 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, today announced 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. 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.

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.

About Cellectar Biosciences, Inc.
Cellectar Biosciences is a late-stage clinical biopharmaceutical company focused on the discovery and development of proprietary drugs for the treatment of cancer, independently and through research and development collaborations. The company’s core objective is to leverage its proprietary Phospholipid Drug Conjugate™ (PDC) delivery platform to develop the next-generation of cancer cell-targeting treatments, delivering improved efficacy and better safety as a result of fewer off-target effects.

The company’s product pipeline includes lead asset iopofosine I 131, a small-molecule PDC designed to provide targeted delivery of iodine-131 (radioisotope), proprietary preclinical PDC chemotherapeutic programs and multiple partnered PDC assets.

For more information, please visit and www.wmclinicaltrial.com or join the conversation by liking and following us on the company’s social media channels: Twitter, LinkedIn, and Facebook.

Forward-Looking Statement Disclaimer

This news release contains forward-looking statements. You can identify these statements by our use of words such as "may," "expect," "believe," "anticipate," "intend," "could," "estimate," "continue," "plans," or their negatives or cognates. These statements are only estimates and predictions and are subject to known and unknown risks and uncertainties that may cause actual future experience and results to differ materially from the statements made. These statements are based on our current beliefs and expectations as to such future outcomes including our expectations regarding the WM CLOVER-WaM pivotal trial. Drug discovery and development involve a high degree of risk. Factors that might cause such a material difference include, among others, uncertainties related to the ability to raise additional capital, uncertainties related to the disruptions at our sole source supplier of iopofosine, the ability to attract and retain partners for our technologies, the identification of lead compounds, the successful preclinical development thereof, patient enrollment and the completion of clinical studies, the FDA review process and other government regulation, our ability to maintain orphan drug designation in the United States for iopofosine, the volatile market for priority review vouchers, our pharmaceutical collaborators' ability to successfully develop and commercialize drug candidates, competition from other pharmaceutical companies, product pricing and third-party reimbursement. A complete description of risks and uncertainties related to our business is contained in our periodic reports filed with the Securities and Exchange Commission including our Form 10-K for the year ended December 31, 2022, and our Form 10-Q for the quarter ended September 30, 2023. These forward-looking statements are made only as of the date hereof, and we disclaim any obligation to update any such forward-looking statements.

Contacts

MEDIA:
Claire LaCagnina
Bliss Bio Health
315-765-1462
clacagnina@blissbiohealth.com

INVESTORS:
Chad Kolean
Chief Financial Officer
investors@cellectar.com

FAQ

What is the name of the proprietary novel alpha-emitting phospholipid radiotherapeutic conjugate mentioned in the press release?

The name of the proprietary novel alpha-emitting phospholipid radiotherapeutic conjugate is CLR 121225.

What type of cancer models did the preclinical data focus on?

The preclinical data focused on pancreatic cancer models.

What was the result of a single administration of CLR 121225 in the refractory pancreatic cancer mouse xenograft models?

A single administration of CLR 121225 resulted in tumor volume reduction in a dose-dependent manner.

What percentage of the infused drug accumulated in the tumor within four hours?

Approximately 15 – 20% of the infused drug accumulated in the tumor within four hours.

What is the expected next step for CLR 121225?

CLR 121225 is expected to enter a Phase 1 first-in-human study later this year or early next year.