Cellectar Biosciences (NASDAQ:CLRB) used an educational webinar to outline the scientific rationale and development strategy for its phospholipid ether, or PLE, platform, which the company is using to deliver radiopharmaceuticals and potentially other therapeutic payloads to cancer cells.
President and CEO Jim Caruso said the company’s approach is intended to address a central challenge in oncology: delivering a therapeutic payload selectively and consistently to tumor cells while limiting exposure to healthy tissue. Rather than targeting a single antigen, mutation or biomarker, Cellectar’s platform is designed to target lipid rafts, which management said are present across many cancer types.
Platform targets cancer-cell lipid rafts
Chief Operating Officer Jarrod Longcor said conventional targeted therapies can face challenges from tumor heterogeneity, changing antigen expression, dense tumor stroma and barriers to intracellular delivery. According to Longcor, Cellectar’s PLE molecules are designed to bind cancer-cell membrane microdomains known as lipid rafts.
Longcor said lipid rafts exist in normal tissues but are larger and more stable in tumor cells, where they can serve as signaling hubs. He described the company’s molecules as having a polar phosphocholine head group and a hydrophobic alkyl chain that can be linked to different payloads.
The company said it has tested more than 180 tumor types in cell culture and observed lipid rafts across those tumor types, although at varying concentrations. Longcor also cited laboratory experiments involving lung cancer and normal fibroblast cells, in which disruption of lipid rafts reduced uptake of a fluorescently tagged PLE molecule.
According to Longcor, the molecules are highly protein-bound, particularly to albumin, which may assist their transport into the tumor microenvironment. Once there, he said the compounds transition from albumin to lipid rafts and are internalized by tumor cells. Management said uptake can continue for 48 to 96 hours and that the compounds show prolonged retention in tumor cells.
Iopofosine and radiopharmaceutical development
Cellectar’s lead candidate, iopofosine I-131, is an iodine-131 radioconjugate. Longcor said the company views it as an antigen-independent radiopharmaceutical approach. In the company’s CLOVER-WaM study in Waldenstrom’s macroglobulinemia, he reported an 84% overall response rate and a median duration of response of about 18 months among heavily pretreated patients. He said roughly 60% to 70% of patients in that setting were refractory to rituximab and BTK inhibitors.
Management also discussed prior or ongoing work involving multiple myeloma, diffuse large B-cell lymphoma, other non-Hodgkin lymphomas, pediatric high-grade glioma and head and neck cancer. Longcor said imaging from patients with metastatic brain tumors showed uptake of iopofosine-related compounds in tumors, though he noted that the company has not established whether its molecules cross the blood-brain barrier in the absence of a brain tumor.
Beyond iodine-131, the company described preclinical programs using several isotope types, including:
- CLR 125, an Auger-emitting isotope now in a Phase Ib dose-finding study at four U.S. centers;
- Actinium-based alpha emitters evaluated in animal models, including pancreatic cancer;
- Astatine and lead-212 programs tested in triple-negative breast cancer models; and
- Lutetium-based beta emitters tested in breast cancer models.
Longcor said the company is seeking to select the appropriate isotope based on tumor characteristics, kinetics and resistance profiles. He identified triple-negative breast cancer and pancreatic ductal adenocarcinoma as areas of interest, while saying the company is not focused on prostate cancer or neuroendocrine tumors.
Potential expansion beyond radioisotopes
Cellectar also described preclinical work pairing its PLE platform with small molecules, siRNA, mRNA, peptides, protein degraders and molecular glues. Longcor said the company has tested these modalities in vitro or in animal models.
When asked which non-radiopharmaceutical approach he would prioritize if funding were not a consideration, Longcor said he would favor an oligonucleotide strategy because of the potential to target tumor-associated genes more specifically. He added, however, that small molecules could be the faster path into clinical development because the company has more complete data in that area.
Caruso said Cellectar remains focused on advancing iopofosine I-131 in Waldenstrom’s macroglobulinemia through the regulatory process. Assuming approval, he said the company sees opportunities to expand into additional hematologic malignancies, including multiple myeloma, diffuse large B-cell lymphoma and other non-Hodgkin lymphomas.
About Cellectar Biosciences (NASDAQ:CLRB)
Cellectar Biosciences, Inc is a clinical‐stage biopharmaceutical company focused on the development of targeted cancer therapies and imaging agents. The company’s proprietary phospholipid drug conjugate (PDC) technology platform is designed to selectively deliver therapeutic and diagnostic payloads to malignant cells while sparing healthy tissue. Through its PDC approach, Cellectar aims to improve the efficacy and safety profile of traditional treatments like chemotherapy and radiotherapy.
Its lead therapeutic candidate, CLR 131, is a radioisotope‐labeled PDC being evaluated in Phase II clinical trials for relapsed or refractory B‐cell malignancies, including multiple myeloma and non‐Hodgkin lymphoma.
