OSLO, Norway--(BUSINESS WIRE)--Oncoinvent AS, a clinical stage company advancing a pipeline of radiopharmaceutical products across a variety of solid cancers, will present new preclinical data supporting the future clinical development of Radspherin®, a novel alpha-emitting radioactive microsphere suspension designed for treatment of metastatic cancers in body cavities, in four digital presentations at the 34th Annual Congress of the European Association of Nuclear Medicine (EANM).
“We are thrilled to present these data at EANM, furthering our confidence in the potential of alpha-emitting radioactive particles for the treatment of metastatic cancers in body cavities,” said Jan A. Alfheim, Chief Executive Officer of Oncoinvent. “These data demonstrate that Radspherin® has potentially robust and retained biodistribution in body cavities, and give us important insights into the safety of clinical doses. We look forward to the continued clinical development of Radspherin® in colorectal and ovarian cancer patients suffering from peritoneal carcinomatosis.”
Synergy of 224Ra-labeled microparticles and chemotherapy in a murine ovarian cancer model
Presenting Author: Roxanne Wouters
Abstract Number: OP-0108
This preclinical study aimed to evaluate the effects of combining 224Ra-CaCO3-MP, radium-224-labeled calcium carbonate microparticles, with either first line chemotherapy for ovarian cancer, carboplatin-paclitaxel, or second line chemotherapy, carboplatin-pegylated liposomal doxorubicin (PLD), in an ovarian cancer model. Ovarian cancer mouse models were treated with 224Ra-CaCO3-MP (5 mg, 14-22 kBq/animal) one day following tumor cell inoculation. Additionally, 224Ra-CaCO3-MP treatment was combined with either carboplatin (100 mg/kg)-paclitaxel (10 mg/kg) on day 14, 21 or 28, or carboplatin (80 mg/kg)-PLD (1.6 mg/kg) on day 14.
- As a single treatment, 224Ra-CaCO3-MP delayed the onset of malignant ascites development compared to control.
- When 224Ra-CaCO3-MP was administered in combination with carboplatin-PLD, survival was significantly prolonged compared to mice that received carboplatin-PLD alone.
Synergy when treating ovarian cancer cell lines with Radium-224 and PARP inhibitors
Presenting Author: Marion Masitsa Malenge
Abstract Number: EPS-064
This study evaluated the potential of combining radium-224 (224Ra), an alpha-emitter with 3.6 days half-life with the PARP inhibitors olaparib and niraparib to inhibit growth of ovarian cancer cell-lines. The effect of 224Ra in combination with olaparib and in combination with niraparib were evaluated in two human non-BRCA-mutated ovarian cancer cell-lines, ES-2 and SKOV-3. Cells were simultaneously treated with 224Ra and PARP inhibitors at escalating concentrations, and cell proliferation was measured 72, 96 and 120 hours after initiation of treatment.
- The combination index (CI) between both evaluated cell-lines was heterogenous across the tested range depending on the PARP inhibitor used in the combination, the concentrations of the combined drugs and the timepoint of assessment.
- Combination treatment with PARP inhibitors and 244Ra was seen to be synergistic.
Biodistribution and dosimetry after intraperitoneal injection of 224Ra-labeled microparticles in rats
Presenting Author: Sara Westrøm
Abstract Number: EP-118
The presentation highlights the ex vivo biodistribution 224Ra-CaCO3-MP in preclinical models. In addition, dosimetry was calculated and extrapolated to the absorbed doses to human. 224Ra-CaCO3-MP (89 kBq/animal, 30 mg CaCO3) or vehicle was administered to preclinical rat models intraperitoneal. Ex vivo biodistribution was assessed at time points ranging from 2 to 336 hours post injection. For dosimetry calculations, the cumulated activity was determined by linear interpolation between the measured values. The dosimetry results were extrapolated to humans and scaling with relative biologically effectiveness (RBE) factors was performed.
- The majority of 224Ra was retained after intraperitoneal administration of 224Ra-CaCO3-MP.
- Analyses of clinical pathology showed no treatment-related adverse effects, apart from a transient depression of neutrophils.
- Dosimetry demonstrated that based on the low absorbed doses for all tissues, administration of up to 7 MBq 224Ra-CaCO3-MP, the maximum activity in ongoing Phase 1 studies, is deemed safe.
Dose response of 212Pb-labeled calcium carbonate microparticles in mice with intraperitoneal ovarian cancer
Presenting Author: Ruth Gong Li
Abstract Number: OP-0111
This study evaluated the intraperitoneal retention and biodistribution of 212Pb-CaCO3 microparticles in mouse models of ovarian cancer. Mice received a single intraperitoneal injection of either 2-5mg with doses ranging from 57-390 kBq 212Pb-CaCO3 microparticles, or vehicle.
- Calcium carbonate microparticles can be labeled with 212Pb in an easy, fast and efficient process; no chelator or co-precipitants are necessary.
- 212Pb-CaCO3 microparticles were retained in the peritoneal cavity.
- The increased survival of mice with tumors that were treated with 212Pb-CaCO3 was dose-dependent and significant for all evaluated doses.
Oncoinvent AS is a clinical stage company developing innovative radiopharmaceutical technology that delivers precise, alpha-emitting particles across solid cancers. By leveraging internal manufacturing and supply chain capabilities to enable a clinical supply of radioisotopes, the company is advancing a pipeline of novel products that use alpha particles, a higher Linear Energy Transfer (LET) form of radiation, that can potentially eradicate cancer cells. Oncoinvent’s lead candidate, Radspherin®, is designed for treatment of metastatic cancers in body cavities, and its versatility allows it to be deployed for the treatment of a variety of cancer indications. Radspherin® is in two ongoing Phase 1 studies to treat peritoneal carcinomatosis from both ovarian cancer and colorectal cancer.