Lantern Pharma Inc. announced promising preclinical data for LP-184 in atypical teratoid rhabdoid tumors (ATRT), a rare and aggressive pediatric brain cancer, with results presented by Dr. Eric Raabe of Johns Hopkins University School of Medicine at the Society for Neuro-Oncology's 8th Biennial Pediatric Neuro-Oncology Conference in San Diego, California.
The independent research validates the data that supported Lantern Pharma's FDA Rare Pediatric Disease Designation for LP-184 in ATRT and strengthens the scientific foundation for the company's planned pediatric clinical trial expected to begin in late 2025 or early 2026.
Dramatic Survival Improvements in Preclinical Models
LP-184, a next-generation acylfulvene clinical-stage drug candidate, significantly extended survival in mouse models of ATRT. In the CHLA06 model, median survival increased from 20 days in the control group to 89 days in the LP-184 treatment group, representing a 345% improvement (p<0.0001). In the BT37 model, median survival increased from 68 days to 98 days (p=0.0422).
"The preclinical data presented by Dr. Raabe and his team at Johns Hopkins provides powerful confirmation of LP-184's potential to address the significant unmet need in pediatric ATRT," said Panna Sharma, CEO and President of Lantern Pharma. "The substantial increase in survival time and the favorable tolerability profile observed in these models underscore the promise of LP-184 as a novel therapeutic option to evaluate clinically for this devastating pediatric cancer."
Broad Anti-Tumor Activity and Blood-Brain Barrier Penetration
The research demonstrated that LP-184 showed potent anti-tumor activity across multiple ATRT cell lines representing different molecular subtypes (MYC, TYR, and SHH), with IC50 values ranging from 17.5 nM to 161 nM. Treatment with LP-184 significantly decreased cancer cell proliferation and increased apoptosis in ATRT cells.
Critically for brain cancer treatment, LP-184 showed strong blood-brain barrier penetrance, with reported Cmax of 730 nM in brain tissue. No apparent toxicity was observed in the mouse models, with stable weight maintained throughout the treatment period.
Mechanism of Action and Clinical Rationale
ATRT is characterized by the deletion or inactivation of the SMARCB1 gene, an epigenetic regulator. LP-184's mechanism of action may be particularly effective against tumors with epigenetic dysregulation, potentially explaining the strong preclinical anti-tumor activity observed in this tumor type.
LP-184 is a prodrug that is converted to its bioactive form inside the cancer cell by PTGR1 (prostaglandin reductase 1), an enzyme that is overexpressed in certain cancers. Once activated, LP-184 creates cytotoxic metabolites that form adducts with DNA, leading to irreparable DNA damage and ultimately tumor cell death.
Addressing Critical Unmet Medical Need
ATRT is a rare, fast-growing tumor of the brain and spinal cord that typically occurs in children aged three years and younger. ATRTs account for approximately 1-2% of all pediatric brain tumors but represent a disproportionately high percentage of brain tumors in infants. Current treatment involves a combination of surgery, intensive chemotherapy, and radiation therapy. Despite aggressive treatment, the prognosis remains poor, with a median survival of approximately 17 months.
"Current treatment options for ATRT are limited to surgery, intensive chemotherapy, and radiation, with poor outcomes and significant treatment-related toxicity," said Dr. Marc Chamberlain, Chief Medical Officer of Starlight Therapeutics and Lantern Executive Director of Clinical Development. "The single-agent activity of LP-184 in these models suggests it could potentially transform the treatment landscape for children with these brain tumors."
Clinical Development Timeline
The company highlighted that the pediatric Phase I trial for LP-184 in brain tumors is targeted to open in winter 2025 or early 2026, following completion of the ongoing Phase I trial in adult solid tumors (NCT05933265) and obtaining future funding and approvals from the pediatric consortium.
LP-184 has received Orphan Drug Designation from the FDA for the treatment of malignant gliomas and pancreatic cancer, as well as Rare Pediatric Disease Designation for ATRT. The drug has shown nanomolar preclinical potency across multiple cancer types, including several that are resistant to standard therapies, and has demonstrated particularly promising preclinical activity in CNS and brain cancers.
