MiNA Therapeutics announces initial results from phase I trial of saRNA candidate in liver cancer patients

MiNA Therapeutics, the pioneer in RNA activation (RNAa) therapeutics, today announced preliminary results from its ongoing Phase I study of small activating RNA (saRNA) candidate MTL-CEBPA in advanced liver cancer. In the study, MTL-CEBPA was generally well tolerated in patients with both healthy and impaired liver function and provided evidence of anti-tumor activity. MTL-CEBPA was also found to mediate RNAa activity in white blood cells. The data are being presented at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting in a poster titled "Preliminary results of a first-in-human, first-in-class phase I study of MTL-CEBPA, a small activating RNA (saRNA) targeting the transcription factor C/EBP-a in patients with advanced liver cancer" in the Developmental Therapeutics - Clinical Pharmacology and Experimental Therapeutics poster discussion session being held on Monday June 4, 2018 from 3:00pm to 4:15pm CDT.

"Despite recent advances in treatment options, liver cancer remains a significant unmet medical need with numerous hurdles for therapeutic intervention. New treatment options are desperately needed, in particular for those patients with impaired liver function," said Dr. Debashis Sarker, Principal Investigator at the National Institute for Health Research Clinical Research Facility at Guy's and St Thomas' and King's College London, and chief investigator of the study. "These preliminary safety data and the evidence of anti-tumor activity are very promising and I look forward to evaluating MTL-CEBPA in the dose expansion part of this Phase I clinical trial."

"We are extremely pleased with the preliminary results of this first-in-human study which include safety and tolerability of MTL-CEBPA, as well as evidence of anti-tumor activity in this very advanced, heavily pre-treated cancer patient population. In particular we have seen many patients achieve stable disease or better, including a patient with advanced hepatocellular carcinoma who has achieved over 70% tumor regression and has continued on the study for over one and half years," said Robert Habib, CEO of MiNA Therapeutics. "Additionally, analysis of patient blood samples has demonstrated upregulation of target CEBPA mRNA in white blood cells, representing a significant milestone in the development of saRNA medicines and for our platform."

MTL-CEBPA was evaluated in the dose escalation part of a Phase I clinical trial in patients with advanced liver cancer. As of the data cut-off date of March 31, 2018, 23 patients had been treated once weekly at six dose levels (ranging from 28 mg/m2 to 160 mg/m2) and 5 patients had been treated twice weekly at 70 mg/m2.

MTL-CEBPA was well tolerated in patients at all doses and no Maximum Tolerated Dose was identified. The large majority of adverse events (AEs) reported by investigators were mild to moderate in severity. 12 (43%) patients experienced AEs no higher than Grade 2. AEs of Grade 3 or higher included hyperbilirubinemia (11%), elevated GGT (11%), hypophosphatemia (11%), anemia (7%) and hypertension (7%). Only 3 (11%) patients discontinued treatment with MTL-CEBPA due to possible drug-related toxicities including acute coronary syndrome, hyperbilirubinemia, and elevated GGT.

Pharmacokinetic data from this study showed that Cmax (peak plasma concentration of drug) and AUC (area under the curve) were dose proportional with no evidence of drug accumulation.

CEBPA gene expression was analyzed in white blood cells of 10 patients across multiple dose levels and timepoints. The level of CEBPA gene expression was significantly higher on treatment than at baseline, supporting target engagement of MTL-CEBPA. Consistent with up-regulation of CEBPA, which has a role in myeloid differentiation, significant and repeated increases in neutrophils were observed after dosing MTL-CEBPA.

Enrollment in the dose escalation part of the Phase I clinical trial has been completed. Enrollment is starting for the dose expansion part of the Phase I clinical trial in multiple sites in the United Kingdom and Asia.

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