Learn more about the science of RNAa therapeutics that underpins our efforts to transform the treatment of diseases.
SCIENTIFIC PUBLICATIONS & PRESENTATIONS
Small activating RNA-mediated induction of HBG via liposome delivery for in vivo treatment of sickle cell disease and beta-thalassemia
saRNA can be delivered to therapeutically relevant ErP cells in vivo using a clinically established liposomal formulation, NOV340. NHP data demonstrates delivery to greater than 60% of committed ErPs and a PD response. The development candidate induces persistent, pancellular levels of %HbF that exceed the protective threshold of 20%. The compound is potent, does not induce cytotoxicity, and has a clean off-target profile. saRNA therapeutics have the potential to be a transformational in vivo treatment for Sickle Cell Disease.
NOV340 liposome encapsulating nucleic acid payload achieves efficient biodistribution to erythroid progenitor cells
saRNA can be delivered to therapeutically relevant ErP cells in vivo using a clinically established liposomal formulation. Rodent data demonstrates PD response. NHP data demonstrates delivery to greater than 60% of committed ErPs, and equivalence to monocytes in which clinical PD has been demonstrated. This delivery data provides foundations for the development of transformational RNAa therapeutics to treat beta-hemoglobinopathies. saRNA therapeutics have the potential to be a simpler treatment paradigm with lower treatment burden for patients when compared to ex vivo cell and gene therapy approaches.
TIMEPOINT, a Phase 1 study of MTL-CEBPA in combination with pembrolizumab, confirms the immunomodulatory effect of MTL-CEBPA in solid tumours
Here we report the findings from a biomarker pharmacodynamic analysis of paired baseline and cycle 2 tumor sample biopsies in 23 patients from the TIMEPOINT trial. Brightplex® IHC and digital pathology analyses of the samples for myeloid and T cell panels were undertaken, alongside gene expression (Nanostring I/O 360) […]
Interim results for Phase 1b dose expansion of MTL-CEBPA in combination with pembrolizumab in patients with advanced solid tumour malignancies
MTL-CEBPA in combination with pembrolizumab is safe and well tolerated, with encouraging early signs of activity in heavily pretreated patients across multiple tumour types. Treatment was associated with intratumoural changes supporting the hypothesis of immunomodulation by MTL-CEBPA and further investigation in combination with ICI is warranted […]
Upregulation of C/EBPα Inhibits Suppressive Activity of Myeloid Cells and Potentiates Antitumor Response in Mice and Patients with Cancer
This report demonstrates that therapeutic upregulation of the transcription factor C/EBPα causes inactivation of immune-suppressive myeloid cells with potent antitumor responses across different tumor models and in cancer patients. MTL-CEBPA is currently being investigated in combination with pembrolizumab in a phase I/Ib multicenter clinical study […]
MTL-CEBPA, a small activating RNA therapeutic up-regulating C/EBP-α, in patients with advanced liver cancer: a first-in-human, multi-centre, open-label, phase I trial
MTL-CEBPA is the first saRNA in clinical trials and demonstrates an acceptable safety profile and potential synergistic efficacy with TKIs in HCC. These encouraging Phase I data validate targeting of C/EBP-α and have prompted MTL-CEBPA + sorafenib combination studies in HCC […]
Development and Mechanism of Small Activating RNA Targeting CEBPA, a Novel Therapeutic in Clinical Trials for Liver Cancer
Here we describe the development of an saRNA that upregulates the transcription factor CCATT/enhancer binding protein alpha (CEBPA), investigate its mode of action, and describe its development into a clinical candidate. […]
MTL-STING increases STING expression and potentiates efficacy of checkpoint inhibitor in murine preclinical model
Here, we present the development of our STING saRNA lead to overcome the downregulation of STING in myeloid cells […]