Through transcriptional activation, saRNA therapeutics promise a revolution in our ability to modulate previously undruggable targets.
Through transcriptional activation, saRNA therapeutics promise a revolution in our ability to modulate previously undruggable targets.
DEVELOPMENT PROGRAMS
MTL-CEBPA
MTL-CEBPA is a new medicine initially being developed as a combination therapy in cancer. The first small activating RNA (saRNA) therapeutic to be tested in a clinical study, MTL-CEBPA is designed to activate the CEBPA gene. MTL-CEBPA comprises a double stranded RNA payload formulated inside a liposomal nanoparticle that is delivered into certain immune cells around the body including subpopulations of myeloid cells.
The CEBPA gene encodes CCAAT/enhancer binding protein alpha (C/EBP-α), a transcription factor that acts as a master regulator of cell lineage determination and differentiation of myeloid cells and other cells types around the body. Myeloid cells are frequently dysregulated in the microenvironment of solid tumours and are understood to be an important resistance hurdle for many anti-cancer medicines. Restoring CEBPA expression in myeloid cells is hypothesised to alter immune cell populations in the tumour microenvironment and improve the efficacy of cancer therapies in solid tumour malignancies.
For more information on MTL-CEBPA check out these publications:
MTL-CEBPA is designed to reduce immune suppression of myeloid cells by restoring C/EBP-α protein to normal levels using the RNA Activation mechanism. MTL-CEBPA has been tested in a range of pre-clinical cancer models and has been shown to enhance the anti-tumour activity of a standard of care cancer treatments.
In a Phase I clinical trial MTL-CEBPA was evaluated as a monotherapy in 39 patients with advanced liver cancer. In the study, MTL-CEBPA was generally well tolerated in patients with both healthy and impaired liver function. MTL-CEBPA was found to mediate RNA Activation and to reduce biomarkers of immune suppression in patients.
In a Phase Ib clinical trial MTL-CEBPA was evaluated in combination with sorafenib standard of care in 36 patients with advanced liver cancer. The combination treatment was found to be well tolerated in patients. The clinical activity observed, including durable and complete tumour responses, suggests that MTL-CEBPA may increase the effectiveness of sorafenib standard of care.
MTL-CEBPA DRUG PRODUCT
OUTREACH CLINICAL TRIAL
OUTREACH is a multi-centre Phase Ib clinical study of MTL-CEBPA in combination with Sorafenib in patients with primary liver cancer. The study is assessing the safety, tolerability, pharmacology and anti-tumour activity of MTL-CEBPA in combination with Sorafenib. The study is ongoing in the United Kingdom, Singapore and Taiwan.
To learn more about the OUTREACH clinical trial, please visit ClinicalTrials.gov.
TIMEPOINT CLINICAL TRIAL
TIMEPOINT is a multi-centre Phase I/Ib clinical study of MTL-CEBPA in combination with Pembrolizumab in patients with advanced solid tumours. The study is assessing the safety, tolerability, pharmacology and anti-tumour activity of MTL-CEBPA in combination with Pembrolizumab. The study is ongoing in the United Kingdom.
To learn more about the TIMEPOINT clinical trial, please visit ClinicalTrials.gov.