On April 2, 2019 MiNA Therapeutics, the pioneer in RNA activation (RNAa) therapeutics, reported pre-clinical data supporting the immunological effects of MTL-CEBPA and its benefits in combination with other anti-cancer interventions including sorafenib, anti-PD1 checkpoint inhibition and radiofrequency ablation (Press release, MiNA Therapeutics, APR 2, 2019, View Source [SID1234534919]). The data will be presented today in two posters at the 2019 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting taking place in Atlanta, Georgia.

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"With these additional pre-clinical studies, we continue to elucidate the benefits that our lead candidate MTL-CEBPA can provide not only alone but also in combination to improve standard of care treatments," said Robert Habib, CEO of MiNA Therapeutics. "We look forward to sharing these results with the scientific community at AACR (Free AACR Whitepaper) which support our ongoing clinical investigation of MTL-CEBPA in severe liver cancer patients."

The first pre-clinical study highlights that the combination of MTL-CEBPA with sorafenib resulted in superior tumour growth inhibition and reduction of tumour biomarker alpha-fetoprotein (AFP) compared to single agents as demonstrated in an immunocompetent rat model of hepatocellular carcinoma. The anti-tumour activity of sorafenib had previously been demonstrated to be enhanced by immunological agents targeting suppressive myeloid cells in the tumour microenvironment. In the presented study, the combination of MTL-CEBPA and sorafenib was administered in a sequential regimen to "prime" tumours with MTL-CEBPA before treating with sorafenib. Most importantly, the results further support the expansion of MiNA’s Phase 1b OUTREACH trial to evaluate MTL-CEBPA in combination with sorafenib.

A second pre-clinical study describes a triple combination of MTL-CEBPA with anti-PD1 checkpoint inhibition and radiofrequency ablation in an immunocompetent mouse model of liver cancer bearing tumours on two opposite flanks. Radiofrequency ablation was performed on one flank only and treatment effects were assessed on the contralateral flank. Compared to single agent or double combinations, the triple combination demonstrated significantly improved immunological responses as well as anti-tumour activity. Immunological responses in the tumour microenvironment were evidenced by superior infiltration of cytotoxic T lymphocytes (TILs) as well as natural killer T (NKT) cells. Anti-tumour activity was evidenced by near complete inhibition of tumour growth including complete responses. Improved tumour growth inhibition in the contralateral flank suggested that the combination of MTL-CEBPA and anti-PD1 checkpoint inhibition increased the effectiveness of the abscopal effects of radiofrequency ablation.

The posters will be made available on the Company’s website in the Publications section under "RNA Activation".

Presentation information

Title: MTL-CEBPA, a drug candidate for hepatocellular-carcinoma enhances efficacy of sorafenib
Abstract No: 4455
Session: Experimental and Molecular Therapeutics – Novel Antitumor Agents 2
Date / time: Tuesday April 2, 2019 from 1:00 pm to 5:00 pm CDT

Title: MTL-CEBPA combined with radiofrequency ablation and immunotherapy enhances immunological anti-tumour response in an HCC mouse model
Abstract No: 4224
Session: Immunology – Combination Immunotherapies 2
Date / time: Tuesday April 2, 2019 from 8:00 am to 12:00 pm CDT
About MTL-CEBPA

MTL-CEBPA consists of a double stranded RNA formulated in a liposomal nanoparticle and is designed to activate the CEBPA gene. 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 in several tissues including myeloid cells, liver cells and adipose tissue. In cancer, C/EBP-α plays important roles in regulating both tumour growth and the tumour immune microenvironment. MTL-CEBPA is currently under evaluation in OUTREACH, a Phase Ib clinical study in patients with advanced liver cancer. The multi-centre study is assessing the safety, tolerability and anti-tumour activity of MTL-CEBPA in combination with sorafenib. To learn more about the OUTREACH clinical study, please visit our listing at clinicaltrials.gov