On May 29, 2020 MiNA Therapeutics, the pioneer in RNA activation therapeutics, reported top line results from the Phase Ib dose escalation and cohort expansion study, OUTREACH, of lead candidate MTL-CEBPA in combination with sorafenib standard of care in patients with advanced hepatocellular carcinoma (HCC or liver cancer) (Press release, MiNA Therapeutics, MAY 29, 2020, View Source [SID1234558715]). The study met its primary endpoints of safety and tolerability for MTL‑CEBPA administered either concomitantly or sequentially with sorafenib. In addition, five patients experienced objective tumour responses, including two complete responses during the combination treatment. The data will be presented during a poster session at the 2020 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, held virtually from May 29 – May 31, 2020.

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"We are delighted to have confirmed objective tumour responses in a Phase Ib study in advanced liver cancer patients who are poorly served by existing treatments," commented Robert Habib, CEO of MiNA Therapeutics. "Combined with previous positive results, these data suggest that by reducing immune suppression in the tumour microenvironment, MTL‑CEBPA may increase the effectiveness of sorafenib standard of care."

At the data cut-off of February 1, 2020, 36 patients with advanced HCC had been treated with MTL‑CEBPA in combination with sorafenib in the Phase Ib study. 22 patients received MTL‑CEBPA and sorafenib concomitantly, and 14 patients received the two agents sequentially. Both concomitant and sequential treatment regimens were generally very well tolerated, and no maximum tolerated dose was determined. The profile of adverse events was consistent with the known safety profile of each agent and the underlying disease. In addition, concomitant sorafenib treatment did not alter the pharmacokinetics of MTL‑CEBPA. Five patients who were naïve to prior tyrosine kinase inhibitor (TKI) treatment experienced objective tumour responses, including two patients who experienced complete remission. Tumour responses were most pronounced in those TKI naïve patients with viral aetiology, where four out of nine evaluable patients experienced objective responses.

Treatment was associated with a reduction in both the number of immature immune suppressor cells as well as genetic markers of immune suppression in patient samples. These biomarker data validate the mechanism of action of MTL‑CEBPA in reducing immune suppression, which has been identified as a resistance mechanism of solid tumours to cancer treatment, including sorafenib.

These encouraging Phase Ib data add to the previously published positive Phase I results in which four out of five patients experienced a durable, objective response to off-study sorafenib treatment after discontinuation of MTL‑CEBPA. As a single agent treatment, sorafenib is associated with a very low objective response rate. In a recent Phase III study, complete responses were observed in 1% of patients and partial responses were observed in 6% of patients based on RECIST 1.1 criteria in 372 patients1.

The poster will be made available on the "Publications" page of MiNA’s website.

Presentation information
Title: Phase Ib dose escalation and cohort expansion study of the novel myeloid differentiating agent MTL-CEBPA in combination with sorafenib in patients with advanced hepatocellular carcinoma (HCC)
Abstract no: 4601
Session: Gastrointestinal Cancer—Gastroesophageal, Pancreatic, and Hepatobiliary
Date / time: Friday, May 29, 2020 / 8:00 am Eastern Time

About MTL-CEBPA

MTL-CEBPA is the first therapy to specifically up-regulate CCAAT/enhancer binding protein alpha (C/EBP-α), a transcription factor that acts as a master regulator of myeloid cell lineage determination and differentiation. Dysregulated myeloid cells have been implicated in several diseases and identified as a critical barrier for many therapies to induce clinical responses in solid tumour cancers. In pre-clinical studies MTL-CEBPA has been shown to improve the anti-tumour activity of cancer therapies by targeting dysregulated myeloid cells and reducing their suppression in the tumour microenvironment.