MiNA Therapeutics, the pioneer in RNA activation (RNAa) therapeutics, today announced translational data supporting the favourable immunological effects of MTL-CEBPA and its benefits in combination with other cancer therapies including anti-PD1 checkpoint inhibition. The studies combine pre-clinical research conducted at the Wistar Institute as well as biomarker analysis of the previously completed OUTREACH clinical trial. MTL-CEBPA is the first candidate from MiNA’s pipeline of small activating RNA therapeutics, a new class of medicines to restore normal cell function. The data will be presented during a poster session at the 2021 American Association for Cancer Research (AACR) Annual Meeting, held virtually from April 10 – April 15, 2021.
“These new translational findings confirm the important role of MTL-CEBPA in cancer immunology,” said Robert Habib, CEO of MiNA Therapeutics. “We continue to deepen our understanding of the immunological effects of MTL-CEBPA for the treatment of patients with advanced cancer and other indications and will analyse its effects as part of our ongoing clinical studies. Collectively, the data further demonstrate how RNA activation can access a previously undruggable target for patient benefit.”
In pre-clinical studies, MTL-CEBPA was shown to counteract a key cancer immune evasion pathway by inhibiting immune suppression by myeloid cells. MTL-CEBPA was also shown to potentiate the anti-tumour activity of immunotherapies including anti-PD1 in models of lung and colon cancer. In addition, samples were analysed from advanced liver cancer patients treated with MTL-CEBPA as part of the OUTREACH clinical trial. Analysis of mRNA, protein and cellular biomarkers in peripheral blood confirmed that MTL-CEBPA reduced markers associated with immunosuppressive myeloid cells. Analysis of cellular biomarkers in tumour biopsies showed that those patients who responded to MTL-CEBPA combination therapy had high tumour infiltrations of immunosuppressive macrophages prior to treatment, which were depleted with treatment.
The results validate and expand on previously presented pre-clinical research findings on MTL-CEBPA as an immunological combination treatment in liver cancer and colon cancer. MTL-CEBPA demonstrated signals of activity in a Phase 1b trial in advanced liver cancer, including durable and complete tumour responses as a combination treatment with a standard of care tyrosine kinase inhibitor. A Phase 2 study in advanced liver cancer is expected to commence later this year. MTL-CEBPA is currently being evaluated in a second study in patients with advanced solid tumours in the TIMEPOINT Phase 1/1b clinical trial in combination with a leading checkpoint inhibitor.
The poster will be made available on the Company’s website in the Publications section under “RNA Activation” at the start of the conference on April 10th, 2021.
Title: Up-regulation of C/EBPα inhibits suppressive activity of myeloid cells and potentiates antitumor response in mice and cancer patients
Abstract No: 1730
Session: Immunology – Immunomodulatory Agents and Interventions
Presenter: Mikael Sodergren
MTL-CEBPA is the first therapy that specifically up-regulates 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 in solid tumour cancers have been identified as a critical barrier for many therapies to induce clinical responses. 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 suppressive effect in the tumour micro-environment. MTL-CEBPA is currently in clinical development as a combination therapy for the treatment of advanced liver cancer and advanced solid tumour malignancies.
About MiNA Therapeutics
MiNA Therapeutics is the leader in small activating RNA therapeutics. Harnessing innate mechanisms of gene activation, small activating RNA therapeutics are revolutionary new class of medicines that can restore normal function to patients’ cells. We are advancing a proprietary pipeline of new medicines with an initial focus on cancer and genetic diseases, while collaborating with leading pharmaceutical companies to apply our technology platform across a broad range of therapeutic areas. Based on our unique know-how in RNA activation, we are expanding the possibilities of RNA-based medicine for patients.
Robert Habib, CEO
Phone: +44 208 811 6700
Stephanie May or Gretchen Schweitzer
Phone: +49 89 2388 7734 or +49 171 185 56 82