DUBLIN – Mina Therapeutics Ltd. raised £23 million (US$29.9 million) in a series A round to take forward a pipeline and a platform based on a novel regulatory RNA species, small activating RNAs, which selectively activate gene expression.

The London-based firm is not exactly a newcomer – it was founded more than a decade ago and has been pursuing its present strategy for the last seven years. Its lead drug candidate, moreover, is already undergoing two separate combination trials. But it is taking on venture capital now following the recent publication of clinical proof-of-concept data for its lead drug, MTL-CEBPA, in advanced liver cancer.

In an open-label phase I/Ib trial of MTL-CEBPA plus the multikinase inhibitor Nexavar (sorafenib, Bayer AG) in 36 patients with advanced hepatocellular carcinoma (HCC), five of 23 evaluable patients had a complete response (CR) or a partial response (PR), including two CRs, while another 16 patients had stable disease. The responses were particularly concentrated in patients with liver cancer associated with viral hepatitis infection – of the nine evaluable patients in that category, there were two CRs and two PRs, while three patients had stable disease and two patients progressed. The data were delivered in a virtual poster presentation at the 2020 annual meeting of the American Society of Clinical Oncology (ASCO) in late May.

The upcoming phase II trial will, therefore, focus on patients in that category. The open-label study will recruit 70 patients in total who will again receive MTL-CEBPA plus sorafenib. “That will be starting next year,” Mina CEO Robert Habib told BioWorld. The expectation is that the combination will yield more responses than sorafenib alone typically does. “Sorafenib has been the standard of care for about 10 years,” Habib said. “We feel we’ve got a good handle on what sorafenib does on its own.”

Robert Habib, CEO, Mina

The drug was approved in HCC on the basis of a modest overall survival (OS) benefit as compared with placebo (median OS 10.7 months vs. 7.9 months). It exhibited a PR rate of just 2% vs. 1% for placebo. When combined with MTL-CEBPA, the responses rates are not only higher, but the responses are more widespread – with effects seen on lung metastases, for example. “We saw things happening way outside the liver,” Habib said.

A combination trial – called Timepoint – of MTL-CEPBA plus the PD-1 inhibitor Keytruda (pembrolizumab, Merck & Co. Inc.) got underway earlier this year and has a recruitment target of 100 patients with advanced solid tumors. Each study will start to deliver interim read-outs during the next 12 to 18 months.

In the meantime, Mina will also use some of the proceeds of the present round to advance its saRNA platform and to explore the technology’s potential in its other chosen areas, metabolic diseases of the liver and rare disease. “We are establishing it as a new modality,” Habib said. “This funding is a major step in that direction.” Mina is essentially attempting to do the same for activation of gene expression what Cambridge, Mass.-based Alnylam Pharmaceuticals Inc. has achieved with inhibition of gene expression with short interfering RNA (siRNA) drugs.

When taken up by cells, double-stranded saRNA molecules are loaded onto argonaute 2 proteins in the cytosol, where they become activated and transported into the nucleus. Once inside the nucleus they recruit endogenous transcription complexes to specific regions of the promoter, where they drive additional transcription.

Mina’s MTL-CEPBA targets the expression of CEPBA, which encodes a transcription factor called ccAAT/enhancer binding protein alpha (C/EBP-alpha), a master regulator of myeloid cell differentiation. The rationale for the therapy is based on correcting the immune dysregulation within the tumor microenvironment. “It has a lot of immature myeloid cells,” Habib said. Those include myeloid-derived suppressor cells, tumor-associated macrophages and M2 macrophages. “In their immature state, they can suppress the immune system,” he said. What’s more, they can also aid tumor growth.

The enabling intellectual property for Mina’s platform has come from the labs of David Corey, of the University of Texas Southwestern Medical Center in Dallas, and Long-Cheng Li, of the University of California, San Francisco. Mina has industrialized the basic platform and has the means to target the expression of every gene in the genome. Delivering the saRNA molecules is a similar challenge to that associated with siRNA delivery – the company is working on tuning the properties of LNPs in order to optimize uptake in tissues of interest.

The company has now raised about $70 million in equity financing and nondilutive funding, Habib said. Prior to the present round, it had obtained a strategic investment from the Sosei Heptares arm of Tokyo-based Sosei Group, as well as investment from several high-net-worth individuals.

Mina’s founders include John Rossi, of City of Hope, Duarte, Calif., an siRNA pioneer who co-founded Lexington, Mass.-based Dicerna Pharmaceuticals Inc., along with his former postdoc, Pål Sætrom, of the Norwegian University of Science and Technology, in Trondheim, and Nagy Habib, of Imperial College London, an early pioneer of gene and cell therapy in liver disease, who leads the company’s R&D.

The present round was led by Ra’anana, Israel-based Amoon, with participation from existing investors. Amoon’s managing director, Gur Roshwalb, has joined the company’s board in conjunction with the investment.

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