'Epigenetic Editing' Venture Moonwalk Raises $57 Million

"Biotechnology startup Moonwalk Biosciences has raised $57 million in venture capital and joined a push to treat diseases through drugs that activate or suppress genes.

Proponents say this new twist on genetic medicine, "epigenetic editing," promises to lead to treatments or cures for a variety of common medical scourges, such as cancer and chronic hepatitis B.

Epigenetic therapy attempts to tap nature's method of regulating what a gene does, or its expression. Cells in various organs harbor the same genes. But a system of controlling which genes are turned on -- epigenetics -- determines what type of cell they become.

South San Francisco, Calif.-based Moonwalk, founded in 2022, seeks to harness a form of epigenetic control that involves adding chemical tags, known as methyl groups, to DNA. Adding a methylation tag suppresses a gene, while removing one can allow it to be activated.

Bing Ren, director of the Center for Epigenomics at the University of California, San Diego, said the approach could be a breakthrough, partly because it could open new angles of attack on diseases.

But there are difficulties, he noted, such as delivering medicines effectively and discovering the sites across the genome that can be targeted and epigenetically edited.

"For epigenetic editing, the question is what are the sites in the genome that you can target and edit and achieve the desired therapeutic effect," said Ren, who has no ties to epigenetic-editing companies.

Genetic medicine is gaining prominence thanks to advances in fields such as genetic sequencing and the ability to molecularly profile individual cells. One form of genetic medicine is gene editing, which alters letters of genetic code.

Epigenetic editing, in contrast, doesn't change underlying DNA. 

Several venture investors are backing it as a means of reprogramming cells and uncovering cures.

No single form of epigenetic editing delivers the desired results in all instances, said David Segal, a professor in the department of biochemistry and molecular medicine at University of California, Davis, who said he advises companies in this field and is developing epigenetic therapies in his lab.

"You might have to search around for the right constellation of components that gives you the level of gene expression that you want," Segal said. "But I think as we do this more, we're going to understand the rules better, and each year we're going to be able to do it more and more easily."

Moonwalk has mapped methyl tags across the genome, said Feng Zhang, a gene-editing researcher and scientist at the Broad Institute of MIT and Harvard and a scientific founder of Moonwalk and other biotechs. This mapping enables scientists to compare healthy and diseased cells and identify ways to restore diseased ones to health, he added.

Moonwalk focuses on some 28 million sites across the genome that can be methylated and become targets for the company's drugs, said co-founder and Chief Executive Dr. Alex Aravanis. 

One way to make epigenetic edits, he said, is by fusing a molecule that binds to specific genome sites with an enzyme that adds or removes methyl markers.

Tune Therapeutics, based in Seattle and Durham, N.C., expects to launch clinical trials later this year of an epigenetic therapy to silence the hepatitis B virus in patients with chronic infections. Currently patients take medication to suppress the virus, but if they stop, the virus rebounds -- increasing their risk of liver disease, said Chief Scientific Officer Derek Jantz.

Tune's treatment targets liver cells, adding methyl markers to DNA to stop viral genes from being expressed and ties the virus up to block the cell's transcription machinery from accessing the virus, Jantz said. The hope is that this will neutralize the virus long-term -- or permanently -- after a single administration.

In 2021, Tune raised $40 million in a Series A venture round. It said it is in the midst of a new financing.

Moonwalk is deciding which diseases to target. Options include engineering T-cell immunotherapies for cancer and treatments for X-chromosome-linked diseases or disorders arising from mutations on the X, Aravanis said.

"The ability to engineer the epigenome, to move things back to a healthier state, represents a huge opportunity for us to create new therapies," he added." [1]

1. Business News: 'Epigenetic Editing' Venture Moonwalk Raises $57 Million. Gormley, Brian.  Wall Street Journal, Eastern edition; New York, N.Y.. 05 Jan 2024: B.6.