Tune Therapeutics to test vaccine-like epigenetics platform

Duke University spinout Tune Therapeutics is rehearsing the overture of its avant-garde therapeutic platform targeting chronic Hepatitis B Virus (HBV) that could also upend many more chronic disease treatments.

Tune, which is jointly based in Durham and Seattle, is one of a small group of gene therapy companies developing a new technology known as epigenetic editing.

One of the global epigenetics leaders is Tune co-founder Charles Gersbach, Ph.D. He’s the John W. Strohbehn Distinguished Professor of Biomedical Engineering at Duke and director of the Duke Center for Advanced Genomic Technologies.

The company’s CEO is Matt Kane, formerly a co-founder and CEO of Precision BioSciences, which is also a Durham company spun out of Duke in 2006. 

Tune - Matt Kane
Tune Therapeutics CEO Matt Kane

When it launched in 2021 Tune raised $40 million in a Series A venture round and is now involved in a new financing round as it readies its first product candidate, TUNE-401, for HBV clinical trials later this year.

TUNE-401 represents a fundamentally new approach to HBV treatment, using the company’s precision genetic “tuning” platform, TEMPO. It’s a lipid nano-particle drug, similar to a COVID vaccine, that travels to a patient’s liver. There it works by attaching so-called methyl markers to the DNA of HBV lurking in the bodies of people who have contracted the virus. This inactivates the virus’s DNA. The “hit-and-run” nature of the therapy provides long-term silencing of the targeted gene, but the drug itself goes away.

The company believes it can neutralize the virus long-term—or permanently—after a single intravenous drip administration of the therapy. That could enable people with HBV to drop other medications without increasing their chance of liver disease. 

If that sounds like a potential cure, Tune isn’t calling it that, because “cure” is a word that is carefully avoided in the halls of therapeutic evolution. But the company is willing to aver that it represents a significant degree of promise for a new battle strategy not only against, HBV but against a wide range of diseases. The company is especially eager to battle chronic diseases, such as HBV and high cholesterol, that affect millions of people yet don’t have elegant solutions.

There are several versions of hepatitis. But HBV is an especially pernicious intruder. Kane says it affects some 300 million people worldwide and remains the main cause of liver cancer. “Sure, we could look at lots of projects, but we’ve decided to make Hep B our major focus today because it’s the right first target for this platform,” he said.

Tune TX logo

According to the U.S. Department of Health and Human Services, “Hepatitis B is transmitted when blood, semen, or another body fluid from a person infected with HBV enters the body of someone who is not infected. This can happen through sexual contact; sharing needles, syringes, or other drug-injection equipment; or from mother to baby at birth.”

Currently, people who have contracted HBV can take medication to suppress the virus. But nothing, so far, shuts it down. If they stop taking their medications, the virus rebounds—increasing their risk of liver disease. Current therapies still don’t disable the extra-chromosomal “viral factories” that enable sustained HBV infection to hide and survive.

The epigenetic processes of the TEMPO platform change the infection process without cutting, damaging, or altering genomic DNA sequences in any way, according to Tune executives. 

“It’s not just an on or off thing,” explained Kane. “Instead, it tunes up and down.” 

That’s a key difference between gene editing and epigenetic editing, explained Chief Scientific Officer Derek Jantz, Ph.D. 

Tune - Derek Jantz
Tune Therapeutics CSO Derek Jantz

“Gene editing is binary. On or off,” Jantz said. “It screws up the underlying DNA sequence. We can actually turn things all the way off with epigenetics, too, but we can also turn things up or down just a little. And in the vast majority of chronic diseases, you don’t want to ‘nuke’ them and turn them off completely. Our goal is to restore the cell back to a state of health from a state of unhealth. I like to think of epigenetic editing as updating software rather than replacing hardware. In most cases, especially chronic diseases, diseases of aging, there’s no need to change the hardware that’s already there, when it’s the software that’s out of whack.”

Kane and Jantz emphasize that epigenetic editing is somewhat similar to gene editing, but not a replacement for it. They say gene editing is an important tool for correcting genetic aberrations, especially in children born with rare genetic defects that can be “edited” out. They also credit the gene editing community for paving the way with regulators and other affected communities to understand the technology, including its risks and benefits.

Meanwhile, they liken the results of epigenetics to those of vaccines, “tuning up” the body’s inherent defense mechanisms to deal with disease-causing situations.

Kane said Tune doesn’t see the handful of other epigenetics startups, such as South San Francisco-based Moonwalk Biosciences, as competitors. “This TEMPO platform is unique and separates TUNE from everybody else,” he says. “It’s a collection of tools that Charlie Gersbach and others have collected over the past 15 years. Most importantly, it’s also the screening platform they bring, to find the locations we’ll want to target and develop specific levels of expression we need to use. The team here is unlike any other I’ve worked with.”

“We’re at least 18 months ahead of where we expected to be,” he added. “We’ll be in HBV trials this year.”
Jantz agrees. “In other epigenetics companies, one company has a hammer and doing things you can do with hammer, and another has a screwdriver. We have the whole tool kit, which allows us to think of things differently than what others do. So we think of using this platform for a wide range of chronic diseases. We don’t just have a hammer or screwdriver or Allen wrench to go after a single-tool disease. We have all of them.”

Kane says Tune has about 85 employees, most of them evenly divided between Durham and Seattle. A few non-lab workers are elsewhere around the country, he said. And the company is hiring. 

“In Seattle, we work on ex-vivo, cell therapy as well as pre-IND and similar work,” he explains. “It has benefited us in recruiting to have a foot in both markets. We’re seeing more and more people excited about moving to the RTP area. We’re huge boosters for this area and shine a light on it all the time.”

Jim Shamp, NCBiotech Writer
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