In genetic medicine, a drumbeat of layoffs and pipeline cuts has replaced the excitement of just a few years ago, when fresh financing rounds were coming almost as often as new editing technologies and seeming breakthroughs.

Tune Therapeutics is hoping to buck the negative sentiment. The startup’s leaders exclusively told Endpoints News that they’ve raised more than $175 million in a Series B, just as the JP Morgan Healthcare Conference kicks off in San Francisco.

Epigenetic editing, or epi-editing for short, attempts to control gene expression in cells, rather than directly edit DNA strands. This year will be a critical test for the technology, with multiple programs expected to enter the clinic. That includes Tune’s lead asset, called Tune-401, an epigenetic editor for hepatitis B that should provide an initial clinical readout in 2025.

“The idea has been around for a very long time,” said Derek Jantz, Tune’s chief scientific officer, but “this is going to be the first demonstration, we hope, that targeted epigenetic control in a patient is possible.”

The Series B was led by New Enterprise Associates, Yosemite, Regeneron Ventures, and Hevolution Foundation. Tune was founded in 2021, largely based on research from Duke University’s Charles Gersbach, and now has about 80 people split between labs in Seattle and Durham, NC. It has presented data on its epigenetic editors producing long-lasting cholesterol drops in non-human primates by targeting the PCSK9 gene, and most recently with its hepatitis B program repressing the virus in human cells and mice.

While it has made scientific progress, it has also weathered the persistent downturn in the market since launching. Its previous CEO, Matt Kane, left last year and is now CEO of Celyad Oncology. Company execs declined to comment on Kane’s exit beyond describing it as personal reasons. A CEO search is ongoing, and board member and Yosemite investor Dan McHugh currently serves as interim CEO.

CFO Akira Matsuno said the Series B raise took most of 2024. He said it was a challenge that the company was something of a “tweener”: not a brand new startup, but still without clinical data to show. He credited its focus on common, chronic conditions as helpful in winning investors, as opposed to starting with rare diseases.

 

Hepatitis B program ‘pretty far ahead’ of rival

The megaround gives Tune the resources to compete with better-capitalized rivals, like nChroma Bio, a newly formed merger of Chroma Medicine and Nvelop Therapeutics. Like Tune, nChroma is pursuing a hepatitis editor that targets co-infections of hepatitis B and D as its lead therapy. It expects to apply to start human testing in 2025.

On paper, Tune’s and nChroma’s editors seem nearly indistinguishable. Jantz said important details on how the two treatments may be different haven’t been disclosed. Tune’s hepatitis B program has been cleared for human testing by regulators in New Zealand and Hong Kong.

“The most obvious difference is, we seem to be pretty far ahead,” Jantz said. “Honestly, we’re rooting for them. What we want to see is epigenetic medicine, in general, becoming a really well-established therapeutic modality.”

The virus is normally treated with daily pills of nucleoside analogs. There is a huge population of patients — Matsuno cites estimates of 300 million people globally — which Matsuno says leaves plenty of room for Tune. Even with today’s treatments, there’s a “really high percentage of patients that ultimately will get fibrosis or liver cancer,” Matsuno said. “While it slows down the viral activity, it doesn’t eliminate it.”

The treatment, Tune-401, is a lipid nanoparticle packaged with an mRNA containing what it calls a TEMPO gene silencer. Through an IV infusion, those lipid nanoparticles are taken up by liver cells, which produce the TEMPO protein. The protein goes into the nucleus and finds the hepatitis B virus, binding to a specific site on the viral genome.

A key difference to existing drugs is that Tune-401 recognizes a virus that exists in two forms: Some integrate into human DNA strands, while others hang out in the nucleus. The protein Tune-401 creates, slaps methyl groups onto the viral DNA, which Jantz said acts like a stop sign for the cell. Human trials will show if that works in the human body as it has in test tubes and mice.

 

Other startups flock to epigenetic control

Tune and nChroma won’t be alone in 2025. Epicrispr Biotechnologies expects to start testing its first epigenetic editor, EPI-321, in early 2025 for facioscapulohumeral muscular dystrophy. (The startup’s timeline, though, has consistently slipped since its 2022 launch, when it forecast reaching the clinic in 2023.)

Another group of buzzy startups is researching a related idea in using transcription factors — proteins that regulate gene activity — to turn cells from diseased to healthy. These include the $3 billion-funded Altos Labs, as well as NewLimit, backed by Coinbase CEO Brian Armstrong, and Retro Biosciences, which is funded entirely by OpenAI CEO Sam Altman. Those companies have yet to provide timelines on when they may be ready to enter the clinic.

Jantz called Tune’s approach more finessed, describing delivering transcription factors as “a little bit more of a blunt instrument.”

Beyond hepatitis B, Tune’s leaders were tight-lipped on specifics. Jantz said if the hepatitis program works, the low-hanging fruit includes any indications with an siRNA medicine. The long-term vision is to do more than just silence disease-causing genes as well.

“The reason the company is named ‘Tune’ as opposed to ‘Off’ is because we’re interested in tuning genes up and down a little bit,” Jantz said. That could include future programs in cellular reprogramming, which could require tweaking multiple genes in the same cell.

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