TUNE-401 by Tune Therapeutics: status and timeline

TUNE-401

First-in-class epigenetic silencer for hepatitis B. LNP-RNA therapy that silences HBV DNA without cutting the genome.

PilotStage 3 of 5

In Phase 1b/2a clinical trials after positive proof-of-concept data; Phase 2 initiation planned for late 2026.

Updated 30 May 2026Checked 10 Oct0 updates this week

Milestones

Next · Phase 2 development initiation

Phase 1b/2a positive proof-of-concept data presented30 May 2026Complete.
Phase 2 development initiationTarget Q4 2026Current milestone.

Most important updates

TUNE-401 shows positive Phase 1b/2a proof-of-concept data for hepatitis B; Phase 2 planned for late 202630 May 2026

Upcoming

Q4 2026Phase 2 development initiation (next)

Current obstacles

Durability of epigenetic marksEpigenetic silencing can be reversed if cells divide or are cleared. Maintaining durable suppression of HBV without immune rejection is the current focus.
Liver-specific delivery without immune activationAchieving high liver concentrations while minimizing innate immune activation (which can clear the therapy or damage liver) is a technical hurdle.

Physics limits

Epigenetic marks can be inherited but also lostWhen a cell divides, its epigenetic marks may be diluted or rewritten by the cell's normal machinery. Hepatitis B-infected liver cells must maintain silencing through multiple rounds of cell division.
Immune system interferenceImmune cells can recognize and destroy cells bearing foreign RNA, or activate inflammatory pathways. Long-term therapy requires evading immune detection.

How it works

3 parts

Epigenetic silencing

Chemical tags, not DNA cuts

TUNE-401 adds methyl groups to hepatitis B DNA, which silences the virus without cutting the genome. This avoids immune activation and integration risks.

LNP delivery

Reaches liver cells in one dose

The therapy is packaged in a lipid nanoparticle and delivered intravenously. The LNP protects the RNA and targets the liver.

Dual targeting

Silences both circular and integrated virus

TUNE-401 methylates cccDNA (circular viral DNA that sits in the nucleus) and integrated HBV DNA, addressing both forms of chronic infection.

Spec sheet

Spec	TUNE-401
Route of administration	Intravenous^R (reported)
Phase 1b/2a dose range tested	0.2–0.85 mg/kg single dose, plus multiple-dose cohort^R (reported)
HBsAg reduction (highest dose)	Dose-dependent repression^R (reported)

^R reported by the company

Papers & demos

1 item

30 May 2026demo
Phase 1b/2a proof-of-concept for TUNE-401 presented at EASL 2026 (opens businesswire.com)First clinical evidence of epigenetic silencing in hepatitis B; all HBV biomarkers showed durable dose-dependent repression.

Update log

1 update

Sat 30 May

Major: TUNE-401 shows positive Phase 1b/2a proof-of-concept data for hepatitis B; Phase 2 planned for late 2026PressTest

About Tune Therapeutics

The team behind TUNE-401

Tune Therapeutics

Gene tuning, epigenetic silencing, TEMPO platform

Tune Therapeutics develops epigenome editing therapies that fine-tune gene activity without altering DNA, treating age-related diseases and chronic conditions. Launched in 2021 with dual headquarters in Seattle and Durham, North Carolina.

TEMPO platform enables epigenome editing: alters gene expression without cutting DNA.
TUNE-401 for hepatitis B showed positive Phase 1b/2a data in May 2026.
Raised $175M Series B in January 2025 to advance clinical development.

tunetx.com (opens tunetx.com)Company profile →

Founded: 20215 yrs
Headquarters: United States
Status: Private
Valuation: $750Mest. privateJan 2025estimate
Staff: ~80Jan 2025
Raised: $175M1 round
Last round: Series B · $175MJan 2025
Works in: BiotechGene editing & therapy
Coverage: 1 program · 3 updateslatest 30 May 2026checked 10 Oct
Lead investors: New Enterprise AssociatesYosemiteRegeneron VenturesHevolution Foundation
Partners: Duke University (opens duke.edu)
People: John McHutchison (opens dukecapitalpartners.duke.edu)CEO and ChairmanCharles Gersbach (opens bme.duke.edu)Co-founder

Spec

TUNE-401

Route of administration

Intravenous^R (reported)

Phase 1b/2a dose range tested

0.2–0.85 mg/kg single dose, plus multiple-dose cohort^R (reported)

HBsAg reduction (highest dose)

Dose-dependent repression^R (reported)