AASLD 2024: Tune-401 Epigenetic Silencer Nearly Represses HepB Virus

DURHAM, N.C. & SEATTLE--(BUSINESS WIRE)--At the American Association for the Study of Liver Diseases (AASLD) conference, Tune Therapeutics, a leading company in epigenome editing, introduced new data supporting its efforts to develop a long-lasting and effective cure for chronic Hepatitis B Virus (HBV). They unveiled their primary HBV program at the 2023 AASLD event, presenting preclinical data that demonstrated significant and enduring effects in targeted human liver cells.

During the event, Brian Cosgrove, the Principal Scientist at Tune Therapeutics, showcased new in vitro and in vivo data. He highlighted the efficacy of Tune’s optimized liver-targeting LNP-RNA epi-silencing drug, Tune-401, which achieved near-complete repression of HBV RNA in human cells and in a 'true infection' FRG mouse model.

Cosgrove explained the dual challenges in addressing chronic HBV infection: the integration of HBV DNA into the host genome and the existence of extrachromosomal cccDNA (covalently closed circular DNA) in liver cell nuclei. Current standard treatments rarely achieve a functional cure (less than 1-3% of patients) because no existing therapy can effectively inactivate both integrated HBV DNA (intDNA) and cccDNA.

"Our innovative approach tackles both integrated viral DNA and the source of viral latency, cccDNA, which current treatments do not address," Cosgrove stated. "The data we've collected reinforces the potential of epi-editing as a uniquely effective treatment for HBV and bolsters our confidence as we progress to human clinical trials."

Tune-401 is an advanced epigenetic silencing treatment designed to target both forms of HBV DNA, aiming to disrupt viral transcription and inhibit the production of new viral particles. According to Cosgrove, preclinical studies have shown highly promising results, including:

- Up to 99.99% suppression of 3.5 kb HBV RNA from cccDNA in infected primary human liver cells (PHHs).
- Corresponding reduction of extracellular Hepatitis B surface antigen (HBsAg) in PHHs—an essential marker of Hepatitis B infection.
- Significant repression of total HBV RNA and extracellular HBsAg from intDNA in Hep3B cell lines.
- A clear inverse relationship between HBV DNA methylation and HBV RNA production, indicating a well-defined mechanism of action for Tune-401.
- Long-lasting virus suppression beyond 550 days after transient delivery to a cell line harboring HBV, demonstrating the persistence of repressive epigenetic marks through over 275 cell divisions.

Blythe Sather, Vice President and Head of Research at Tune Therapeutics, commented, "Tune-401 provides a unique opportunity to demonstrate the impact of epi-editing. Chronic Hepatitis B affects over 250 million people globally, each grappling with this debilitating disease daily. I genuinely believe that our innovative epi-silencing approach, which targets all HBV viral reservoirs, could represent the crucial scientific breakthrough needed—a new strategy that could significantly alter the treatment landscape for this disease."

About Tune Therapeutics
Tune Therapeutics is advancing gene, cell, and regenerative therapies through its innovative genetic tuning platform, TEMPO. The company seeks to expand the application of these therapies to common, chronic, and age-related diseases, striving to mitigate the strain on healthcare systems and enhance human healthspan globally.

About Tune-401
Tune-401 is a pioneering investigational product candidate for treating Hepatitis B (HBV) infection. Utilizing the TEMPO platform, Tune-401 epigenetically silences viral HBV intDNA and cccDNA necessary for sustained HBV infection. The lipid nanoparticle technology for Tune-401 has been provided by Acuitas Therapeutics Inc.