New Tune preclinical data suggests HBV therapy is hitting the right notes

There’s no cure for chronic hepatitis B virus infection, or HBV, a condition that infects nearly 300 million people around the world. Progress on new drugs is slow, partly because HBV is “under-prioritized” by pharmaceutical companies, as a Hepatitis B Foundation executive recently told Fierce Biotech. 

Enter Tune Therapeutics, which on Dec. 6 at the annual Hep DART conference presented new preclinical data demonstrating the efficacy of its epigenome editing technology against HBV. The company’s therapeutic, TUNE-401, repressed HBV DNA almost completely in human liver cells and infected mouse models. 

“Based on the breadth of our preclinical data, we have every reason to believe that this novel therapeutic will translate,” Derek Jantz, chief scientific officer at Tune, said in a press release. “We sincerely hope that this will revitalize the field and lead to the standalone functional cure that HBV patients have been waiting for.” 

TUNE-401 is built on Tune’s TEMPO epigenetic editing platform, which is delivered to cells in lipid nanoparticles, or LNPs. Rather than irreversibly altering the DNA itself by knocking out or deleting genes like other gene editing technologies do, TEMPO adjusts gene expression in a non-permanent way. It uses a peptide complex called a DNA-binding domain coupled with a small molecule called an effector. The DNA-binding domain guides the effector to the target site. There, it fine-tunes gene expression by modifying proteins, stimulating transcription to RNA or adding or removing chemical groups to the DNA. 

TUNE-401 is programmed to stop the expression of HBV genes in the liver cells where it takes root. The new preclinical data shows that it’s capable of doing this in human cell lines at a rate of 90 to 95% for at least 550 days, with the modifications holding even as the cells continue to proliferate. They saw similar results in a mouse model for HBV infection, which contains transplanted human hepatocytes that the company described in a press release as “effectively ‘humanizing’ the liver”. 

In the presentation, the company noted that while there is no primate model for HBV, they already have evidence that their tech gets to the liver in monkeys. A surrogate epigenetic silencer targeting the gene PCSK9 has suppressed the gene for at least nine months in monkeys, with a “comparable safety profile in NHP to other LNP-delivered therapeutics at efficacious doses,” the presentation said. The PCSK9-targeting therapy works via the same mechanism of action as TUNE-401. 

Tune anticipates that TUNE-401 will enter human clinical trials by the end of 2024.