Assembly Biosciences Teases Gilead HSV-2 Decision, Liver Disease Data Ahead

Key Points

• Assembly Biosciences highlighted a key upcoming decision on its HSV-2 program with Gilead, including whether to enter a 40/60 U.S. cost and profit share or stay on a milestones-and-royalties path. Gilead is expected to clarify which HSV-2 molecule, or whether both, will advance.
• The company said its lead HSV-2 candidates showed strong Phase 1b results, including more than 95% reduction in viral shedding and over 90% lesion reduction, supporting once-weekly oral dosing and potential superiority to Valtrex. Assembly expects head-to-head data against Valtrex potentially in the second half of next year.
• Assembly also outlined progress for 6250, an oral NTCP inhibitor, with a Phase 2 hepatitis delta study planned by the end of this year and interim data due by end-2027. The drug is also being expanded into PBC and PSC, with those studies expected to start by Q1 2027 and data in the first half of 2028.

Assembly Biosciences NASDAQ: ASMB outlined its antiviral and liver disease development strategy during a fireside chat at the 47th Annual Goldman Sachs Healthcare Conference, highlighting upcoming decisions tied to its herpes simplex virus type 2 program, expansion of its hepatitis delta candidate into cholestatic liver diseases and expected clinical data readouts in 2027 and 2028.

Jason, an Assembly representative identified by the moderator, described the South San Francisco-based biotechnology company as focused primarily on recurrent genital herpes caused by HSV-2 and hepatitis delta, with a recent expansion into primary biliary cholangitis, or PBC, and primary sclerosing cholangitis, or PSC. He said the company historically has been virology-focused and is now broadening into liver disease, drawing on the experience of team members who previously worked in antiviral and liver disease programs, including at Gilead Sciences.

HSV-2 Program Moves Forward Under Gilead Collaboration

Assembly’s lead HSV-2 candidates, 5366 and 1179, are helicase-primase inhibitors being developed for patients with high-recurrence genital herpes. Jason said the target product profile for both compounds is once-weekly oral dosing, with the goal of superior efficacy compared with Valtrex, the current standard of care.

Jason said Assembly’s Phase 1b data showed more than 95% reduction in viral shedding, more than 90% lesion reduction and more than 98% reduction in high viral load shedding, which the company views as a potential surrogate for transmission. He said those results contributed to Gilead opting into the HSV-2 program before the Phase 1b studies were complete.

Katie Kitrinos, senior vice president of preclinical research and development at Assembly Biosciences, said the recurrent genital herpes patient population remains underserved, with no new advancements in more than 30 years. She said Valtrex reduced transmission by less than 50% from infected individuals to partners and said Assembly’s two molecules could improve both efficacy and convenience.

Jason said the next key HSV-2 catalyst is Assembly’s decision on whether to opt into a 40/60 U.S. cost and profit share with Gilead or instead participate through milestones and royalties. He said that decision will be based on Gilead’s clinical development plan, which is expected to clarify which molecule, or whether both molecules, will advance. He said Assembly would expect head-to-head data against Valtrex potentially in the second half of next year, if timelines align with the company’s assumptions.

6250 Positioned as Oral NTCP Inhibitor for Hepatitis Delta

Assembly also discussed 6250, an oral small-molecule inhibitor of NTCP, a receptor on hepatocytes involved in bile acid transport and used by hepatitis delta and hepatitis B viruses to enter liver cells. Kitrinos said the program was initiated based on bulevirtide, an approved NTCP inhibitor that has demonstrated efficacy but requires daily subcutaneous injection and cold chain storage.

Kitrinos said 6250 has low nanomolar potency in inhibiting hepatitis delta entry into cells and bile acid transport. She said Phase 1a data recently presented at EASL showed “excellent” pharmacokinetics, including a three- to four-day half-life supporting daily oral dosing, along with elevations in serum bile acids that met or exceeded levels seen with approved doses of bulevirtide. She also said the company observed good safety over 10 days of dosing and no adverse events of pruritus, and that chronic toxicology studies provided safety margins for planned Phase 2 doses.

Jason said Assembly plans to initiate a Phase 2 hepatitis delta study by the end of this year, with interim data expected by the end of 2027. He said the company will look for ALT reduction and results compared with bulevirtide.

Expansion Into PBC and PSC

Assembly recently announced that 6250 would also be evaluated in PBC and PSC, both cholestatic liver diseases. Jason said the decision followed discussions with key opinion leaders, development of a clinical plan and a pre-IND meeting with the U.S. Food and Drug Administration. He said Assembly believes the drug’s hepatoprotective mechanism could be additive to, or potentially replace, existing second-line therapies in PBC, though he noted that the company must prove that in clinical data.

Kitrinos said cholestatic liver disease is driven by accumulation of bile acids in hepatocytes and that 6250 directly prevents bile acids from moving from serum into hepatocytes. She said the drug could potentially reduce alkaline phosphatase more than PPAR agonists, which primarily reduce de novo bile acid production, though she emphasized that this remains to be demonstrated in studies.

On pruritus risk, Kitrinos said Assembly did not observe pruritus adverse events in Phase 1a or chronic toxicology studies. She said the company expects 6250 could reduce IL-31, a cytokine associated with itch, by preventing bile acid accumulation in hepatocytes.

Jason said the PBC clinical plan is designed to evaluate 6250 both as a standalone second-line therapy after UDCA and as an add-on to PPAR therapy. He said studies in PBC and PSC are expected to begin by the first quarter of 2027, with data expected in the first half of 2028.

Upcoming Milestones

• Decision on whether Assembly will opt into the 40/60 U.S. HSV-2 cost and profit share with Gilead.

• Gilead’s clinical development plan for the HSV-2 program, including molecule selection and timing.

• Initiation of a Phase 2 hepatitis delta study for 6250 by the end of this year.

• Interim hepatitis delta data expected by the end of 2027.

• PBC and PSC studies expected to start by the first quarter of 2027, with data expected in the first half of 2028.

Jason said financing completed in August 2025 and a more recent financing are expected to fund the HSV-2 program through Phase 2 proof-of-concept data against Valtrex and the PBC and PSC programs past the mid-2028 proof-of-concept readouts. He also said Assembly continues to maintain a research pipeline and expects to nominate additional programs.

About Assembly Biosciences NASDAQ: ASMB

Assembly Biosciences, Inc NASDAQ: ASMB is a clinical-stage biotechnology company dedicated to the discovery, development and commercialization of novel therapies for hepatitis B virus (HBV) and hepatitis D virus (HDV) infections. The company's core expertise lies in small-molecule modulation of viral proteins and host-targeted pathways to achieve sustained viral suppression and potential functional cure. Assembly's research model integrates medicinal chemistry, structural biology and translational virology to advance its pipeline from early discovery through clinical development.

The company's lead programs include core protein allosteric modulators (CpAMs) designed to disrupt the HBV lifecycle by interfering with capsid assembly and viral DNA replication, as well as prenylation inhibitors targeting the HDV lifecycle.

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