Assembly Biosciences Eyes Gilead HSV Plan as ABI-6250 Liver Pipeline Expands

Key Points

• Assembly Biosciences is waiting on Gilead’s development plan for its HSV assets ABI-5366 and ABI-1179, which showed strong Phase 1b proof of concept and were opted into by Gilead in December. The plan will determine whether the programs advance into later-stage trials, and Assembly will decide around mid-year whether to take a 40/60 U.S. cost-and-profit share.
• ABI-6250 is expanding beyond hepatitis delta into cholestatic liver diseases, with planned Phase 2 studies in hepatitis delta, primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC). The company cited positive early safety and target-engagement data, and expects the PBC/PSC program to begin in Q1 2027 with readouts in the first half of 2028.
• Assembly is also seeking a partner for its hepatitis B program, ABI-4334, after reclaiming full rights. Management says the goal is to find a global partner that can advance the asset as part of a potential HBV cure regimen, while the company’s cash runway now appears to extend into at least the second half of 2028.

Assembly Biosciences NASDAQ: ASMB is awaiting a key development plan from partner Gilead Sciences for its herpes simplex virus programs while advancing ABI-6250 into multiple liver disease indications, Chief Executive Officer Jason Okazaki said during a Jefferies biotech event.

Okazaki said 2024 was “a pretty big year” for the company’s HSV work, with ABI-5366 and ABI-1179 both showing “high proof of concept” in Phase 1b studies. Gilead opted into both programs in December and now controls development and commercialization, he said.

The next expected catalyst is Gilead’s clinical development plan, which Okazaki said should indicate whether one or both molecules will move into Phase 2 and Phase 3, as well as outline commercialization plans. Assembly then has the option to opt into a 40/60 U.S. cost and profit share, a decision Okazaki said the company expects to make around mid-year.

Okazaki said Assembly will evaluate the opportunity largely through a quantitative analysis comparing the potential U.S. profit share against the costs of development and commercialization, as well as the alternative of receiving milestones and royalties without sharing costs. He added that funding a 40% share of Phase 2, Phase 3 and commercial launch expenses would likely require “a significant raise down the road,” making dilution a consideration.

ABI-6250 Expands Beyond Hepatitis Delta

Assembly is also preparing to advance ABI-6250, an NTCP inhibitor, in hepatitis delta and cholestatic liver diseases. Okazaki said the company reported positive Phase 1a data last year showing target engagement and bile acid elevation, and has completed chronic toxicology studies. Assembly plans to start a Phase 2 study in hepatitis delta by the end of this year, with data expected in the second half of next year.

The company recently announced plans to study ABI-6250 in primary biliary cholangitis, or PBC, and primary sclerosing cholangitis, or PSC. Okazaki said the expansion followed about 18 months of discussions with key opinion leaders and a pre-IND meeting with the FDA. He said Assembly has received funding for the program through the end of Phase 2 and expects to initiate PBC and PSC studies in the first quarter of 2027, with data expected in the first half of 2028.

Katie Kitrinos, Assembly’s senior vice president of preclinical R&D, said ABI-6250 was initially developed as a small-molecule NTCP inhibitor for chronic hepatitis delta because NTCP is the receptor the virus uses to enter cells. She said Phase 1a results showed dose-dependent increases in serum bile acids that were “consistent with or actually higher than” levels observed with 2 milligram and 8.5 milligram doses of bulevirtide.

Kitrinos said preclinical work also showed ABI-6250 had low nanomolar potency against bile acid transport, supporting its potential use in cholestatic liver disease. The company views the drug as potentially hepatoprotective because it is designed to prevent bile acids from entering hepatocytes.

PBC and PSC Study Design

Kitrinos said the planned PBC and PSC basket study is intended to be operationally efficient because the same clinical sites could enroll patients with either disease. Okazaki said the study design includes testing ABI-6250 as a second-line single agent and as an add-on to PPAR therapy, reflecting how the company believes the drug could be positioned commercially if successful.

Kitrinos said the company will evaluate biochemical endpoints such as alkaline phosphatase, ALT and bilirubin, as well as non-invasive fibrosis measures including FibroScan and ELF score. The study will also assess pruritus, or itch, and quality-of-life measures.

For PBC, Kitrinos said Assembly will focus heavily on alkaline phosphatase because biochemical endpoints are considered approvable in that indication. For PSC, she said current approvable endpoints are based on clinical outcomes, but the planned 12-week Phase 2 study will instead look for directional changes across biomarkers, fibrosis measures and pruritus scores.

On safety, Kitrinos said the Phase 1a study showed a favorable profile over 10 days of dosing, with no adverse events of pruritus. She added that chronic toxicology studies showed “great safety margins” and no notable safety signals requiring follow-up.

Hepatitis Delta and Potential Oral Advantage

In hepatitis delta, Kitrinos said Assembly expects to run a longer Phase 2 trial, likely 24 to 48 weeks, with multiple doses. The goal is to achieve serum bile acid elevations consistent with or greater than those observed with bulevirtide, which she said have been associated with multiple-log reductions in RNA and ALT normalization.

Kitrinos said ABI-6250 could offer an advantage as a daily oral small molecule. Because hepatitis delta patients are also infected with hepatitis B and typically take a daily oral nucleoside therapy, she said ABI-6250’s expected low dose could make it suitable for co-formulation with a nucleoside, potentially allowing treatment of both viruses in one daily pill.

HBV Program Seeking Partner

Okazaki also discussed ABI-4334, Assembly’s hepatitis B program for which sole rights were returned to the company. He said Assembly has begun a formal partnering process with a bank to identify potential global partners.

Okazaki said Assembly continues to believe a core inhibitor, or CAM, could be one of the cornerstones of a hepatitis B cure regimen alongside a nucleoside backbone. However, he said the company does not have the additional immunomodulatory component needed to pursue the combination strategy on its own.

“Most important for us is making sure somebody could actually take that to the next stage,” Okazaki said, adding that Assembly is flexible on deal structure and focused on finding a partner with a scientific rationale for advancing the asset.

Cash Runway

Okazaki said Assembly’s last published cash runway extended into 2028 and that the company has not updated guidance since a recent $115 million financing. He said the financing should fund the company beyond the planned PBC and PSC trials in 2028, and that it is “safe to say” the runway extends into the second half of 2028, potentially longer depending on the Gilead development plan and Assembly’s opt-in decision.

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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