Hepathera Unveils Latest Research Findings at AASLD 2025 |Capturing the Forefront of International Hepatology

The 76th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2025) was held in Washington, D.C., USA from November 7 to 11, 2025. AASLD is one of the most influential and authoritative international academic conferences in the field of hepatology, dedicated to advancing the development of liver disease research and research workforce, as well as promoting liver health and high-quality patient management. The research team from Hepathera presented its latest research findings as a Late Breaking Parallel Presentation at this year’s conference.

Research Background:

HT-101 Injection and HT-102 Injection are two anti‑hepatitis B virus drugs developed by Hepathera. HT-101 is a GalNAc‑conjugated small interfering RNA (siRNA) designed to target hepatocytes, enabling precise silencing of HBV transcripts and blocking HBsAg production at the source. HT-102 is a fully human neutralizing antibody that rapidly captures and clears HBsAg from the blood, helping the body restore immune recognition. The combination of the two forms a closed‑loop therapeutic model of “suppression + clearance,” significantly enhancing the cure efficacy.

Mechanism of Action of the HT-101/HT-102 Combination:

In preclinical studies, the combination of HT-101 and HT-102 demonstrated strong efficacy and safety. Both drugs individually showed favorable safety, tolerability, and pharmacokinetic profiles in Phase I monotherapy trials (HT-101: NCT06746311; HT-102: NCT06744686). Preclinical combination data further indicated a significant reduction in HBsAg levels. At the 2025 Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2025) held in Washington, D.C., researchers presented the results of a Phase Ib/IIa clinical trial of the two drugs in combination.

Methods:

This randomized, multicenter Phase Ib/IIa clinical trial (NCT07183306) was designed to evaluate the safety and efficacy of HT-101 and HT-102 as monotherapy or in combination in patients with chronic hepatitis B (CHB). The study enrolled 56 HBeAg‑negative CHB patients with long‑term nucleos(t)ide analogue (NUC) suppression, baseline HBsAg levels between 100–3,000 IU/mL, and HBV DNA <100 IU/mL. Patients were assigned to five groups:

• Group A: HT-101 monotherapy 400 mg;

• Group B: HT-102 300 mg followed sequentially by HT-101 400 mg;

• Groups C–E: combination therapy (HT-101 100 mg, 200 mg, or 400 mg plus a fixed dose of HT-102 300 mg).

Subjects received once‑monthly dosing for 24 weeks. After the treatment period, subjects continued NUC monotherapy alone for an additional 24 weeks. At Week 48, subjects entered an additional 24‑week follow‑up period, during which continued NUC use or discontinuation was decided based on NUC withdrawal criteria. NUC discontinuation was permitted only for subjects who achieved a complete response (CR), defined as HBsAg <0.05 IU/mL and HBV DNA <10 IU/mL.

Results:
By Week 24, the overall HBsAg seroclearance rate in the combination therapy groups increased to 22/28 (79%) (Week 20 data for Group E). In Group E, 90% of patients achieved HBsAg clearance by Week 20, and 2/10 (20%) of participants in Group E achieved HBsAg clearance as early as Week 4.

For HT-101 monotherapy, the mean HBsAg decline reached 3.17 log₁₀ IU/mL by Week 24. For HT-102 monotherapy, the mean HBsAg decline was 2.27 log₁₀ IU/mL by Week 24. In the combination therapy groups (Groups C–E), the mean HBsAg declines were 4.21 log₁₀ IU/mL (Group C, Week 24), 4.4 log₁₀ IU/mL (Group D, Week 24), and 4.6 log₁₀ IU/mL (Group E, Week 20), respectively.

应答率与基线HBsAg水平相关：基线HBsAg <1,000 IU/mL的受试者在第20周达到14/14（100%）HBsAg清除;基线HBsAg ≥ 1,000 IU/mL的受试者8/14（57%）HBsAg清除。

Response rates correlated with baseline HBsAg levels: Among subjects with baseline HBsAg <1,000 IU/mL, 14/14 (100%) achieved HBsAg clearance by Week 20; among those with baseline HBsAg ≥1,000 IU/mL, 8/14 (57%) achieved HBsAg clearance.

Conclusions:

• The HT‑101 + HT‑102 combination leads to rapid, deep, and sustained HBsAg decline, distinct from the effects of either drug alone.

• In the high‑dose combination group, 90% of patients achieved HBsAg clearance by Week 20, with 20% of participants achieving HBsAg clearance as early as Week 4.

• Monotherapy and combination therapy with HT‑101 and HT‑102 were generally safe and well tolerated.

• These clinical results led to the formal inclusion of HT‑101 and HT‑102 as Breakthrough Therapy Designation products on September 23, 2025.

Clinical Progress:
The Phase IIb randomized controlled trial (RCT) of the HT-101 + HT-102 combination is currently ongoing.

Professor Hou Jinlin, the leading principal investigator, noted that this study represents a critical step forward in hepatitis B treatment, from "long‑term suppression" toward "functional cure." "The combination of RNAi and antibody represents a major leap forward in hepatitis B therapy. We are accelerating subsequent research, and the post‑treatment follow‑up results after drug discontinuation are expected to be released in the first half of 2026."
This study was led by the research team of Hepathera and Nanfang Hospital, in collaboration with multiple liver disease centers in Shanghai, Sichuan, Beijing, Xiamen, Guangzhou, and other cities. These findings not only bring new hope for a cure to chronic hepatitis B patients worldwide but also demonstrate the rise and contribution of China’s original therapeutic strategies in the global field of hepatology research.