Assembly Biosciences Reports Interim Phase 1b Results from Clinical Trial Evaluating Next-Generation Capsid Assembly Modulator Candidate ABI-4334 in Chronic Hepatitis B
Assembly Biosciences (ASMB) announced interim results from its Phase 1b trial of ABI-4334, a next-generation capsid assembly modulator for chronic hepatitis B virus. The first cohort, receiving 150 mg daily oral dose, showed strong antiviral activity with a mean HBV DNA reduction of 2.9 log IU/mL over 28 days. The drug demonstrated favorable safety profile and half-life supporting once-daily dosing.
Among participants with detectable HBV RNA at baseline, a mean decline of 2.5 log10 U/mL was observed. Enrollment is ongoing for the final 400 mg cohort, with data expected in 1H 2025. Under the collaboration agreement, Gilead has the option to further develop and commercialize ABI-4334 after Phase 1b study completion.
Assembly Biosciences (ASMB) ha annunciato risultati intermedi dal suo trial di Fase 1b per ABI-4334, un modulatori dell'assemblaggio della capsula di nuova generazione per il virus dell'epatite B cronica. Il primo gruppo, che ha ricevuto una dose orale giornaliera di 150 mg, ha mostrato una forte attività antivirale con una riduzione media dell'HBV DNA di 2.9 log IU/mL nel corso di 28 giorni. Il farmaco ha dimostrato un profilo di sicurezza favorevole e una emivita che supporta un dosaggio una volta al giorno.
Tra i partecipanti con RNA HBV rilevabile all'inizio, è stata osservata una declino medio di 2.5 log10 U/mL. L'arruolamento è ancora in corso per il gruppo finale da 400 mg, con dati attesi nella prima metà del 2025. Ai sensi dell'accordo di collaborazione, Gilead ha l'opzione di sviluppare ulteriormente e commercializzare ABI-4334 dopo il completamento dello studio di Fase 1b.
Assembly Biosciences (ASMB) anunció resultados intermedios de su ensayo de Fase 1b de ABI-4334, un modulador de ensamblaje de cápsides de nueva generación para el virus de la hepatitis B crónica. El primer grupo, que recibió una dosis oral diaria de 150 mg, mostró una fuerte actividad antiviral con una reducción media de HBV DNA de 2.9 log IU/mL a lo largo de 28 días. El medicamento demostró un perfil de seguridad favorable y una vida media que apoya la dosificación una vez al día.
Entre los participantes con RNA HBV detectable al inicio, se observó una disminución media de 2.5 log10 U/mL. La inscripción sigue en curso para el grupo final de 400 mg, con datos esperados en la primera mitad de 2025. Según el acuerdo de colaboración, Gilead tiene la opción de desarrollar y comercializar aún más ABI-4334 después de la finalización del estudio de Fase 1b.
Assembly Biosciences (ASMB)는 만성 B형 간염 바이러스에 대한 차세대 캡시드 조립 조절제 ABI-4334의 1b 단계 시험에서 중간 결과를 발표했습니다. 150 mg의 경구 복용량을 받는 첫 번째 집단은 28일 동안 HBV DNA 평균 감소 2.9 log IU/mL의 강력한 항바이러스 활성을 보여주었습니다. 이 약물은 일일 1회 복용을 지원하는 유리한 안전성 프로파일과 반감기를 보여주었습니다.
기본선에서 HBV RNA가 검출된 참가자들 중에서 평균 2.5 log10 U/mL 감소가 관찰되었습니다. 400 mg의 마지막 집단에 대한 등록은 진행 중이며, 2025년 1분기 중 데이터가 기대됩니다. 협력 계약에 따라, Gilead는 1b 단계 연구 완료 후 ABI-4334를 추가로 개발하고 상용화할 옵션을 가지고 있습니다.
Assembly Biosciences (ASMB) a annoncé des résultats intermédiaires de son essai de phase 1b concernant ABI-4334, un modulateur d'assemblage de capsides de nouvelle génération pour le virus de l'hépatite B chronique. La première cohorte, recevant une dose orale quotidienne de 150 mg, a montré une forte activité antivirale avec une réduction moyenne de l'ADN du VHB de 2,9 log IU/mL sur 28 jours. Le médicament a démontré un profil de sécurité favorable et une demi-vie soutenant une posologie une fois par jour.
Parmi les participants ayant un ARN VHB détectable au départ, une diminution moyenne de 2,5 log10 U/mL a été observée. L'inscription est en cours pour la cohorte finale de 400 mg, avec des données attendues au cours de la première moitié de 2025. Selon l'accord de collaboration, Gilead a l'option de développer et de commercialiser davantage l'ABI-4334 après l'achèvement de l'étude de phase 1b.
Assembly Biosciences (ASMB) hat Zwischenresultate aus seiner Phase-1b-Studie zu ABI-4334, einem modulatorischen Mittel zur Assemblierung von Kapsiden für das chronische Hepatitis-B-Virus, bekannt gegeben. Die erste Kohorte, die eine tägliche orale Dosis von 150 mg erhielt, zeigte eine starke antivirale Aktivität mit einer mittleren HBV-DNA-Reduktion von 2,9 log IU/mL über 28 Tage. Das Medikament wies ein günstiges Sicherheitsprofil und eine Halbwertszeit auf, die eine einmal tägliche Dosierung unterstützt.
Bei Teilnehmern mit nachweisbarem HBV-RNA-Baseline wurde ein mittlerer Rückgang von 2,5 log10 U/mL beobachtet. Die Einschreibung für die endgültige Kohorte mit 400 mg ist weiterhin im Gange, mit Daten, die in der ersten Jahreshälfte 2025 erwartet werden. Im Rahmen der Zusammenarbeit hat Gilead die Option, ABI-4334 nach Abschluss der Phase-1b-Studie weiterzuentwickeln und zu kommerzialisieren.
- Strong antiviral activity with 2.9 log IU/mL reduction in HBV DNA
- Favorable safety profile with no serious adverse events
- Half-life supports convenient once-daily oral dosing
- Partnership with Gilead provides commercialization pathway
- changes in viral antigens observed during treatment period
- Two grade three lab abnormalities reported in 150 mg cohort
Insights
The interim Phase 1b results for ABI-4334 demonstrate remarkable antiviral efficacy with a
The safety profile is particularly encouraging, with manageable and self-resolving laboratory abnormalities. The achievement of double-digit multiples over protein-adjusted EC50 suggests a robust therapeutic window, indicating potential for strong efficacy while maintaining safety. This positions ABI-4334 as a potentially best-in-class capsid assembly modulator.
A simple explanation: Think of HBV like a virus factory in the liver. ABI-4334 acts like a wrench in the machinery, significantly reducing virus production. The 2.9 log reduction means the drug reduced virus levels by about 800 times - a substantial improvement.
The strong interim data significantly enhances Assembly Bio's partnership potential with Gilead Sciences. The opt-in structure of their collaboration agreement creates a important near-term catalyst, as positive Phase 1b completion could trigger Gilead's development and commercialization rights. For a company with a market cap of just
The chronic HBV market represents a substantial commercial opportunity, currently valued at approximately
In simpler terms: Assembly Bio has created a promising new hepatitis B drug that their bigger partner Gilead might want to buy or license. This could mean a significant payday for Assembly Bio, whose current market value might be underestimating this potential.
– ABI-4334 was well-tolerated with a favorable safety profile and half-life supporting once-daily oral dosing observed –
– In the first 150 mg dose cohort, ABI-4334 showed strong antiviral activity with a mean reduction of 2.9 log IU/mL in plasma HBV DNA over 28 days of treatment –
– Enrollment in final cohort of 400 mg ongoing with data anticipated in 1H 2025 –
SOUTH SAN FRANCISCO, Calif., Dec. 26, 2024 (GLOBE NEWSWIRE) -- Assembly Biosciences, Inc. (Nasdaq: ASMB), a biotechnology company developing innovative therapeutics targeting serious viral diseases, today announced encouraging interim safety, pharmacokinetic (PK) and efficacy results from participants with chronic hepatitis B virus (HBV) infection in its ongoing Phase 1b study evaluating ABI-4334, an investigational next-generation capsid assembly modulator (CAM).
Improvements in trial-defined measures of antiviral activity were observed in the first Phase 1b cohort that received an oral, once-daily dose of 150 mg of ABI-4334 over a 28-day treatment period. A mean decline in HBV DNA of 2.9 log10 IU/mL was observed in a population of predominately hepatitis B e antigen (HBeAg) negative participants. Among the subset of participants with detectable HBV RNA at baseline, a mean decline of 2.5 log10 U/mL for HBV RNA was observed. As anticipated, limited changes in viral antigens were observed for the study population over the 28-day treatment period. These initial antiviral data are consistent with the high potency seen preclinically for ABI-4334.
In this initial 150 mg cohort, ABI-4334 continued to show a half-life supportive of once-daily oral dosing and maintained clinical exposures multiple-folds above those anticipated to be required for potent antiviral activity and inhibition of cccDNA formation. Safety data for study participants in both cohorts to date demonstrated that ABI-4334 was well-tolerated with a favorable safety profile observed.
“We are pleased to see strong antiviral activity in this first Phase 1b cohort for ABI-4334, our most potent CAM,” said Anuj Gaggar, MD, PhD, chief medical officer of Assembly Bio. “While this is an early read, these interim data reinforce the potential of ABI-4334 to achieve our target clinical profile. The goal of this Phase 1b study is to provide an initial efficacy and safety profile for ABI-4334 in the chronic HBV population and, when completed, the trial will support our evaluation of next steps for the program in tandem with our partner Gilead’s evaluation of their option.”
Enrollment is ongoing for the second cohort, evaluating an oral once-daily dose of ABI-4334 of 400 mg. Based on antiviral activity observed in the first cohort, Assembly Bio expects that the 400 mg cohort will be the final cohort for this Phase 1b study and anticipates releasing data from this cohort in the first half of 2025. Under the collaboration agreement between Assembly Bio and Gilead Sciences, Inc. (Gilead), Gilead has the right to opt in to further development and commercialization for ABI-4334 after Assembly Bio’s delivery of a data package following completion of this Phase 1b study.
ABI-4334 is an investigational product candidate that has not been approved anywhere globally, and its safety and efficacy have not been established.
Study ABI-4334-102 – Phase 1b Interim Results
Study Overview
ABI-4334-102 is a randomized, blinded, placebo-controlled, dose-ranging Phase 1b clinical study evaluating the safety, PK and antiviral activity of ABI-4334. The study is being conducted in treatment-naive or off-treatment participants with HBeAg positive or negative chronic HBV infection. The study is anticipated to enroll two sequential cohorts of 10 subjects each, randomized 8:2 to receive ABI-4334 or placebo daily for a 28-day treatment period. Dosing is complete for the first cohort, evaluating a dose of 150 mg, and enrollment is ongoing for the second cohort, evaluating a dose of 400 mg.
Data for the first cohort evaluating a 150 mg dose are reported here. Safety data to date for the second cohort evaluating a 400 mg dose are also included. The study team remains blinded and the reported interim safety data include pooled data from both active and placebo treatment groups reported collectively.
Interim Results
In safety data to date for both cohorts, ABI-4334 was well-tolerated with a favorable safety profile observed. No safety signals have been identified and there were no serious adverse events or adverse events that led to study drug discontinuation. Two grade three lab abnormalities were observed in the 150 mg cohort, one alanine aminotransferase (ALT) elevation and one total bilirubin elevation. These elevations were observed in separate participants and both resolved with continued dosing of ABI-4334 or placebo. No other grade three or four laboratory abnormalities were observed.
In the predominately HBeAg negative participants receiving 150 mg of ABI-4334, a mean decline in HBV DNA of 2.9 log10 IU/mL and a mean decline in HBV RNA of 2.5 log10 U/mL in the subset with detectable HBV RNA at baseline were observed over 28 days. As expected, given the patient population and 28-day treatment period, limited changes in viral antigens were observed.
In the 150 mg cohort, ABI-4334 continued to show a half-life supportive of once-daily oral dosing. In addition, based on PK data from this cohort and preclinical studies, daily minimum plasma trough concentrations (Cmin) at the 150 mg dose achieved double-digit multiples over protein-adjusted EC50 for both antiviral activity and cccDNA formation.
Additional information about the Phase 1b trial is available at clinicaltrials.gov using the identifier NCT06384131. Assembly Bio expects to submit complete data from the trial for presentation at future scientific meetings.
About Assembly Biosciences
Assembly Biosciences is a biotechnology company dedicated to the development of innovative small-molecule therapeutics designed to change the path of serious viral diseases and improve the lives of patients worldwide. Led by an accomplished team of leaders in virologic drug development, Assembly Bio is committed to improving outcomes for patients struggling with the serious, chronic impacts of herpesvirus, hepatitis B virus (HBV) and hepatitis delta virus (HDV) infections. For more information, visit assemblybio.com.
Forward-Looking Statements
The information in this press release contains forward-looking statements that are subject to certain risks and uncertainties that could cause actual results to materially differ. These risks and uncertainties include: Assembly Bio’s ability to maintain financial resources necessary to continue its research activities, clinical studies and other business operations; Assembly Bio’s ability to realize the potential benefits of its collaboration with Gilead Sciences, Inc., including all financial aspects of the collaboration and equity investments; Assembly Bio’s ability to initiate and complete clinical studies involving its therapeutic product candidates, including studies contemplated by Assembly Bio’s collaboration with Gilead, in the currently anticipated timeframes or at all; safety and efficacy data from clinical or nonclinical studies may not warrant further development of Assembly Bio’s product candidates; clinical and nonclinical data presented at conferences may not differentiate Assembly Bio’s product candidates from other companies’ candidates; results of nonclinical studies may not be representative of disease behavior in a clinical setting and may not be predictive of the outcomes of clinical studies; and other risks identified from time to time in Assembly Bio’s reports filed with the U.S. Securities and Exchange Commission (the SEC). You are urged to consider statements that include the words may, will, would, could, should, might, believes, hopes, estimates, projects, potential, expects, plans, anticipates, intends, continues, forecast, designed, goal or the negative of those words or other comparable words to be uncertain and forward-looking. Assembly Bio intends such forward-looking statements to be covered by the safe harbor provisions contained in Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. More information about Assembly Bio’s risks and uncertainties are more fully detailed under the heading “Risk Factors” in Assembly Bio’s filings with the SEC, including its most recent Annual Report on Form 10-K, Quarterly Reports on Form 10-Q and Current Reports on Form 8-K. Except as required by law, Assembly Bio assumes no obligation to update publicly any forward-looking statements, whether as a result of new information, future events or otherwise.
Contacts
Investor and Corporate:
Shannon Ryan
SVP, Investor Relations, Corporate Affairs and Alliance Management
(415) 738-2992
investor_relations@assemblybio.com
Media:
Sam Brown Inc.
Hannah Hurdle
(805) 338-4752
ASMBMedia@sambrown.com
FAQ
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