Assembly Biosciences Reports Interim Phase 1a Data from Clinical Study of Oral Entry Inhibitor Candidate ABI-6250 for Hepatitis Delta Virus
Assembly Biosciences (Nasdaq: ASMB) has reported promising interim Phase 1a data for ABI-6250, their oral hepatitis delta virus (HDV) entry inhibitor candidate. The study demonstrated a four-day half-life, supporting once-daily oral dosing, and showed dose-dependent elevations in total serum bile acids, indicating effective target engagement.
Key findings include successful completion of two single-dose cohorts (5mg and 25mg) and three multiple-dose cohorts (0.05mg, 0.2mg, and 1mg). Safety data showed mostly Grade 1 adverse events, with one Grade 2 ALT elevation in the highest dose cohort. All ALT elevations were self-limited without signs of liver injury.
The company plans to conduct additional pharmacological assessment while preparing for Phase 2 studies, positioning ABI-6250 as potentially the first oral therapy for chronic HDV infection.
Assembly Biosciences (Nasdaq: ASMB) ha riportato dati promettenti intermedi della Fase 1a per ABI-6250, il loro candidato orale inibitore dell'ingresso del virus dell'epatite delta (HDV). Lo studio ha dimostrato un emivita di quattro giorni, supportando una somministrazione orale una volta al giorno, e ha evidenziato aumenti dose-dipendenti degli acidi biliari totali nel siero, indicando un efficace coinvolgimento del target.
I risultati principali includono il completamento con successo di due coorti a dose singola (5mg e 25mg) e di tre coorti a dose multipla (0,05mg, 0,2mg e 1mg). I dati di sicurezza hanno mostrato prevalentemente eventi avversi di grado 1, con un unico aumento di ALT di grado 2 nella coorte a dose pi霉 alta. Tutti gli aumenti di ALT si sono risolti spontaneamente senza segni di danno epatico.
L'azienda prevede di condurre ulteriori valutazioni farmacologiche mentre si prepara per gli studi di Fase 2, posizionando ABI-6250 come potenzialmente la prima terapia orale per l'infezione cronica da HDV.
Assembly Biosciences (Nasdaq: ASMB) ha informado datos interinos prometedores de la Fase 1a para ABI-6250, su candidato oral inhibidor de la entrada del virus de la hepatitis delta (HDV). El estudio demostr贸 una vida media de cuatro d铆as, lo que respalda una dosificaci贸n oral una vez al d铆a, y mostr贸 elevaciones dependientes de la dosis en los 谩cidos biliares totales en suero, indicando un compromiso efectivo del objetivo.
Los hallazgos clave incluyen la finalizaci贸n exitosa de dos cohortes de dosis 煤nica (5 mg y 25 mg) y tres cohortes de dosis m煤ltiples (0,05 mg, 0,2 mg y 1 mg). Los datos de seguridad mostraron principalmente eventos adversos de grado 1, con una elevaci贸n de ALT de grado 2 en la cohorte de dosis m谩s alta. Todas las elevaciones de ALT fueron autolimitadas sin signos de da帽o hep谩tico.
La compa帽铆a planea realizar evaluaciones farmacol贸gicas adicionales mientras se prepara para los estudios de Fase 2, posicionando a ABI-6250 como potencialmente la primera terapia oral para la infecci贸n cr贸nica por HDV.
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欤检殧 瓴瓣臣搿滊姅 霊� 臧滌潣 雼殞 韴棳 旖旐樃韸�(5mg 氚� 25mg)鞕� 靹� 臧滌潣 雼ろ殞 韴棳 旖旐樃韸�(0.05mg, 0.2mg, 1mg)毳� 靹标车鞝侅溂搿� 鞕勲頃� 鞝愳澊 韽暔霅╇媹雼�. 鞎堨爠靹� 雿办澊韯半姅 雽�攵�攵� 1霌标笁 鞚挫儊氚橃潙鞚� 氤挫榾鞙茧┌, 臧�鞛� 雴掛潃 鞖╇焿 旖旐樃韸胳棎靹� 2霌标笁 ALT 靸侅姽鞚� 頃� 瓯� 氤搓碃霅橃棃鞀惦媹雼�. 氇摖 ALT 靸侅姽鞚� 鞛愱皜 鞝滍暅鞝侅澊氅� 臧� 靻愳儊 歆曧泟電� 鞐嗢棃鞀惦媹雼�.
須岇偓電� 2靸� 鞐瓣惮 欷�牍勳檧 頃粯 於旉皜 鞎诫Μ 韽夑皜毳� 瓿勴殟頃橁碃 鞛堨溂氅�, ABI-6250鞚� 毵岇劚 HDV 臧愳椉鞐� 雽�頃� 觳� 瓴疥惮 旃橂鞝�搿� 鞛愲Μ毵り箑頃� 臧�電レ劚鞚� 臧栮碃 鞛堨姷雼堧嫟.
Assembly Biosciences (Nasdaq : ASMB) a rapport茅 des donn茅es interm茅diaires prometteuses de la phase 1a pour ABI-6250, leur candidat inhibiteur oral de l'entr茅e du virus de l'h茅patite delta (VHD). L'茅tude a d茅montr茅 une demi-vie de quatre jours, soutenant une administration orale une fois par jour, et a montr茅 des 茅l茅vations d茅pendantes de la dose des acides biliaires totaux s茅riques, indiquant un engagement efficace de la cible.
Les r茅sultats cl茅s incluent la r茅ussite de deux cohortes 脿 dose unique (5 mg et 25 mg) et trois cohortes 脿 dose multiple (0,05 mg, 0,2 mg et 1 mg). Les donn茅es de s茅curit茅 ont montr茅 principalement des 茅v茅nements ind茅sirables de grade 1, avec une 茅l茅vation de l'ALT de grade 2 dans la cohorte 脿 la dose la plus 茅lev茅e. Toutes les 茅l茅vations d'ALT 茅taient auto-limitantes sans signes de l茅sion h茅patique.
La soci茅t茅 pr茅voit de r茅aliser des 茅valuations pharmacologiques suppl茅mentaires tout en se pr茅parant aux 茅tudes de phase 2, positionnant ABI-6250 comme potentiellement la premi猫re th茅rapie orale pour l'infection chronique par le VHD.
Assembly Biosciences (Nasdaq: ASMB) hat vielversprechende Zwischenresultate der Phase 1a f眉r ABI-6250 berichtet, ihren oralen Hepatitis-Delta-Virus-(HDV)-Entry-Inhibitor-Kandidaten. Die Studie zeigte eine Halbwertszeit von vier Tagen, was eine einmal t盲gliche orale Dosierung unterst眉tzt, und zeigte dosisabh盲ngige Erh枚hungen der Gesamtserumgallenfl眉ssigkeit, was auf eine effektive Zielbindung hinweist.
Wesentliche Ergebnisse umfassen den erfolgreichen Abschluss von zwei Einzeldosis-Kohorten (5mg und 25mg) sowie drei Mehrfachdosis-Kohorten (0,05mg, 0,2mg und 1mg). Sicherheitsdaten zeigten 眉berwiegend Nebenwirkungen vom Grad 1, mit einer einzigen ALT-Erh枚hung Grad 2 in der h枚chsten Dosis-Kohorte. Alle ALT-Erh枚hungen waren selbstlimitierend ohne Anzeichen von Lebersch盲den.
Das Unternehmen plant weitere pharmakologische Bewertungen durchzuf眉hren, w盲hrend es sich auf Phase-2-Studien vorbereitet, und positioniert ABI-6250 als potenziell erste orale Therapie f眉r chronische HDV-Infektionen.
- Demonstrated four-day half-life supporting convenient once-daily oral dosing
- Showed dose-dependent target engagement through bile acid elevation biomarkers
- Potential to become first oral therapy for chronic HDV infection
- Most adverse events were Grade 1 with no serious adverse events reported
- Grade 2 ALT elevation observed in highest dose cohort (25mg)
- Off-target engagement of liver transporters detected in highest dose cohort
- Additional studies needed to explore ALT elevations
Insights
Assembly Bio's HDV drug ABI-6250 shows promising early clinical data with once-daily dosing potential, though safety signals warrant additional investigation.
The interim Phase 1a data for ABI-6250 presents several encouraging signals for Assembly Biosciences' oral hepatitis delta virus (HDV) entry inhibitor. The observed four-day half-life supports the targeted once-daily oral dosing regimen, which represents a potential convenience advantage in the treatment landscape. The dose-dependent elevations in total serum bile acids (TBA) provide clear evidence of target engagement with the sodium taurocholate cotransporting polypeptide (NTCP), the receptor HDV uses to infect liver cells.
However, the safety signals deserve careful consideration. The grade 2 ALT elevation at the highest single dose (25mg) and grade 1 elevations in other cohorts indicate potential liver effects that require further characterization. While these were self-limited without bilirubin elevations or other markers of serious liver injury, this finding is particularly relevant given NTCP's role as a bile acid transporter. The company's decision to pursue additional studies to understand these elevations is prudent.
The accumulation profile is noteworthy - with exposures reaching 6-7 fold higher after multiple dosing, which explains why the company selected lower doses (鈮�1mg) for the multiple-dose cohorts. This helped characterize the lower end of the dose-response curve while managing potential safety concerns.
The biomarker findings reveal a secondary signal: at the highest dose (25mg), coproporphyrin I (CP-1) elevations indicate potential off-target effects on OATP1B1/OATP1B3 transporters, which could explain some of the observed ALT elevations.
For a disease with limited treatment options (only one approved therapy in the EU and none in the US), these results position ABI-6250 as a potential first oral therapy for chronic HDV infection, addressing a significant unmet need. However, Assembly Bio must carefully balance efficacy and safety as they advance toward Phase 2 studies in HDV-infected patients.
鈥� Data to date in single- and multiple-ascending dose cohorts of healthy participants demonstrate a four-day half-life for ABI-6250, supporting target daily oral dosing profile and dose-dependent elevations in biomarker of target engagement 鈥�
鈥� Further pharmacological assessment to be conducted in parallel with Phase 2 preparation 鈥�
SOUTH SAN FRANCISCO, Calif., Aug. 06, 2025 (GLOBE NEWSWIRE) -- Assembly Biosciences, Inc. (Nasdaq: ASMB), a biotechnology company developing innovative therapeutics targeting serious viral diseases, today announced interim data from several cohorts from the ongoing Phase 1a clinical trial of ABI-6250, the company鈥檚 orally bioavailable, small molecule hepatitis delta virus (HDV) entry inhibitor candidate.
In the cohorts evaluated to date, a mean half-life of four days was observed for ABI-6250 when dosed orally, supporting the target daily oral dosing profile. Additionally, dose-dependent elevations of total serum bile acids (TBA) were seen over both single- and multiple-dose cohorts. These biomarker data indicate ABI-6250's potent engagement of the sodium taurocholate cotransporting polypeptide (NTCP) target, the receptor used by HDV to infect hepatocytes, and inform the potential dose range for evaluation of antiviral activity in further studies in participants with chronic HDV (cHDV) infection.
As the study remains blinded, combined safety data for ABI-6250 and placebo recipients are reported. A grade 2 alanine transaminase (ALT) elevation was observed in the cohort evaluating the highest single-dose level, and grade 1 elevations were seen at a low frequency in the other cohorts. All were self-limited and none were accompanied by bilirubin elevations or other markers of liver injury. Additional studies are planned to explore potential factors associated with these elevations given the role of ABI-6250's target as a bile acid transporter. This assessment is expected to include further pharmacological characterization of ABI-6250 and may incorporate additional cohorts in this Phase 1a study. Assembly Bio expects to conduct these activities in parallel with preparations for Phase 2 clinical studies and the completion of ongoing chronic toxicology studies.
鈥淚n this first clinical study of ABI-6250, we are encouraged by the observed half-life supportive of once-daily oral dosing and bile acid elevations indicative of NTCP target engagement,鈥� said Anuj Gaggar, MD, PhD, chief medical officer of Assembly Bio. 鈥淎s we continue to evaluate these Phase 1a clinical data, we plan to further explore ABI-6250's pharmacologic and biologic profile in preparation for proceeding to further clinical studies in participants with cHDV infection. With just one approved therapy for cHDV in the European Union and none in the U.S., the need for new treatment options for this underserved patient population remains critical 鈥� a need we believe ABI-6250 could have an important role in addressing given its potential to be the first oral therapy.鈥�
ABI-6250 is an investigational product candidate that has not been approved anywhere globally, and its safety and efficacy have not been established.
Study ABI-6250-101 鈥� Phase 1a Interim Results
Study Overview
ABI-6250-101 is an ongoing randomized, blinded and placebo-controlled Phase 1a clinical study evaluating the safety, tolerability and pharmacokinetics (PK) of ABI-6250 following single- and multiple-ascending oral dose administration in healthy participants. Changes in TBAs are also evaluated as a biomarker for NTCP engagement. Dosing is complete in two single-dose cohorts evaluating doses of 5 mg and 25 mg and three multiple-dose cohorts evaluating doses of 0.05 mg, 0.2 mg and 1 mg, each randomized 6:2 between ABI-6250 and placebo. Multiple-dose cohorts evaluated repeat daily dosing over 10 days.
Data are reported here for all cohorts dosed to date through completion of the study follow-up period of 10 days after dosing. As the study remains blinded, combined safety data for ABI-6250 and placebo recipients are reported.
Results
PK: Across the cohorts evaluated to date, a mean half-life of approximately four days was observed for ABI-6250 when dosed orally, supporting the once-daily oral dosing profile target. Given this half-life, accumulation was observed in the multiple-dose cohorts with exposures on the last day of dosing generally reaching 6- to 7-fold higher than the exposure seen after the first dose.
Biomarkers: Dose-dependent elevations of TBAs were observed for both the 5 mg and 25 mg single-dose cohorts, indicative of NTCP target engagement. In the highest single-dose cohort of 25 mg, coproporphyrin I (CP-1), a biomarker for off-target engagement of the organic anion transporters, OATP1B1 and/or OATP1B3, was also elevated.
Given the predicted ABI-6250 accumulation driven by the long half-life and the observed elevations in TBAs for the single-dose cohorts, doses at and below 1 mg daily were selected for the multiple-dose cohorts to characterize the lower end of the dose-response curve. Elevation of TBAs was observed for both the 0.2 mg and 1 mg daily multiple-dose cohorts, consistent with the respective ABI-6250 exposures. Minimal TBA elevation was observed in the 0.05 mg daily multiple-dose cohort.聽聽
Safety: Treatment-emergent adverse events (AEs) and laboratory abnormalities were all grade 1 or 2 in severity with the majority being grade 1. There were no serious AEs in any dose cohort. No protocol defined stopping criteria were met. There were no clinically significant electrocardiogram abnormalities or patterns of AEs noted.
One grade 2 ALT elevation was observed in the cohort evaluating the highest single-dose level of 25 mg. In this cohort, off-target engagement of other liver transporters was also seen as indicated by elevated CP-1 levels. Grade 1 ALT elevations were observed at a low frequency across the other cohorts. All ALT elevations were self-limited, and none were accompanied with elevations in bilirubin or other markers of liver injury.
Additional information about the Phase 1a trial is available at using the identifier NCT06740474. 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鈥檚 ability to maintain financial resources and secure additional funding necessary to continue its research activities, clinical studies, other business operations and continue as a going concern; Assembly Bio鈥檚 ability to realize the potential benefits of its collaboration with Gilead Sciences, Inc. (Gilead), including all financial aspects of the collaboration and equity investments; Assembly Bio鈥檚 ability to initiate and complete clinical studies involving its therapeutic product candidates, including studies contemplated by Assembly Bio鈥檚 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鈥檚 product candidates; clinical and nonclinical data may not differentiate Assembly Bio鈥檚 product candidates from other companies鈥� candidates; potential effects of changes in government regulation, including as a result of the change in U.S. administration in 2025; 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鈥檚 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鈥檚 risks and uncertainties are more fully detailed under the heading 鈥淩isk Factors鈥� in Assembly Bio鈥檚 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
Media:
Sam Brown Healthcare Communications
Alyssa Kuciunas
(331) 481-3751
FAQ
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