Assembly Biosciences Doses First Participant in Phase 1a Clinical Study of Oral Entry Inhibitor Candidate ABI-6250 for Hepatitis Delta Virus
Assembly Biosciences (ASMB) has initiated dosing in a Phase 1a clinical trial for ABI-6250, their oral hepatitis delta virus (HDV) entry inhibitor candidate. The study will evaluate safety, tolerability, and pharmacokinetics across single and multiple ascending dose cohorts in healthy participants, with data expected in Q3 2025.
The trial will monitor serum bile acids as a biomarker of ABI-6250's engagement with its target, the NTCP transporter. Currently, only one therapy is approved for chronic HDV infection in the EU, requiring daily injections, with no approved treatments in the US.
In preclinical studies, ABI-6250 has shown low nanomolar potency across multiple HDV genotypes, selectivity for NTCP versus other bile acid transporters, and a pharmacokinetic profile supporting once-daily oral dosing. Chronic HDV is considered the most severe form of viral hepatitis, with 70% of patients progressing to cirrhosis within 10 years.
Assembly Biosciences (ASMB) ha avviato la somministrazione in uno studio clinico di fase 1a per ABI-6250, il loro candidato inibitore orale dell'ingresso del virus dell'epatite delta (HDV). Lo studio valuterà la sicurezza, la tollerabilità e la farmacocinetica attraverso coorti di dosi ascendenti singole e multiple in partecipanti sani, con dati attesi nel Q3 2025.
Il trial monitorerà gli acidi biliari sierici come biomarcatore dell'interazione di ABI-6250 con il suo bersaglio, il trasportatore NTCP. Attualmente, solo una terapia è approvata per l'infezione cronica da HDV nell'UE, che richiede iniezioni quotidiane, senza trattamenti approvati negli Stati Uniti.
Negli studi preclinici, ABI-6250 ha mostrato una bassa potenza nanomolare attraverso più genotipi di HDV, selettività per NTCP rispetto ad altri trasportatori di acidi biliari e un profilo farmacocinetico che supporta la somministrazione orale una volta al giorno. L'HDV cronico è considerato la forma più grave di epatite virale, con il 70% dei pazienti che progrediscono verso la cirrosi entro 10 anni.
Assembly Biosciences (ASMB) ha iniciado la dosificación en un ensayo clínico de fase 1a para ABI-6250, su candidato a inhibidor de entrada del virus de la hepatitis delta (HDV) por vía oral. El estudio evaluará la seguridad, la tolerabilidad y la farmacocinética en cohortes de dosis ascendentes únicas y múltiples en participantes sanos, con datos esperados en Q3 2025.
El ensayo monitorizará los ácidos biliares séricos como un biomarcador del compromiso de ABI-6250 con su objetivo, el transportador NTCP. Actualmente, solo hay una terapia aprobada para la infección crónica por HDV en la UE, que requiere inyecciones diarias, sin tratamientos aprobados en EE. UU.
En estudios preclínicos, ABI-6250 ha mostrado baja potencia nanomolar en múltiples genotipos de HDV, selectividad por NTCP en comparación con otros transportadores de ácidos biliares y un perfil farmacocinético que respalda la dosificación oral una vez al día. La HDV crónica se considera la forma más grave de hepatitis viral, con el 70% de los pacientes progresando a cirrosis en un plazo de 10 años.
Assembly Biosciences (ASMB)는 ABI-6250의 1상 임상 시험에서 투약을 시작했습니다. 이는 그들의 경구용 간염 델타 바이러스(HDV) 침입 억제제 후보입니다. 이 연구는 건강한 참가자들을 대상으로 단일 및 다중 상승 용량 집단에서 안전성, 내약성 및 약리학적 동태를 평가하며, 데이터는 2025년 3분기에 예상됩니다.
이 시험은 ABI-6250의 목표인 NTCP 수송체와의 상호작용을 바이오마커로서 혈청 담즙산을 모니터링할 것입니다. 현재, EU에서는 HDV 만성 감염에 대해 하루에 한 번 주사하는 치료법 하나만 승인되어 있으며, 미국에서는 승인된 치료법이 없습니다.
전임상 연구에서 ABI-6250는 여러 HDV 유전자형에서 낮은 나노몰 농도의 효능을 보였으며, 다른 담즙산 수송체에 비해 NTCP에 대한 선택성을 나타내었고, 하루 한 번 경구 투여를 지원하는 약리학적 동태 프로필을 가지고 있습니다. 만성 HDV는 가장 심각한 형태의 바이러스성 간염으로 간주되며, 환자의 70%가 10년 이내에 간경변으로 진행됩니다.
Assembly Biosciences (ASMB) a lancé la dose dans un essai clinique de phase 1a pour ABI-6250, leur candidat inhibiteur de l'entrée du virus de l'hépatite delta (HDV) par voie orale. L'étude évaluera la sécurité, la tolérance et la pharmacocinétique à travers des cohortes de doses uniques et multiples chez des participants sains, avec des données attendues au T3 2025.
L'essai surveillera les acides biliaires sériques comme biomarqueur de l'engagement d'ABI-6250 avec sa cible, le transporteur NTCP. Actuellement, seule une thérapie est approuvée pour l'infection chronique par HDV dans l'UE, nécessitant des injections quotidiennes, sans traitements approuvés aux États-Unis.
Dans les études précliniques, ABI-6250 a montré une faible puissance nanomolaire à travers plusieurs génotypes de HDV, une sélectivité pour NTCP par rapport à d'autres transporteurs d'acides biliaires, et un profil pharmacocinétique soutenant une posologie orale quotidienne. L'HDV chronique est considéré comme la forme la plus sévère d'hépatite virale, 70 % des patients progressant vers la cirrhose dans les 10 ans.
Assembly Biosciences (ASMB) hat die Dosierung in einer Phase-1a-Studie für ABI-6250 begonnen, ihren oralen Eintrittshemmstoff gegen das Hepatitis-Delta-Virus (HDV). Die Studie wird Sicherheit, Verträglichkeit und Pharmakokinetik in einzelnen und mehrfachen aufsteigenden Dosierungsgruppen bei gesunden Teilnehmern bewerten, wobei Daten für Q3 2025 erwartet werden.
Die Studie wird Serumgalle als Biomarker für die Bindung von ABI-6250 an sein Ziel, den NTCP-Transporter, überwachen. Derzeit ist nur eine Therapie in der EU für chronische HDV-Infektionen zugelassen, die tägliche Injektionen erfordert, während es in den USA keine zugelassenen Behandlungen gibt.
In präklinischen Studien hat ABI-6250 eine niedrige nanomolare Potenz über mehrere HDV-Genotypen gezeigt, eine Selektivität für NTCP im Vergleich zu anderen Gallensäuretransportern und ein pharmakokinetisches Profil, das eine einmal tägliche orale Dosierung unterstützt. Chronisches HDV wird als die schwerste Form der viralen Hepatitis angesehen, wobei 70 % der Patienten innerhalb von 10 Jahren zu Zirrhose fortschreiten.
- First-in-class oral HDV therapy potential
- Phase 1a trial initiated on schedule
- Promising preclinical efficacy data
- Addresses unmet medical need with no approved US treatments
- Phase 1a results not expected until Q3 2025
- Early-stage development with no proven clinical efficacy
- Faces competition from EU-approved treatment
Insights
Assembly Biosciences has dosed the first participant in a Phase 1a trial for ABI-6250, potentially the first oral entry inhibitor for hepatitis delta virus (HDV). This represents a significant clinical milestone addressing a critical unmet need in a severe disease with treatment options.
The Phase 1a study will evaluate safety, tolerability, and pharmacokinetics in healthy participants, with data expected in Q3 2025. Notably, the study will also assess serum bile acids as a biomarker of target engagement with NTCP (sodium taurocholate cotransporting polypeptide), the transporter HDV uses to infect liver cells.
This development is particularly significant given the current treatment landscape: only one therapy is approved for chronic HDV in the EU (none in the US), which requires daily injections. An effective oral therapy could substantially improve treatment adherence and patient quality of life for this devastating condition, where 70% of patients progress to cirrhosis within 10 years.
Preclinical data shows promising characteristics including low nanomolar potency across multiple HDV genotypes, selectivity for NTCP versus other transporters, and pharmacokinetics supporting once-daily dosing. However, investors should recognize this remains an early-stage program with significant development hurdles ahead before potential commercialization.
While this news indicates positive progress in Assembly Bio's pipeline advancement, the extended timeline to data readout and subsequent development stages means any commercial impact remains years away. The market opportunity for an effective oral HDV therapy could be substantial given the competition and severe disease progression, but significant clinical and regulatory milestones must be achieved first.
– Phase 1a study will evaluate single and multiple ascending doses of ABI-6250 in healthy participants with data expected in Q3 2025 –
– Biomarker of ABI-6250 target engagement, serum bile acids, will be assessed in addition to safety and pharmacokinetic measures –
SOUTH SAN FRANCISCO, Calif., Feb. 26, 2025 (GLOBE NEWSWIRE) -- Assembly Biosciences, Inc. (Nasdaq: ASMB), a biotechnology company developing innovative therapeutics targeting serious viral diseases, today announced that the first participant has been dosed in the Phase 1a trial of ABI-6250, the company’s orally bioavailable, small molecule hepatitis delta virus (HDV) entry inhibitor candidate.
This Phase 1a study will evaluate the safety, tolerability and pharmacokinetics (PK) of ABI-6250 across single and multiple ascending dose cohorts in healthy participants. In addition, the study will look at serum bile acids as a biomarker of ABI-6250’s engagement of its target, the transporter used by HDV to infect hepatocytes (sodium taurocholate cotransporting polypeptide or NTCP). Assembly Bio expects to share data from the Phase 1a study in Q3 2025.
Currently, one therapy is approved for chronic HDV infection (cHDV) in the European Union with no therapies approved in the United States. This approved therapy is a peptide inhibitor of NTCP requiring daily injections. Well-tolerated serum bile acid elevations have been observed clinically with the approved NTCP inhibitor.
“ABI-6250 has the potential to be the first oral therapy for cHDV, a life-threatening chronic viral infection with limited treatment options available,” said Anuj Gaggar, MD, PhD, chief medical officer of Assembly Bio. “Chronic HDV is the most severe form of viral hepatitis with
In preclinical studies, ABI-6250 has demonstrated low nanomolar potency across multiple HDV genotypes in vitro, selectivity for NTCP versus other bile acid transporters and a PK profile supportive of once-daily oral dosing.
ABI-6250 is an investigational product candidate that has not been approved anywhere globally, and its safety and efficacy have not been established.
About ABI-6250-101
ABI-6250-101 is a randomized, blinded and placebo-controlled Phase 1a clinical study evaluating the safety, tolerability and PK of ABI-6250 following single and multiple ascending dose administration. Healthy participants will be randomized between ABI-6250 and placebo in up to five single-dose and five multiple-dose cohorts at different doses. Multiple-dose cohorts will evaluate repeat dosing over 10 days.
In addition to assessing safety, tolerability and PK, this Phase 1a study will also measure changes in serum bile acid levels, a biomarker of NTCP engagement. The trial results will support dose selection for future clinical studies.
Additional information about the Phase 1a trial is available at clinicaltrials.gov using the identifier NCT06740474.
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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