Assembly Biosciences, Inc. announced encouraging interim antiviral activity, clinical outcomes, safety, and pharmacokinetic (PK) results from its phase 1b study evaluating ABI-5366, an investigational long-acting herpes simplex virus (HSV) helicase-primase inhibitor, in participants seropositive for HSV-2 with recurrent genital herpes.
Key Antiviral Efficacy Results
- Primary Antiviral Endpoint (HSV-2 Shedding Rate)
- 94% reduction compared to placebo (p<0.01) at 350 mg weekly dose
- Exceeds study target of 80–85% reduction
- Secondary Endpoint – Genital Lesion Rate
- 94% reduction compared to placebo (p<0.01) at 350 mg weekly dose
- Secondary Endpoint – High Viral Load Reduction
- 98% reduction (p<0.05) in samples with >10⁴ copies/mL HSV DNA at 350 mg weekly dose
- No viral shedding above this threshold in the absence of lesions for this cohort
Safety and Tolerability
- Dosing
- Well-tolerated at oral doses up to 350 mg weekly
- PK profile supports once-weekly and potentially once-monthly dosing - Adverse Events (AEs)
- Treatment-emergent AEs reported in 90% of both ABI-5366 and placebo groups
- Mostly Grade 1 or Grade 2 events
- One Grade 3 event (hypertriglyceridemia) — not treatment-related - Laboratory Abnormalities
- Placebo: 90%; ABI-5366: 67.5%
- All Grade 3 abnormalities unrelated to treatment - No serious adverse events reported to date
Study Design Overview (ABI-5366-101)
- Type: Randomized, blinded, placebo-controlled phase 1a/b study
- Part A (Phase 1a): Single-dose safety, tolerability, and PK in healthy participants — previously reported positive results
- Part B (Phase 1b): Participants with recurrent HSV-2 infection, 29-day dosing period
- Cohort B1: 150 mg loading + 30 mg weekly
- Cohort B2: 350 mg weekly (loading dose included)
- Cohort B3: Monthly dosing regimen (ongoing)
- Allocation: 20:5 randomization (ABI-5366:placebo) with pooled placebo analysis
- Endpoints
- Antiviral activity (shedding rate, HSV DNA levels
- Clinical outcomes (lesion rate, lesion duration)
- Safety and PK profile assessment
Company Plans
- Move directly to phase 2 clinical study preparation in parallel with phase 1b completion
- Phase 2 initiation expected mid-2026
- Monthly dosing cohort results and ABI-1179 interim data expected fall 2025
Additional Context
- Another long-acting HSV helicase-primase inhibitor
- Being evaluated in a separate phase 1b study
- Originated from Assembly Bio–Gilead Sciences collaboration
- Gilead holds exclusive license option after phase 1b review
Genital Herpes Epidemiology
- Over 4 million people in the US and five major European countries have recurrent genital herpes
- Caused by HSV-1 or HSV-2; recurrences more frequent with HSV-2
- Current standard of care: nucleoside analogs — only partially effective, no new drugs in over 25 years
Mechanism of Action
- HSV helicase-primase inhibitors target a viral enzyme complex essential for replication
- Conserved across HSV-1 and HSV-2, with no host equivalent
- Offers potential superior efficacy vs nucleoside analogs
Quote from Assembly Bio’s CMO
“We are thrilled to see these interim data for ABI-5366 far exceeding the targets we had set in this study for antiviral activity and clinical outcomes in participants with recurrent genital herpes. These results underscore our conviction in the potential for ABI-5366 to reduce outbreaks and improve quality of life for those affected. We will now work quickly to move into longer-duration phase 2 clinical studies.”
- Anuj Gaggar, MD, PhD, Chief Medical Officer.
