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TKM-130803
- Development stage
- Discontinued
- Lead developer
- Arbutus Biopharma
- Modality
- Chemically Modified siRNA → Small Interfering RNA (siRNA) → Small RNA Therapeutics → RNA Therapeutics → Nucleic Acid Therapeutics, Conjugated siRNA → Small Interfering RNA (siRNA) → Small RNA Therapeutics → RNA Therapeutics → Nucleic Acid Therapeutics, Lipid-based Nanoparticles → Nanoparticles → Drug Delivery Systems
- Administration
- Intravenous
01
Overview
**TKM-130803** is a lipid nanoparticle-formulated small interfering RNA (siRNA) therapeutic developed by Tekmira Pharmaceuticals specifically for treating Ebola virus disease (EVD) caused by the Makona variant of Zaire ebolavirus during the 2014–2016 West African outbreak. It contains a 1:1 mixture of two siRNAs, **siLpol-2** targeting Ebola virus L polymerase (Lpol) mRNA and **siVP35-2** targeting viral protein 35 (VP35) mRNA, to silence viral gene expression and inhibit replication. Administered intravenously at 0.3 mg/kg/day for up to 7 days, it demonstrated 100% survival in non-human primates when given 72 hours post-challenge but failed a phase 2 single-arm trial in Sierra Leone, where only 3 of 12 evaluable patients survived to day 14 (probability 0.27 vs. futility threshold of 0.55), likely due to advanced disease and high viral loads at treatment initiation. The drug was well-tolerated with no significant infusion reactions or toxicity observed.[1][2][3][4]
- Brand names
- TKM-Ebola-Guinea
- Other names
- siEbola-3siEbola3siEbola 3
02
Targets
VP35 (Ebola virus VP35)Ebola virus RNA-directed RNA polymerase L mRNA (EBOV L mRNA)
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