Drug name
Last update: Aug 2026Ultra Long-Acting Tenofovir ProTide
Developer(s)
Drug information
Tenofovir ProTide Nanoformulation
Not provided
Small molecule
prodrug of tenofovir (nucleotide analog reverse-transcriptase inhibitor (NRTI))
NM1TFV is a novel ultra-long-acting (ULA) tenofovir (TFV) prodrug nanoformulation in preclinical development for chronic hepatitis B virus (HBV) infection and human immunodeficiency virus type 1 (HIV-1). Utilising a modified ProTide approach, the formulation replaces conventional alanyl and short chain amino acid esters with a hydrophobic phenylalanine-docosyl ester linkage to enhance lipophilicity and intracellular delivery of TFV. This modification results in an extended TFV half-life and improved antiviral potency against both HBV and HIV-1. Preclinical studies indicated prolonged drug release profiles and stability for NM1TFV relative to nanoformulated TAF, with IM NM1TFV achieving suppression of HBV replication for 3 months, and concentrations above HIV-1 EC90 in PBMCs for 2 months.
Formulation is in preclinical development and not yet approved in any jurisdiction.
Unknown
Therapeutic area(s)
- HBV
- HIV
- Treatment
Administration route
Intramuscular
Associated long-acting platforms
Aqueous drug particle suspension, Solid Drug Nanoparticles
Use of drug
- Administered by a community health worker
- Administered by a nurse
- Administered by a specialty health worker
Not provided
Dosage
Not provided
Not provided
The preclinical NM1TFV formulation suppressed HBV replication for 3 months after a single parenteral injection.
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Associated compounds, formulations and regimens
Not provided
Associated technologies
Not provided
Additional information
Developer(s)
Exavir Therapeutics
Exavir Therapeutics is a biopharmaceutical company focused on developing ultra-long-acting therapeutics for chronic viral infections and CNS disorders. Headquartered in San Francisco, CA, they utilise prodrug nano-formulation technology to extend the half-life of drugs. Their current research focus primarily targets HIV, with the goal of improving treatment adherence and patient outcomes.
Drug structure
Scale-up and manufacturing prospects
Production scale-up viability for NM1TFV solid drug nanoformulations by high-pressure homogenization and/or wet bead milling processes have been established.
Not provided
Lipophilic ProTides of TFV bearing phenylalanine and alanine amino acid esters were created by replacing optimal short chain alkyl ester groups utilised by conventional ProTide strategies. The docosanol masking ester motif was selected based on inherent lipophilicity and synergy with nucleoside analogs. NM1TFV was synthesised by coupling a phenylalanyl or alanyl docosyl ester to monophenyl TFV in the presence of Et3N. As the conjugation step is moisture sensitive, further improvements to the chemical yields could be achieved by either optimizing the coupling reagents or reaction vessels.
Dynamic light scattering (DLS) and HPLC to measure nanoparticle size, Autoflex maX MALDI-TOF/TOF mass spectrometer to confirm molecular mass.
Excipients & delivery device(s)
No proprietary excipient used
No novel excipient or existing excipient used
Not provided
No delivery device
Safety, Efficacy and Evidence Summary
Not provided
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Tenofovir M1TFV prodrug crystalline compound, synthesis and formulation manufacturing
The present invention provides prodrugs and methods of use thereof.
WO2019140365
Compound
BOARD OF REGENTS OF THE UNIVERSITY OF NEBRASKA
Not provided
January 14, 2039
Granted: US Pending: CA Not in force: EP