Drug name
Last update: Oct 2026PGT121.414.LS (mAb)
Drug information
Not provided
PGT121.414.LS; PGT121.BIJ414.LS
Not applicable (investigational; no brand name assigned)
Biotherapeutic
mAb (Monoclonal antibody) — bNAb targeting the V3-glycan supersite of HIV-1 envelope gp120. LS-modified engineered variant of PGT121.
Active / In Development (Phase 1/2/3) — Phase 1 in adults complete (HVTN 136/HPTN 092, published 2025). Phase 2 in adults without HIV ongoing (HVTN 206/HPTN 114). Phase 1 in HIV-exposed neonates recruiting since January 2026 (IMPAACT 2037). Phase 1/2 in children recruiting (Tatelo Plus/IMPAACT 2042).
PGT121.414.LS is a V3-glycan-targeting broadly neutralising antibody derived from PGT121 and engineered with LS (M428L/N434S) Fc mutations to extend serum half-life and enhance stability. Its elimination half-life is 71 days (95% CI 66-75), three times that of parental PGT121, with dose-proportional peak serum concentrations from 3 to 30 mg/kg IV and an estimated subcutaneous bioavailability of 86.1% (95% CI 64.0-95.5). In the first-in-human trial HVTN 136/HPTN 092 (NCT04212091), IV and SC infusions alone and with VRC07-523LS were safe and well tolerated in 33 adults without HIV, with no serious adverse events or dose-limiting toxicities. Co-administration with VRC07-523LS did not alter the pharmacokinetics of either antibody, and neutralisation activity was greater in the higher-dose and dual-combination IV groups than in the SC groups. INFANT USE: PGT121.414.LS is the V3-glycan component of the lead infant post-natal prophylaxis regimen with VRC07-523LS given SC within 72 hours of birth to 48 HIV-exposed infants at high risk of peripartum or breastfeeding transmission, at 80 mg or 80 mg followed by 100 mg after 12 weeks depending on weight.
Not yet approved
Not yet approved
Therapeutic area(s)
- HIV
- Pre-Exposure Prophylaxis (PrEP)
- Treatment
- Prevention
Administration route
Subcutaneous, Intravenous
Associated long-acting platforms
Monoclonal antibodies and antibody drug conjugates
Use of drug
- Administered by a nurse
- Administered by a specialty health worker
- Every 6 months
- Every 4 months
- Every 3 months
To be determined. Mild-to-moderate solicited adverse events resolving within 3 to 4 days in adults. In the triple combination, local reactions concentrated in the subcutaneous groups and systemic symptoms in the intravenous groups. Subcutaneous bioavailability of 86.1% alone and 77.7% in combination supports an SC presentation, which is the route chosen for the neonatal study.
Dosage
Investigational. Adults: 3, 10, 20 and 30 mg/kg IV; 5 and 20 mg/kg SC; fixed doses 400 mg and 1,600 mg IV and 1.4 g IV or SC. Neonates and infants: 80 mg and 100 mg SC fixed doses.Supplied at 100mg/mL
40 mg/kg IV (HVTN 140 Part B, T10); 1.6 g fixed dose IV (HVTN 206/HPTN 114). Highest neonatal dose: 100 mg SC.
No approved regimen. Adults, with VRC07-523LS: 20 mg/kg IV each sequentially at days 0, 112 and 224; or 5 mg/kg SC each sequentially at days 0, 112 and 224 (HVTN 136/HPTN 092). Adults, triple combination two doses four months apart (HVTN 140/HPTN 101 Part B): 20 mg/kg each IV (T6); 20 mg/kg each SC (T7); 1.4 g each fixed IV (T8); 1.4 g each fixed SC (T9); 40 mg/kg each IV (T10). Adults, triple combination two doses six months apart (HVTN 206/HPTN 114): 400 mg or 1,600 mg IV with VRC07-523LS and PGDM1400LS at Month 0 and Month 6. Neonates and infants: 80 mg SC within 72 hours of birth, or 80 mg SC followed by 100 mg SC after 12 weeks, weight-dependent, alone or with VRC07-523LS at the same doses (IMPAACT 2037). Children from 24 weeks of age: IV with VRC07-523LS and PGDM1400LS (dose unknown)
The neonatal fixed-dose schedule (80 mg at birth, 100 mg at week 12) is carried over from the VRC01LS and VRC07-523LS experience in IMPAACT P1112. Rapid infant growth increases volume of distribution and clearance over the first 12 weeks, diluting exposure, which is why a second dose is given at week 12 for infants with continued breastfeeding exposure. Note the caution from VRC07-523LS modelling (Huynh et al., JAC 2026): concentration targets can be met while the PT80 pharmacodynamic target is not sustained across the dosing interval. No equivalent PK-PD modelling has been published for PGT121.414.LS in infants.
Not provided
Additional information
Developer(s)
Beth Israel Deaconess Medical Center
The Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center, led by Dr Dan Barouch, developed the PGT121 variant antibodies including PGT121.414.LS and holds the representative patent WO2019226829A1.
National Institute of Allergy and Infectious Diseases (NIAID)
The NIAID Vaccine Research Center and Division of AIDS sponsor the clinical development programme for PGT121.414.LS across HVTN, HPTN, ACTG and IMPAACT networks, including the neonatal study IMPAACT 2037.
IAVI
IAVI and partners isolated the parental PGT121 antibody from donor samples in Protocol G, an IAVI cohort study of adults living with HIV.
Drug structure
Scale-up and manufacturing prospects
Manufactured by Just-Evotec Biologics, whose continuous-manufacturing platform is oriented to lower cost of goods, and formulated at 100 mg/mL, which supports low-volume subcutaneous presentation. Fixed dosing was shown to be pharmacokinetically comparable to weight-based dosing across this antibody class (HVTN 140 Part B; Huang et al. 2025), which simplifies manufacture, presentation and field administration for LMIC settings by removing per-patient calculation and vial flexibility from the delivery chain.
Bioreactors, incubators, filtration units, lyophilizers, formulation vessels, vial filling and sealing equipment.
Engineered from parental PGT121 by Just-Evotec Biologics. Substitution of heavy and light chain variable region residues on the PGT121 framework, plus LS (M428L/N434S) Fc mutations for half-life extension; the stated aims of the modification were improved stability, half-life and manufacturability. Expressed in mammalian cell culture and purified by affinity chromatography; the cell line and process are not publicly disclosed.
HPLC, mass spectrometry, multiplex serum concentration assay, TZM-bl neutralisation assay, surface plasmon resonance, anti-drug antibody assay, pH meter.
Excipients & delivery device(s)
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No delivery device
Safety, Efficacy and Evidence Summary
Adults: safe and well tolerated in HVTN 136/HPTN 092 (n=33). No serious adverse events and no dose-limiting toxicities across 3, 10 and 30 mg/kg IV, 5 mg/kg SC, and repeated 20 mg/kg IV or 5 mg/kg SC in combination with VRC07-523LS. Solicited adverse events were mild to moderate and resolved within 3 to 4 days. In the three-antibody combination (HVTN 140/HPTN 101 Part B, n=80) local solicited events clustered in the SC groups and systemic events in the IV groups, with no serious adverse events and no treatment-induced anti-drug antibodies. Neonates and infants: no safety data yet. The proportion of infants with at least one grade 3 or higher adverse event is the primary endpoint of IMPAACT 2037.
No efficacy data. Neutralisation activity is maintained in vivo; activity was greater in the higher-dose and dual-combination IV groups than in the SC groups (HVTN 136/HPTN 092). In the triple combination, neutralisation coverage and breadth were preserved against bNAb-sensitive viruses and the 11 AMP placebo-arm viruses. The first-in-human investigators concluded that the findings support further evaluation in combination with other monoclonal antibodies for HIV-1 prevention.
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Antibody characteristics
Molecular identity
IgG monoclonal
IgG1
Lambda
Human (donor-derived)
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Engineered from parental PGT121. The modification was made to improve stability, half-life and manufacturability.
Epitope and engineering
PGT121-class
V3-glycan supersite
Epitope centered on the conserved N332 glycan of gp120, with both peptide and glycan contacts at the base of the V3 loop
LS (M428L/N434S)
3.0
Half-life extension of approximately 3-fold (71 days versus approximately 22 days for parental PGT121). The V3-glycan supersite depends on the N332 glycan, which is absent from roughly one third of circulating HIV-1 isolates. This is the principal determinant of the class's breadth ceiling and the reason PGT121.414.LS is developed in combination with CD4-binding-site and V2-apex antibodies.
Delivery
Not provided
100.0 mg/mL
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No
Adult prevention: 0.8 g/year at 400 mg IV 6-monthly, or 3.2 g/year at 1,600 mg IV 6-monthly (HVTN 206/HPTN 114); approximately 4.2 g/year at 1.4 g 4-monthly (HVTN 140 Part B). Infant post-natal prophylaxis: approximately 0.18 g total per infant for the 80 mg plus 100 mg schedule over the first 12 weeks. volume: at 100 mg/mL: 0.8 mL for an 80 mg infant dose and 1.0 mL for 100 mg infant dose
Neutralisation and resistance profile
Assay context
TZM-bl Env-pseudovirus
panel of 12 Env-pseudotyped viruses+ 208-virus multi-clade pseudoviruses+11 AMP
208
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Potency and breadth
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The HVTN 136/HPTN 092 publication reports reasonable concordance in IC50 and IC80 between parental PGT121 and PGT121.414.LS across a 208-virus panel and states the LS mutation is not expected to affect neutralisation
Resistance and sensitivity
Under evaluation
Loss of the N332 glycan sequon (N332-X-S/T), typically through substitution at position 332, abolishes or substantially reduces susceptibility to V3-glycan antibodies including the PGT121 family.
Partially
N332 glycan
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Transmitted/founder virus sensitivity
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Clade coverage
Not provided
There are either no relevant patents or these were not yet submitted to LAPaL