Drug name
Last update: Oct 2026PGDM1400LS (mAb)
Drug information
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PGDM1400LS; PGDM1400-LS
Not applicable (investigational; no brand name assigned)
Biotherapeutic
mAb (Monoclonal antibody) — bNAb targeting the V2-apex of the HIV-1 envelope trimer. LS-modified, half-life-extended variant of PGDM1400.
Active / In Development (Phase 1/2/3) — Phase 1 complete in adults, both as monotherapy (HVTN 140/HPTN 101 Part A, published 2025) and in triple combination (Part B, published 2026). Phase 2 in adults without HIV ongoing (HVTN 206/HPTN 114, closed to accrual). Phase 1 combination studies ongoing in adults (HVTN 141/HPTN 105) and in children from 24 weeks of age (Tatelo Plus/IMPAACT 2042). Not yet studied in neonates.
PGDM1400LS is a V2-apex-targeting broadly neutralising antibody, engineered from the parental antibody PGDM1400 with the LS (M428L/N434S) Fc modification to extend serum half-life. It is the V2-apex component of the three-epitope bNAb combination being advanced for HIV prevention alongside VRC07-523LS (CD4 binding site) and PGT121.414.LS (V3 glycan). In the first-in-human trial HVTN 140/HPTN 101 Part A, 15 adults without HIV received single doses of 5, 20 or 40 mg/kg IV or 20 or 40 mg/kg SC. The median elimination half-life was 55 days (range 48-59), approximately two to three times that of parental PGDM1400 (25 days), with dose-proportional concentrations by route and peak levels immediately after IV infusion or around day 6 after SC dosing. Estimated SC bioavailability relative to IV was 50-60%. In Part B, where the antibody was given in triple combination to 80 adults in Kenya, South Africa, the USA and Zimbabwe, the median half-life was 54 days (range 30-73) and SC bioavailability 75.5%. Antibody remained detectable for at least six months. No pharmacokinetic interactions among PGDM1400LS, VRC07-523LS (median half-life 45 days) and PGT121.414.LS (66 days) when co-administered
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
Dosage
Investigational. Weight-based: 5, 20 and 40 mg/kg IV; 20 and 40 mg/kg SC. Fixed: 400 mg and 1,600 mg IV (HVTN 206); 1.4 g IV and SC (HVTN 140 Part B); 100 mg SC in triple combination
40 mg/kg IV; 1.6 g fixed dose IV (HVTN 206/HPTN 114)
No approved regimen. Monotherapy (HVTN 140/HPTN 101 Part A): single dose of 5, 20 or 40 mg/kg IV, or 20 or 40 mg/kg SC. Triple combination with VRC07-523LS and PGT121.414.LS, 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). Triple combination, two doses six months apart (HVTN 206/HPTN 114): 400 mg or 1,600 mg IV with VRC07-523LS and PGT121.414.LS at Month 0 and Month 6. Triple combination, 12-weekly SC (HVTN 141/HPTN 105 Group 8): PGDM1400LS 100 mg with ePGT121v1-LS 125 mg and VRC07-523LS 100 mg at Week 0 and Week 12. Paediatric (Tatelo Plus/IMPAACT 2042): IV with VRC07-523LS and PGT121.414.LS in children from 24 weeks of age.
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Additional information
Developer(s)
National Institute of Allergy and Infectious Diseases (NIAID)
Beth Israel Deaconess Medical Center
The Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center is reported as the source of the LS-modified PGDM1400 variant, with JustBio.
JustBio
Named alongside Beth Israel Deaconess Medical Center as a source of the LS-modified PGDM1400 variant in IAVI portfolio material from October 2023, selected for high cell-line productivity
Cornell University
Joint holder of EP2975053A1 covering the parental PGDM1400 antibody lineage.
IAVI
Joint holder of EP2975053A1 covering the parental PGDM1400 antibody lineage.
Scripps Research Institute
Joint holder of EP2975053A1 covering the parental PGDM1400 antibody lineage.
Drug structure
Scale-up and manufacturing prospects
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Excipients & delivery device(s)
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No delivery device
Safety, Efficacy and Evidence Summary
In the first-in-human trial HVTN 140/HPTN 101 Part A (n=15, monotherapy): safe and well tolerated with mild-to-moderate solicited symptoms. Part B (n=80, triple combination): mostly mild-to-moderate solicited adverse events. 60 local solicited events, 54 in SC groups and 6 in IV groups, of which 6 were severe and all in SC groups (erythema and induration). 125 related systemic solicited events, 87 in IV groups and 38 in SC groups, with one severe (malaise and fatigue). Three infusion-related reactions, all grade 2. No serious adverse events, no pregnancies, no HIV seroconversions, and no treatment-induced anti-drug antibodies.
No efficacy data. Neutralisation activity is maintained in vivo: measured ID80 titres agreed with titres predicted from serum concentrations in both Part A and Part B. In combination, neutralisation coverage and breadth were preserved against bNAb-sensitive viruses and against the 11 AMP placebo-arm viruses. The Part B investigators concluded that the safety, tolerability and absence of PK interactions support advancing the triple combination to efficacy trials.
Two peer-reviewed phase 1 publications in adults: Seaton et al., Lancet HIV 2025 (Part A, monotherapy, first-in-human) and Mahomed et al., Lancet HIV 2026 (Part B, triple combination). Phase 2 data pending from HVTN 206/HPTN 114 (186 of 200 target enrolled, closed to accrual). No paediatric data published. No neonatal exposure.
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Antibody characteristics
Molecular identity
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Epitope and engineering
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Delivery
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There are either no relevant patents or these were not yet submitted to LAPaL