Drug name
Last update: Oct 2026PGDM1400LS (mAb)
Drug information
Not provided
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
To be determined. Route drives the tolerability profile: in HVTN 140 Part B local reactions concentrated in the subcutaneous groups, including all six severe local events, while systemic symptoms concentrated in the intravenous groups. Subcutaneous bioavailability of 75.5% in combination, together with the viability of fixed dosing, supports a subcutaneous presentation for LMIC delivery, but local tolerability at the volumes required for a 1.4 g fixed dose may warrant further investigation.
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.
The demonstration that 1.4 g fixed dosing matches weight-based dosing pharmacokinetically is the most operationally important dosing finding for this molecule, because it removes per-patient calculation and vial flexibility from the delivery chain, a precondition for administration outside specialist settings. The caveat is exposure at the extremes of the weight distribution, where weight bands or weight-based dosing may still be needed.
Not provided
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
Cell-line productivity was the decisive criterion in selecting this molecule: IAVI reported setting aside the more potent ePGDM1400v9 because of low productivity in favour of the LS variant from Beth Israel Deaconess Medical Center and Just-Evotec Biologics, which had high productivity. For LMIC-indicated products where cost of goods determines access, that precedent is worth recording. Fixed dosing at 1.4 g per antibody gave pharmacokinetics comparable to weight-based dosing (HVTN 140 Part B; Huang et al. 2025), which further simplifies manufacture, presentation and field administration. The counterpoint is that fixed dosing produced different exposures below the 15th and above the 85th weight percentiles.
Bioreactors, incubators, filtration units, formulation vessels, vial filling and sealing equipment.
LS-modified (M428L/N434S) variant of the parental V2-apex antibody PGDM1400, produced by recombinant DNA technology. Parental PGDM1400 heavy and light chain variable regions were identified from B cells of IAVI Protocol G donor 84 and cloned into expression vectors with IgG1 constant regions; expression in HEK293 or CHO cells; purification by protein A/G affinity chromatography. The LS variant was reported in 2023 to originate from Beth Israel Deaconess Medical Center and Just-Evotec Biologics, selected over the IAVI candidate ePGDM1400v9 on the grounds of high cell-line productivity.
Protein A/G affinity chromatography, SDS-PAGE, HPLC, ELISA, multiplex serum concentration assay, TZM-bl neutralisation assay, anti-drug antibody assay.
Excipients & delivery device(s)
Not provided
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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.
Not provided
Antibody characteristics
Molecular identity
IgG monoclonal
IgG1
Kappa
Human (donor-derived)
Not provided
Not provided
Parental PGDM1400 was isolated from peripheral blood mononuclear cells of IAVI Protocol G donor 84, a chronically HIV-1-infected elite neutraliser, who was also the source of the PGT141-145 antibodies. PGDM1400 is the lead candidate of a set of 13 related antibodies, PGDM1400 to PGDM1412. Parental PGDM1400 was expressed in HEK293 or CHO cells and purified by protein A/G affinity chromatography.
Epitope and engineering
Other
V1/V2-apex
Not provided
LS (M428L/N434S)
2.2
PGT145-like V2-apex (trimer apex) class, quaternary-structure dependent. Same donor lineage as PGT141-145; related in function to PG9 and PG16. Quaternary epitope at the trimer apex, demonstrated on the BG505 SOSIP.664 soluble trimer. Binding depends on the positively charged C strand of V2 and, at class level, on the N160 glycan; the anionic CDRH3 tip engages the basic apex surface.
Delivery
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No
Subcutaneous bioavailability improved markedly between the two parts of the first-in-human programme, from an estimated 50 to 60% as monotherapy in Part A to 75.5% in combination in Part B. Local solicited adverse events concentrated in the subcutaneous groups (54 of 60 events, including all six severe local events) while systemic events concentrated in the intravenous groups (87 of 125).
Neutralisation and resistance profile
Assay context
TZM-bl Env-pseudovirus
Not provided
106
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Not provided
Potency and breadth
Not provided
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0.003 µg/mL
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Resistance and sensitivity
Not provided
loss of the N160 glycan abolishes binding of V2-apex antibodies, and substitutions in the positively charged C strand of V2 around positions 168 to 171 reduce susceptibility.
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Not reported for PGDM1400LS. No treatment-induced anti-drug antibodies observed
Likely needed for treatment and remission use. Pre-existing resistance is a weakness of this molecule: two of twelve participants in an adult study carried baseline mutations conferring PGDM1400 resistance. Precedent exists in the class, as ACTG A5357 required documented VRC07-523LS susceptibility (IC50 at or below 0.25 microgram/mL) for enrolment.
Transmitted/founder virus sensitivity
Not provided
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Clade coverage
Not provided
There are either no relevant patents or these were not yet submitted to LAPaL