PGT121.414.LS (mAb)

Associated long-acting platforms

Monoclonal antibodies and antibody drug conjugates

Administration route

Subcutaneous, Intravenous

Therapeutic area(s)

Use case(s)

Use of drug

Dosage

Drug information

Delivery device(s)

No delivery device

Antibody characteristics

Molecular identity

Epitope and engineering

Delivery

Neutralisation and resistance profile

Assay context

Potency and breadth

Resistance and sensitivity

Transmitted/founder virus sensitivity

Clade coverage

Scale-up 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.

Tentative equipment list for manufacturing

Bioreactors, incubators, filtration units, lyophilizers, formulation vessels, vial filling and sealing equipment.

Manufacturing

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.

Specific analytical instrument required for characterization of formulation

HPLC, mass spectrometry, multiplex serum concentration assay, TZM-bl neutralisation assay, surface plasmon resonance, anti-drug antibody assay, pH meter.

IMPAACT 2037

Identifier

NCT06517693

Link

https://clinicaltrials.gov/study/NCT06517693

Phase

Phase I

Status

Recruiting

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

More details

The purpose of this study is to evaluate the safety and pharmacokinetics (PK) of the potent, broadly neutralizing anti-HIV monoclonal antibodies (mAb) PGT121.414.LS alone and in combination with VRC07-523LS soon after birth in infants exposed to HIV-1.

Purpose

Safety and Pharmacokinetics Study of PGT121.414.LS Alone and in Combination With VRC07-523LS in Infants Exposed to HIV-1

Interventions

Intervention 1

Intervention 2

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
2025-06-01

Actual Start Date
2026-01-05

Anticipated Date of Last Follow-up
2026-08-24

Estimated Primary Completion Date
2027-12-31

Estimated Completion Date
2028-06-30

Actual Primary Completion Date
Not provided

Actual Completion Date
Not provided

Studied populations

Age Cohort

• Children

Genders

• All

Accepts pregnant individuals
Unspecified

Accepts lactating individuals
Unspecified

Accepts healthy individuals
Yes

Comments about the studied populations

Inclusion Criteria: * Birthing parent is of legal age or circumstance to provide independent informed consent and is willing and able to provide written informed consent for themselves and permission for their infant's participation in this study. * Birthing parent has confirmed HIV-1 infection based on positive test results from two samples collected from two separate blood collection tubes. * Infant was singleton or twin. * Infant's gestational age at birth was at least 36 weeks. * At birth, infant's weight was at least 2 kg. * At entry, infant is less than 72 hours of age and is anticipated to receive study product within 72 hours after birth. * At screening, infant has the following laboratory test results: * Hemoglobin, normal or grade 1 (≥13 g/dL or ≥8.05 mmol/L) * Platelets, n

Health status

Not provided

Study type

Interventional (clinical trial)

Enrollment

48

Allocation

Not provided

Intervention model

Sequential assignment

Intervention model description

Not provided

Masking

Open label

Masking description

Not provided

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

Treatment

Indication(s)

HIV

Key resources

HVTN 136/HPTN 092

Identifier

NCT04212091

Link

https://clinicaltrials.gov/study/NCT04212091

Phase

Phase I

Status

Completed

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

More details

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and antiviral activity of the monoclonal antibody PGT121.414.LS administered alone and in combination with VRC07-523LS via intravenous or subcutaneous infusions in healthy, HIV-uninfected adult participants.

Purpose

Evaluating the Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of the Monoclonal Antibody PGT121.414.LS Administered Alone and in Combination With VRC07-523LS Via Intravenous or Subcuta

Interventions

Intervention 1

Intervention 2

Intervention 3

Intervention 4

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2020-11-10

Anticipated Date of Last Follow-up
2024-12-10

Estimated Primary Completion Date
Not provided

Estimated Completion Date
Not provided

Actual Primary Completion Date
2023-01-18

Actual Completion Date
2023-01-18

Studied populations

Age Cohort

• Adults

Genders

• All

Accepts pregnant individuals
Unspecified

Accepts lactating individuals
Unspecified

Accepts healthy individuals
Yes

Comments about the studied populations

Inclusion Criteria: General and Demographic Criteria * Age of 18 to 50 years * Access to a participating Clinical Research Site (CRS) and willingness to be followed for the planned duration of the study * Ability and willingness to provide informed consent * Assessment of understanding: volunteer demonstrates understanding of this study and completes a questionnaire prior to first study product administration with verbal demonstration of understanding of all questionnaire items answered incorrectly * Agrees not to enroll in another study of an investigational research agent until completion of the last required protocol clinic visit * Good general health as shown by medical history, physical exam, and screening laboratory tests HIV-Related Criteria: * Willingness to receive HIV test re

Health status

Not provided

Study type

Interventional (clinical trial)

Enrollment

33

Allocation

Randomized

Intervention model

Sequential assignment

Intervention model description

Not provided

Masking

Open label

Masking description

Not provided

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

Treatment

Indication(s)

HIV

Key resources

HVTN 206/HPTN 114

Identifier

NCT06812494

Link

https://clinicaltrials.gov/study/NCT06812494

Phase

Phase II

Status

Active, not recruiting

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

More details

HVTN 206/HPTN 114 is a randomized, double blind, controlled, phase 2 clinical trial to evaluate the safety, tolerability, pharmacokinetics, and neutralization of VRC07-523LS, PGT121.414.LS, and PGDM1400LS broadly neutralizing monoclonal antibodies given intravenously in adult participants without HIV. The hypothesis of the study is that the combination of VRC07-523LS and PGT121.414.LS and PGDM1400LS antibodies when administered via the intravenous (IV) route will be safe and tolerable in adult participants without HIV. The study aims to enroll 200 participants across multiple sites with an estimated total duration of participation of eighteen (18) months.

Purpose

A Study of VRC07-523LS, PGT121.414.LS, and PGDM1400LS Broadly Neutralizing Monoclonal Antibodies Given Intravenously in Adult Participants Without HIV

Interventions

Intervention 1

Intervention 2

Intervention 3

Intervention 4

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2025-03-07

Anticipated Date of Last Follow-up
2026-08-19

Estimated Primary Completion Date
2027-01-15

Estimated Completion Date
2027-09-15

Actual Primary Completion Date
Not provided

Actual Completion Date
Not provided

Studied populations

Age Cohort

• Adults
• Older Adults

Genders

• All

Accepts pregnant individuals
Unspecified

Accepts lactating individuals
Unspecified

Accepts healthy individuals
Yes

Comments about the studied populations

Inclusion Criteria: * Participants need to be between 18 and 65 years old. * Participants must have access to a participating clinical research site and be willing to follow the study schedule. * Participants should understand the study details and be willing to give informed consent. * Participants must agree not to join any other clinical trials until they finish this study. * Participants must be willing to receive HIV test results. * Participants should be open to discussing HIV prevention. * Clinic staff should assess participants as having a low risk of getting HIV, and participants must commit to avoiding high-risk behaviors during the study. * Hemoglobin: Participant meets minimum levels depending on gender and hormone therapy status. * White Blood Cells (WBC): Should be within th

Health status

Study type

Interventional (clinical trial)

Enrollment

200

Allocation

Randomized

Intervention model

Parallel Assignment

Intervention model description

Not provided

Masking

Double-blind masking

Masking description

Not provided

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

Prevention, PrEP

Indication(s)

HIV

Key resources

Tatelo plus - IMPAACT 2042

Identifier

NCT06508749

Link

https://clinicaltrials.gov/study/NCT06508749

Phase

Phase I/II

Status

Active, not recruiting

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

More details

The purpose of this study is to advance pediatric HIV treatment and cure research by evaluating the impact of a combination of three anti-HIV-1 broadly neutralizing antibodies (bNAbs) or analytic treatment interruption (ATI) on viral reservoir, immune function, and maintenance of HIV suppression in early-treated children.

Purpose

The Tatelo Plus Study

Interventions

Intervention 1

Intervention 2

Intervention 3

Intervention 4

Intervention 5

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2024-11-11

Anticipated Date of Last Follow-up
2026-09-09

Estimated Primary Completion Date
2027-09-03

Estimated Completion Date
2028-02-18

Actual Primary Completion Date
Not provided

Actual Completion Date
Not provided

Studied populations

Age Cohort

• Neonates (0 to 28 days)
• Infants (0 to 12 months)
• Children
• Adults

Genders

• All

Accepts pregnant individuals
Unspecified

Accepts lactating individuals
Unspecified

Accepts healthy individuals
No

Comments about the studied populations

Inclusion Criteria, Step 1 * Previously enrolled in the EIT/Tatelo, or Moso Cohort Study * Receiving prescribed ART for at least 24 weeks prior to study entry as determined by the site investigator based on participant/parent/guardian report and available medical records * 24 weeks to 12 years of age at enrollment, inclusive * If entering Step 1a: HIV-1 RNA \<40 copies/mL for at least 24 weeks prior to entry, including documented suppression to \<40 copies/mL within 30 days of Step 1 entry * If entering Step 1b: HIV-1 RNA \<200 copies/mL for at least 24 weeks prior to entry, including documented suppression to \<40 copies/mL within 30 days of Step 1 entry. * Normal temperature (\<37.4°C axillary, or \<38°C non-axillary) and no signs or symptoms of acute illness at entry as determined by t

Health status

Study type

Interventional (clinical trial)

Enrollment

41

Allocation

Non-randomized

Intervention model

Parallel Assignment

Intervention model description

Not provided

Masking

Open label

Masking description

Not provided

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

Treatment

Indication(s)

HIV

Key resources

A5388

Identifier

NCT05719441

Link

https://clinicaltrials.gov/study/NCT05719441

Phase

Phase II

Status

Suspended

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

More details

A5388 is a phase II, two-arm, randomized, double-blind, placebo-controlled study that will enroll 48 antiretroviral therapy (ART)-naïve adults with acute HIV infection (AHI) in order to determine whether: * Administration of combination HIV-specific broadly neutralizing antibody (bNAb) therapy in addition to ART during acute HIV infection (AHI) will be safe. * Participants who receive combination bNAb therapy in addition to ART during AHI will be more likely to demonstrate a delay in time to HIV-1 RNA ≥1,000 copies/mL for 4 consecutive weeks compared to participants who receive placebo plus ART. * Participants who receive combination bNAb therapy in addition to ART during AHI will demonstrate lower viral reservoirs and enhanced HIV-specific immunity compared to participants who receive pl

Purpose

A Clinical Trial of Combination HIV-Specific Broadly Neutralizing Monoclonal Antibodies Combined With ART Initiation During Acute HIV Infection to Induce HIV Remission

Interventions

Intervention 1

Intervention 2

Intervention 3

Intervention 4

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2024-08-19

Anticipated Date of Last Follow-up
2025-04-17

Estimated Primary Completion Date
2028-04-06

Estimated Completion Date
2028-09-06

Actual Primary Completion Date
Not provided

Actual Completion Date
Not provided

Studied populations

Age Cohort

• Adults
• Older Adults

Genders

• All

Accepts pregnant individuals
Unspecified

Accepts lactating individuals
Unspecified

Accepts healthy individuals
No

Comments about the studied populations

Inclusion Criteria: Step 1: 1. Appropriate documentation from medical records of diagnosis of AHI prior to enrollment that includes one of the following: 1. A detectable HIV-1 RNA within 28 days prior to study entry AND a non-reactive HIV-1 antibody within 7 days prior to entry; OR 2. A detectable HIV-1 RNA or a reactive HIV-1 antibody within 28 days prior to study entry AND a negative/indeterminate Western Blot (WB) or negative/indeterminate Geenius HIV-1/HIV-2 Supplemental Assay within 7 days prior to entry; OR 3. A documented non-reactive HIV-1 antibody or negative HIV-1 RNA within 90 days prior to study entry AND a documented reactive HIV-1 antibody or positive WB that is negative for p31 band or a positive Geenius HIV-1/HIV-2 Supplemental Assay that is negative for p31 ban

Health status

Not provided

Study type

Interventional (clinical trial)

Enrollment

48

Allocation

Randomized

Intervention model

Parallel Assignment

Intervention model description

Not provided

Masking

Double-blind masking

Masking description

Not provided

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

Treatment

Indication(s)

HIV

Key resources

A5389

Identifier

NCT06987318

Link

https://clinicaltrials.gov/study/NCT06987318

Phase

Phase I

Status

Not yet recruiting

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

More details

The purpose of this study is to evaluate the safety, tolerability, and efficacy of combination broadly neutralizing antibodies (bNAbs), to induce HIV-1 control during analytic treatment interruption (ATI).

Purpose

A Study to Evaluate the Safety and Antiviral Activity of Two Human Monoclonal Antibodies (VRC07-523LS and PGT121.414.LS) During Analytic Treatment Interruption in Participants Living With HIV Who Init

Interventions

Intervention 1

Intervention 2

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
2026-12-01

Actual Start Date
Not provided

Anticipated Date of Last Follow-up
2026-06-12

Estimated Primary Completion Date
2027-08-29

Estimated Completion Date
2028-05-07

Actual Primary Completion Date
Not provided

Actual Completion Date
Not provided

Studied populations

Age Cohort

• Adults
• Older Adults

Genders

• All

Accepts pregnant individuals
Unspecified

Accepts lactating individuals
Unspecified

Accepts healthy individuals
No

Comments about the studied populations

Inclusion Criteria: * Ability and willingness of participant to provide informed consent. * Initiation of combination ART within 90 days of acute HIV diagnosis as defined by any of the criteria listed below: * A negative HIV Ab or HIV Ag/Ab Combination Assay and a detectable HIV-1 RNA (qualitative or quantitative) or a subsequently positive Western blot (WB) or equivalent HIV-1 confirmatory assay (e.g. Geenius assay) if no positive HIV-1 RNA test was available. * A positive HIV Ab or HIV Ag/Ab Combination Assay or p24 antigen test and a negative or indeterminate HIV confirmatory/differentiating test with a detectable HIV-1 RNA (qualitative or quantitative). * A positive HIV Ab or HIV-1 RNA or p24 antigen and positive WB or Geenius HIV-1/HIV-2 Supplemental Assay that is negative for

Health status

Not provided

Study type

Interventional (clinical trial)

Enrollment

40

Allocation

Not provided

Intervention model

Sequential assignment

Intervention model description

Not provided

Masking

Open label

Masking description

Not provided

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

Treatment

Indication(s)

HIV

Key resources

Proprietary excipients used

Not provided

Novel excipients or existing excipients at a concentration above Inactive Ingredients Database (IID) for the specified route of administration

Not provided

Residual solvents used

Not provided

There are either no relevant patents or these were not yet submitted to LAPaL

Publications

Broadly neutralizing antibodies for treatment of HIV in children in the Global South: rationale and challenges

Tagarro, A. — Frontiers in Pediatrics — 2026-07-23

Link: https://www.frontiersin.org/journals/pediatrics/articles/10.3389/fped.2026.1833681/full

Summary: Review of the paediatric bNAb landscape. Notes that children account for about 15% of AIDS-related deaths worldwide while bNAb trials have overwhelmingly enrolled adults in high-income countries. Reports that IMPAACT 2037 (NCT06517693) is a recruiting phase 1 study in HIV-exposed infants, n=24 per arm, testing PGT121.414.LS alone at 80 mg, or 80 mg then 100 mg after 12 weeks depending on weight, and in combination with VRC07-523LS. States that PGT121.414.LS is a different molecule from ePGT121v1-LS.

Despite the rapid scale-up of early infant diagnosis and antiretroviral therapy, pediatric HIV type 1 (HIV-1) remains a remarkable public health as children account for 15% of all AIDS-related deaths worldwide. Broadly neutralizing antibodies (bNAbs) have emerged as a promising strategy for the prevention, treatment, and potential cure of HIV. In adults, bNAbs have proven to be safe and effective, capable of suppressing plasma viremia and delaying viral rebound during analytical treatment interruptions. bNAbs provide immediate passive immunity and long-acting coverage, which makes them suitable for children where high baseline viral loads drive rapid disease progression and reservoir establishment. Several trials have demonstrated that subcutaneous administration of bNAbs is safe and pharmacokinetically feasible in neonates and have provided a proof-of-concept for bNAb-mediated viral control in children. However, the clinical evaluation of bNAbs has primarily been directed towards adult populations in the Global North, leading to limited pediatric clinical data. This research lag represents a critical ethical inequity that risks denying life-saving therapeutics to the most vulnerable populations. Therefore, equitable access in the Global South requires the elimination of structural barriers that currently delay pediatric access through a strategy of intentional early inclusion, technology transfer, and parallel clinical development. Similarly, a multi-faceted approach involving governments in the Global South, funders, stakeholders, and pharmaceutical developers is essential to address intellectual property sharing, licensing, regulatory harmonization, and local manufacturing. The ongoing development of pediatric trials represents an opportunity to achieve long-term viral remission, providing a definitive pathway to end the pediatric HIV epidemic. Prioritizing these studies is a scientific and moral necessity to ensure that children are finally placed at the center of medical innovations and no longer excluded from therapeutic advancements.

Safety, tolerability, pharmacokinetics, and neutralisation activities of the anti-HIV-1 monoclonal antibody PGT121.414.LS administered alone and in combination with VRC07-523LS in adults without HIV in the USA (HVTN 136/HPTN 092): a first-in-human, open-label, randomised controlled phase 1 trial

Edupuganti, S. — The Lancet HIV — 2025-01-12

Link: https://pubmed.ncbi.nlm.nih.gov/39667379/

Summary: First-in-human phase 1 trial in 33 adults without HIV in the US. Part A: escalating single IV doses or SC infusion of PGT121.414.LS at 3 mg/kg IV (n=3), 10 mg/kg IV (n=4), 30 mg/kg IV (n=3) and 5 mg/kg SC (n=3). Part B: repeated sequential IV administration of 20 mg/kg PGT121.414.LS plus 20 mg/kg VRC07-523LS (n=10) and sequential SC administration of 5 mg/kg of each (n=10) on days 0, 112 and 224. Safe and well tolerated without serious adverse events or dose-limiting toxicities. Dose-proportional serum concentrations from 3 to 30 mg/kg IV, with median peaks of 63.3, 221.7 and 554.7 microgram/mL, and 714.2 microgram/mL at 20 mg/kg in combination. Estimated elimination half-life 71 days (95% CI 66-75), three times that of parental PGT121 (about 22 days). Estimated SC versus IV bioavailability 86.1% (95% CI 64.0-95.5). Neutralisation measured by TZM-bl assay against a 12-virus magnitude-breadth panel; a 208-virus multi-clade panel showed reasonable concordance in IC50 and IC80 between parental PGT121 and PGT121.414.LS. Neutralisation activities were greater in the higher-dose and dual-combination IV groups than in the SC groups. Product supplied at 100 mg/mL in 10 mL vials with a 4.75 mL fill, engineered by Just-Evotec Biologics, Dan Barouch and CAVD.

Background: Multiple broadly neutralising monoclonal antibodies (mAbs) are in development for HIV-1 prevention. The aim of this trial was to test the PGT121.414.LS and VRC07-523LS mAbs for safety and pharmacokinetics in adults.

Methods: In this first-in-human phase 1 trial (HVTN 136/HPTN 092), adults without HIV were enrolled at six university-affiliated clinical research sites in the USA. Part A evaluated escalating single intravenous doses or subcutaneous infusion of PGT121.414.LS, in four groups: 3 mg/kg intravenous (treatment group 1; n=3), 10 mg/kg intravenous (treatment group 2; n=4), 30 mg/kg intravenous (treatment group 3; n=3), and 5 mg/kg subcutaneous (treatment group 4; n=3). Part B evaluated repeated sequential intravenous administrations of 20 mg/kg PGT121.414.LS plus 20 mg/kg VRC07-523LS (treatment group 5; n=10) and sequential subcutaneous administrations of 5 mg/kg PGT121.414.LS plus 5 mg/kg VRC07-523LS (treatment group 6; n=10) on days 0, 112, and 224. Participants in treatment groups 1 and 2 were enrolled sequentially, with participants enrolled and randomly assigned to treatment groups 3 and 4 after a review of safety data. Participants in treatment groups 5 and 6 were randomly assigned in blocks after a review of safety data from treatment groups 1-4. The primary endpoints were safety and tolerability of mAbs, serum concentrations and pharmacokinetics of mAbs, and serum neutralising activity, assessed in participants who received all scheduled product administrations. Serum concentrations of each mAb were measured via a multiplex assay, and neutralisation activity against multiple HIV viruses was measured via the TZM-bl assay. Serum concentrations were estimated via an open, two-compartment model with first-order elimination from the central compartment. This study was registered with ClinicalTrials.gov (NCT04212091) and has been completed.

Findings: Between Nov 10, 2020, and Oct 5, 2021, we enrolled 33 participants without HIV: median age was 31 years (range 22-48); 19 were assigned female sex at birth and 11 were assigned male sex at birth. Three participants and four participants were sequentially assigned to treatment groups 1 and 2, respectively, and, after safety review, six participants were randomly assigned to treatment groups 3 (n=3) and 4 (n=3); after safety review, 20 participants were randomly assigned to treatment groups 5 (n=10) and 6 (n=10). Intravenous and subcutaneous infusions were safe and well tolerated, without serious adverse events or dose-limiting toxicities. Dose escalation of PGT121.414.LS from 3 mg/kg to 30 mg/kg (intravenous) resulted in a dose-proportional increase in serum concentration of PGT121.414.LS, whether administered alone or in combination with VRC07-523LS. The estimated elimination half-life of PGT121.414.LS was 71 days (95% CI 66-75), three times that of its parental form, PGT121. The estimated subcutaneous (vs intravenous) bioavailability of PGT121.414.LS was 86·1% (95% CI 64·0-95·5). Neutralisation activities were greater in the higher-dose and dual combination intravenous groups than in the subcutaneous administration groups.

Interpretation: These findings support further evaluation of PGT121.414.LS in combination with other mAbs for HIV-1 prevention.

Additional documents

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Useful links

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