ePGT121v1LS

Associated long-acting platforms

Monoclonal antibodies and antibody drug conjugates

Administration route

Intravenous, Subcutaneous

Therapeutic area(s)

Use case(s)

Use of drug

Dosage

Drug information

Delivery device(s)

Not provided

Antibody characteristics

Molecular identity

Epitope and engineering

Delivery

Scale-up prospects

GMP production at 2,000 L (2KL) batch scale was reported in 2023, with clinical trial material formulated at 125 mg/mL. High formulation concentration supports low-volume subcutaneous administration, which is a practical requirement for neonatal and infant dosing. To be confirmed.

Tentative equipment list for manufacturing

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

Manufacturing

Engineered from parental PGT121 by IAVI with Scripps Research using yeast surface display and directed evolution to enhance affinity, with glycoengineering to improve Fc effector function (ADCC) and LS (M428L/N434S) Fc mutations to extend half-life. Expressed in mammalian cell culture, purified by affinity chromatography. GMP clinical trial material formulated at 125 mg/mL. Cell line and process details are not publicly disclosed.

Specific analytical instrument required for characterization of formulation

HPLC, mass spectrometry, yeast surface display and FACS (used in the directed-evolution engineering), deep sequencing, surface plasmon resonance, TZM-bl neutralisation assay for serum neutralising activity.

ENABLE 2

Identifier

NCT07655141

Link

https://clinicaltrials.gov/study/NCT07655141

Phase

Phase I/II

Status

Not yet recruiting

Sponsor

Hospital Universitario 12 de Octubre

More details

The goal of this clinical trial is to learn if subcutaneous ePGT121v1-LS and VRC07-523-LS added to standard antiretroviral therapy (ART) is safe and helps improve HIV viral suppression in infants living with HIV in Mozambique and Cameroon. The study will also learn how the body processes ePGT121v1-LS and VRC07-523-LS and whether caregivers and health workers find this treatment approach acceptable. The main questions it aims to answer are: * Are ePGT121v1-LS and and VRC07-523-LS safe and well tolerated in infants living with HIV? * Does adding ePGT121v1-LS and VRC07-523-LS to standard ART increase the number of infants who achieve HIV viral suppression by week 48? * How long does it take participants receiving ePGT121v1-LS and VRC07-523-LS to achieve viral suppression compared with stand

Purpose

Early Neutralizing Antibodies in Infants Living With HIV to Enhance Their Life (2)

Interventions

Intervention 1

Intervention 2

Intervention 3

Countries

Not provided

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
2027-01-01

Actual Start Date
Not provided

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

Estimated Primary Completion Date
2029-07-01

Estimated Completion Date
2029-12-31

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

Genders

• All

Accepts pregnant individuals
Unspecified

Accepts lactating individuals
Unspecified

Accepts healthy individuals
No

Comments about the studied populations

Inclusion Criteria: * Infants from 1 to 365 days old at the time of enrolment. * Living with HIV-1, diagnosed with an approved assay detecting HIV nucleic acids in blood. * Weight \> 2.5 kg at enrolment. * ART-naïve or ≤ 30 days of triple ART at screening (not including prophylaxis in HIV-exposed). * Clinically stable and can be managed as outpatient (participants identified in-hospital can start the trial at their first routine visit). * Parent or legal guardian able to provide Informed consent (IC). Exclusion Criteria: * Participation in other concurrent research studies that, in the opinion of the principal investigator and central team, would interfere with the objectives of this study. * Previous receipt of bNAbs against HIV. * Serious Adverse Reactions (SARs) to the investigationa

Health status

Not provided

Study type

Interventional (clinical trial)

Enrollment

73

Allocation

Randomized

Intervention model

Parallel Assignment

Intervention model description

Not provided

Masking

Quadruple-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

HVTN 141/HPTN 105

Identifier

NCT07390955

Link

https://clinicaltrials.gov/study/NCT07390955

Phase

Phase I

Status

Recruiting

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

More details

This study is testing a lab-made antibody called ePGT121v1-LS that targets a specific part of HIV. Researchers will give it by vein (IV) and under the skin (SC), both on its own and together with two other antibodies, VRC07-523LS and PGDM1400LS, which target different parts of the virus. They will assess safety and side effects, determine the right dose, study how the body processes the drug (pharmacokinetics or PK), and measure how well it neutralizes HIV in the blood (serum neutralizing activity). The expectation is that ePGT121v1-LS, whether given alone or with PGDM1400LS and VRC07-523LS, by IV or SC, will be safe in generally healthy adults and that the antibodies will not interfere with each other when used together.

Purpose

A Study of Safety and Drug Levels of ePGT121v1-LS, PGDM1400LS, and VRC07-523LS in Adult Participants Without HIV-1

Interventions

Intervention 1

Intervention 2

Intervention 5

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2026-03-19

Anticipated Date of Last Follow-up
2026-08-31

Estimated Primary Completion Date
2027-08-30

Estimated Completion Date
2027-08-30

Actual Primary Completion Date
Not provided

Actual Completion Date
Not provided

Studied populations

Age Cohort

• Adults

Genders

• All

Accepts pregnant individuals
No

Accepts lactating individuals
No

Accepts healthy individuals
Yes

Comments about the studied populations

Inclusion Criteria: 1. Age 18 to 55 years. 2. Can visit a participating clinic and is willing to stay in the study for its full duration. 3. Understands the study and is able and willing to give informed consent. 4. Agrees not to join another experimental study until the final required clinic visit. 5. In good overall health based on medical history, physical exam, and screening lab tests. 6. Willing to receive HIV test results. 7. Willing to discuss personal risk of getting HIV and to have HIV prevention counseling. 8. Judged by clinic staff to have a low risk of getting HIV and agrees to avoid higher risk behaviors through the last clinic visit. 9. Hemoglobin levels: * Women: at least 11.0 g/dL * Men: at least 13.0 g/dL 10. White blood cell count between 2,500 and 12,000 cells/mm

Health status

Study type

Interventional (clinical trial)

Enrollment

83

Allocation

Non-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

Prevention, PrEP, Treatment

Indication(s)

HIV

Key resources

ENABLE 1

Identifier

NCT07655128

Link

https://clinicaltrials.gov/study/NCT07655128

Phase

Phase I/II

Status

Not yet recruiting

Sponsor

Hospital Universitario 12 de Octubre - Servicio Madrileno de Salud (SERMAS)

More details

The goal of this clinical trial is to learn if subcutaneous ePGT121v1-LS added to standard antiretroviral therapy (ART) is safe and helps improve HIV viral suppression in infants living with HIV in South Africa. The study will also learn how the body processes ePGT121v1-LS and whether caregivers and health workers find this treatment approach acceptable. The main questions it aims to answer are: * Is ePGT121v1-LS safe and well tolerated in infants living with HIV? * Does adding ePGT121v1-LS to standard ART increase the number of infants who achieve HIV viral suppression by week 48? * How long does it take participants receiving ePGT121v1-LS to achieve viral suppression compared with standard treatment alone? * How does ePGT121v1-LS behave in the body after repeated subcutaneous injection

Purpose

Early Neutralizing Antibodies in Infants Living With HIV to Enhance Their Life

Interventions

Intervention 1

Intervention 2

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
2027-01-01

Actual Start Date
Not provided

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

Estimated Primary Completion Date
2029-07-01

Estimated Completion Date
2029-12-31

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

Genders

• All

Accepts pregnant individuals
No

Accepts lactating individuals
No

Accepts healthy individuals
No

Comments about the studied populations

Inclusion Criteria: * Infants from 1 to 365 days old at the time of enrolment. * Living with HIV-1, diagnosed with an approved assay detecting HIV nucleic acids in blood. * Weight \> 2.5 kg at enrolment. * ART-naïve or ≤ 30 days of triple ART at screening (not including prophylaxis in HIV-exposed). * Clinically stable and can be managed as outpatient (participants identified in-hospital can start the trial at their first routine visit). * Parent or legal guardian able to provide Informed consent (IC). Exclusion Criteria: * Participation in other concurrent research studies that, in the opinion of the principal investigator and central team, would interfere with the objectives of this study. * Previous receipt of bNAbs against HIV. * Serious Adverse Reactions (SARs) to the investigationa

Health status

Study type

Interventional (clinical trial)

Enrollment

87

Allocation

Randomized

Intervention model

Parallel Assignment

Intervention model description

The goal of this clinical trial is to learn whether subcutaneous ePGT121v1-LS added to standard antiretroviral therapy (ART) is safe and helps improve HIV viral suppression in infants living with HIV in South Africa. The study will also learn how the body processes ePGT121v1-LS and whether caregivers and health workers find this treatment approach acceptable. Part of the ENABLE project (Early Neutralizing Antibodies in Infants Living with HIV to Enhance their Life), a four-year, 21-partner project launched 1 January 2026 and funded by Global Health EDCTP3 and the European Union (grant agreement 101190620). Secondary endpoints address biomarkers of long-term remission and the feasibility of cure approaches.

Masking

Quadruple-blind masking

Masking description

Not provided

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

Infant post-exposure prophylaxis, Treatment, Paediatric 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

There are no publication

Additional documents

No documents were uploaded

Useful links

• IAVI announces the onset of first-in-human Phase 1 clinical trial of ePGT121v1-LS broadly neutralizing antibodies (bnAbs) to prevent HIV transmission — IAVI website, 2026-03-19