VRC07-523LS / National Institute of Allergy and Infectious Diseases, IAVI, TaiMed Biologics - LARVOL DELTA

Correlates of HIV-1 control after combination immunotherapy. (PubMed, Nature) - P1/2 | "We performed a single-arm, proof-of-concept study in ten people with HIV on ART combining the following three approaches: (1) therapeutic vaccination with an HIV/Gag conserved element (CE)-targeted DNA+IL-12 prime/MVA boost regimen followed by (2) administration of two bNAbs (10-1074, VRC07-523LS) and a toll-like receptor 9 agonist (lefitolimod) during ART suppression, followed by (3) repeat bNAb administration at the time of ART interruption (NCT04357821). Robust expansion of activated CD8+ T cells early in response to rebounding virus correlated with lower median viral load following peak viremia off ART. These data suggest that combination immunotherapy approaches might prove effective to induce sustained control of HIV by slowing rebound and improving CD8+ T cell responses, and that these approaches should continue to be optimized."

Journal • Human Immunodeficiency Virus • Infectious Disease • CD8 • IL12A

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 Initiated ART During Acute/Early HIV-1 Infection (clinicaltrials.gov) - P1 | N=40 | Not yet recruiting | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Initiation date: Oct 2025 ➔ Feb 2026

Trial initiation date • Human Immunodeficiency Virus • Infectious Disease

Decision-making and acceptability of subcutaneously administered broadly neutralising monoclonal antibodies for HIV prevention amongst CAPRISA 012A trial participants in Durban, South Africa. (PubMed, Sci Rep) - "This study explored the acceptability of subcutaneously administered broadly neutralising antibodies, receiving either one or two doses of VRC07-523LS and/or PGT121, from the perspective of women living without HIV in KwaZulu-Natal, South Africa. The findings underscore the importance of integrating clear messaging on product efficacy, linking potential HIV prevention products to broader healthcare services, and supporting different users to make the decision to use this product. This study provides a novel contribution to understanding the complex dynamics of acceptability and behaviour change, essential for successful implementation and uptake of HIV prevention strategies."

Journal • Human Immunodeficiency Virus • Infectious Disease

Safety and analytical treatment interruption outcomes in a clinical trial of 2 broadly neutralizing antibodies plus vesatolimod in early-treated South African women with clade C HIV-1 (EACS 2025) - P2 | "Method : Twenty women living with HIV who initiated antiretroviral therapy (ART) during the hyperacute infection phase (suppressed viremia <50 copies/mL and CD4 + T-cell counts ≥500 cells/μL at enrollment) were treated with a biweekly regimen of VES (up to 10 doses) and 2 bNAbs, CAP256V2LS and VRC07-523LS, infused 1 week after the first VES dose. Conclusions : Overall, the combination of bNAbs and VES was generally safe, and safety was comparable across 3 viral control groups, suggesting the potential of an HIV cure regimen with a favorable benefit-risk profile. However, conclusions are limited given the low participant numbers and lack of placebo arm."

Clinical • Human Immunodeficiency Virus • Infectious Disease • CD4

VISTA: HIV-1 Virologic Suppression With TMB-365 and TMB-380 Antibodies Study (clinicaltrials.gov) - P2 | N=75 | Not yet recruiting | Sponsor: TaiMed Biologics Inc.

New P2 trial • Human Immunodeficiency Virus • Infectious Disease

A Clinical Trial of Combination HIV-Specific Broadly Neutralizing Monoclonal Antibodies Combined With ART Initiation During Acute HIV Infection to Induce HIV Remission (clinicaltrials.gov) - P2 | N=48 | Recruiting | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Suspended ➔ Recruiting

Enrollment open • Human Immunodeficiency Virus • Infectious Disease • CD4

Rapid loss of activity but not serum concentration in a passive infusion clinical trial of an HIV neutralizing antibody. (PubMed, medRxiv) - "However, it is not a given that the mAbs will retain full functionality over time, emphasizing the need for integrated PK and functional assessments. In a re-analysis of data from the CAPRISA 012B trial, a previously published phase 1 study evaluating mAbs CAP256V2LS and VRC07-523LS in HIV-negative women, we report an unexpected disconnect between serum bNAb concentrations and HIV neutralization activity of CAP256V2LS, with implications for ongoing assessment of passive immunization trials."

Journal • Human Immunodeficiency Virus • Infectious Disease

RV630 - Approach to Control HIV With Immune Enhancement and Vaccination (ACHIEV (clinicaltrials.gov) - P1 | N=48 | Recruiting | Sponsor: Henry M. Jackson Foundation for the Advancement of Military Medicine | Active, not recruiting ➔ Recruiting

Enrollment open • Human Immunodeficiency Virus • Infectious Disease

Hyaluronidase-enhanced subcutaneous delivery of bNAbs: a phase 1 randomized controlled clinical trial in HIV-uninfected women. (PubMed, Nat Commun) - "CAP256V2LS and VRC07-523LS-potent HIV-1 bNAbs targeting conserved envelope epitopes-were administered SC with and without EDP. EDP was well tolerated with no safety concerns. These findings support EDP-enhanced SC delivery as a scalable and simplified strategy for long-acting antibody-based HIV prevention."

Clinical • Journal • P1 data • Human Immunodeficiency Virus • Infectious Disease

Vesatolimod pharmacodynamic responses in a trial of vesatolimod and broadly neutralizing antibodies in early-treated South African women with clade C HIV-1 (IAS-HIV 2025) - P2 | "We investigated VES pharmacodynamic responses and associations with analytical treatment interruption (ATI) outcomes in an open-label study of VES combined with 2 broadly neutralizing antibodies (bNAbs), VRC07-523LS and CAP256V2LS, in virologically suppressed (VS) women with clade C HIV-1 (NCT05281510). This study enrolled 20 acutely treated VS Black women (age =18 years, antiretroviral therapy [ART] for =12 months) from the Females Rising through Education, Support, and Health (FRESH) cohort in South Africa. VES induced consistent upregulation of ISGs in Black female participants in this small study, suggesting a similar pharmacodynamic effect in this population, compared with previously studied populations."

Clinical • IO biomarker • PK/PD data • Human Immunodeficiency Virus • Infectious Disease • CCL19 • CCL8 • CD4 • IL1R1 • MX1

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 Initiated ART During Acute/Early HIV-1 Infection (clinicaltrials.gov) - P1 | N=40 | Not yet recruiting | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Initiation date: Jun 2025 ➔ Oct 2025

Trial initiation date • Human Immunodeficiency Virus • Infectious Disease

Synergizing expertise: lessons learned from conducting the first HIV cure interventional trial in Africa with collaboration between academia, government, and industry (IAS-HIV 2025) - P2 | "Participants received 2 broadly neutralizing antibodies (bNAbs; VRC07-523LS and CAP256V2LS) and a Toll-like receptor 7 agonist, vesatolimod (VES), and underwent ATI for up to 55 weeks or until meeting antiretroviral therapy (ART) restart criteria. It is critical to consider context and have a concrete plan for monitoring participants who remain off ART after study conclusion. This trial was a culmination of a productive partnership between academia, government, and industry, and demonstrated the feasibility of conducting complex HIV cure trials in Africa, where the most stand to benefit from these interventions."

Human Immunodeficiency Virus • Infectious Disease • Novel Coronavirus Disease

RV630 - Approach to Control HIV With Immune Enhancement and Vaccination (ACHIEV (clinicaltrials.gov) - P1 | N=48 | Active, not recruiting | Sponsor: Henry M. Jackson Foundation for the Advancement of Military Medicine | Not yet recruiting ➔ Active, not recruiting

Enrollment closed • Human Immunodeficiency Virus • Infectious Disease

Psychological impact of analytical treatment interruption on young women enrolled in an HIV cure-related trial in Durban, South Africa (IAS-HIV 2025) - "For the first time, this study assessed mental health among young women during an ATI-inclusive HIV cure-related trial testing a combination of two broadly neutralizing antibodies, VRC07-523-LS and CAP256V2LS, with a toll-like receptor 7 agonist (Vesatolimod) in Durban, South Africa. Twenty women (23–32 years old) participating in an ATI-inclusive trial were co-enrolled in a socio-behavioral study. ATI was well-tolerated psychologically among young women enrolled in ATI-inclusive HIV cure trial in South Africa. Sustained or improved decisional certainty, self-esteem, and resilience were observed during participation, while increased anxiety and depression were associated with prolonged-ATI (late ART restart). Findings support the inclusion of young women in ATI-inclusive trials but highlight the need for mental health assessments and directed psychosocial support, especially for trials that include prolonged ATIs."

Clinical • Late-breaking abstract • CNS Disorders • Depression • Human Immunodeficiency Virus • Infectious Disease • Mood Disorders • Psychiatry

PedMAb1 trial: safety of two broadly neutralising antibodies, CAP256V2LS and VRC07-523LS, administered singly or concurrently at birth and 3 months to breastfeeding HIV-1 exposed neonates and infants born without HIV (IAS-HIV 2025) - "CAP256V2LS and VRC07-523LS are safe when administered alone and in combination to HEI. Phase 2/3 trials are needed to investigate the efficacy of bNAbs to interrupt vertical HIV transmission, thus increasing the armamentarium against postnatal HIV transmission and creating an HIV-free paediatric population. Progress has been hampered by current global development."

Clinical • Late-breaking abstract • Anemia • Hematological Disorders • Human Immunodeficiency Virus • Infectious Disease • Pediatrics

Broadly neutralizing antibody VRC07-523LS persists at four months in mucosal tissue following intravenous administration at 10mg/kg and 30mg/kg (HVTN128) (IAS-HIV 2025) - "Except for rectal secretions, both doses of VRC07-523LS reach mucosal compartments and persist four months post-third infusion in most participants, suggesting this dosing regimen provides detectable bnAb trough levels. In rectal biopsies, FSAB have higher VRC07-523LS than MSAB, suggesting a sex-specific difference in mAb penetration and accumulation. Persistence of passively infused VRC07-523LS in the mucosa supports the use of this bnAb in HIV-1 prevention and treatment."

Human Immunodeficiency Virus • Infectious Disease

A randomized, double-blind, controlled, phase 2 clinical trial to evaluate safety, tolerability, pharmacokinetics, and neutralization of VRC07-523LS, PGT121.414.LS, and PGDM1400LS broadly neutralizing monoclonal antibodies given intravenously in adults without HIV (IAS-HIV 2025) - "HVTN206/HPTN114 represents a critical step in advancing HIV prevention strategies by testing a triple-bnAb combination informed by robust evidence from the AMP efficacy trials and phase 1 trials with next-generation bnAbs, including HVTN140/HPTN101 with the same triple-bnAb combination. This trial will inform the design of the combo-AMP efficacy trials and could establish HIV bnAbs immunoprophylaxis (passive immunization) as a biannual, long-acting option for HIV prevention, addressing key gaps in current strategies and enhancing global HIV prevention programs."

Clinical • P2 data • PK/PD data • Human Immunodeficiency Virus • Infectious Disease

Phase 2 Trial of Long-Acting Cabotegravir and VRC07-523LS for Viral Suppression in Adults with HIV-1: ACTG A5357. (PubMed, Clin Infect Dis) - "The VRC07-523LS plus CAB-LA regimen maintained viral suppression in 93% of participants, with only transient infusion reactions observed; however, instances of virologic breakthrough suggest that future studies should focus on optimizing efficacy outcomes. These results support continued investigation of bNAb-based long-acting ART combinations."

Journal • P2 data • Human Immunodeficiency Virus • Infectious Disease • CD4

Distinct neutralization sensitivity between adult and infant transmitted/founder HIV-1 subtype C viruses to broadly neutralizing monoclonal antibodies. (PubMed, PLoS Pathog) - "The bnAbs VRC07-523LS, CAP256-VRC26.25, PGDM1400, 10E8 and PGT151 displayed higher neutralization breadth and potency than other bnAbs against FRESH TF viruses (>70% coverage, starting concentration of 10 μg/ml). Moreover, high transmission of escape variants in both vertical and heterosexual transmissions is of concern. This information may be important in the selection of bnAbs that will undergo clinical testing in subtype C settings."

Journal • Human Immunodeficiency Virus • Infectious Disease • Pediatrics

Fixed dosing versus weight-based dosing of HIV-1 prophylactic monoclonal antibodies in adults: a post-hoc, cross-protocol pharmacokinetics modelling study. (PubMed, EBioMedicine) - "For HIV-1 prophylactic mAbs, a fixed-dose approach, possibly banded by weight categories may be advantageous over weight-based dosing, as it offers increased operational efficiency while maintaining comparable pharmacokinetics and inter-individual consistency."

Journal • PK/PD data • Retrospective data • Human Immunodeficiency Virus • Infectious Disease

The Tatelo Plus Study (clinicaltrials.gov) - P1/2 | N=41 | Recruiting | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Trial primary completion date: Feb 2028 ➔ Nov 2027

Trial primary completion date • Human Immunodeficiency Virus • Infectious Disease

Population pharmacokinetics of weight-based compared with fixed dosing of CAP256V2LS, a broadly neutralizing antibody for HIV prevention in women. (PubMed, J Antimicrob Chemother) - "For women weighing 60-93 kg, a fixed-dose of 1200 mg of CAP256V2LS produced similar adverse events and pharmacokinetic profiles as weight-based dosing. The fixed dose reduced variability in the plasma concentrations and product wastage compared with weight-based dosing."

Journal • PK/PD data • Human Immunodeficiency Virus • Infectious Disease

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 Initiated ART During Acute/Early HIV-1 Infection (clinicaltrials.gov) - P1 | N=40 | Not yet recruiting | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

New P1 trial • Human Immunodeficiency Virus • Infectious Disease

Combinatorial Therapy to Induce an HIV Remission (clinicaltrials.gov) - P1/2 | N=11 | Active, not recruiting | Sponsor: University of California, San Francisco | Trial primary completion date: Dec 2024 ➔ Dec 2025

Trial primary completion date • Human Immunodeficiency Virus • Infectious Disease • CD4

Broadly-neutralizing antibodies and CCR5 -edited hematopoietic stem cell transplantation synergistically delay virus recrudescence in a nonhuman primate model of HIV (ASGCT 2025) - "Bulk CD34+ HSPCs were collected after G-CSF/Plerixafor mobilization, edited with NHP CCR5-specific CRISPR ribonucleoprotein (RNP) complexes, cryopreserved, and transplanted after conditioning with either myeloablative busulfan or an anti-CD45 antibody-drug conjugate (ADC)...At ART withdrawal, a subset of animals received a single infusion of VRC07.523.LS, a safe and effective bNAb with potency against HIV and SHIV.C.CH505.v2, and is currently in clinical trials in people living with HIV (PWH)...Our ongoing efforts are focused on quantitative comparisons between busulfan- and CD45-ADC conditioning regimens, the latter of which may also directly deplete latently-infected cells. Disease Focus of Abstract:HIV"

Preclinical • Bone Marrow Transplantation • Gene Therapies • Human Immunodeficiency Virus • Infectious Disease • Transplantation • CD34