CAP256V2LS / National Institute of Allergy and Infectious Diseases - LARVOL DELTA

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

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

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

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

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

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

Evaluation of 2 bNAbs Plus Vesatolimod in Early-Treated South African Women With HIV-1 During ATI (CROI 2025) - P2 | "Background Antiretroviral therapy (ART) can reduce morbidity and mortality but does not eradicate HIV. VES, VRC07-523LS, and CAP256V2LS were safe and well tolerated in acutely treated South African women. Potential mechanisms for the variable patterns of virologic control observed in this novel study are under investigation."

Clinical • Human Immunodeficiency Virus • Infectious Disease • Inflammation • CD4

Landmark HIV Cure Clinical Trial Conducted in South Africa (Businesswire) - P2a | N=20 | NCT05281510 | Sponsor: Gilead Sciences | "Results presented at CROI showed the treatment combination was generally well-tolerated with no treatment-related serious adverse events (TEAEs) reported. The most common study TEAEs were infusion-related reactions (n = 18; 16 grade 1, 2 grade 2). Seventy percent of participants (n=14) met ART restart criteria. Thirty percent (n=6) remained off ART through Week 48, of which 4 remained off ART through Week 60. While the data suggest that the trial regimen alone is not sufficient as an HIV cure regimen, the mechanistic learnings will inform the development of future cure approaches."

P2a data • Human Immunodeficiency Virus • Infectious Disease

Study of VRC07-523LS, CAP256V2LS, and Vesatolimod, in Early Antiretroviral-treated HIV-1 Clade C-infected Women (clinicaltrials.gov) - P2 | N=20 | Completed | Sponsor: Gilead Sciences | Active, not recruiting ➔ Completed

Trial completion • Human Immunodeficiency Virus • Infectious Disease

Cryo-EM characterization of diverse antibody interactions with HIV envelope to facilitate vaccine and therapeutic antibody development (HIVR4P 2024) - "Third, we determined cryo-EM structures of PGDM1400 (currently in clinical trials for the treatment of HIV-1) and an improved variant of the clonal relative PGT145 bound to BG505 envelope trimers; these structures revealed how different clades of a single antibody lineage can adopt different strategies for broad recognition at the V2 apex-site of vulnerability. Collectively, these vignettes demonstrate how structural biology will continue to accelerate the development of vaccines and therapeutics against HIV-1."

Human Immunodeficiency Virus • Infectious Disease

PedMAb1 clinical trial: Safety and dose escalation of CAP256V2LS and VRC07-523LS given to HIV-1 exposed uninfected neonates informed simultaneous administration of two bNAbs and dosing interval to prevent breastmilk HIV-transmission (HIVR4P 2024) - "CAP256V2LS and VRC07-523LS administered SC to infants are safe. Data on safety and PK of two bNAbs administered simultaneously at birth and 12-weeks is forthcoming."

Clinical • Late-breaking abstract • Gastroenterology • Human Immunodeficiency Virus • Infectious Disease • Pediatrics

PedMAb1 clinical trial: safety assessment of CAP256V2LS and VRC07-523LS to prevent breastmilk HIV transmission in HIV-1 exposed and negative neonates (AIDS 2024) - "CAP256V2LS and VRC07-523LS at the doses here administered SC to infants within max 96 hours of birth are safe and showed overall low reactogenicity. Reported product related AEs were rare and expected. Analysis of the pharmacokinetics of the study products is ongoing."

Clinical • Gastroenterology • Human Immunodeficiency Virus • Infectious Disease

Safety and pharmacokinetics of subcutaneous administration of broadly neutralizing anti-HIV-1 monoclonal antibodies (bNAbs), given to HIV-1 exposed, uninfected neonates and infants: study protocol for a phase I trial. (PubMed, BMC Infect Dis) - "The results of this trial will guide further studies on bNAbs to prevent breast milk transmission of HIV."

Clinical • Clinical protocol • Journal • P1 data • PK/PD data • Human Immunodeficiency Virus • Infectious Disease • Pediatrics

Circulating immunoglobulins and transient lymphocytopenia in a sub-study of CAPRISA 012B, testing HIV monoclonal antibodies in a phase 1 trial. (PubMed, Sci Rep) - "Acute, transient lymphocytopenia, not clinically significant was observed in the CAPRISA 012B phase 1 clinical trial following administration of broadly neutralizing antibodies (bnAb)-CAP256V2LS alone or with VRC07-523LS. This sub study presents preliminary findings to support the monitoring of baseline immunological markers including lymphocyte counts for assessing the development of transient lymphocytopenia. In high-risk settings conducting clinical trials testing bnAbs for HIV prevention, understanding factors that could amplify rates of lymphocytopenia, even if transient, remain undefined."

Clinical • Journal • Lymphopenia • P1 data • P1 data • Hematological Disorders • Human Immunodeficiency Virus • Infectious Disease • CCL11 • CCL4 • CXCL8 • FGF • IFNG • IL17A • IL1R1 • IL4 • IL6 • TNFA

Ultrapotent Broadly Neutralizing Human-llama Bispecific Antibodies against HIV-1. (PubMed, Adv Sci (Weinh)) - "The resultant human-llama bispecific antibody CAP256L-R27×3LS exhibited ultrapotent neutralization and breadth exceeding other published HIV-1 broadly neutralizing antibodies, with pharmacokinetics determined in FcRn-Fc mice similar to the parent CAP256V2LS. Vaccine-elicited llama nanobodies, when combined with V2-apex broadly neutralizing antibodies, may therefore be able to fulfill anti-HIV-1 therapeutic and prophylactic clinical goals."

Journal • Human Immunodeficiency Virus • Infectious Disease • CD4

Study of VRC07-523LS, CAP256V2LS, and Vesatolimod, in Early Antiretroviral-treated HIV-1 Clade C-infected Women (clinicaltrials.gov) - P2 | N=21 | Active, not recruiting | Sponsor: Gilead Sciences | Trial completion date: Nov 2024 ➔ Mar 2025 | Trial primary completion date: Nov 2024 ➔ Mar 2025

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

Study of VRC07-523LS, CAP256V2LS, and Vesatolimod, in Early Antiretroviral-treated HIV-1 Clade C-infected Women (clinicaltrials.gov) - P2 | N=20 | Active, not recruiting | Sponsor: Gilead Sciences | Recruiting ➔ Active, not recruiting | Phase classification: P2a ➔ P2

Enrollment closed • Phase classification • Human Immunodeficiency Virus • Infectious Disease

Extended safety and tolerability of subcutaneous CAP256V2LS and VRC07-523LS in HIV-negative women: study protocol for the randomised, placebo-controlled double-blinded, phase 2 CAPRISA 012C trial. (PubMed, BMJ Open) - "Results will be disseminated through conference presentations, peer-reviewed publications and the clinical trial registry. PACTR202112683307570."

Journal • P2 data • Human Immunodeficiency Virus • Infectious Disease • Preventive care

VRC 611: Human Monoclonal Antibody (mAb) VRC-HIVMAB0102-00-AB (CAP256V2LS)Administered Via Subcutaneous and Intravenous Injection in Healthy Adults (clinicaltrials.gov) - P1 | N=10 | Completed | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Active, not recruiting ➔ Completed | N=20 ➔ 10 | Trial completion date: May 2023 ➔ Nov 2022 | Trial primary completion date: May 2023 ➔ Nov 2022

Enrollment change • Trial completion • Trial completion date • Trial primary completion date • Human Immunodeficiency Virus • Infectious Disease

Safety and pharmacokinetics of escalating doses of neutralising monoclonal antibody CAP256V2LS administered with and without VRC07-523LS in HIV-negative women in South Africa (CAPRISA 012B): a phase 1, dose-escalation, randomised controlled trial. (PubMed, Lancet HIV) - "CAP256V2LS administered alone and in combination with VRC07-523LS was safe with favourable pharmacokinetics and neutralisation activity, supporting further assessment in larger clinical studies."

Journal • P1 data • PK/PD data • Fatigue • Hematological Disorders • Human Immunodeficiency Virus • Infectious Disease • Pain • Renal Disease

Study of VRC07-523LS, CAP256V2LS, and Vesatolimod, in Early Antiretroviral-treated HIV-1 Clade C-infected Women (clinicaltrials.gov) - P2a | N=25 | Recruiting | Sponsor: Gilead Sciences | Trial completion date: Feb 2024 ➔ Nov 2024 | Trial primary completion date: Feb 2024 ➔ Nov 2024

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

PHASE 1 TRIAL OF CAP256V2LS AND VRC07-523LS ANTIBODIES AMONG WOMEN IN SOUTH AFRICA (CROI 2023) - "CAP256V2LS and VRC07-523LS administered subcutaneously alone and in combination with recombinant hyaluronidase was safe and well tolerated, with detectable antibody concentrations up to 6 months post administration. CAP256V2LS is one of the most potent antibodies described to date and in combination with VRC07-523LS is predicted to provide significant coverage of global HIV strains. These data support further assessment in larger clinical studies."

Clinical • P1 data • Fatigue • Hematological Disorders • Human Immunodeficiency Virus • Infectious Disease • Pain • Renal Disease

Bispecific antibody CAP256.J3LS targets V2-apex and CD4-binding sites with high breadth and potency. (PubMed, MAbs) - "The optimized bispecific antibody, which we named CAP256.J3LS, had a half-life similar to CAP256V2LS in human FcRn knock-in mice and exhibited suitable auto-reactivity, manufacturability, and biophysical risk. CAP256.J3LS neutralized over 97% of a multiclade 208-strain panel (geometric mean concentration for 80% inhibition (IC) 0.079 μg/ml) and 100% of a 100-virus clade C panel (geometric mean IC of 0.05 μg/ml), suggesting its anti-HIV utility especially in regions where clade C dominates."

Journal • Human Immunodeficiency Virus • Infectious Disease • CD4