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

CAPRISA 012C: A Phase II Trial to Assess Extended Safety and Tolerability of Subcutaneous CAP256V2LS and VRC07-523LS in HIV- Negative Women (clinicaltrials.gov) - P2 | N=990 | Completed | Sponsor: Centre for Infectious Disease Research in Zambia

New P2 trial • Human Immunodeficiency Virus • Infectious Disease

Safety and preliminary efficacy of 6-monthly subcutaneous CAP256V2LS plus VRC07-523LS for HIV prevention in African women: results of the CAPRISA 012C phase 2 randomised controlled trial (AIDS 2026) - "Fixed-dose subcutaneous CAP256V2LS plus VRC07-523LS was safe but not effective in reducing overall HIV incidence. Higher than expected bnAb resistance may explain the lack of overall efficacy as there was a trend towards protection for viruses sensitive to one or both bnAbs. Matching bnAbs with circulating viruses will be important for future bnAb studies."

Clinical • Late-breaking abstract • P2 data • Human Immunodeficiency Virus • Infectious Disease

Safety and virological outcomes of CAP256V2LS and VRC07-523LS administered at ART initiation with analytical treatment interruption: preliminary results from the NeutART HIV cure trial (AIDS 2026) - "Administration of CAP256V2LS and VRC07-523LS at ART initiation was safe and generally well tolerated. Viral rebound occurred rapidly during ATI among most participants, with similar VL kinetics across groups. These findings provide important early data on the feasibility and biological impact of administering bnAbs at ART initiation."

Clinical • Human Immunodeficiency Virus • Infectious Disease • CD4

Cervicovaginal microbiome diversity was not associated with mucosal pharmacokinetics of systemically delivered HIV broadly neutralizing antibodies. (PubMed, Sci Rep) - "Mucosal concentrations of CAP256V2LS were measured from Soft-cup® cervicovaginal fluid using the Meso Scale Discovery (MSD) platform with electrochemiluminescence (ECL) detection...In this exploratory sub-analysis, cervicovaginal microbiome composition was not clearly associated with differences in mucosal concentrations of systemically administered bNAbs. These findings suggest that systemic bNAb delivery may achieve measurable genital tract exposure across diverse vaginal microbial communities; however, larger studies incorporating inferential pharmacokinetic and immunological analyses are needed to confirm these observations and exclude subtle microbiome-associated effects."

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

Monitoring broadly neutralising HIV antibody concentrations using microsampling on dried blood spots in infants. (PubMed, J Infect) - "DBS microsampling allows accurate bNAb concentration measure in neonates, which will facilitate on-going paediatric clinical trials and possible subsequent monitoring in adults with home-sampling if deployed at scale."

Journal • Human Immunodeficiency Virus • Infectious Disease • Pediatrics

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