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

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

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

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

Engineering of HIV-1 neutralizing antibody CAP256V2LS for manufacturability and improved half life. (PubMed, Sci Rep) - "We also added the half-life extending mutation LS, which improved the in vivo persistence in animal models, but did not impact neutralization activity; we observed the same preservation of neutralization for bNAbs VRC01, N6, and PGDM1400 with LS on a 208-virus panel. The final engineered antibody, CAP256V2LS, retained the extraordinary neutralization potency of the parental antibody, had a favorable pharmacokinetic profile in animal models, and was negative in in vitro assessment of autoreactivity. CAP256V2LS has the requisite potency, developability and suitability for scale-up, allowing its advancement as a clinical candidate."

Journal • Human Immunodeficiency Virus • Infectious Disease

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

Enrollment closed • Human Immunodeficiency Virus • Infectious 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 | Not yet recruiting ➔ Recruiting

Enrollment open • Human Immunodeficiency Virus • Infectious Disease

VRC 611: Human Monoclonal Antibody (mAb) VRC-HIVMAB0102-00-AB (CAP256V2LS)Administered Via Subcutaneous and Intravenous Injection in Healthy Adults (clinicaltrials.gov) - P1 | N=20 | Recruiting | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Trial completion date: Jun 2022 ➔ Dec 2022 | Trial primary completion date: Jun 2022 ➔ Dec 2022

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

Quantification of prefusion conformation for HIV vaccine using size-exclusion chromatography. (PubMed, J Chromatogr B Analyt Technol Biomed Life Sci) - "The mAb CAP256V2LS (250 µg/mL) specific to prefusion conformation was mixed with HIV trimer (250 µg/mL) at 2:1 volume ratio, incubated at 37 °C for 30 mins and injected onto HPLC column. The percent of non-prefusion conformation was calculated based on ratio of peak area of unbound trimer and total area of control trimer sample (without mAb)."

Journal • Human Immunodeficiency Virus • Infectious Disease

Tyrosine O-sulfation proteoforms affect HIV-1 monoclonal antibody potency. (PubMed, Sci Rep) - "Interestingly, highly variable levels of 4-SO were produced by different clonal CHO cell lines, which helped the bNAb process development towards production of a highly potent CAP256V2LS clinical product with high 4-SO proteoform. This study presents powerful insight for any biotherapeutic protein development where sulfation may play an important role in product efficacy."

Journal • Human Immunodeficiency Virus • Infectious Disease