VH3810109 / GSK, ViiV Healthcare, National Institute of Allergy and Infectious Diseases - LARVOL DELTA

Population Pharmacokinetics, Antidrug Antibodies and Exposure-Response of VH3810109 (N6LS) in Virologically Suppressed Adults Living With HIV From the Phase 2b EMBRACE Study (EACS 2025) - "In EMBRACE, N6LS was administered 60 mg/kg intravenously (IV) or 3000 mg subcutaneously (SC) with rHuPH20 Q4M together with approved monthly (Q1M) cabotegravir as a 2-drug combination in virologically suppressed adults. Conclusions : A low occurrence of plasma HIV-1 RNA ≥50 c/mL at Month 6 was observed in EMBRACE. This modeling i) indicates multiple factors contribute to the observations of plasma HIV-1 RNA ≥50 c/mL at Month 6; ii) supports moving from mg/kg to flat IV dosing; and iii) demonstrates ADAs had no impact following Q4M dosing in virally suppressed participants"

Clinical • P2b data • PK/PD data • Human Immunodeficiency Virus • Infectious Disease • CD4

Safety and Tolerability of N6LS Administered Intravenously or Subcutaneously: Promising Results From Part 1 of the EMBRACE Study (EACS 2025) - "From both a participant experience and tolerability standpoint, N6LS was deemed highly acceptable, with few ISRs observed with IV administration. These data support the progression of IV N6LS administered twice yearly in part 2 of EMBRACE."

Clinical • Human Immunodeficiency Virus • Infectious Disease • CD4 • CD8

Evaluation of VH3810109 (N6LS) and Cabotegravir Long-Acting, Dual Modality, Injections for HIV Treatment: People With HIV and Staff Perspectives (EACS 2025) - "PWH reported feeling healthier and more liberated with the longer intervals between treatments, while staff appreciated the ease and comfort of administration for both IV and SC. LA and ULA treatment (≥Q4M) have the potential to transform lives of PWH."

Human Immunodeficiency Virus • Infectious Disease

Cutoff for Baseline Phenotypic Sensitivity to VH3810109 (N6LS) Did Not Impact Occurrence of Confirmed Virologic Failure in the Phase 2b EMBRACE Study (EACS 2025) - "Conclusions : In this virologically suppressed population, 72% of participants with results met inclusion criteria for N6LS phenotypic sensitivity. Occurrence of CVF was not attributed to the phenotypic sensitivity cutoff or N6LS exposures; identifying additional risk factors requires further investigation."

P2b data • Human Immunodeficiency Virus • Infectious Disease • CD4

VH3810109 Efficacy, Safety, Pharmacokinetics, and Incidence of Anti-drug Antibodies in Adults With HIV-1 Naive to Antiretroviral Therapy: BANNER Study Results. (PubMed, J Infect Dis) - P2 | "N6LS was efficacious and generally safe, supporting further development of N6LS dosed IV or SC for the treatment of HIV-1 (ClinicalTrials.gov, NCT04871113)."

Clinical • Journal • PK/PD data • Human Immunodeficiency Virus • Infectious Disease • CD4

The Clinical Development of VH3810109 (N6LS): Advancing Ultra-Long-Acting HIV Treatment into the Future (IDWeek 2025) - No abstract available

Clinical • Human Immunodeficiency Virus • Infectious Disease

VH3810109 (N6LS) broadly neutralizing antibody safety, pharmacokinetics, and anti-drug antibody incidence in adults without HIV: phase 1 SPAN study results. (PubMed, Antimicrob Agents Chemother) - P1 | "N6LS administered IV or SC + rHuPH20 had a favorable safety profile and was well tolerated. Results support the ongoing development of N6LS 3,000 mg SC + rHuPH20 and 60 mg/kg IV into phase 2b.CLINICAL TRIALSRegistered at ClinicalTrials.gov (NCT05291520)."

Journal • P1 data • PK/PD data • Dermatology • Human Immunodeficiency Virus • Infectious Disease • Pain • CD4

ENTRANCE: A Study to Investigate the Use of VH3810109 With or Without Fostemsavir (FTR) to Reduce the Size and Activity of the Viral Reservoir in People Living With HIV (clinicaltrials.gov) - P1 | N=100 | Recruiting | Sponsor: ViiV Healthcare | Not yet recruiting ➔ Recruiting

Enrollment open • Human Immunodeficiency Virus • Infectious Disease

ENTRANCE: A Study to Investigate the Use of VH3810109 With or Without Fostemsavir (FTR) to Reduce the Size and Activity of the Viral Reservoir in People Living With HIV (clinicaltrials.gov) - P1 | N=100 | Not yet recruiting | Sponsor: ViiV Healthcare

New P1 trial • Human Immunodeficiency Virus • Infectious Disease

Safety and pharmacokinetics of N6LS, a broadly neutralising monoclonal antibody for HIV: a phase 1, open-label, dose-escalation study in healthy adults. (PubMed, Lancet HIV) - P1 | "N6LS showed a promising safety and pharmacokinetics profile while retaining its potent neutralisation characteristics in serum, making it a promising candidate for inclusion in HIV-1 prevention and therapeutic combination strategies. The addition of EDP can enable safe subcutaneous administration of higher doses and larger volumes of N6LS, supporting additional methods for prophylactic and therapeutic bNAb administration."

Journal • P1 data • PK/PD data • Allergy • Dermatology • Human Immunodeficiency Virus • Immunology • Infectious Disease • Pain

Preclinical Evaluation of Effector Function-Enhanced Variants of N6 bNAb (CROI 2025) - P2 | "The contribution of native effector functions to the antiviral activity of N6LS has previously been explored (Wang, et al...Conclusions Multiple variants of the N6 bnAb displayed suitable developability properties and varying degrees of effector function enhancement in vitro. Four variants were identified for continued in vitro and in vivo assessment, including initiation of stable cell lines for potential manufacture."

Preclinical • Human Immunodeficiency Virus • Infectious Disease • FCGR2A • FCGR3A

VH3810109 (N6LS) Efficacy and Safety in Adults Who Are Virologically Suppressed: The EMBRACE Study (CROI 2025) - "Grade ≥3 N6LS-related infusion site reactions (ISRs) were reported in 0/50 (0%) participants receiving N6LS 60 mg/kg IV and 7/49 (14%) receiving N6LS 3000 mg SC + rHuPH20; mean (SD) duration of all ISRs was 2.0 (0.8) and 6.4 (5.2) days with N6LS dosed IV or SC + rHuPH20, respectively. Conclusions N6LS administered IV or SC + rHuPH20 every 4 months in combination with monthly CAB LA maintained viral suppression in most adults who were sensitive to N6LS at baseline, with tolerability favoring IV N6LS."

Clinical • Late-breaking abstract • Human Immunodeficiency Virus • Infectious Disease • CD4

EMBRACE: A Study to Investigate the Virologic Efficacy and Safety of VH3810109 + Cabotegravir Compared to Standard of Care (SOC) in Male and Female Adults Living With Human Immunodeficiency Virus (HIV) (clinicaltrials.gov) - P2 | N=135 | Active, not recruiting | Sponsor: ViiV Healthcare | Trial completion date: Jun 2026 ➔ Jan 2029

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

VH3810109 (N6LS) administration dose‐responsively enhances anti‐HIV antibody‐dependent cellular cytotoxicity (ADCC) and antibody‐dependent cellular phagocytosis (ADCP) activity in ex vivo models (HIV-Glasgow 2024) - "We demonstrate that VH3810109 has immunological activities ex vivo that correlate with clinically relevant virological outcomes. These data underscore the importance of the immunological activities of bNAbs and support continued development of these agents as direct-acting antiviral agents as well as components of remission/cure regimens."

Preclinical • Human Immunodeficiency Virus • Infectious Disease • GLI2

Correlation of baseline phenotypic sensitivity with virological response to VH3810109 (N6LS) in BANNER (HIV-Glasgow 2024) - "Baseline N6LS viral sensitivity correlated with magnitude and duration of antiviral response, which were linked to dose and resulting N6LS serum concentration. Other factors (baseline VL, baseline CD4+ T-cell count, inherent control by the individual) may impact response to N6LS. Overall, 81% of participants with successful phenotypic testing met protocol-defined N6LS sensitivity criteria for enrolment in the ongoing phase IIb study."

Human Immunodeficiency Virus • Infectious Disease • CD4

Potent and broadly neutralizing HIV-1 antibodies with improved pharmacokinetics achieved by negative supercharging (AIDS 2024) - "While confirmation is needed regarding whether the enhanced potency observed in in vitro pseudovirus assays translates to improved protection in non-human primates, the conservation of the CH1 and CL domains in IgG1 suggests that these substitutions in the CH1 and CL, along with the addition of acidic tails, have the potential to enhance the PK and potency of various therapeutic antibodies."

Late-breaking abstract • PK/PD data • Human Immunodeficiency Virus • Infectious Disease

EMBRACE: A Study to Investigate the Virologic Efficacy and Safety of VH3810109 + Cabotegravir Compared to Standard of Care (SOC) in Male and Female Adults Living With Human Immunodeficiency Virus (HIV) (clinicaltrials.gov) - P2 | N=99 | Active, not recruiting | Sponsor: ViiV Healthcare | N=45 ➔ 99

Combination therapy • Enrollment change • Human Immunodeficiency Virus • Infectious Disease • CD4

EMBRACE: A Study to Investigate the Virologic Efficacy and Safety of VH3810109 + Cabotegravir Compared to Standard of Care (SOC) in Male and Female Adults Living With Human Immunodeficiency Virus (HIV) (clinicaltrials.gov) - P2 | N=45 | Active, not recruiting | Sponsor: ViiV Healthcare | Recruiting ➔ Active, not recruiting | N=150 ➔ 45

Combination therapy • Enrollment change • Enrollment closed • Human Immunodeficiency Virus • Infectious Disease • CD4

High-Dose VH3810109 (N6LS) ± Recombinant Human Hyaluronidase PH20: Phase I SPAN Study Safety Results (CROI 2024) - P1 | "High-dose N6LS, when given IV or SC + rHuPH20, was generally safe and well tolerated in this study. These results support the ongoing clinical development of N6LS 3000 mg SC + rHuPH20 and N6LS 60 mg/kg IV into phase IIb."

Clinical • P1 data • Dermatology • Human Immunodeficiency Virus • Infectious Disease • Pain • CD4

VH3810109 (N6LS) in Adults With HIV-1 Who Are ART-Naive-: Phase IIa BANNER Efficacy Data (CROI 2024) - "Robust antiviral activity was observed after IV and SC administration of N6LS; response was correlated with N6LS exposure. Response with SC vs IV dosing was lower and likely due to differences in BL susceptibility, serum antibody levels, and slower time to reach Cmax. Overall, N6LS led to dose-dependent declines in VL consistent with antiviral activity reported for other bNAbs."

Clinical • P2a data • Human Immunodeficiency Virus • Infectious Disease • CD4

EMBRACE: A Study to Investigate the Virologic Efficacy and Safety of VH3810109 + Cabotegravir Compared to Standard of Care (SOC) in Male and Female Adults Living With Human Immunodeficiency Virus (HIV) (clinicaltrials.gov) - P2 | N=150 | Recruiting | Sponsor: ViiV Healthcare | Phase classification: P2b ➔ P2

Combination therapy • Phase classification • Human Immunodeficiency Virus • Infectious Disease • CD4

A Study to Evaluate the Antiviral Effect, Safety and Tolerability of GSK3810109A in Viremic Human Immunodeficiency Virus (HIV)-1 Infected Adults (clinicaltrials.gov) - P2 | N=63 | Completed | Sponsor: ViiV Healthcare | Active, not recruiting ➔ Completed | Phase classification: P2a ➔ P2

Phase classification • Trial completion • Human Immunodeficiency Virus • Infectious Disease • CD4

Pharmacokinetics/Pharmacodynamics and Virological Activity of VH3810109 (N6LS) in Antiretroviral-Naive Viremic Adults From the Phase IIa BANNER Study (EACS 2023) - "Baseline viral sensitivity to N6LS was an important predictor of drug exposure required to achieve response. This modeling demonstrates N6LS has a viable PK/PD profile whether administered IV or SC and has been successfully applied to support dose selection for the planned Phase IIb study."

Clinical • P2a data • PK/PD data • Human Immunodeficiency Virus • Infectious Disease • CD4

Pharmacokinetics/Pharmacodynamics and Virological Activity of VH3810109 (N6LS) in Antiretroviral-Naive Viremic Adults From the Phase IIa BANNER Study (EACS 2023) - "Baseline viral sensitivity to N6LS was an important predictor of drug exposure required to achieve response. This modeling demonstrates N6LS has a viable PK/PD profile whether administered IV or SC and has been successfully applied to support dose selection for the planned Phase IIb study."

Clinical • P2a data • PK/PD data • Human Immunodeficiency Virus • Infectious Disease • CD4

Safety and Tolerability of VH3810109 (N6LS) Among Antiretroviral Therapy–Naive Adults Living With HIV-1: Results From the Monotherapy Phase of the Phase IIa BANNER Study (EACS 2023) - "No clinically significant safety trends in vital signs, electrocardiograms, or laboratory tests were observed across dose groups. Conclusions : N6LS was well tolerated when given IV or SC, with few drug-related AEs, including mild ISRs, and no serious AEs."

Clinical • Monotherapy • P2a data • Human Immunodeficiency Virus • Infectious Disease • CD4