VGA039 / Star Therapeutics - LARVOL DELTA

A protein S-targeting monoclonal antibody, VGA039, improves both primary and secondary hemostatic activity of von Willebrand disease patient blood in an ex vivo vascularized hemostasis-on-a-chip (ASH 2025) - "In this study, we showed that VGA039, an anti-PS monoclonal antibody, promoted bothplatelet deposition and fibrin accumulation at sites of endothelial cell injury, thus enhancing bothprimary and secondary hemostasis that led to the restoration of hemostatic activity of VWD patient bloodin our ex vivo vascularized hemostasis-on-a-chip bleeding tests. The data presented here support recentclinical trial results in which VGA039 administration led to significant reductions in annualized bleedingrates (ABR) in VWD patients with high historic ABR (Wheeler et al., HTRS 2025). Our assessment positionsVGA039 as a promising prophylactic treatment option for patients with bleeding disorders, includingVWD."

Preclinical • Hematological Disorders • Hemophilia • PROS1

VGA039 as a protein S-targeted hemostatic promoting monoclonal antibody, promotes in-vitro thrombin generation in plasma samples from subjects across a broad range of bleeding disorders, including von Willebrand disease, hemophilia A, hemophilia B and hemophilia C (ASH 2025) - P1/2 | "In a prior single-ascending-dose clinical study in VWD, VGA039 induced marked reductionsin bleeding rates associated with VGA039 plasma concentrations ≥25 µg/mL. Here, VGA039 added toplasma samples derived from patients with Hemophilia A, Hemophilia B or Hemophilia C reversedexogenous APC mediated inhibition of thrombin generation with a similar potency and to a nearequivalent extent as plasma samples from von Willebrand Disease (including type 1-3). These data showthe broad hemostatic potential of VGA039 and support the potential clinical utility of VGA039 acrossmultiple congenital bleeding disorders."

Preclinical • Hematological Disorders • Hemophilia • Hemophilia A • Hemophilia B • Rare Diseases • PROS1

Subcutaneous, every-four-week maintenance dosing of a novel protein S antibody is well-tolerated and substantially reduces bleeding rates: Results from A phase 1/2 multidose study of VGA039 in patients with von Willebrand disease (ASH 2025) - P1/2 | "VGA039 was safe and well tolerated over multiple doses in Type 1, 2, and 3 VWD subjectsweighing 45-160.5 kg. Preliminary findings suggest substantial reductions in bleeding rates following asingle SC loading dose and every-four-week maintenance dosing schedule in patients reporting highhistorical bleed rates prior to entering the study. These data inform selection of a dosage regimenoptimized for durable bleed control with a favorable safety profile for assessment in a Phase 3 trial ofVGA039 as every-4-week subcutaneous prophylaxis for patients with VWD of all types."

Clinical • P1/2 data • Cardiovascular • Hematological Disorders • Hemophilia • PROS1

Tranexamic Acid and Desmopressin for Heavy Menstrual Bleeding and Their Impact on Iron Level Tests: The West-Central Mexican Experience (ASH 2024) - "There are other options for HMB (Blood Adv 2023; 7 : 7501-7505) : plasma derived products, recombinant vW factor, bridging therapies as emicizumab, investigational (rondoraptivon pegol, VGA039, HMB-001 and platelet inspired hemostatic nanoparticles), but these have high financial costs or are not available in clinical trial in developing countries. We recommend the use of these drugs to provide either of the treatments, as they are easy to administrate low cost access and have a good security profile. This is an original report from Mexico, no other results were find in PubMed."

Anemia • Hematological Disorders • Hemophilia • Rare Diseases

A Phase Ia Study of VGA039, a Protein S-Targeting Monoclonal Antibody, in Individuals with Von Willebrand Disease Demonstrates Concentration-Dependent Increases in Thrombin Generation for Reducing Bleeding (ASH 2024) - P1/2 | "Drug concentration data continue to support the potential for weekly or less frequent SC prophylactic dosing. Further SAD evaluation of VGA039 in VWD patients is ongoing, and future multi-dose and surgical prophylaxis investigation is planned."

Clinical • P1 data • Cardiovascular • Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases

Star Therapeutics has raised $125 million in new venture funding that will help propel its experimental blood disease drug through late-stage testing. (BioPharma Dive) - "The company spun out one subsidiary, Electra Therapeutics, and has taken its top program, VGA039, from preclinical development to a Phase 3 trial..."

Financing • Hemophilia

Rebalancing agents in hemophilia: knowns, unknowns, and uncertainties. (PubMed, Haematologica) - "Fitusiran is a small interfering RNA agent that reduces antithrombin synthesis in hepatocytes, favoring a procoagulant state. Other promising rebalancing agents are concizumab and marstacimab, which selectively bind to the K2 domain of the tissue factor pathway inhibitor, thus restoring thrombin generation. SerpinPC is a subcutaneous biological inhibitor that blocks the anticoagulant activated protein C pathway, while VGA039 is a monoclonal antibody that targets its cofactor protein S. Although the available clinical data are promising, several important challenges remain. These include the thrombotic risk of rebalancing agents, perioperative and bleeding management, availability in low-income countries, efficacy and FVIII equivalence compared to existing treatments, ideal target populations, and potential application in other hemostatic disorders. The primary aim of this review is to summarize the best available evidence on these novel rebalancing agents, while..."

Journal • Hematological Disorders • Hemophilia • Rare Diseases

VIVID-6: Study to Evaluate Subcutaneous (SC) VGA039 in Patients With Von Willebrand Disease (VWD) (clinicaltrials.gov) - P3 | N=60 | Recruiting | Sponsor: Vega Therapeutics, Inc | Not yet recruiting ➔ Recruiting

Enrollment open • Hemophilia

VIVID-6: Study to Evaluate Subcutaneous (SC) VGA039 in Patients With Von Willebrand Disease (VWD) (clinicaltrials.gov) - P3 | N=60 | Not yet recruiting | Sponsor: Vega Therapeutics, Inc

New P3 trial • Hemophilia

The anti-Protein S antibody VGA039 enhances ex vivo coagulation as assessed by thromboelastometry (ISTH 2025) - "VGA039 dose-dependently reduced the sum of CT and CFT by ~12 to 38% at the concentrations 3-200µg/mL. Table or Figure Upload"

Preclinical • Hematological Disorders • Hemophilia • Rare Diseases • PROS1

Study of VGA039 in Healthy Volunteers and Patients with Von Willebrand Disease (VIVID) (clinicaltrials.gov) - P1/2 | N=116 | Recruiting | Sponsor: Vega Therapeutics, Inc | Phase classification: P1 ➔ P1/2 | N=64 ➔ 116 | Trial completion date: Dec 2024 ➔ Dec 2029 | Trial primary completion date: Nov 2024 ➔ Dec 2029

Enrollment change • Phase classification • Trial completion date • Trial primary completion date • Hematological Disorders • Hemophilia

Phase I Study of VGA039, a Protein S-targeting Monoclonal Antibody, in Individuals with Von Willebrand Disease Demonstrates Sustained Drug Concentrations, Increased Thrombin Generation, and Decreased Bleeding Following a Single Subcutaneous Injection (EAHAD 2025) - No abstract available

Clinical • P1 data • Hemophilia

Star Therapeutics Receives FDA Fast Track Designation for VGA039 in Von Willebrand Disease (VWD) (Businesswire) - "Star Therapeutics...today announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation for VGA039 in von Willebrand disease (VWD)....It is potentially the first subcutaneous therapy that addresses all types of VWD and has a convenient dosing regimen."

Fast track • Hematological Disorders

VGA039, a novel anti-Protein S antibody, enhances ex vivo coagulation with hemophilia A blood as assessed by thromboelastometry (ISTH 2024) - "In an experimentally induced non-human primate model of von Willebrand disease featuring administration of caplacizumab and neutralizing anti-factor VIII antibody (FVIII nAb), VGA039 reduced bleeding time from mucosal cuts and prevented blood loss. The median age of the included people with hemophilia A was 28 (range 14–52) years, median factor VIII activity was 3.5 (range < 1-27) IU/dL. The mean ± SD baseline CT was 698 ± 160 seconds, and the mean ± SD CFT 301 ± 58 seconds. VGA039 significantly reduced the CT at the concentrations 6.25, 50, 100, and 200µg/mL by ~9 to 13% and significantly reduced the CFT at concentrations 6.25, 50, 100, and 200µg/mL by ~7 to 13%."

Preclinical • Hematological Disorders • Hemophilia • Rare Diseases • PROS1

VGA039, a Protein S-targeting monoclonal antibody, demonstrates in a Phase Ia healthy volunteer trial the potential of subcutaneous weekly or less frequent prophylactic dosing for bleeding disorders (ISTH 2024) - "To date, a total of 30 healthy volunteers in 4 IV and 2 SC SAD cohorts have been dosed. No adverse events related to VGA039, including thromboembolic events, DLTs, or infusion-related/injection-site reactions, have occurred. Plasma concentrations of VGA039 have increased dose dependently across the IV and SC cohorts (Figure 1)."

Clinical • P1 data • Cardiovascular • Hematological Disorders • Hemophilia

PROPHYLACTIC TREATMENT OF ACQUIRED VON WILLEBRAND DISEASE IN NON-HUMAN PRIMATES WITH VGA039, AN ANTI-PROTEIN S MONOCLONAL ANTIBODY (THSNA 2024) - "Efficacy of VGA039 was demonstrated in a novel NHP model of acquired VWD. This proof-of-concept study supports clinical evaluation of VGA039 for the treatment of VWD."

Hematological Disorders • Hemophilia • PROS1

VGA039, an anti-protein S monoclonal antibody, is prophylactically efficacious in a novel non-human primate model of acquired von Willebrand disease (WFH 2024) - No abstract available

Preclinical • Hemophilia • PROS1

New and Emerging Therapies for Women, Girls and People with the Potential to Menstruate with VWD. (PubMed, Blood Adv) - "Although currently existing treatments of antifibrinolytics, desmopressin and plasma-derived von Willebrand factor (pdVWF) replacement are considered effective, multiple studies report poor quality of life in VWD patients, especially those with heavy menstrual bleeding (HMB). We also present emerging data on emicizumab for the treatment of VWD, BT200 (rondoraptivon pegol), generalized hemostatic therapies (VGA039 and HMB-011) as well as treatments based on nanotechnology (platelet-inspired nanoparticles and KB-V13A12). We are optimistic as we move towards pivotal clinical trials for these elegant and innovative treatments."

Journal • Hematological Disorders • Hemophilia • Rare Diseases

Prophylactic Efficacy Of VGA039, An Anti-Protein S Monoclonal Antibody, In A Novel Non-Human Primate Model Of Acquired Von Willebrand Disease (ISTH 2023) - "Administration of anti-VWF or anti-FVIII alone produced minimal and/or inconsistent decreases in hemoglobin and prolongation of bleed time. In contrast, coadministration produced a severe VWD-like phenotype characterized by VWF and FVIII deficiency, decreased TG, prolonged aPTT, markedly decreased hemoglobin (Figure 1A), and prolonged bleed times (Figure 1B), demonstrating establishment of the model. Prophylactic VGA039 administration reduced the hemoglobin decrease (Figure 2A) and prevented bleed time prolongation (Figure 2B).Conclusion(s): Efficacy of VGA039 was demonstrated in a novel NHP model of acquired VWD."

Clinical • Preclinical • Hematological Disorders • Hemophilia • PROS1

Vega Therapeutics Receives FDA Orphan Drug Designation for VGA039 for the Treatment of von Willebrand Disease (Businesswire) - "Vega Therapeutics, Inc...today announced that the U.S. Food and Drug Administration (FDA) has granted the company orphan drug designation for VGA039 for the treatment of the rare bleeding disorder, von Willebrand disease (VWD)."

Orphan drug • Hematological Disorders

Study of VGA039 in Healthy Volunteers and Patients With Von Willebrand Disease (clinicaltrials.gov) - P1 | N=64 | Recruiting | Sponsor: Vega Therapeutics, Inc | Phase classification: P1a ➔ P1

Phase classification • Hemophilia

Study of VGA039 in Healthy Volunteers and Patients With Von Willebrand Disease (clinicaltrials.gov) - P1a | N=56 | Recruiting | Sponsor: Vega Therapeutics, Inc

New P1 trial • Hemophilia