latarcibart (VGA039) / Incyte - LARVOL DELTA

Latarcibart is being evaluated in a global Phase 3, single-arm crossover study (VIVID-6) assessing the safety and efficacy of once-monthly SC administration of latarcibart as prophylaxis for bleeding in patients with all types of VWD. (Businesswire) - "Topline data from the VIVID-6 study are anticipated in early 2029."

P3 data: top line • Genetic Disorders • Hematological Disorders

In July, the Company completed its acquisition of Vega Therapeutics, Inc. (Businesswire) - "The acquisition adds latarcibart, a novel investigational monoclonal antibody in Phase 3 development for patients with VWD, to its late-stage pipeline."

M&A • Genetic Disorders • Hematological Disorders

Qualitative Study Exploring the Lived Experiences of Adolescents and Adults with von Willebrand Disease Treated with VGA039 and Their Families in the VIVID-3 Phase 1/2 Clinical Study (ISTH 2026) - "Table or Figure Upload (1) Table 1. Representative quotes from participants in the VGA039 qualitative study Page 2 DOI*10.1016/j.rpth.2026.106039"

Clinical • P1/2 data • Hemophilia

Pharmacokinetic and Pharmacodynamic Characterization of VGA039, a Protein S-targeting Monoclonal Antibody, Supports Subcutaneous Every-4-Week Dosing for Routine Prophylaxis in Phase 3 VWD Trial (ISTH 2026) - P3 | "These PK/PD findings establish and confirm the popPK model used for dose and regimen selection for VGA039 as a routine prophylactic therapy being investigated in the ongoing Phase 3 VWD trial. DOI*10.1016/j.rpth.2026.104822"

P3 data • PK/PD data • Hemophilia • PROS1

Subcutaneous Four-Week Dosing of the Novel Protein S Antibody VGA039 Demonstrates Safety and Clinically Meaningful Bleed Reduction in Patients with Von Willebrand Disease: Phase 1/2 Multi-Dose Study Results (ISTH 2026) - P1/2, P3 | "These findings support continued clinical development in the ongoing Phase 3 VWD trial (NCT07115004). Table or Figure Upload (1) Reductions in Bleeding Rates in Participants who Completed the VGA039 Treatment Period DOI*10.1016/j.rpth.2026.103621"

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

Incyte said on Monday it will buy Vega ​Therapeutics, a wholly owned subsidiary of privately held Star Therapeutics, in a deal ‌worth up to $2 billion, expanding its pipeline for blood disorder therapies (Reuters) - "The deal includes $1.25 billion cash upfront and up to $750 million in milestone payments, the U.S. drugmaker said....The ​acquisition gives Incyte a late-stage drug candidate for bleeding disorders....Its lead experimental ​drug, VGA039, is a monoclonal antibody being tested in patients with von Willebrand disease, the most common inherited bleeding disorder, in which blood does not clot properly due to ​the absence of a protein....VGA039 is in a late-stage trial, with results expected in early 2029 and a potential launch after Jakafi ​is expected to ​lose patent protection....The transaction is expected to close in the third quarter of ​2026."

M&A • P3 data • Hematological Disorders

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 | N=16 ➔ 60

Enrollment change • Trial initiation date • Hemophilia

Star Therapeutics Receives FDA Rare Pediatric Disease and Breakthrough Therapy Designations for VGA039 in Von Willebrand Disease Prophylaxis (Businesswire) - "This designation is supported by interim data from the Phase 1/2 multidose study of VGA039 in adult and adolescent patients with VWD."

Breakthrough therapy • FDA event • Hematological Disorders

VIVID-6: Study to Evaluate Subcutaneous (SC) VGA039 in Patients With Von Willebrand Disease (VWD) (clinicaltrials.gov) - P3 | N=16 | 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 | Recruiting | Sponsor: Vega Therapeutics, Inc

Trial initiation date • Hemophilia

Subcutaneous Four-Week Dosing of the Novel Protein S Antibody VGA039 Demonstrates Safety and Clinically Meaningful Bleed Reduction in Patients with Von Willebrand Disease: Phase 1/2 Multi-Dose Study Results (THSNA 2026) - P1/2, P3 | "VGA039 administered subcutaneously every four weeks was safe, well tolerated, and associated with clinically meaningful reductions in bleeding across VWD subtypes in this interim analysis. These findings support the ongoing Phase 3 trial (NCT07115004). No part of this publication may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the author."

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

VGA039-CP002: Phase 3 study of VGA039 prophylaxis in adolescent and adult patients with von Willebrand Disease (clinicaltrialsregister.eu) - P2/3 | N=14 | Not yet recruiting | Sponsor: Vega Therapeutics Inc.

New P2/3 trial • Hemophilia

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