zemocimig (RG6512) / Roche - LARVOL DELTA

ZEBRHA 3: Clinical Trial of NXT007 for the Prophylactic Treatment of Hemophilia A in Infants and Children (clinicaltrials.gov) - P3 | N=50 | Not yet recruiting | Sponsor: Hoffmann-La Roche

New P3 trial • Hematological Disorders • Hemophilia • Hemophilia A • Pediatrics • Rare Diseases

Mechanism of action and impact on thrombin generation of denecimig (Mim8), emicizumab, and zemocimig (NXT007): comparative analysis using sequence-identical analogs. (PubMed, Res Pract Thromb Haemost) - "Activated factor VIII (FVIIIa) mimetic antibodies restore hemostasis in hemophilia A by bridging FIXa and FX. These data indicate distinct mechanistic strategies among the 3 FVIIIa mimetics, with efficient complex assembly for emicizumab-SIA and zemocimig-SIA versus lower-affinity assembly but higher catalytic activity for denecimig. Despite these differences, zemocimig-SIA and denecimig exhibit comparable thrombin generation potential, supporting similar improvement in hemostatic potential relative to emicizumab-SIA."

Clinical • Journal • Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases

MAD: A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of NXT007 in Persons With Severe or Moderate Hemophilia A (clinicaltrials.gov) - P1/2 | N=60 | Recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Jun 2030 ➔ Dec 2033 | Trial primary completion date: Jun 2030 ➔ Dec 2033

Trial completion date • Trial primary completion date • Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases

ZEBRHA 2: A Clinical Study to Evaluate the Effects of NXT007 Compared to Emicizumab Prophylaxis in People With Hemophilia A (clinicaltrials.gov) - P3 | N=360 | Recruiting | Sponsor: Hoffmann-La Roche | Not yet recruiting ➔ Recruiting

Enrollment open • Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases

NXT007 prophylaxis in people with hemophilia A with or without factor VIII inhibitors: Combined analysis of two Phase I/II multiple-ascending-dose studies (ISTH 2026) - P1/2 | "Background NXT007, a next-generation bispecific antibody based on emicizumab that mimics activated factor (F)VIII function in people with hemophilia A (HA), was investigated in two Phase I/II, open-label, non- randomized, multicenter, multiple-ascending-dose (MAD) studies: one in Asia (NXTAGE Part B; jRCT2080224835), one Global (NCT05987449). Safety summary Table or Figure Upload (2) Figure. Treated bleeding rates* Page 3 DOI*10.1016/j.rpth.2026.103470"

P1/2 data • Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases

Assessment of the Bleeding Phenotype Normality in People with Hemophilia A Treated with NXT007 Prophylaxis: Analysis of All-Bleed Data Comparing with Healthy Volunteers within the NXTAGE Study (ISTH 2026) - "Background NXT007, an activated factor VIII-mimetic bispecific antibody engineered based on emicizumab, showed low annualized bleeding rates (ABRs) for treated bleeds in people with hemophilia A (PwHA) in a phase I/II study (NXTAGE). (Funded by Chugai Pharmaceutical Co., Ltd.) Table or Figure Upload (1) Table1. Summary of All Bleeds Page 2 DOI*10.1016/j.rpth.2026.104804"

Clinical • Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases

Major Surgeries in People with Hemophilia A under NXT007 Prophylaxis: Experience from NXTAGE Phase I/II Study (ISTH 2026) - "Background NXT007 is an investigational, next-generation, bispecific antibody, based on emicizumab and optimized to provide increased activated FVIII-mimetic activity...Perioperatively, oral tranexamic acid was used but not coagulation factor products...These findings support hemostatic normalization with NXT007, although further accumulation of surgical cases is warranted. Funding: Chugai Pharmaceutical DOI*10.1016/j.rpth.2026.103471"

P1/2 data • Surgery • Hematological Disorders • Hemophilia • Hemophilia A • Orthopedics • Rare Diseases

ZEBRHA 2: A Clinical Study to Evaluate the Effects of NXT007 Compared to Emicizumab Prophylaxis in People With Hemophilia A (clinicaltrials.gov) - P3 | N=360 | Not yet recruiting | Sponsor: Hoffmann-La Roche

New P3 trial • Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases

WO45886: A Clinical Study to Evaluate the Effects of NXT007 Compared to Factor VIII Prophylaxis in People With Hemophilia A (clinicaltrialsregister.eu) - P2/3 | N=42 | Not yet recruiting | Sponsor: F. Hoffmann-La Roche AG

New P2/3 trial • Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases

NXT007 Prophylaxis in People With Hemophilia a With/Without Inhibitors: A Global Phase I/II Study (ASPHO 2026) - P1/2 | "Background: NXT007 is a next-generation bispecific antibody, based on emicizumab, that mimics cofactor function of activated factor (F)VIII in people with hemophilia a (PwHA). NXT007 had a favorable safety profile at all doses, with low overall treated bleed ABRs. ADAs did not impact pharmacokinetics. These data support progression to Phase III trials."

Clinical • P1/2 data • Hematological Disorders • Hemophilia • Hemophilia A • Mood Disorders • Rare Diseases

Regarding NXT007, we will initiate two Phase III trials in Q2, aiming for a regulatory filing in 2028. (Chugai Press Release)

Filing • New P3 trial • Hemophilia A

FVIIIa Mimetics: New Approaches and Next-Generation Initiatives. (PubMed, Haemophilia) - "Emicizumab has revolutionized hemophilia A care, yet limitations regarding the "ceiling" of hemostatic efficacy (equivalent to mild hemophilia) and global access persist...Mim8 (denecimig) demonstrated superiority over prior prophylaxis in the FRONTIER 2 phase 3 study, offering flexible weekly to monthly dosing options. NXT007, engineered with FAST-Ig technology to incorporate dual light chains, has shown potential to achieve non-hemophilic coagulation ranges in recent Phase 1/2 studies...While acknowledging their potential to reduce treated bleeds, we provide a critical appraisal of their limitations, particularly regarding the lack of sensitive joint health monitoring and the risk of subclinical breakthrough bleeding. This review provides a comprehensive roadmap for advancing the standard of care while addressing global equity."

Journal • Review • Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases

ZEBRHA 1: A Clinical Study to Evaluate the Effects of NXT007 Compared to Factor VIII Prophylaxis in Participants With Hemophilia A (clinicaltrials.gov) - P3 | N=126 | Recruiting | Sponsor: Hoffmann-La Roche | Not yet recruiting ➔ Recruiting

Enrollment open • Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases

NXT007 prophylaxis in people with hemophilia A with or without FVIII inhibitors: A global Phase I/II multiple-ascending-dose study (THSNA 2026) - P1/2 | "Introduction: NXT007 is a next-generation bispecific antibody, based on emicizumab, that mimics the cofactor function of activated factor (F)VIII in people with hemophilia A (PwHA). NXT007 had a favorable safety profile at all doses. Overall treated bleed ABR was low. The presence of ADAs did not impact pharmacokinetics."

Clinical • P1/2 data • Hematological Disorders • Hemophilia • Hemophilia A • Mood Disorders • Rare Diseases

Role of Bispecific Antibody in Hemophilia (ICKSH 2026) - "This represented not only a remarkable scientific achievement but also a poten tial solution for effective prophylactic therapy in people with hemophilia who have developed anti -FVIII alloantibodies (PWHI), since the activity of the therapeutic molecule is not affected by anti -FVIII inhibitors due to the lack of homology between the sequences of emicizumab and FVIII. A first -in-human study of NXT007, a next -generation, activated factor VIII -mimetic bispecific antibody, in healthy participants . J Thromb Haemost 2025; 23: 3098 -3110 ."

Hematological Disorders • Hemophilia • Hemophilia A • Immunology • Inflammation • Rare Diseases

Chugai and Roche Advance NXT007 Into Phase III to Challenge Emicizumab in Hemophilia A (TipRanks) - "The trial tests NXT007, a next generation antibody given under the skin, against emicizumab, now a leading prophylaxis for Hemophilia A....The study is interventional and randomized, so patients are assigned by chance to either NXT007 or emicizumab for a head to head comparison. It uses a parallel, open label design, which means both doctors and patients know which drug they receive, and the main goal is to judge treatment benefit in regular clinical practice."

Trial status • Hemophilia A

Next-generation FVIIIa-mimetic bispecific antibody NXT007: evaluation in preclinical models of hemostasis and thrombosis. (PubMed, Blood Adv) - "In a ferric chloride carotid injury model, the administration of NXT007 and emicizumab at plasma concentrations of ∼20 to 200 μg/mL had no effect on maximum blood flow reduction, indicating that they do not present a prothrombotic profile in this model. Overall, our data support the ongoing clinical evaluation of NXT007 and suggest that it can substantially improve therapeutic efficacy for PwHA."

Journal • Preclinical • Cardiovascular • Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases • Thrombosis

Factor-VIII mimetic bispecific antibodies for the treatment of hemophilia A: an update. (PubMed, Expert Rev Clin Pharmacol) - "Emicizumab is a bispecific antibody that mimics FVIII activity, reducing bleeds in people with hemophilia A (PwHA)...Other FVIII-mimetic bispecific antibodies are in clinical trials (Mim8 and NXT007)...Despite advances, challenges remain in monitoring activity, managing breakthrough bleeds, and understanding non-hemostatic FVIII roles. As long-acting, subcutaneous agents mature, they may redefine care, enabling personalized, safer, and more accessible prophylaxis across the lifespan."

Journal • Review • Hematological Disorders • Hemophilia • Hemophilia A • Musculoskeletal Diseases • Rare Diseases

NXT007 Suggests Favorable Tolerability and Efficacy in Phase I/II Study for Hemophilia A Following Direct Switch from Emicizumab without Washout Period (Chugai Press Release) - "Data presented were from Part C, a multiple ascending dose part of the study in people aged 12 to <65 years with hemophilia A with or without factor VIII inhibitors who have been receiving continuous emicizumab treatment for at least 12 weeks...NXT007 was well tolerated when switching from emicizumab. No thromboembolic events were observed, the frequency of adverse events did not increase in a dose-dependent manner, and there were no adverse events leading to treatment discontinuation or NXT007-related serious adverse events. Among NXT007-related adverse events, injection site reactions (14.3%) were most commonly reported, all of which were mild."

P1/2 data • Hemophilia A

ZEBRHA 1: A Clinical Study to Evaluate the Effects of NXT007 Compared to Factor VIII Prophylaxis in Participants With Hemophilia A (clinicaltrials.gov) - P3 | N=126 | Not yet recruiting | Sponsor: Hoffmann-La Roche

New P3 trial • Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases

NXTAGE: a phase 1/2 study of NXT007 to assess safety, pharmacokinetics, and efficacy in hemophilia A without inhibitors. (PubMed, Blood) - "Pharmacokinetics-affecting NXT007 ADAs were observed in two participants, including the participant in B1 who discontinued. NXTAGE Part B demonstrates that NXT007 could provide non-hemophilic coagulation activity in PwHA, with a less burdensome dose regimen than currently available therapies."

Journal • P1/2 data • PK/PD data • Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases

Ex vivo evaluation of the procoagulant effect of NXT007 prophylaxis in people with Hemophilia A without factor VIII inhibitors: Phase I/II study (NXTAGE) (ASH 2025) - No abstract available

P1/2 data • Preclinical • Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases

Pharmacodynamic biomarkers in people with hemophilia A receiving multiple ascending doses of NXT007 (ASH 2025) - P1/2 | "NXT007 was engineered and optimized based on emicizumab. PD markers were well correlated with NXT007 concentrations and demonstrated stableactivity throughout the maintenance-dosing period, while safety biomarkers remained unaffected. InPwHA receiving prophylaxis with NXT007, the TG peak height during the steady state was in the non-hemophilia range and comparable to that obtained in participants with FVIII levels in the normal range."

Biomarker • PK/PD data • Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases • SPDEF

Ex vivo evaluation of the procoagulant effect of NXT007 prophylaxis in people with Hemophilia A without factor VIII inhibitors: Phase I/II study (NXTAGE) (ASH 2025) - "Introduction:NXT007, an emicizumab-based next-generation bispecific antibody, mimics the cofactor function ofactivated factor VIII (FVIII) and has higher FVIII-mimetic activity and a longer half-life compared toemicizumab. These results suggest that NXT007 has the potential to provide a non-hemophilic range of coagulationactivity in PwHA."

P1/2 data • Preclinical • Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases

Effects and interferences of NXT007, a novel bispecific antibody, on coagulation assays (ASH 2025) - "As expected based on its mode of action, and similar to emicizumab, NXT007 had a verystrong effect on aPTT that resulted in interference with all aPTT-based assays. NXT007 also affected PT atthe supratherapeutic concentration of 100 µg/mL, potentially due to inhibition of FX. PT was also affectedin samples with an already increased INR."

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