RG6512 / Roche - LARVOL DELTA

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

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

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

NXT007 prophylaxis in people with hemophilia A with or without FVIII inhibitors: A global Phase I/II multiple-ascending-dose study (ASH 2025) - P1/2 | "Background : NXT007 is a next-generation bispecific antibody, based on emicizumab, that mimics thecofactor function of activated factor (F)VIII to restore intrinsic tenase activity in people with hemophilia A(PwHA). NXT007 was well tolerated, with a tolerable safety profile in all dose cohorts. Treated bleedABRs were low; one pt per cohort experienced a treated bleed in the maintenance period, except for onenotable outlier in cohort 3 with multiple bleeds. Presence of ADA had no impact on PK."

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

NXT007 enhances in vitro coagulation potential in the coexistence of emicizumab in hemophilia A through distinct complex formation. (PubMed, Res Pract Thromb Haemost) - "NXT007 enhanced TG capacity of HA plasma in vitro in the coexistence of emicizumab without an abnormal synergistic increase or reduction in coagulation potential, consistent with their competitive antigen binding. These findings suggest that switching from emicizumab to NXT007 can be achieved without emicizumab washout."

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

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, administration of NXT007 and emicizumab at plasma concentrations ~20-200µg/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 has potential to substantially improve therapeutic efficacy for PwHA."

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

Haemophilia A (Roche Press Release) - "Hemlibra (emicizumab): New post-marketing data from the Beyond ABR study show that, in the first year after switching to Hemlibra prophylaxis from factor VIII prophylaxis, people with various levels of baseline joint impairment had low bleeding rates, associated with overall improvements in joint health, and a shift towards higher activity levels...NXT007: Positive phase I/II results, including new data from a global study in people with haemophilia A with and without factor VIII inhibitors....SPK-8011QQ: Pre-clinical data on Roche’s next-generation investigational AAV gene therapy, show significantly enhanced haemostatic potency compared with SPK-8011 (dirloctocogene samoparvovec) in ex vivo and in vivo mouse models. Findings support the ongoing evaluation of SPK-8011QQ, furthering previous learnings on the safety and durability of SPK-8011, with phase IIb study initiation planned for 2026."

Clinical data • New P2b trial • Preclinical • Hemophilia A

Preclinical Evaluation of NXT007 Using in Vitro and In Vivo Models of Hemostasis and Thrombosis (ASH 2024) - "The molecule was developed by optimizing the framework of emicizumab to increase FVIIIa-mimetic activity and half-life, with the goal of improving potency, efficacy and dosing convenience. Further, there was no evidence of hypercoagulability or prothrombotic effects at anticipated therapeutic or supratherapeutic concentrations. Overall, our preclinical data support the ongoing clinical evaluation of NXT007 and suggest that it has the potential to bring even greater benefit to PwHA."

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

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 2032 ➔ Jun 2030 | Trial primary completion date: Jun 2032 ➔ Jun 2030

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

A First-in-Human Study of NXT007, a Next-Generation, Activated Factor VIII-Mimetic Bispecific Antibody, in Healthy Participants. (PubMed, J Thromb Haemost) - "A single subcutaneous injection of NXT007 was well tolerated without occurrence of thrombotic events. The long half-life, pharmacological effect, and safety profile supported study progression to the subsequent multiple-ascending-dose parts of the NXTAGE study in PwHA."

Journal • P1 data • Dermatology • Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases

Phase I/II Study in Hemophilia A Suggests NXT007 May Have the Potential to Provide Hemostatic Normalization (Chugai Press Release) - P1/2 | N=60 | NCT05987449 | Sponsor: Hoffmann-La Roche | "The presented data was from Part B of the study, which was the multiple ascending dose part including Hemlibra-naïve people with severe hemophilia A without FVIII inhibitors aged ≥12 years and <65 years. Participants were included in 4 cohorts, and following 4- to 6-week loading doses, they received subcutaneous maintenance doses of NXT007 at different dosage levels every 4 weeks. The primary analysis was conducted when at least 6 participants had completed 16 weeks of NXT007 treatment in all Part B cohorts.In Part B, dose dependent increase of NXT007 plasma concentration was observed. Plasma concentrations in the high dose cohorts B-3 and B-4 reached the predicted normal range of FVIII–equivalent activity based on preclinical data."

P1/2 data • Hemophilia A

NXT007 exerts in vitro cofactor activity in the co-presence of emicizumab with overlapping epitopes (ISTH 2025) - "In the simulation with emicizumab at 50 μg/mL, (1) the formation of the FIX-NXT007-FX complex was minimally affected and (2) at 10 μg/mL of NXT007, the FIX-NXT007-FX complex was formed in much higher level than the FIX-emicizumab-FX complex. Table or Figure Upload"

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

NXT007 exerts in vitro cofactor activity in the co-presence of emicizumab with overlapping epitopes (ISTH 2025) - No abstract available

Preclinical • Hematological Disorders

NXT007 Prophylaxis in Emicizumab-Naive Persons with Hemophilia A without Inhibitor: Phase I/II Study (ISTH 2025) - "Participants in B-3 and B-4, for whom >40 U/dL of equivalent FVIII activity is predicted to be kept, did not experience any treated bleeds during MD period. No participants showed remarkable increase of D-dimer after NXT007 administration."

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

Invitation to Roche’s Virtual Hematology Investor Event (Roche Press Release) - "We are pleased to invite investors and analysts to participate in our virtual event on Monday, 23 June 2025, to highlight new results from Roche’s Hematology pipeline including...Phase I/II (NXTAGE) data for NXT007 in Hemophilia A presented at the Congress of the International Society on Thrombosis and Haemostasis (ISTH) from 21-25 June 2025."

P1/2 data • Hemophilia A