RG6512 / Roche - LARVOL DELTA

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

Chugai Announces 2025 1st Quarter Results (Chugai Press Release) - "Core revenue, core operating profit, and core net income at ¥288.5 billion (+21.8%), ¥139.5 billion (+36.6%), and ¥99.2 billion (+30.5%), respectively (all changes year-on-year)...Regarding revenue, domestic sales remained nearly flat with a slight decrease of 0.2% year-on-year. In the oncology field, sales decreased by 5.3% compared to the previous year. While our new product Phesgo performed well, this was offset by the decline in Perjeta and Herceptin along with the market penetration of Phesgo which includes the same active pharmaceutical ingredients. Additionally, products including our mainstay product Avastin were affected by NHI drug price revisions and biosimilars...Overseas sales increased significantly by 54.7% year-on-year, driven by a substantial increase in exports of Hemlibra and Actemra to Roche."

Commercial • Ankylosing Spondylitis • Hemophilia • HER2 Breast Cancer • Lupus • Myelodysplastic Syndrome • Non Small Cell Lung Cancer • Ovarian Cancer • Rheumatoid Arthritis • Schizophrenia

Insights from in vitro global assays on possible doses of concomitant hemostatic agents in the presence of NXT007 in hemophilia A. (PubMed, J Thromb Haemost) - "Concomitant addition of coagulation agents increased coagulation potentials in vitro in the presence of NXT007. A dose of 10 U/kg may serve as a rough indicator for the initial dose when exploring the concomitant use of aPCC at plasma NXT007 levels of approximately 30 μg/mL. Importantly, plasma NXT007 at ≥10 μg/mL demonstrated non-hemophiliac coagulation potentials in vitro."

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

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 | N=40 ➔ 60

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

A Study to Evaluate Single Subcutaneous Doses of NXT007 Among Injection Sites Abdomen, Upper Arm, and Thigh in Healthy Male Participants (clinicaltrials.gov) - P1 | N=48 | Completed | Sponsor: Hoffmann-La Roche | Active, not recruiting ➔ Completed

Trial completion

NXT007 does not interfere with the anticoagulant effects on tissue factor pathway inhibitor. (PubMed, Haemophilia) - No abstract available

Journal

NXT007, a novel bispecific antibody, in FVIII chromogenic substrate assays (ISTH 2024) - "NXT007 was engineered and optimized based on emicizumab, which shows FVIII-like activity in CSAs containing human, but not bovine coagulation factors. NXT007 concentration dependent increase in FVIII-like activity was seen in CSA with human reagents and using the human-bovine Technoclone kit, which gave the highest FVIII-like activities (137 IU/dL at 30 µg/mL of NXT007) (Table 1). Some FVIII-like activity (9-13 IU/dL at 30 µg/ml NXT007) was observed in the other human-bovine CSAs. No FVIII-like activity of NXT007 was detected in purely bovine CSAs."

Hematological Disorders • Hemophilia • Rare Diseases

A Study to Evaluate Single Subcutaneous Doses of NXT007 Among Injection Sites Abdomen, Upper Arm, and Thigh in Healthy Male Participants (clinicaltrials.gov) - P1 | N=48 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Recruiting ➔ Active, not recruiting

Enrollment closed

Directed Assembly of Bispecific Antibodies by Electrostatic Steering—The FAST-Ig Platform (IO-SUMMIT EUROPE 2024) - "Using NXT007 as an example, I will discuss critical factors like pairing potency, titre, physicochemical properties, and purification when applying FAST-Ig to clinical candidate antibodies. Additionally, I will introduce a next-generation T cell engager targeting CLDN6 that also utilises FAST-Ig."

CLDN6

Antithrombin exhibits anticoagulant effects on the emicizumab-based engineered bispecific antibody (NXT007)-mediated blood coagulation. (PubMed, Thromb Res) - No abstract available

Journal • Hematological Disorders • Hemophilia • Rare Diseases