Inno8 / Novo Nordisk - LARVOL DELTA

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

A multinational, open-label study to investigate efficacy and safety of denecimig (Mim8) in adults with acquired haemophilia A: study enrolment 2026 (ISTH 2026) - "The FVIIIa-mimetic antibody emicizumab was recently used for prophylaxis in AHA but is not licensed and access for affected patients remains limited by regional availability, bleeding risk, and treatment burden. The trial will investigate denecimig's potential to provide sustained haemostatic coverage and reduce recurrent bleeding risk, which may support less intensive or delayed initiation of IST. Table or Figure Upload (1) Denecimig dosing Page 2 Table or Figure Upload (2) Study design Page 3 DOI*10.1016/j.rpth.2026.105669"

Clinical • Hematological Disorders • Hemophilia • Hemophilia A • Immunology • Infectious Disease • Rare Diseases

Thrombin generation of hemophilia B-causing factor IX variants with non-factor therapies (ISTH 2026) - "Methods TG of FIX-variant purified recombinant protein or HB-patient plasma was determined with therapeutic (or likely therapeutic) concentrations of FVIIIa-mimetics (300 nM emicizumab, 34 nM Mim8, 10 nM Inno8) and anti-TFPI antibodies (30 nM concizumab,113 nM mastacimab-SIA). Bars represent mean of ≥2 experiments done in duplicate and error bars are SEM. Page 2 DOI*10.1016/j.rpth.2026.104810"

Hematological Disorders • Hemophilia • Hemophilia B • Rare Diseases

Denecimig (Mim8) enhances in vitro thrombin generation in von Willebrand disease type 3 plasma (ISTH 2026) - "FVIIIa mimetic antibodies could potentially mitigate the reduced FVIIIa activity and decrease bleeding episodes in VWD. Clinical case studies suggest that emicizumab is effective in type 3 VWD patients with or without VWF alloantibodies (Shanmukhaiah et al...Conclusions By mimicking FVIIIa, denecimig restores in vitro thrombin generation in VWD type 3 plasma and could potentially mitigate the consequences of reduced FVIII levels in patients living with VWD. Table or Figure Upload (1) Thrombin generation in VWD type 3 plasma spiked with increasing levels of denecimig and triggered with either 1 pM TF or 0.11 nM FXIa, both without FVIII neutralization Page 2 Table or Figure Upload (2) Peak thrombin level with increasing levels of denecimig in absence and presence of FVIII neutralization DOI*10.1016/j.rpth.2026.106032"

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

FVIIIa-mimetic bispecific antibody (Mim8) enhances thrombus formation of von Willebrand disease (VWD) under high shear flow condition. (ISTH 2026) - "We previously reported that the FVIIIa-mimetic bispecific antibody, emicizumab, which substitutes for activated FVIII (FVIIIa), improved thrombus formation in VWD. These findings suggest that Mim8 may represent a novel therapeutic option for patients with VWD. DOI*10.1016/j.rpth.2026.106045"

Bispecific • Hematological Disorders • Hemophilia • Thrombosis

Inno8, the first orally administered factor VIII mimetic shows favorable safety, pharmacokinetic, and pharmacodynamic properties in healthy male participants (ISTH 2026) - No abstract available

Clinical • Late-breaking abstract • PK/PD data

A Research Study Looking at How Food Intake Affects Inno8 in the Body of Healthy People (clinicaltrials.gov) - P1 | N=80 | Completed | Sponsor: Novo Nordisk A/S | Recruiting ➔ Completed

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

VOYAGER1: A Study Looking at How Different Doses of Study Medicine (Inno8) Works in the Body of Healthy Men (clinicaltrials.gov) - P1 | N=95 | Completed | Sponsor: Novo Nordisk A/S | Recruiting ➔ Completed

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

VOYAGER2: A Research Study Looking at How Different Doses of Study Medicine (Inno8) Work in the Body of People With Haemophilia A (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: Novo Nordisk A/S | N=20 ➔ 30

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

NN7442-7582: A research study looking at how different doses of study medicine (Inno8) works in the body of healthy men. (clinicaltrialsregister.eu) - P1 | N=108 | Active, not recruiting | Sponsor: Novo Nordisk A/S | Recruiting ➔ Active, not recruiting

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

NN7442-8454: A research study looking at how different doses of study medicine (Inno8) work in the body of people with haemophilia A (clinicaltrialsregister.eu) - P1 | N=21 | Recruiting | Sponsor: Novo Nordisk A/S

New P1 trial • Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases

A Research Study Looking at How Food Intake Affects Inno8 in the Body of Healthy People (clinicaltrials.gov) - P1 | N=80 | Recruiting | Sponsor: Novo Nordisk A/S | Not yet recruiting ➔ Recruiting

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

Mim8 improves the In Vivo hemostasis of select hemophilia B causing factor IX variants (ASH 2025) - "Mim8 (denecimig) is a next-generation FVIIIa-mimetic with distinct binding epitopes and increased potency compared toemicizumab; it is in late-stage clinical development for HA. This clot size approaches the clot size inour previous studies of wild-type mice (platelets 400 ± 40 µm2 and fibrin 280 ± 40 µm2).ConclusionMim8 improves the in vitro and in vivo hemostatic activity of select HB-causing FIX variants. Themagnitude of this improvement for some variants—such as R333Q and I397T, which account for 5.7% ofpeople with HB—is likely therapeutically relevant."

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

VOYAGER2: A Research Study Looking at How Different Doses of Study Medicine (Inno8) Work in the Body of People With Haemophilia A (clinicaltrials.gov) - P1 | N=20 | Recruiting | Sponsor: Novo Nordisk A/S | Not yet recruiting ➔ Recruiting | Trial completion date: May 2026 ➔ Dec 2026 | Trial primary completion date: May 2026 ➔ Dec 2026

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

A Research Study Looking at How Food Intake Affects Inno8 in the Body of Healthy People (clinicaltrials.gov) - P1 | N=80 | Not yet recruiting | Sponsor: Novo Nordisk A/S

New P1 trial • Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases

FVIII Inhibitors can Accurately be Measured in the Presence of Mim8 in Hemophilia A Plasma (ASH 2023) - "Using aPTT-based Modified Nijmegen-Bethesda Assays in the presence of FVIIIa Mimetics such as Mim8 is not recommended due to interference. This study showed that by using FVIII chromogenic assays containing bovine reagents, FVIII inhibitors levels up to at least ⁓5. 0 BU/mL can be accurately determined in severe hemophilia A plasma in the presence of up to 40 µg/mL Mim8."

Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases

VOYAGER2: A Research Study Looking at How Different Doses of Study Medicine (Inno8) Work in the Body of People With Haemophilia A (clinicaltrials.gov) - P1 | N=20 | Not yet recruiting | Sponsor: Novo Nordisk A/S

New P1 trial • Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases

VOYAGER1: A Study Looking at How Different Doses of Study Medicine (Inno8) Works in the Body of Healthy Men (clinicaltrials.gov) - P1 | N=108 | Recruiting | Sponsor: Novo Nordisk A/S | Trial completion date: Sep 2025 ➔ May 2026 | Trial primary completion date: Jun 2025 ➔ May 2026

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

In vitro effects of Mim8 and combined Mim8-bypassing therapy on thrombin generation, thromboelastography and fibrin clot ultrastructure. (PubMed, Thromb Res) - "Mim8 significantly improves TG in vitro in both PPP and PRP from patients with severe HA, with ETP levels comparable to those of FVIII at 100 IU/dL. The TGA can effectively monitor the combined treatment with Mim8 and either rFVIIa or APCC, which is not possible with currently available routine laboratory tests."

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

VOYAGER1: A Study Looking at How Different Doses of Study Medicine (Inno8) Works in the Body of Healthy Men (clinicaltrials.gov) - P1 | N=92 | Recruiting | Sponsor: Novo Nordisk A/S

New P1 trial • Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases