Frehemgo (denecimig) / Novo Nordisk, Genmab - LARVOL DELTA

FRONTIERAHA: A Research Study Investigating Denecimig (Mim8) in Adults With Acquired Haemophilia A (clinicaltrials.gov) - P3 | N=84 | Not yet recruiting | Sponsor: Novo Nordisk A/S

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

An evaluation of denecimig for bleeding prophylaxis in hemophilia A. (PubMed, Expert Opin Biol Ther) - "Despite advances in factor VIII (FVIII) replacement and emicizumab prophylaxis, people with hemophilia A may experience breakthrough bleeding, progressive joint disease, treatment burden, and inhibitor-related limitations. Denecimig (Mim8) is a fully human, next-generation FVIIIa-mimetic bispecific antibody engineered to provide subcutaneous prophylaxis irrespective of FVIII inhibitor status...However, it has not demonstrated superiority over established prophylactic therapies. Its clinical value will ultimately depend on mature thrombotic and immunogenic safety, perioperative evidence, head-to-head or real-world comparative effectiveness, treatment persistence, cost-effectiveness, and equitable global access rather than apparently favorable early pivotal-trial annualized bleeding rates alone."

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

Novo: CHMP recommends EU approval of FREHEMGO (denecimig), the first factor VIIIa mimetic offering monthly, once every two weeks and weekly dosing in a pre-filled pen, for the treatment of haemophilia A (GlobeNewswire) - "The CHMP recommendation is based on the FRONTIER trial programme....Novo expects to launch FREHEMGO in the first European countries in Q4 2026 and broadly across the EU starting early 2027."

CHMP • Launch Europe • Hemophilia A

Novo's denecimig demonstrates tolerability after switch from emicizumab in FRONTIER5 study of people with hemophilia A as published in the Journal of Thrombosis and Haemostasis (Novo Nordisk Press Release) - "The 26-week results showed that a direct switch to the subcutaneous denecimig pen injector from the emicizumab vial and syringe injection system, without a washout period or a denecimig loading dose, was well tolerated with no unforeseen safety concerns in adolescents and adults living with hemophilia A (congenital factor VIII deficiency) with or without inhibitors. Compared to their previous emicizumab vial and syringe system, most patients preferred the denecimig pen injector and found it easier to use, as measured by the Hemophilia Device Handling and Preference Assessment (HDHPA) as a supportive secondary endpoint...A supportive secondary endpoint studied among 59 of the 61 enrolled patients showed most participants (98.3%) rated the denecimig injection pen as 'easy' or 'very easy' to use (Hemophilia Device Handling and Preference Assessment, HDHPA)."

P3 data • Hemophilia A

FRONTIER5: Safety and patient experience of a direct switch from emicizumab to denecimig (Mim8) in patients with haemophilia A with or without inhibitors. (PubMed, J Thromb Haemost) - P3 | "The direct switch from emicizumab to denecimig without a washout period was well tolerated in adolescents and adults with HA with or without inhibitors. No new safety concerns were observed."

Journal • Cardiovascular • Hematological Disorders • Hemophilia • Hemophilia A • Immunology • Musculoskeletal Diseases • Musculoskeletal Pain • Orthopedics • Pain • Rare Diseases

SFDA becomes first global regulator to approve Frehemgo for Hemophilia A bleeding prevention (Saudi Gazette) - "The SFDA stated that the approval followed a comprehensive assessment of efficacy, safety, and quality based on the totality of evidence submitted in the registration dossier. The efficacy and safety of denecimig were evaluated in participants with all severities of hemophilia A, with or without FVIII inhibitors, across four Phase 3 studies: one involving adults and adolescents, another involving pediatric patients, an open-label extension study involving all age groups, and a safety-only study evaluating the switch from emicizumab in adults and adolescents."

Approval • Hemophilia A

New and novel pharmacotherapies for hemophilia A: an update. (PubMed, Expert Opin Pharmacother) - "In replacement therapy, efanesoctocog alfa maintains normal-to-near-normal factor VIII (FVIII) levels weekly by bypassing endogenous von Willebrand factor dependence. In non-replacement therapies, the focus centers on rebalancing agents - the anti-tissue factor pathway inhibitor (TFPI) monoclonal antibodies concizumab and marstacimab, and the antithrombin-targeting small interfering RNA (siRNA) fitusiran - as well as next-generation FVIII-mimetics like denecimig...Rebalancing therapies present potential thromboembolic risks, complex breakthrough bleed protocols, and standard laboratory assay interference (requiring antithrombin monitoring or specialized assays). Critical goals for contemporary hemophilia management include tailoring therapies through multidisciplinary collaboration, monitoring subclinical joint disease via point-of-care ultrasound, and implementing standardized, real-world protocols for emergency hemostasis."

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

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

Denecimig (Mim8) prophylaxis once-every-2-weeks for hemophilia A with or without inhibitors - 26-week results from FRONTIER. (PubMed, Blood Adv) - P3 | "In summary, denecimig administered Q2W was well tolerated, with few patients experiencing treated bleeds and no safety concerns. NCT05685238."

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

Physicians' Preferences in the Treatment of Hemophilia: A Discrete-Choice Experiment (ISTH 2026) - "With efficacy and risk varying, 98.0% and 96.9% were predicted to choose denecimig for once-monthly and once-weekly administration, respectively, when compared with emicizumab...Physicians highly valued a denecimig-like profile and favored treatment features that aligned with a denecimig-like profile, such as mode of administration, dosing considerations, and storage requirements. DOI*10.1016/j.rpth.2026.104854"

Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases

Denecimig (Mim8) restores thrombin generation into the normal range in people with haemophilia A: Post hoc analysis of the phase 3 FRONTIER2 and FRONTIER5 studies (ISTH 2026) - P3 | "Previous ex vivo and in vitro analyses demonstrated an ~15-fold increase in potency for TG with denecimig versus emicizumab. These findings support denecimig as an ultra-potent activated FVIII mimetic, confirmed by efficacy outcomes demonstrated in phase 3 clinical studies in people with HA, independent of inhibitor status. Table or Figure Upload (1) Mean thrombin peak height with FVIII neutralisation in FRONTIER2 and FRONTIER5 Page 2 Table or Figure Upload (2) Geometric mean thrombin peak height in FRONTIER5 and in vitro FVIII DOI*10.1016/j.rpth.2026.104808"

P3 data • Retrospective data • 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

New post hoc analyses of participants aged 12 and older with available thrombin generation data from the phase 3 FRONTIER2 and FRONTIER5 studies... (Novo Nordisk Press Release) - "...found that denecimig prophylaxis increased thrombin generation, a measure of the body’s ability to form clots, into the normal reference range in adolescents and adults without excessive response. These findings further support denecimig’s data across the clinical program."

Retrospective data • Hemophilia A

Novo Nordisk’s denecimig (Mim8) demonstrated positive results in long term safety and efficacy in phase 3 hemophilia A FRONTIER extension study at ISTH 2026 (Novo Nordisk Press Release) - "Injection-site reactions (ISR) were reported at low rates in children (2.0% of injections) and in adolescents and adults (1.8% of injections), and all were mild and transient. No clinical evidence of neutralizing antibodies was observed. For the secondary study endpoints of efficacy, estimated mean annualized bleeding rates (ABRs) were consistent with findings from the FRONTIER research program across all dosing regimens and regardless of inhibitor status (ABRs: 0.75; 95% CI 0.60, 0.93 for adults and adolescents; 0.37; 95% CI 0.17, 0.76 for children)....The interim assessment of exploratory patient-reported outcomes (PROs) from the long-term FRONTIER4 study showed findings from prior FRONTIER trials were maintained long-term in all dosing frequencies studied, including improved joint pain for people aged 12 and older (Joint Pain Rating Scale, JPRS) and reduced treatment burden for those aged one and older..."

P3 data • Patient reported outcomes • Hemophilia A

Mim8 (denecimig) prophylaxis in adults, adolescents and children with haemophilia A with or without inhibitors: Interim patient-reported outcomes from the long-term extension study (FRONTIER4) (ISTH 2026) - P3 | "Patient-reported outcomes (PROs) of adults, adolescents and children in long-term follow up with complete PRO data Page 2 Table or Figure Upload (2) Figure 1. Haemophilia Device Assessment Tool answers among adults, adolescents and children DOI*10.1016/j.rpth.2026.104846"

Clinical • Patient reported outcomes • Hematological Disorders • Hemophilia • Hemophilia A • Musculoskeletal Diseases • Musculoskeletal Pain • Orthopedics • Rare Diseases

Effects of denecimig (Mim8) and tranexamic acid in an in vitro clot lysis assay (ISTH 2026) - "Denecimig enhanced the resistance to fibrinolysis at low, suboptimal TxA levels, but not at higher TxA concentrations. Table or Figure Upload (1) Clot formation and tPA-mediated lysis in the presence of denecimig and TxA Table or Figure Upload (2) Area under the clot lysis curve Page 2 DOI*10.1016/j.rpth.2026.104832"

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

Canine FIXa homodimeric antibody reduces annualized bleeding and infusion rates in severe hemophilia A dogs with canine FVIII inhibitors (ISTH 2026) - "The FIXa binding arm of denecimig (Mim8) recognizes an epitope that is identical between human and canine FIXa (amino acids 320 to 350)...Conclusions k-IX-2 is a novel, safe, well-tolerated hemostatic that significantly improves hemophilic coagulopathy and reduces both the ABR and AIR in HemA dogs with inhibitors to canine FVIII. DOI*10.1016/j.rpth.2026.104806"

Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases • Subarachnoid Hemorrhage • Thrombosis

Denecimig (Mim8) tiered dosing achieves consistent exposure and bleed control in phase 3 FRONTIER studies (ISTH 2026) - P3 | "Bleed protection was maintained regardless of body weight and denecimig exposure level. Table or Figure Upload (1) Individual model-derived denecimig exposure across dosing frequencies Page 2 Table or Figure Upload (2) Annualised bleeding rate by A) patient body weight, and B) observed denecimig exposure DOI*10.1016/j.rpth.2026.104811"

P3 data • Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases

Mim8 (denecimig) prophylaxis in children with haemophilia A with or without inhibitors: Interim safety and efficacy results from the FRONTIER4 long-term extension study (ISTH 2026) - P3 | "Adverse events among children Page 2 Table or Figure Upload (2) Figure 1. Annualised bleed rates for treated bleeding episodes DOI*10.1016/j.rpth.2026.103473"

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

Mim8 (denecimig) prophylaxis in adults and adolescents with haemophilia A with or without inhibitors: Interim results from the FRONTIER4 long-term safety and efficacy study (ISTH 2026) - P3 | "Adverse events among adults/adolescents a Page 2 Table or Figure Upload (2) Figure 1. Estimated mean annualised bleed rates for treated bleeding episodes DOI*10.1016/j.rpth.2026.103472"

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

FRONTIER4: A Research Study Looking at Long-term Treatment With Mim8 in People With Haemophilia A (clinicaltrials.gov) - P3 | N=451 | Recruiting | Sponsor: Novo Nordisk A/S | Active, not recruiting ➔ Recruiting

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

Novo Nordisk to showcase new data across its haemophilia portfolio at the ISTH Congress 2026, featuring investigational denecimig (Novo Nordisk Press Release) - "The broad range of oral and poster presentations spans the Novo Nordisk haemophilia portfolio and is highlighted by multiple analyses of the phase 3 FRONTIER4 study evaluating the long-term efficacy and safety of investigational denecimig (Mim8) across a range of age groups and dosing frequencies, including once-monthly, once-every-two-weeks, and once-weekly prophylaxis. Additional insights from the portfolio will span clinical and real-world treatment data as well as patient-reported outcomes....Additionally, data from the open-label phase 3 explorer10 study will be presented for the first time, evaluating the efficacy and safety of concizumab in children up to 11 years of age living with haemophilia A or B (HA/HB), with inhibitors."

Clinical data • P3 data • Patient reported outcomes • Preclinical • Hemophilia A • Hemophilia B