denecimig (Mim8) / Novo Nordisk, Genmab - LARVOL DELTA

FRONTIER4: A Research Study Looking at Long-term Treatment With Mim8 in People With Haemophilia A (FRONTIER 4) (clinicaltrials.gov) - P3 | N=451 | Active, not recruiting | Sponsor: Novo Nordisk A/S | Trial primary completion date: Jun 2028 ➔ Dec 2030 | Trial completion date: Jun 2028 ➔ Dec 2030

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

Novo Nordisk A/S: Mim8 prophylaxis treatment shown to be well-tolerated when switching from emicizumab in people with haemophilia A in new phase 3 data presented at the ISTH 2025 Congress (GlobeNewswire) - P3b | N=61 | FRONTIER 5 (NCT05878938) | Sponsor: Novo Nordisk A/S | "Novo Nordisk...presented results from the phase 3b FRONTIER5 trial showing that a direct switch to investigational Mim8 (denecimig) prophylaxis from emicizumab treatment...was well-tolerated with no safety concerns in adults and adolescents living with haemophilia A, with or without inhibitors. Additionally, a FRONTIER5 Patient-Reported Outcomes (PROs) assessment found the Mim8 pen-injector easy to use, with an overall strong user preference for the pen-injector compared to the previous emicizumab injection system....The PROs data from FRONTIER5 indicated a strong overall preference for the Mim8 pen-injector, with 97% (n=57/59) of patients reporting a 'very strong' or 'fairly strong' preference....Novo Nordisk expects to submit Mim8 for regulatory review during 2025. Data from the ongoing phase 3 FRONTIER programme will be disclosed at upcoming congresses and in publications in 2025 and 2026."

Filing • P3 data • Patient reported outcomes • Hemophilia A

ASSESSMENT OF NOVEL POINT-OF-CARE WHOLE BLOOD COAGULATION ASSAY TO EVALUATE COAGULATION RESPONSE TO BIAB FVIIIA MIMETIC AND FVIII THERAPY (EHA 2025) - "This study assessed the dose-dependent response of ClotChip to Mim8, a next generation FVIIIa mimetic antibody, and to rFVIII (Novoeight®, Novo Nordisk) in whole blood samples deficient in FVIII clotting factor. The ClotChip Tpeak parameter responds to Mim8 and rFVIII in a dose-dependent manner with no plateau in the range tested (see Figure), demonstrating the potential for ClotChip to evaluate the coagulation response of patient samples to these hemophilia therapies. Ongoing studies are focused on clinical assessment with ClotChip to further assess patient response to various next-generation mimetic and traditional factor-replacement therapies at POC."

Hematological Disorders • Hemophilia • Rare Diseases

In vivo correction of canine hemophilia A by an anti-factor IXa antibody (ISTH 2025) - "These antibodies recognize both human factors IXa and X to enhance factor X activation but do not recognize canine factors IXa and X. However, the factor IXa binding arm of denecimig (Mim8) recognizes an epitope that is identical between human and canine factor IXa...Using a TGA standard curve, recovery of k-IX-2 activity revealed an initial clearance from plasma (half-life 18 hours) with a slower subsequent clearance (5 days). Using a standard curve of factor VIII in HemA plasma, equivalent activity peaked at 0.2 U/mL and declined over 48 hours to about 0.02 U/mL but remained above 0.01 U/mL for 24 days during which there were no bleeding events."

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

Evaluating pen-injector handling and PROs in patients switching from emicizumab to Mim8 in FRONTIER5 (ISTH 2025) - P3 | "Mean change from baseline [standard deviation] to Week 26 ranged from: –6.2 [9.6] to –3.5 [10.9] for Hemo-TEM scores, none of which were considered clinically relevant (≥8 points); –0.4 [1.4] to 0.6 [2.8] for JPRS; and –0.7 [8.7] to 3.6 [9.1] for PedsQL physical functioning. Table or Figure Upload"

Clinical • Hematological Disorders • Hemophilia • Hemophilia A • Musculoskeletal Diseases • Musculoskeletal Pain • Orthopedics • Pain • Pediatrics • Rare Diseases

FRONTIER5 direct switch study: Safety of initiating Mim8 prophylaxis without washout of emicizumab (ISTH 2025) - P3 | "No exaggerated thrombin peak height response was observed. Table or Figure Upload"

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

Mim8 Enhances Procoagulant Activity of Select Hemophilia B-causing Factor IX Variants (ISTH 2025) - "Background We recently reported that the first-generation FVIIIa-mimetic emicizumab can rescue procoagulant activity of select hemophilia B (HB)-causing FIX variants with dysfunctional Xase formation (Lee et al. Further, with Mim8, a 50% and 70% FIX correction generated a similar amount of thrombin as a 100% correction without Mim8 (for rFIX-R333Q and rFIX-I397T, respectively). Table or Figure Upload"

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

Model-informed drug development of Mim8 - a next-generation bispecific antibody for treatment of haemophilia A. (PubMed, Eur J Pharm Sci) - P2 | "Model-informed drug development was used to design a novel treatment paradigm for patients living with haemophilia A by utilising a tiered dosing strategy with Mim8, to be evaluated in phase 3 trials."

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

Novo Nordisk to present phase 3 trials across hemophilia portfolio, reinforcing commitment to research in rare blood disorders, at ISTH 2025 (PRNewswire) - "Key presentations include two updates from a phase 3 trial evaluating investigational treatment with Mim8 (denecimig) and five assessing treatment outcomes with concizumab in hemophilia; A phase 3 trial analysis from FRONTIER5 will evaluate the safety of switching directly from emicizumab to Mim8 (denecimig) in people living with hemophilia A/B; Findings from explorer7 and explorer8 phase 3 trials will assess data including non-joint bleeds, annualized bleeding rates and additional studies including thrombin generation with concizumab in hemophilia A/B."

P3 data • Hemophilia A • Hemophilia B

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

FRONTIER2: A Research Study Investigating Mim8 in Adults and Adolescents With Haemophilia A With or Without Inhibitors (clinicaltrials.gov) - P3 | N=281 | Completed | Sponsor: Novo Nordisk A/S | Active, not recruiting ➔ Completed

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

Factor VIII Activity and Factor VIII Inhibitors Can Be Measured Accurately in Plasma Containing Mim8 by Using Specific Chromogenic Assays. (PubMed, Haemophilia) - "FVIII:C of SHL and EHL products and FVIII inhibitor levels can be accurately monitored in the presence of Mim8 using bovine CSAs at all FVIII levels, and bovine-human CSAs at FVIII concentrations >20 IU/dL."

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

Novo Nordisk A/S: Once-weekly Mim8 is well-tolerated and efficacious in children living with haemophilia A with and without inhibitors (GlobeNewswire) - P3 | N=70 | FRONTIER3 (NCT05306418) | Sponsor: Novo Nordisk A/S | "Novo Nordisk today announced interim results from the phase 3 FRONTIER3 trial of 70 children (aged 1-11 years old) with haemophilia A with and without inhibitors....The median (middle or central value in the data set) ABR was zero; 74.3% of participants had zero treated bleeds. All children with haemophilia A with inhibitors (n=14) reported zero treated bleeds. After completing the initial 26 weeks of the study, 45% of participants chose to move to once-monthly Mim8, and the rest (55%) remained on the once-weekly dose....Novo Nordisk expects Mim8 regulatory submission during 2025. Data from the ongoing phase 3 FRONTIER programme will be disclosed at upcoming congresses and in publications in 2025 and 2026."

FDA filing • P3 data • Hemophilia A

Mim8 Prophylaxis Beyond Bleeding: Multifaceted, Patient-reported Outcomes for Haemophilia A in FRONTIER2 (EAHAD 2025) - No abstract available

Clinical • Patient reported outcomes • Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases

Safety and Efficacy of Mim8 Prophylaxis Once Every Two Weeks in Haemophilia A: A FRONTIER4 Interim Analysis (EAHAD 2025) - No abstract available

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

Expedited learning and enhanced usability of a pre-filled Mim8 pen injector for the management of haemophilia A (EAHAD 2025) - No abstract available

Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases

Ex vivo Comparison of Mim8 Combined with Activated Factor XI Versus Tissue Factor in Thrombin Generation Assays (EAHAD 2025) - No abstract available

Preclinical

In Vitro Effects of Mim8 and Combined Mim8-Bypassing Therapy on Thrombin Generation, Thromboelastography and Fibrin Clot Ultrastructure (EAHAD 2025) - No abstract available

Preclinical

Patient- and caregiver-reported outcomes with subcutaneous Mim8 prophylaxis in paediatric patients with haemophilia A with or without factor VIII inhibitors: phase 3 FRONTIER3 study (EAHAD 2025) - No abstract available

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

Antibodies to watch in 2025. (PubMed, MAbs) - "In particular, we report on 21 antibody therapeutics granted a first approval in at least one country or region during 2024, including bispecific antibodies tarlatamab (IMDELLTRA®), zanidatamab (Ziihera®), zenocutuzumab (BIZENGRI®), odronextamab (Ordspono®), ivonescimab (®), and antibody-drug conjugate (ADC) sacituzumab tirumotecan (®). We also discuss 30 investigational antibody therapeutics for which marketing applications were undergoing review by at least one regulatory agency, as of our last update on December 9, 2024, including ADCs datopotamab deruxtecan, telisotuzumab vedotin, patritumab deruxtecan, trastuzumab botidotin, becotatug vedotin, and trastuzumab rezetecan. Of 178 antibody therapeutics we include in the late-stage pipeline, we summarize key data for 18 for which marketing applications may be submitted by the end of 2025, such as bi- or multispecific antibodies denecimig, sonelokimab, erfonrilimab, and anbenitamab. Key..."

Journal • Review • Oncology

Mim8 Prophylaxis Beyond Bleeding: Investigating Multifaceted, Patient-Reported Outcomes for Hemophilia A in the FRONTIER2 Study (ASH 2024) - P3 | "Joint pain intensity was not severe at baseline in all arms and did not change notably with Mim8 PPX. These findings demonstrate the holistic benefits of Mim8 beyond bleed protection and provide insights into opportunities for individualized care."

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

Safety and Efficacy of Mim8 Prophylaxis Administered Once Every Two Weeks for Patients with Hemophilia A with or without Inhibitors: Interim Analysis of the FRONTIER4 Open-Label Extension Study (ASH 2024) - P2, P3 | "These data are consistent with the findings from FRONTIER2, which reported no safety concerns and a low number of treated bleeding episodes with either QW or QM prophylaxis. Further data from this ongoing arm of FRONTIER4, as well as data for participants enrolled from other studies in the FRONTIER program, will provide valuable long-term data for different Mim8 dosing regimens."

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

In Vitro Effects of Mim8 and Combined Mim8-Bypassing Therapy on Thrombin Generation and Thromboelastography (ASH 2024) - "This enhances the proteolytic activity of FIXa and allows effective activation of FX, making it suitable for prophylaxis in patients with hemophilia A. While Mim8 and emicizumab have similar modes of action, differences in their respective anti-FIXa and anti-FX arms influence their FVIIIa-like function.Aim : This study investigates the in vitro hemostatic activity of Mim8 in blood samples from six patients with severe hemophilia A using a thrombin generation assay (TGA) and thromboelastography. The combination of Mim8 with rFVIIa at 90 µg/kg does not induce hypercoagulability, whereas the combination of Mim8 with APCC may carry a significant risk of hypercoagulability. 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."

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

FRONTIER4: A Research Study Looking at Long-term Treatment With Mim8 in People With Haemophilia A (FRONTIER 4) (clinicaltrials.gov) - P3 | N=451 | Active, not recruiting | Sponsor: Novo Nordisk A/S | Recruiting ➔ Active, not recruiting

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

A Research Study Looking at Mim8 in Children With Haemophilia A With or Without Inhibitors (clinicaltrials.gov) - P3 | N=70 | Completed | Sponsor: Novo Nordisk A/S | Recruiting ➔ Completed | Trial completion date: Apr 2025 ➔ Nov 2024 | Trial primary completion date: Apr 2025 ➔ Nov 2024

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