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

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

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

A Research Study Looking at How Safe it is to Switch From Emicizumab to Mim8 in People With Haemophilia A (FRONTIER 5) (clinicaltrials.gov) - P3 | N=61 | Completed | Sponsor: Novo Nordisk A/S | Active, not recruiting ➔ Completed | Trial completion date: Dec 2024 ➔ Jul 2024

Trial completion • Trial completion date • 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=267 | Active, not recruiting | Sponsor: Novo Nordisk A/S | Recruiting ➔ Active, not recruiting

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

Efficacy and safety of Mim8 prophylaxis in adults and adolescents with hemophilia A with or without inhibitors: Phase 3, open-label, randomized, controlled FRONTIER2 study (ISTH 2024) - P3 | "Overall, 254 patients were randomized (Table 1). In patients previously treated on-demand, estimated mean ABR [95% CI] for treated bleeds was 0.45 [0.18;1.14] for QW and 0.20 [0.06;0.72] for QM Mim8 prophylaxis, versus 15.75 [10.7;23.2] for continued on-demand treatment (Table 1). Mim8 prophylaxis was superior to on-demand treatment, with ABR reduction of 97.1% (QW) and 98.7% (QM)."

Clinical • Late-breaking abstract • P3 data • Hematological Disorders • Hemophilia • Rare Diseases

FVIII In Vitro Bioequivalence of Mim8 Haemostatic Effect by Thrombin Generation Assays (ISTH 2024) - "We used TG assays (TGAs) in plasma to predict FVIII in vitro bioequivalence of Mim8 and a sequence-identical analogue of emicizumab (emi-SIA). FVIII in vitro bioequivalence was dependent on trigger type, concentration, and TGA parameter. The mean FVIII in vitro bioequivalence of Mim8 was 36.8% and 16.4% for emi-SIA, based on peak thrombin using a commonly-used trigger (1 pM TF) (Figure 1). Generally, the highest FVIII in vitro bioequivalence was observed at trigger conditions where activated factor IX (FIXa) generation is limited (Table 1)."

Preclinical • Hematological Disorders • Hemophilia • Rare Diseases

A Research Study Investigating Mim8 in Adults and Adolescents With Haemophilia A With or Without Inhibitors (clinicaltrials.gov) - P3 | N=267 | Recruiting | Sponsor: Novo Nordisk A/S | Trial completion date: Feb 2025 ➔ Sep 2024

Trial completion date • Hematological Disorders • Hemophilia • Rare Diseases

ACCURATE MEASUREMENT OF FACTOR VIII ACTIVITY AND INHIBITORS IN THE PRESENCE OF MIM8 (THSNA 2024) - " To assess FVIII activity of SHL and EHL products, severe HA plasma was spiked with ADVATE®, Novoeight®, Esperoct®, or ELOCTATE® (5, 10, 15, 20, and 100 IU/dL final concentrations) and Mim8 (0, 3, 6, and 12 µg/mL final concentrations). FVIII activity of SHL and EHL products was accurately measured in the presence of Mim8 using bovine CSAs. Using FVIII CSAs with bovine reagents, FVIII inhibitor levels up to approximately 5.0 BU were accurately measured in HA plasma in the presence of up to 40 µg/mL Mim8."

Hematological Disorders • Hemophilia • Rare Diseases

A Research Study Looking at How Safe it is to Switch From Emicizumab to Mim8 in People With Haemophilia A (FRONTIER 5) (clinicaltrials.gov) - P3 | N=48 | Active, not recruiting | Sponsor: Novo Nordisk A/S | Recruiting ➔ Active, not recruiting

Enrollment closed • Hematological Disorders • Hemophilia • Rare Diseases

FVIII inhibitors can be accurately determined in haemophilia A plasma in the presence of Mim8 (EAHAD 2024) - No abstract available

Hematological Disorders • Hemophilia • Rare Diseases

FRONTIER1: a partially randomized phase 2 study assessing the safety, PK, and PD of Mim8, a factor VIIIa mimetic. (PubMed, J Thromb Haemost) - P2 | "These data support the continued clinical development of Mim8, and FRONTIER1 has proceeded onto an extension phase."

Journal • P2 data • Hematological Disorders • Hemophilia • Mood Disorders • Pain • Psychiatry • Rare Diseases