Novo Nordisk's FIXa/FX Bispecific Antibody Mim8 Meets Primary Endpoint in Phase 3 Trial, NDA Filing Planned by Year-End

About the FRONTIER 2 Trial

This is a 52-week Phase 3 trial with a 26-52 week run-in period, comparing the efficacy and safety of weekly and monthly Mim8 versus no prophylaxis and versus factor prophylaxis prior to enrollment in patients aged 12 years and older with Hemophilia A. The primary 26-week trial has been completed, and the 26-week extension phase is currently ongoing.Results:

• In patients who had not previously received preventive treatment, weekly and monthly doses of Mim8 reduced bleeding by 97% and 99%, respectively;

• Among patients receiving preventive treatment, 86% of those receiving weekly Mim8 treatment and 95% of those receiving monthly Mim8 treatment did not experience bleeding.

• In patients with prior prophylactic use of clotting factors, weekly and monthly Mim8 treatments reduced bleeding by 48% and 43%, respectively; additionally, 66% of patients receiving weekly Mim8 and 65% receiving monthly Mim8 experienced no bleeding episodes.

• In terms of safety, the safety and tolerability were good, with no reports of death or thromboembolic events.

About Mim8

Mim8 (NNC0365-3769) is a next-generation bispecific antibody developed by Novo Nordisk that targets FIXa and FX. It is designed for once-weekly or once-monthly subcutaneous administration in patients with hemophilia A, with or without inhibitors. As an FVIIIa mimetic, Mim8 facilitates the binding of FIXa to FX on the active phospholipid surface and enhances the proteolytic activity of FIXa (the ability to activate FX), thereby mimicking the function of FVIIIa in vivo.

According to the disclosed information, in in vitro coagulation experiments and animal models, Mim8 enhanced the proteolytic activity of FIXa by 23*10³ times, with good hemostatic activity observed in mice; regardless of the dosing regimen, direct conversion from emicizumab to Mim8 can rapidly establish higher hemostatic activity levels without exceeding the normal range.

In addition, currently marketed hemophilia treatment drugs require dose calculation based on body weight, but due to limitations in drug specifications, this may lead to waste. Mim8 has a longer half-life, a wider target exposure range of plasma drug concentration, and limited inter-individual variability. The dosing regimen in its Phase III clinical trial can maintain the target plasma concentration level of Mim8 and significantly reduce the risk of bleeding. These characteristics suggest that Mim8 has the feasibility of simplified, weight-based dosing.

About Hemophilia A

Hemophilia A (HA) is a hereditary bleeding disorder, presenting as X-linked recessive inheritance. Clinically, it is mainly characterized by qualitative or quantitative abnormalities of coagulation factor VIII (FⅧ). The clinical manifestations include spontaneous or minor trauma-induced bleeding in joints, muscles, internal organs, and deep tissues that is difficult to stop. The condition often begins in childhood, and repeated joint bleeding can gradually lead to joint mobility impairment and disability.

Clinical Classification of Hemophilia A

According to the World Federation of Hemophilia (WFH), with an estimated prevalence of 20.9 per 100,000 males, the current global number of hemophilia patients is 760,000. Assuming that Hemophilia A (HA) patients account for 80-85% of all hemophilia cases, it is estimated that there are over 610,000 HA patients globally, including more than 140,000 HA patients in China. According to the "Diagnosis and Treatment Guidelines for Hemophilia A (2022 Edition)," the incidence rate of Hemophilia A among males is approximately 1 in 5,000, while female hemophilia patients are extremely rare. The prevalence of hemophilia in China is 2.73 per 100,000 people, of which HA accounts for 80-85%.

Currently, the treatment for Hemophilia A can be divided into replacement therapy with Factor VIII and non-factor therapy. Replacement therapy with Factor VIII is further divided into on-demand treatment and prophylactic treatment; specific treatment methods are summarized as follows:

About Novo Nordisk's Layout in Blood Diseases

According to incomplete statistics, Novo NordiskIn the field of blood diseases, 21 drugs have been laid out, and the approved products are mainly coagulation factors.