Introducing The Affinity Anti-FcRn Antibody Clinical Research Initiative
From Momenta Pharmaceuticals

Our Commitment To Research

Momenta Pharmaceuticals is a biotechnology company committed to improving treatment options for patients with rare immune-mediated diseases. Momenta is pleased to announce the Affinity Clinical Research Initiative. Powered by M281, an investigational product, an anti-FcRn antibody, Momenta is conducting new clinical research into rare and hard-to-treat immune-mediated diseases, beginning with hemolytic disease of the fetus and newborn (HDFN) and myasthenia gravis (MG).

About M281

A hallmark of immune-mediated diseases is the presence of pathogenic (disease-causing) antibodies leading to tissue damage and organ dysfunction. Immunoglobulin G (IgG) is the most common subclass of antibodies reported to be associated with these immune-mediated diseases. Reduction of these IgG pathogenic antibodies may be addressable by targeting FcRn, the neonatal Fc receptor, which recycles IgG into circulation, maintaining the long half-life of IgG.

Using proprietary antibody engineering technology, Momenta has developed M281, an investigational product, a fully human, anti-FcRn, aglycosylated IgG1 monoclonal antibody. M281 is engineered to bind FcRn with high affinity and block FcRn to:

  • Reduce pathogenic IgG through inhibition of IgG recycling
  • Inhibit the transport of pathogenic IgG across the placenta in pregnancy

In preclinical models, M281 rapidly diminishes levels of circulating IgG antibodies. M281 has been shown to effectively improve disease in preclinical animal models of immune-mediated diseases.

In a phase 1, randomized, double-blind, placebo-controlled study in healthy volunteers, M281 was found to be well tolerated with no serious adverse events. A consistent and close relationship between FcRn receptor occupancy, IgG reduction, and M281 pharmacokinetics was observed. These findings support further evaluation of M281 in immune-mediated diseases driven by pathogenic IgG antibodies. LINK

Hemolytic Disease of the Fetus and Newborn

Hemolytic disease of the fetus and newborn (HDFN) is a rare and potentially life-threatening condition that affects approximately 4,000 – 8,000 United States (US) pregnancies per year. The disease is caused by antibodies from the mother which target proteins (also called antigens) on the fetal red blood cells (a process known as red cell alloimmunization). The most common antigen is RhD, although other antigens, such as Rhc, RhE, and Kell, may also be involved in the process.

During pregnancy, antibodies can cross the placenta and bind to the antigens on the surface of the fetus’ red blood cells, leading to fetal red blood cell destruction (hemolysis) and anemia (low red blood cell count). Anemia causes less oxygen to be delivered to all the fetal tissues and can lead to organ damage and ultimately fetal heart failure and even fetal death. In addition, sometimes fetuses that have suffered anemia during pregnancy may have significant consequences like cerebral palsy.

In the case of RhD antigen incompatibility, this antibody formation is typically preventable; however, it is not always 100% effective. Moreover, HDFN can occur with other antigen incompatibilities where there is no preventative treatment. Thus, non-invasive, safe and effective treatment alternatives are needed.

M281, an investigational product is intended to reduce the risk and severity of fetal anemia through two mechanisms:

  • 1. By blocking FcRn-mediated immunoglobulin G (IgG) recycling, thereby reducing the amount of antibodies against the fetus red blood cells in maternal circulation; and
  • 2. By reducing the placental transfer of maternal IgG, including pathogenic alloantibodies (antibodies against the fetus’ red blood cells), to the fetus.

For more information about HDFN, click the Learn More button.

Myasthenia Gravis

Myasthenia gravis (MG) is a chronic autoimmune neuromuscular disease which affects skeletal muscles that are responsible for eye movements, breathing, and moving parts of the body, resulting in muscle weakness and fatigue. All muscle movements occur when the muscle receptors receive signals from nerve cells. In MG, the immune system mistakenly attacks muscle receptors by producing anti-receptor antibodies (most commonly acetylcholine receptor [AChR] or muscle-specific kinase, [MuSK] antibodies) that can block or destroy these muscle receptors, preventing the signals from effectively reaching the muscles. Over time, this may lead to symptoms such as limb weakness, drooping eyelids, and double vision, as well as difficulties with chewing, swallowing, speech, and breathing.

While many patients with MG may be managed with current therapies, some patients may 1) fail to respond adequately despite multiple therapies, 2) not tolerate these therapies, and/or 3) have conditions that do not allow the use of these therapies. These patients may continue to experience profound muscle weakness and severe disease symptoms that limit their functions and their quality of life. Research is needed to develop new treatment options for patients with MG.

M281, an investigational product has the potential to improve the clinical signs and symptoms of myasthenia gravis by blocking FcRn-mediated IgG recycling, thereby reducing pathogenic autoantibodies.

For more information about MG, click the Learn More button.

News & Publications

For more information about the Affinity Clinical Research Initiative and Momenta Pharmaceuticals, click on the links below.

Let’s Talk About Affinity

For more information about the Affinity Clinical Research Initiative, contact us via the information to the right.

Get In Touch


Momenta Pharmaceuticals, Inc.

301 Binney Street

Cambridge, MA 02142

United States


Delaney M, Wikman A, van de Watering L, Schonewille H, Verdoes JP, Emery SP, et al. Blood group antigen matching influence on gestational outcomes (AMIGO) study. Transfusion 2017;57:525–32.

ACOG Practice Bulletin No 192: Management of Alloimmunization during Pregnancy, Obstet Gynecol 2018;131:e82–90.

Gajjar K, Spencer C. Diagnosis and management of non-anti-D red cell antibodies in pregnancy. The Obstetrician & Gynaecologist. 2009;11(2):89-95.

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Ghesquiere L, et al. Management of red blood cell alloimmunization in pregnancy. J Gynecol Obstet Hum Reprod 2018;47:197-204.

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Sanders, D, et al. International consensus guidance for management of myasthenia gravis. Neurology® 2016;87:419–425

Bird, SJ. Clinical manifestations of myasthenia gravis. Shefner JM, Targoff IN, eds. UpToDate Inc. Retrieved November, 2018, from https://www.uptodate.com (Accessed November 2018).

Bird, SJ. Diagnosis of myasthenia gravis. Shefner JM, Targoff IN, eds. UpToDate Inc. Retrieved November, 2018, from https://www.uptodate.com (Accessed November 2018).

Bird, SJ. Treatment of myasthenia gravis. Shefner JM, Targoff IN, eds. UpToDate Inc. Retrieved November, 2018, from https://www.uptodate.com (Accessed November 2018).