ARGENX SE / ARGENX SE ADR : Tip of the Iceberg: More under the Surface

Research evidence excerpt

ARGENX SE / ARGENX SE ADR : Tip of the Iceberg: More under the Surface

Autoantibodies are believed to drive myositis pathogenicity, thus supporting

Vyvgart’s use. In myositis, antibodies play an important role not only for diagnosis, but

also as drivers of the disease. There are in fact many different myositis-specific

antibodies targeting several antigens leading to a breadth of additional clinical symptoms

on top of the common hallmark of myositis: proximal muscle weakness. For instance,

anti-synthetase syndrome antibodies and dermatomyositis antibodies are associated

with interstitial lung disease and skin rashes, while certain IMNM antibodies can lead to

difficulty in swallowing and inflammation of the heart muscle. Together with the observed

treatment effects of IVIg (see the ProDERM study) and rituximab, the role of

autoantibodies in myositis pathogenicity support the development of Vyvgart in this

indication.

Figure 6: Vyvgart reduces IMNM antibodies and restores mouse muscle function

Source: Argenx

Preclinical data directly supports Vyvgart’s potential in IMNM. We believe it is no

surprise that management has particularly highlighted Vyvgart’s potential in IMNM

(flagging a CIDP-like opportunity) considering the preclinical data in this specific subset.

In IMNM, autoantibodies are believed to cause muscle damage while impairing muscle

regeneration, thus making Vyvgart a potential therapeutic option. Preclinical data from

mice injected with IMNM autoantibodies show that Vyvgart reduces autoantibody levels,

while restoring grip and muscle strength compared to untreated mice. Biopsies further

revealed that Vyvgart reduced the number of necrotic cells while generating clusters of

regenerating muscle fibers, supporting its potency on the two hallmarks of the