A Long-Term, Single-Arm, Open-label, Multicenter Phase 3 Study to Evaluate the Safety and Tolerability of Multiple Subcutaneous Injections of Efgartigimod PH20 SC in Patients With Generalized Myasthenia Gravis

gMG is a rare, chronic, neuromuscular autoimmune disease caused by pathogenic
IgGs targeting the neuromuscular junction (NMJ), producing reduced
neuromuscular transmission and debilitating and potentially life-threatening
muscle weakness and chronic fatigue. Generalized muscle weakness results in
difficulties in mobility, speech, swallowing, vision, and respiration. Up to
20% of patients develop potentially life-threatening myasthenic crisis
involving respiratory failure requiring mechanical ventilation.

ARGX 113 (efgartigimod) is an investigational antibody fragment and a
first-in-class neonatal Fc receptor (FcRn) antagonist that is being evaluated
for the treatment of patients with severe autoimmune diseases mediated by
pathogenic IgG autoantibodies, including gMG. Approximately 90% of patients
with gMG have detectable levels of IgG autoantibodies in the serum. Most
commonly, these antibodies are against the acetylcholine receptor (AChR).
Efgartigimod leads to degradation circulating disease-causing pathogenic
antibodies by blocking FcRn.

FcRn is present throughout life and expressed predominantly in endothelial
cells and cells of myeloid lineage. FcRn has a specific role in IgG
homeostasis, recycling all IgG subtypes, which rescues them from lysosomal
degradation. This FcRn-mediated recycling results in the longer half-life and
higher concentrations of IgG, including pathogenic IgG autoantibodies, as
compared to other Igs that are not recycled by FcRn. FcRn also promotes
transcytosis of IgG into tissues. Additionally, FcRn recycles albumin using a
site that is distinct from the IgG binding site.

Efgartigimod is a human IgG1 antibody Fc fragment, a natural ligand of FcRn,
engineered for increased FcRn affinity at both physiological and acidic pH.
Efgartigimod outcompetes endogenous IgG binding, preventing FcRn-mediated
recycling of IgGs and increasing IgG degradation.

The efficacy of efgartigimod IV based on the percentage of MG-ADL responders
was demonstrated against placebo in study ARGX-113-1704. Further, there was a
strong association between total IgG and AChR-Ab reductions and clinical
response, as measured by the percentage
of MG-ADL responders. This strong association was used to bridge from
efgartigimod IV to efgartigimod PH20 SC in study ARGX-113-2001. This study
showed noninferiority of the pharmacodynamic effect (as measured by IgG percent
reduction at week 4) of efgartigimod
PH20 SC 1000 mg compared with efgartigimod IV 10 mg/kg in participants with gMG
after 1 treatment cycle of 4 weekly administrations.

Given efgartigimod*s mechanism of action of reducing IgG levels, the strong
association btween total IgG reduction and clinical response in patients with
gMG, the SC formulation of efgartigimod PH20 SC may provide an alternative to
efgartigimod 10 mg/kg IV, giving patientswith gMG treatment optionality and
flexibility.. A detailed description of the chemistry, pharmacology, efficacy,
and safety of efgartigimod is provided in the Investigator*s Brochure (IB).

Primary:
To evaluate the long-term safety and tolerability of efgartigimod PH20 SC in
participants with Generalized Myasthenia Gravis (gMG).

Secondary:
• To evaluate the impact of efgartigimod PH20 SC on disease severity
• To evaluate the effect of efgartigimod PH20 SC on Pharmacodynamic (PD)
• To evaluate the immunogenicity of efgartigimod PH20 SC
• To evaluate the impact of efgartigimod PH20 SC on the quality of life (QoL)
of the participants
• To evaluate feasibility of self administration of efgartigimod PH20 SC

Exploratory:
•To assess participant preference for and satisfaction with efgartigimod PH20
SC treatment

• This is a phase 3, multicenter, long-term, single-arm, open-label study to
evaluate the long-term safety and tolerability of efgartigimod PH20 SC 1000 mg.
The clinical efficacy, PD, PK, immunogenicity, impact on the QoL of the
participants, treatment satisfaction, mode of administration participant
preference and the feasibility of self administration will also be assessed.

• Study duration and treatment duration: from the participant*s first visit in
this study until, at the latest, 31 Dec 2024
- Year 1: 3-week TPs of once weekly injections, repeated as needed with at
least 28 days between TPs
- Year 2 onward: 3-week TPs of once weekly injections. It is recommended to
have IPs of at least 28 days, but a subsequent treatment period can be
administered earlier based on clinical evaluation at the discretion of the
investigator. A minimal interval of 7 days after the last investigational
medicinal product (IMP) administration of the previous cycle must be maintained.


• At study entry, participants will be evaluated for the need of retreatment.
Refer to the SoA in Section 1.3 of the protocol for timing of retreatment.

• Efgartigimod PH20 SC 1000 mg will be administered by injection into the
abdominal subcutaneous tissue or into the subcutaneous tissue of another
appropriate injection site. Participants or their caregivers will be trained in
self-administration. If the participant or caregiver completes the training to
the satisfaction of the investigator, the participant or caregiver will be
permitted to administer the investigational medicinal product (IMP).

• Participants and their caregivers must complete the training to the
satisfaction of the site staff (a minimum of 1 site visit) before
(self-)administering efgartigimod PH20 SC under the supervision of the site
staff. Participants and caregivers who were in the SC arm in antecedent study
ARGX-113-2001 and considered competent to (self-)administer may
(self-)administer efgartigimod PH20 SC at home as of the second visit of the
first TP. Participants and caregivers from the IV antecedent studies who are
considered competent to (self-)administer may do so at home as of the second
visit of the second TP onward. All participants must come to the site for the
first administration of a TP, even if the participant or caregiver administers.

Overall, available data confirm that efgartigimod PH20 SC has been well
tolerated across studies in different indications and has an acceptable safety
profile. More detailed information about the known and expected benefits and
risks and reasonably expected AEs of efgartigimod PH20 SC is provided in the
current IB.