From Helsinki: Expert Perspectives on the Next Generation of Clinical Evidence for FcRn Inhibitors in Myasthenia Gravis

In this activity, experts in neurology explore recently presented data on emerging FcRn inhibitors for generalised myasthenia gravis.

1. PeerVoice

From Helsinki: Expert Perspectives on the Next Generation of Clinical
Evidence for FcRn Inhibitors in Myasthenia Gravis

Learning Objectives

Summarise the latest clinical data on emerging FcRn inhibitors in generalised
myasthenia gravis (gMG)

Evaluate how emerging evidence is advancing identification of the need for, and
optimised management with, FcRn inhibitors in patients with gMG

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Part 1 of 2: The Next Generation of FcRn Inhibitors for Myasthenia Gravi:
A Review of Emerging Data

Carlo Antozzi, MD

Neurologist and Head of Immunotherapy and Apheresis Unit
Neuroimmunology and Muscle Pathology Unit

Neurological Institute Foundation C. Besta

Milan, Italy

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Disclosures
Carlo Antozzi, MD, has a financial interest/relationship or affiliation in the

form of:
Advisory Board for argenx and Janssen Inc.

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Current and Emerging Targeted Therapies for gMG

<> Rapsyn
O Acetyicholine
Acetylcholine
receptor
Cytokines and chemokines
Cl complex + Iscalimab
2 Belimumab
I: ! Toad
attack comple: Satralizumab
R coro Fanon
Complement inhibitors + Efgartigimod (EFG)
Eculizumab (ECU) * Rozanolixizumab (RZN)
Qrrernaisesigs + Ravulizumab (RVZ) + Nipocalimab (NIP)
2 Zilucoplan (ZI) + Batoclimab (BAT)
\Y Post-synaptic membrane + Pozelimab (POZ)
N sche antivoay - Cemdisiran (CEM)

Nair SS, Jacob S. Immunotargets Ther. 2023:1225-45.

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MOA of FcRn Inhibition

Monocyte endothelial cell: FcRn-mediated recycling

Fern
©

.
186 Freenet

ea À

À 4 S

7 y 6) “

Protein pH Ta

+ Recycled igG an
albumin released

‘Albumin +

Acicitied
endosome

Sorting ot
FoRn-IgG complexes.

The binding of IgG and albumin to the FcRn

receptors prolongs their half-lives due to the

prevention of lysosomal degradation

Bho

| Bil V. Front Neurol. 202344122912.

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Fern

Protein
.

Fon blocking agent À
156
À

eA
N

‘Albumin +

Acidified
‘endosome

Binding of the FcRn therapeutic agent, thus
preventing the recycling of IgG due to
increased lysosomal degradation

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6. PeerVoice

Real-World Experience With Efgartigimod

i= 17 ested witeFa 5 Ra fe paints were hopitaed
(Fengamere Rett [RG abe ge Nov2021= apn 2024 [ras patent reduced trod cose
Ut cenas R= wena win oS
(Don quer: Gi Ave with on arch 2022 = iy 2028 cae atan erates
|EPO-200) [MG-ADL score 25 points june rm
Germany =2cenres = 68 rested with FG o REN E

ir moderate short ficcy RVZ ad E

(Stascheit F et al: (EFG:n = 21; RZN:n = 42) [san 2023 - Dec 2023 5
(essen Ro menu y Ma AL and O core
[China - 14 centres IN = 61 treated with EFG |CMI was rapidly achieved in 97% of patients at 13 + 0.7
[(Luo S et al; |AChR Ab+ gMG (n = 56) [Sept 2023 - Dec 2023 | weeks -70% of all participants had a mild disease
lEpR=244) 'ACHR Ab- gMG (n = 5) [status with MG-ADL s4 after EFG treatment
hay 4 cones i= 63 weoted with €or EGU ECUhadebttr affect nthe QU score beter NG
\(Sacca F et al; KEFG: n = 31; ECU: n = 32) [Sept 2023 - Jan 2024 _|deterioration/crisis prevention, and better steroid-
[OPR-081) JACHR Ab+ gMG |sparing effect compared with EFG.

* Based on data presented at the 10th Congress of the European Academy of Neurology (EAN 2024).

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Efgartigimod: Updates From the ADAPT-SC+ Trial

Mean Change in MG-ADL Total Score From Baseline

iv-sc sc-sc
o sara ° a
sE one, ES se yee en
CEN 20290) 74(030) 837 20:0 6005)
98: ow par
de ite
HE E
s s
Wao 1 2 3 4 > weno Tr
En
TORT tt tttt
Sc dosing Sc dosing

Data shown in AChR Ab+ patients.
CMI: 22-point improvement in total MG-ADL score from study baseline.

Hoffmann $ et al EAN 2024. EPO-802.

HRQOL Improvements
m0-201-180
ÿ my m erase
$ en de ES
o
23
21, =
so 23
HE s
BP 4| See
1e roma
nor" ADAPT-SC+
nv M me
ER (em)
Bs
33% ns
5S 0
is”
HR “
HE
g 6
Soced Feta EN 2024 EPO-208

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Efgartigimod for AChR Ab-Negative MG

Improvement in Mean MG-ADL Score Across 6 Cycles MG-ADL Improvement
RWD (IV administration of EFG)
ADAPTS ADAPT-sc+ re E
Orce 1 2 3 4 5 6 [
8 00-400 5 HE ss

Mean Change in Tots! MG-ADL Score
From Study Baseline, Wook 4

‘Mean Change in Total MG-ADL Score
From Study Being, Wook 3

6
8
0
mano 107 NO m 108 00 103 Memo 89 85 82 82 04 77
eee EE) (020) (050) (95) (000) (00 (72) denna (066) (052) (002) (084) (07) (020)

eoncagynsere

Data shown in AChR Ab- patients.
MG-ADL measured at week 3 during ADAPT+ when maximal IgG reduction
and clinical improvement may have occurred.

(CMI: 22-point improvement in total MG-ADL score.

en Change see

EAN 2024. EPO-209, Antozzi C et al EAN 2024. OPR-080.

Hoffmann $ et

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Nipocalimab: Efficacy Outcomes From the Vivacity-MG3 Trial

Mean Change in MG-ADL NP + soc(n= 77) LS Mean QMG Change
2 A PBO + SOC (n = 76)
se 4 o
88 £ à
2S 2 $
sl lo
08 + 23°
si HA
2
5 s
~
gaine 2 4 6 2 + 22

6
077 4176 8 6 0 4 6 B20 2% À

Time Since Baseline, wk TAN
Average (SE) change with NIP from baseline over Average (SE) change with NIP from baseline over
weeks 22, 23, 24: -4.7 (0.329) vs -3.25 (0.335) with PBO weeks 22, 24: -4.86 (0.504) vs -2.05 (0.499) with PBO
Difference of LS means (SE): -1.45 (0.470); P = .002 Difference of LS means (SE): -2.81 (0.710); P < .001

Antozzi C et al. EAN 2024. EPR-N6.

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Abbreviations

Current and Emerging Targeted Therapies for gMG

Abbreviation(s): ACHR: acetylcholine receptor; FcRn: neonatal Fc receptor; gMG: generalised myasthenia gravis; Ig:
immunoglobulin.

MOA of FcRn Inhibition
Abbreviation(s): MOA: mechanism of action.

Real-World Experience With Efgartigimod

Abbreviation(s): Ab: antibody; CMI: clinically meaningful improvement; MG-ADL: MG Activities of Daily Living; QMG:
Quantitative Myasthenia Gravis.

Efgartigimod: Updates From the ADAPT-SC+ Trial

Abbreviation(s): EQ-5D-5L VAS: EuroQOL Health Questionnaire visual analogue scale; HRQOL: health-related quality of
life; PBO: placebo; MG-QOL-ISr: MQ QOL-15 Revised; SE: standard error.

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Abbreviations

Efgartigimod for AChR Ab-Negative MG
Abbreviation(s): MGC: MG Composite; RWD: real-world data.

Nipocalimab: Efficacy Outcomes From the Vivacity-MG3 Trial
Abbreviation(s): SOC: standard of care.

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Part 2 of 2: Identifying the Need for and Optimal Management of
Myasthenia Gravis With FcRn Inhibitors in the Real World:
How the Latest Insights Inform Clinical Practice

Francesco Saccá, MD

Associate Professor of Neurology
Federico Il University of Naples
Assistant Medical Director of Neurology
AOU Federico Il

Naples, Italy

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Disclosures

Francesco Sacca, MD, has a financial interest/relationship or affiliation in
the form of:

Grant/Research Support from AIFA; AISA ODV; Almirall Hermal GmbH; F.
Hoffmann-La Roche Ltd; Friedreich's Ataxia Research Alliance; and TARFfa.
Advisory Board for Alexion Pharmaceuticals, Inc.; argenx; AstraZeneca;
Biogen Inc.; Dianthus Therapeutics; Lexeo Therapeutics, Inc.; NEOPHARM
Ltd.; Novartis AG; Reata Pharmaceuticals, Inc.; Sandoz AG; and Zai Lab
Limited.

Speaker or Participant in Accredited CME/CPD for Alexion
Pharmaceuticals, Inc.; argenx; AstraZeneca; Biogen Inc.; Genpharm
Services; Medison Pharma; Medpharma; NEOPHARM Ltd.; and Zai Lab
Limited.

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Real-World Experience With Efgartigimod

i= 17 ested witeFa 5 Ra fe paints were hopitaed
(Fengamere Rett [RG abe ge Nov2021= apn 2024 [ras patent reduced trod cose
Ut cenas R= wena win oS
(Don quer: Gi Ave with on arch 2022 = iy 2028 cae atan erates
|EPO-200) [MG-ADL score 25 points june rm
Germany =2cenres = 68 rested with FG o REN E

ir moderate short ficcy RVZ ad E

(Stascheit F et al: (EFG:n = 21; RZN:n = 42) [san 2023 - Dec 2023 5
(essen Ro menu y Ma AL and O core
[China - 14 centres IN = 61 treated with EFG |CMI was rapidly achieved in 97% of patients at 13 + 0.7
[(Luo S et al; |AChR Ab+ gMG (n = 56) [Sept 2023 - Dec 2023 | weeks -70% of all participants had a mild disease
lEpR=244) 'ACHR Ab- gMG (n = 5) [status with MG-ADL s4 after EFG treatment
hay 4 cones i= 63 weoted with €or EGU ECUhadebttr affect nthe QU score beter NG
\(Sacca F et al; KEFG: n = 31; ECU: n = 32) [Sept 2023 - Jan 2024 _|deterioration/crisis prevention, and better steroid-
[OPR-081) JACHR Ab+ gMG |sparing effect compared with EFG.

* Based on data presented at the 10th Congress of the European Academy of Neurology (EAN 2024).

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A Real-World Study of Ravulizumab and Efg mod in MG

Clinical Efficacy Measured by QMG Score QMG Score
RVZ EFG

(OMG: Minimum Improvement in Second

Stascheit F et al. EAN 2024. EPR-242.

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A Real-World Study of Eculizumab and Efgartigimod in MG

Mean Change in MG-ADL Mean QMG Change
o ecu
E
Ex u EN bea
A +
E
3
E
i.
ol

Pete ee eee eee ss Buire Week S/S Wei? Week26 week 36 Week 48
Treatment Time wk

Week 4 in QMG graph refers to patients receiving EFG; week 5 refers to patients receiving ECU.

Saccà F et al. EAN 2024. OPR-OBI.

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17. PeerVoice

ADAPT NXT: Cyclic and Continuous Dosing of IV Efgartigimod

Entry Criteria

+ Adults (218 y) with ACHR
Ab+ gMG

+ MG-ADL score 25 (>50%
nonocular)
MGFA Class I I, or IV
Concomitant gMG
treatment required®
IgG 26 g/L

EFG IV 10 mg/kg, fix

AAAA_AAAA AAAA

4 weeks

Part A

Part B (<105 weeks)
(21 weeks) i

Ongoing extension pr

>

With option to
extend to @3W

4 weeks 4 weeks

r
Week 0 3.

Triangles indicate EFG infusion.

* Including NSISTs and/or AChEls. If receiving corticosteroids and/or NSISTs, must be on a stable dose for 21 month prior to screening
» All patients entering Part B to be transitioned to Q2W with the option to extend to @3W dosing; patients in the fixed cycle arm will

receive another cycle before Q2W transition.

Cortes-Vicente E et al EAN 2024, EPO-612.

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ADAPT NXT: MG-ADL

LS Mean Change From Baseline in MG-ADL Total Score (Week 1-21)
e EFGIV fixed cycles (n=17) e EFGIVQ2W (n= 52)

LS Mean (+SE) Change in
MG-ADL Total Score

0123456789101121314 15 16 17 18 19 20 21
Time, wk

Solid data points indicate weeks in which EFG was administered and open data points indicates weeks in which EFG was not
administered in each respective dosing regimen.
Cortes-Vicente E et al EAN 2024. EPO-612

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Vivacity-MG3: QMG

LS Mean QMG Change
@ NIP + SOC (n = 77)
© A PBO + SOC (n = 76)
2
eo
ER
ES
33
=
3
Baseline 2 4 8 2 16 20 2 24

Time, wk

Average (SE) change with NIP from baseline over
weeks 22, 24: -4.86 (0.504) vs -2.05 (0.499) with PBO
Difference of LS means (SE): -2.81 (0.710); P < .0O1

Antozi C et al. EAN 2024. EPR-16.
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Abbreviations

Real-World Experience With Efgartigimod
Abbreviation(s): ACHR Ab: acetylcholine receptor antibody; CM£ clinically meaningful improvement; ECU: eculizumab;
EFG: efgartigimod; gMG: generalised myasthenia gravis; MG-ADL: MG Activities of Daily Living; RZN: Rozanolixizumab;
QMG: Quantitative Myasthenia Gravis.

AReal-World Study of Eculizumab and Efgartigimod in MG
Abbreviation(s): SE: standard error.

ADAPT NXT: Cyclic and Continuous Dosing of IV Efgartigimod

Abbreviation(s): AChEl: acetylcholinesterase inhibitor; Ig: immunoglobulin; MGFA: MG Foundation of America; NSIST:
nonsteroidal immunosuppressive therapy.

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Abbreviations

ADAPT NXT: MG-ADL
Abbreviation(s): LS: least squares.

Vivacity-MG3: QMG
Abbreviation(s): NIP: nipocalimab; PBO: placebo; SOC: standard of care.

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