Data-Driven Decision-Making in Primary Biliary Cholangitis: Evaluating the Expanding Evidence Base for PPAR Agonists

Stuart C. Gordon, MD and Marco Carbone, MD, PhD discuss primary biliary cholangitis in this CME activity titled "Data-Driven Decision-Making in Primary Biliary Cholangitis: Evaluating the Expanding Evidence Base for PPAR Agonists." For the full presentation, please visit us at www.peervoice.com/AEX870.

1. PeerVoice

Data-Driven Decision-Making in Primary Biliary Cholangitis:
Evaluating the Expanding Evidence Base for PPAR Agonists

Learning Objectives

Describe key efficacy and safety outcomes observed with use of PPAR agonists
in specific subgroups of people with primary biliary cholangitis (PBC), including
those with previous exposure to fibrates or obeticholic acid and those with
compensated cirrhosis

Evaluate rates of biochemical response and alkaline phosphatase normalisation
observed with novel PPAR agonists in individuals with PBC

Assess the impact of novel PPAR agonists on pruritus and quality-of-life
measures in individuals with PBC

PeerVoice is an EBAC® accredited provider since 2022.
This program has been supported by an independent educational grant from Gilead Sciences, Inc.

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2. PeerVoice

Part 1 of 7: Making Sense of the Evidence: Spotlight on
Second-Line Treatment Options for PBC

Stuart C. Gordon, MD

Professor of Medicine

Wayne State University School of Medicine
Michigan State College of Medicine

Grand Rapids, Michigan, USA

As

Marco Carbone, MD, PhD
Professor of Gastroenterology
University of Milano-Bicocca
Milano, Italy

Copyright © 2010-2025, Pe

3. PeerVoice

Stuart C. Gordon, MD, has a financial interest/relationship or affiliation in the

form of:

Grant/Research Support from AbbVie Inc.; GSK plc.; Ipsen Biopharmaceuticals, Inc.;
and Mirum Pharma.

Speakers Bureau participant with Gilead Sciences, Inc.

Advisory Board for Gilead Sciences, Inc.; GSK plc.; and Ipsen Biopharmaceuticals,
Inc.

Marco Carbone, MD, PhD, has a financial interest/relationship or affiliation in the
form of:

Consultant for Cascade Biotechnology Inc; Gilead Sciences, Inc.; GSK plc.;

Ipsen Biopharmaceuticals, Inc.; Mirum Pharma; and Zydus Pharmaceuticals, Inc.
Speakers Bureau participant with Amgen Inc.; Gilead Sciences, Inc.; GSK plc.;
Ipsen Biopharmaceuticals, Inc.; and Mirum Pharma.

Advisory Board for Gilead Sciences, Inc.; GSK plc.; Ipsen Biopharmaceuticals, Inc.;
and Mirum Pharma.

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4. PeerVoice

PBC: Current Treatment Paradigm

Diagnosis

Initiate UDCA (13-15 mg/kg/day)
y

At 12 months
Assess biochemical response to UDCA

Adequate response

| Inadequate response

Second-line therapy options

y t + (OCA)
Continue UDCA Add second-line ||. Elafibranor
indefinitely therap + Seladelpar
+ Fibrates (off-label)
| Assess response — If complete response

Change second-line
treatment or refer

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patient to a clinical trial

y
Ifno or incomplete
response

Continue second-line
therapı

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5. PeerVoice

PPAR Agonists: Novel Second-Line Treatment Opti in PBC

FDA

EMA

www.peervoice.com/AEX870

Elafibranor
PPAR a/6 agonist

(ELATIVE)

Seladelpar
PPAR 8 agonist
(RESPONSE)

2024

2024

2024

2025

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6. PeerVoice
ELATIVE Study: Outcomes With Elafibranor vs Placebo

Change in Score on the Worst Itch

Biochemical Response
Numeric Rating Seale (WI-NRS)

Eutbrance Placa
es en Pr Mea Pt
« 1, Eliane ac
*s E oe The LS mean change did not
Edo En differ significantly between
¿o se groups (-1.93 vs -1.15
2% ES difference, -0.78
o a 95% Cl, -1.99 to 0.42; P = .20)
“mm Ye 0 4 8 @ 6 20 24 26 82 36 40 da 48 82
Time, wi Time, wk
ALP Normalisation Most Frequent AEs With Elafibranor vs Placebo
brane Placebo
35 . Event, Placebo
: % of patients 3)
5
y Abdominal pain m 56
go
¿ Diarrhoea m 94
s
= Nausea m 56
o
4 76 26 ss Vomiting mi 18
Time, wk Pruritus 20.4 26.4

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7. PeerVoice

ELATIVE: OLE Study With Elafibranor

Screening Double-Blind (DB) Long-Term Extension
Patients with PBC Elafibranor 80 mg (n = 108)
with inadequate
response or —— Elafibranor 80 mg
intoleranceto R21|
UDCA (N = 161) Placebo (n = 53)
‘Common DB Variable DB
2-12wk 52 wk 0-52 wk 4-5y
Safety phone calls/ i Safety phone calls/
Study visits study visita
terrae aternate
every 26 wk every 26 w
jetta ey! q q e t 4
>
SRA A ge A at

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8. PeerVoice

RESPONSE Study: Outcomes With Seladelpar vs Placebo

Rates of Biochemical ALP Patients With BL Pruritus NRS Score 24
Response Normalisation =

wo o

23 P<.001 P<.001

ss] — — Los

ar e +
x» 8 16 15
$ so aly 5 at —
E E = 26
E
& 3-3 33
Placebo Seledeiper Placebo Selber
(3/68) sas) (ores) (228) Time, mo
Most Frequent AEs With Seladelpar vs PBO Seladelpar, n = 49

Event, —— Placebo,
% of patients
COVID-19 180
Headache 78
‘Abdominal pain 70
Nausea 6.2
Abdominal distention 62
Pruritus 47

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verVoice

9. PeerVoice

ASSURE: OLE Study With Seladelpar

Phase 3 RESPONSE: ;
Pivotal PBO-controlled ee
10 mg. 12 mo NE
MESS Ongoing

Rollover to ASSURE

RESPONSE Seladelpar 10 mg

Seladelpar 10 mg
RESPONSE RESPONSE Placebo
Screening

ÄL variable zopin

eolndelpar treatment

RES weety/monthy ws Is Ines
O EE
BPH Me? Hye? 2e

é #

* 180 patients from legacy studies; 104 patients from RESPONSE seladelpar group (continuous seladelpar):
55 patients from RESPONSE PBO group (crossover seladelpar).

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erVeice

10. PeerVoice

Abbreviations and References

PBC: Current Treatment Paradigm

Abbreviation(s): OCA: obeticholic acid; PBC: primary biliary cholangitis; UDCA: ursodeoxycholic acid.
Reference(s): Sohal A, Kowdley KV. Hepat Med. 2023;31:63-77.
Trivella J et al. Hepatol Commun. 2023;7:e0179. doi: 101097/HC90000000000000179.

PPAR Agonists: Novel Second-Line Treatment Options in PBC

Abbreviation(s): PPAR: peroxisome proliferator-activated receptor.
Reference(s): Elafibranor Prescribing Information (PI).
httpsi//www.accessdata.fda.gov/drugsatfde_docs/label/2024/218860s000!bl.pdf. Accessed 20 October 2025.
Elafibranor Summary of Product Characteristics (SmPC). https://www.ema.europa.eu/en/documents/product-
information/igirvo-epar-product-information_enpaf. Accessed 20 October 2025.

Seladelpar Pl. https:/wwwaccessdata.fda gov/drugsatfda_docs/label/2024/217899s0001blpdf. Accessed 20 October
2025.

Seladelpar SmPC. https://www.ema.europa.eu/en/documents/product-information/lyvdelzi-epar-product-
information_en.pdf. Accessed 20 October 2025.

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11. PeerVoice

Abbreviations and References (Cont'd)

ELATIVE Study: Outcomes With Elafibranor vs Placebo

Abbreviation(s): ALP: alkaline phosphatase; BL: baseline; LS: least squares; NRS: numerical rating scale; WI: worst itch.
Reference(s): Kowdley KV; ELATIVE Study Investigators’ Group. N Engl J Med. 2024;390:795-805.

ELATIVE: OLE Study With Elafibranor

Abbreviation(s): OLE: open-label extension.

Reference(s): Kowdley KV et al. Z Gastroenterol, 2025:8:e456-e457. doi: 10.1055/s-0045-1810778.

RESPONSE Study: Outcomes With Seladelpar vs Placebo

Abbreviation(s): LSM: least-squares mean; NRS: numerical rating scale; PBO: placebo.

Reference(s): Hirschfield GM; RESPONSE Study Group. N Engl J Med. 2024:390:783-794

ASSURE: OLE Study With Seladelpar
Reference(s): Levy C; ASSURE Investigators. Am J Gastroenterol, 2025 Jun 24. doi: 10.14309/ajg.0000000000003603.

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12. PeerVoice

Part 2 of 7: Breaking Down the Baseline Characteristic:
How Well Do Study Populations Represent Real-World Practice?

Stuart C. Gordon, MD

Professor of Medicine

Wayne State University School of Medicine
Michigan State College of Medicine

Grand Rapids, Michigan, USA

NE

Marco Carbone, MD, PhD
Professor of Gastroenterology
University of Milano-Bicocca
Milano, Italy

Copyright © 2010-2025, Poervoi

13. PeerVoice

Stuart C. Gordon, MD, has a financial interest/relationship or affiliation in the

form of:

Grant/Research Support from AbbVie Inc.; GSK plc.; Ipsen Biopharmaceuticals, Inc.;
and Mirum Pharma.

Speakers Bureau participant with Gilead Sciences, Inc.

Advisory Board for Gilead Sciences, Inc.; GSK plc.; and Ipsen Biopharmaceuticals,
Inc.

Marco Carbone, MD, PhD, has a financial interest/relationship or affiliation in the
form of:

Consultant for Cascade Biotechnology Inc; Gilead Sciences, Inc.; GSK plc.;

Ipsen Biopharmaceuticals, Inc.; Mirum Pharma; and Zydus Pharmaceuticals, Inc.
Speakers Bureau participant with Amgen Inc.; Gilead Sciences, Inc.; GSK plc.;
Ipsen Biopharmaceuticals, Inc.; and Mirum Pharma.

Advisory Board for Gilead Sciences, Inc.; GSK plc.; Ipsen Biopharmaceuticals, Inc.;
and Mirum Pharma.

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14. PeerVoice

FOLD Cohort: Characteristics and Clinical Status of Patients

With PBC

Mi
Region, %
B Northeast

West
‘South
White

Yes
Gender, % Hispanic, %
jomen
Total of 4,241 cases of PBC in

FOLD healthcare systems.

unseat Unknown,

AA
BM ase
%

Race,

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15. PeerVoice

ELATIVE and RESPONSE Studies: Baseline Demographics

Characteristic

Sample size

ELATIVE (1

Elafibranor: n
Placebo: n = 53

RESPONSE (N = 193)

Seladelpar: n = 128
Placebo: n = 65

Age, y

Overall: 571: 87
Elafibranor: 57.5 = 8.4
Placebo: 56.4 + 93

Seladelpar: 56.6 + 10.0
Placebo: 57.0 + 9.2

Other ethnic groups, %.

Not specified

E Seladelpar: 49.2 + 9.9
Age at diagnosis, y Not reported TON
‘Overall: 96 Overall: 948
Female sex, % Elafibranor: 94 Seladelpar: 96.1
Placebo: 98 Placebo: 92.3
Overall: 91 Overall: 88
White race, % Elafibranor: 94 Seladelpar: 89.1
Placebo: 87 Placebo: 86.2
Asian 5,5%, Black 16%,

American Indian/Alaska Nas
3.2%, Hispanic or Latino 22.7%
(Seladelpar arm)

Time since disease/
Duration of disease, y

Overall: 8.0 + 6.2
Elafibranor: 7.9 + 5.9
Placebo: 8.3 + 6.8

Overall: 8.4 + 6.7
Seladelpar: 82 + 67
Placebo: 8.6 + 6.5

Data are from separate trials and cannot be directly compared.

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16. PeerVoice

Abbreviations and References

FOLD Cohort: Characteristics and Clinical Status of Patients With PBC
Abbreviation(s): AA: African American; ASINPI: Asian American, American Indian, or Pacific Islander; PBC: primary biliary
cholangitis.

Reference(s): Lu M; FOLD Investigators. Clin Gastroenterol Hepatol. 2018;161333-1341.e6.

ELATIVE and RESPONSE Studies: Baseline Demographics

Reference(s): Hirschfield GM; RESPONSE Study Group. N Engl J Med. 2024;390:783-794.
Kowdley KV; ELATIVE Study Investigators’ Group. N Engl J Med. 2024;390:795-805.

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17. PeerVoice

Part 3 of 7: Appreciating the Primary Outcomes:
Can We Reach Biochemical Response?

NE

Stuart C. Gordon, MD Marco Carbone, MD, PhD
Professor of Medicine Professor of Gastroenterology
Wayne State University School of Medicine University of Milano-Bicocca
Michigan State College of Medicine Milano, Italy

Grand Rapids, Michigan, USA

Copyright © 2010-2025, Poervoi

18. PeerVoice

Stuart C. Gordon, MD, has a financial interest/relationship or affiliation in the

form of:

Grant/Research Support from AbbVie Inc.; GSK plc.; Ipsen Biopharmaceuticals, Inc.;
and Mirum Pharma.

Speakers Bureau participant with Gilead Sciences, Inc.

Advisory Board for Gilead Sciences, Inc.; GSK plc.; and Ipsen Biopharmaceuticals,
Inc.

Marco Carbone, MD, PhD, has a financial interest/relationship or affiliation in the
form of:

Consultant for Cascade Biotechnology Inc; Gilead Sciences, Inc.; GSK plc.;

Ipsen Biopharmaceuticals, Inc.; Mirum Pharma; and Zydus Pharmaceuticals, Inc.
Speakers Bureau participant with Amgen Inc.; Gilead Sciences, Inc.; GSK plc.;
Ipsen Biopharmaceuticals, Inc.; and Mirum Pharma.

Advisory Board for Gilead Sciences, Inc.; GSK plc.; Ipsen Biopharmaceuticals, Inc.;
and Mirum Pharma.

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19. PeerVoice

ELATIVE and RESPONSE Studies: Biochemical-Related Endpoints

a Biochemical response defined as
His Y ALP <1.67 x ULN,
napoint 215% Reduction in ALP, and
TB <1.0 x ULN at month 12

Key
Percentage of participants with
secondary ALP <1.0 x ULN at month 12
Endpoint

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20. PeerVoice

ELATIVE and RESPONSE Studies: Lab Threshold Criteria

Lab Parameters
ALP

ELATIVE

21.67 x ULN

RESPONSE

Total bilirubin

<2 x ULN

AST/ALT

< 5 x ULN
Excluded if <3.0 g/dL or

<3 x ULN

Albumin Excluded if Rotterdam advanced*
Rotterdam advanced*

INR <1 (due to hepatic dysfunction) <11 (unless on anticoagulants)

Platelets 2150 x 10°/uL 2100 x 10°/uL

Renal function Creatinine <1.5 mg/dL or eGFR 260 eGFR >45 mL/min/1.73 m*

Other CPK <2 x ULN =

* Rotterdam advanced: TB >ULN and albumin <LLN.

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21. PeerVoice

ELATIVE Study: Primary Endpoint in Patient Subgroups

Subgroup. n

Age «65 y
Ago 265 y

Fem:
white

UDCA at baseline, yes
Prior OCA, no

ALP at baseline >3 x ULN yes
ALP at baseline >3 x ULN no.
TB at baseline >ULN, no

TB at baseline «ULB or ALB at baseline «LLN no.
TB at baseline >06 x ULN, yes

TB at baseline >0.6 x ULN, no

Europe

North America

Latin America

ALP >3 xULN or TB >ULN at baseline, yes.

ALP 23 xULN or TB >ULN at base

WI-NRS score 24 at baseline, yes.
WI-NRS score 24 at baseline, no

Cirrhosis at baseline, no

Elafibranor

83
25

102
101
102
100

43
65

104
104
2
a
a
a
18
43
65

44
64

99

Risk difference = % difference in response (change from baseline).

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20

si
E]
18 is E
40
15
28

1 +=
y
: =
| —=
a —
“8 i —
| =
a ==
i >

H =
! ——
=
M, .

a —

2 ! =.

! —.—
El H ——
o
<PBO _: Elafibranor 80 mg >
20 0 20 40 60 80 100
Risk Difference, % (95% Cl)

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22. PeerVoice

RESPONSE Study: Primary Endpoint in Patient Subgroups

Subgroup, Placebo Seladelpa
Age at serooning «85 y 53 99 re
‘Age at scrooning 265 y ” 29 .
‘Ago at diagnosis «SO y 32 al +
Age at diagnosis 250 y 33 67 .
Female so 123 *
Malo 5 5 2
white 56 na =
North America 13 50

Europe 24 39

Rest of world 28 39

ALP <350 U/L at boselino a 93 :
ALP 2350 U/L at baselne 18 35 +

T8 «O8 xUuN 32 59 >
78206 XULN 33 69 >
T8 x UN 60 108 :
TS >1KUN 5 20 q
Cirrosis, yes 2 a +
Girhosis no se 10 >
Pruritis NRS «4 42 7m

Pruritis NAS 24 23 49

UDCA, yes. si no =
Prior OCA andor fibrates, yes 1 20 a
Prior OCA andor fibrates, no 52 108 >

720 | sandr omg.
Ak Deena (95%)

Risk difference = % difference in response (change from baseline).

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23. PeerVoice

ly: Change From Baseline in ALP

Patients With Cirrhosis Patients Without Cirrhosis

LS Mean + SE

-134.8

Change From BL in ALP, U/L,

Change From BL in ALP, U/L,
LS Mean + SE

a1 3 6 9 2
Time, mo

-0- Seladelpar 10mg —0- Placebo

*P<.0001,** P «05.

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24. PeerVoice

Abbreviations and References

ELATIVE and RESPONSE Studies: Biochemical-Related Endpoints
Abbreviation(s): ALP: alkaline phosphatase; TB: total bilirubin; ULN: upper limit of normal.
Reference(s): Hirschfield GM; RESPONSE Study Group. N Engi J Med. 2024;390:783-794.
Kowdley KV; ELATIVE Study Investigators’ Group. N Engl J Med. 2024;390:795-805.

ELATIVE and RESPONSE Studies: Lab Threshold Criteria

Abbreviation(s): ALT: alanine aminotransferase; AST: aspartate aminotransferase; CPK: creatine phosphokinase; eGFR:
estimated glomerular filtration rate; INR: international normalised ratio; LLN: lower limit of normal.

Reference(s): Hirschfield GM; RESPONSE Study Group. N Engl J Med. 2024;390:783-794.

Kowdley KV; ELATIVE Study Investigators’ Group. N Engl J Med. 2024;390:795-805.

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25. PeerVoice

Abbreviations and References (Cont'd)

ELATIVE Study: Primary Endpoint in Patient Subgroups
Abbreviation(s): ALB: albumin; NRS: numerical rating scale; OCA: obeticholic acid; PBO: placebo; UDCA: ursodeoxycholic
acid; WI: worst itch.

Reference(s): Kowdley KV; ELATIVE Study Investigators’ Group. N Engl J Med. 2024;390:795-805.

RESPONSE Study: Primary Endpoint in Patient Subgroups

Reference(s): Hirschfield GM; RESPONSE Study Group. N Engl J Med, 2024:390:783-794.

RESPONSE Study: Change From Baseline in ALP

Abbreviation(s): BL: baseline; LS: least squares; SE: standard error.
Reference(s): Villamil A et al. American Association for the Study of Liver Diseases (AASLD) 2024. Presentation 164.

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26. PeerVoice

Part 4 of 7: Surveying Key Secondary Outcome:
Can We Achieve Alkaline Phosphatase Norm:

Stuart C. Gordon, MD

Professor of Medicine

Wayne State University School of Medicine
Michigan State College of Medicine

Grand Rapids, Michigan, USA

Marco Carbone, MD, PhD
Professor of Gastroenterology
University of Milano-Bicocca
Milano, Italy

Copyright © 2010-2025, Pe

27. PeerVoice

Stuart C. Gordon, MD, has a financial interest/relationship or affiliation in the

form of:

Grant/Research Support from AbbVie Inc.; GSK plc.; Ipsen Biopharmaceuticals, Inc.;
and Mirum Pharma.

Speakers Bureau participant with Gilead Sciences, Inc.

Advisory Board for Gilead Sciences, Inc.; GSK plc.; and Ipsen Biopharmaceuticals,
Inc.

Marco Carbone, MD, PhD, has a financial interest/relationship or affiliation in the
form of:

Consultant for Cascade Biotechnology Inc; Gilead Sciences, Inc.; GSK plc.;

Ipsen Biopharmaceuticals, Inc.; Mirum Pharma; and Zydus Pharmaceuticals, Inc.
Speakers Bureau participant with Amgen Inc.; Gilead Sciences, Inc.; GSK plc.;
Ipsen Biopharmaceuticals, Inc.; and Mirum Pharma.

Advisory Board for Gilead Sciences, Inc.; GSK plc.; Ipsen Biopharmaceuticals, Inc.;
and Mirum Pharma.

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28. PeerVoice

Next Steps to a PBC Diagnosis

Assess disease stage

Conti ogoels tinto in rat

Asics symptons ER ont on JOGA

Anson icono singe wath UDCA ing biochemical
aci mejia cor

prognostic criteria

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29. PeerVoice

ELATIVE OLE Study: Long-Term ALP Changes

ALP Normalisation

fo
À 0 | Goo tz
À i n Zu
5 2 poros
El IA il à à
olae Boo Pa Pi fo 1
4 8 © 9 2 m & m 8 Mm wo w 1
ALP Mean Change From Baseline 138 patients entered the OLE:
o + Previously receiving elafibranor: 93
¿ Sobran _ | * Previously receiving placebo: 45
3
ee
83
H
g
= 0. 4 B 2% 39 52 52 65 7% 9 104 7 BO M3 156
a + & E
Time, wk
Praia wo 104 1 » us 3 4 o 7 . o.
Bann nn a

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30. PeerVoice

ASSURE Study: Long-Term ALP Changes

ALP Mean Percent Change From Baseline
ALP Normalisation

æ 60 £
5 ä
3 40 :
5 E
- A [TT TT i
= i
4 0 *
2 18 24 30 a
“ime mo a ar3 6 9 2 68 2% 9%
Patients, n/N V332 98/331 7326 112/297 106/280 84/234 47/124 15/37 Timenme
Patients. 397339391 926 298 281284 14 97
+ ASSURE: Long-term, open-label, pooled analysis of seladelpar 10 mg (N = 337)
+ 124 patients had »24 months of seladelpar exposure
+ By month 30, seladelpar resulted in 41% ALP normalisation rate

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31. PeerVoice

Abbreviations and References

Next Steps to a PBC Diagnosis
Abbreviation(s): ALP: alkaline phosphatase; PBC: primary biliary cholangitis; UDCA: ursodeoxycholic acid; ULN: upper
limit of normal.

Reference(s): Leung KK et al. Aliment Pharmacol Ther. 2020;52:150-1164.

ELATIVE OLE Study: Long-Term ALP Changes

Abbreviation(s): BL: baseline; OLE: open-label extension; SE: standard error.

Reference(s): Kowdley VK et al. American Association for the Study of Liver Diseases (AASLD) 2024. Poster 5041
ASSURE Study: Long-Term ALP Changes

Reference(s): Lawitz EJ et al. AASLD 2024; Poster 132.

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32. PeerVoice

Part 5 of 7: Looking Beyond Biochemical Markers:
Can We P e Control of Pruritus?

As

Stuart C. Gordon, MD Marco Carbone, MD, PhD
Professor of Medicine Professor of Gastroenterology
Wayne State University School of Medicine University of Milano-Bicocca
Michigan State College of Medicine Milano, Italy

Grand Rapids, Michigan, USA

Copyright © 2010-2025, Pe

33. PeerVoice

Stuart C. Gordon, MD, has a financial interest/relationship or affiliation in the

form of:

Grant/Research Support from AbbVie Inc.; GSK plc.; Ipsen Biopharmaceuticals, Inc.;
and Mirum Pharma.

Speakers Bureau participant with Gilead Sciences, Inc.

Advisory Board for Gilead Sciences, Inc.; GSK plc.; and Ipsen Biopharmaceuticals,
Inc.

Marco Carbone, MD, PhD, has a financial interest/relationship or affiliation in the
form of:

Consultant for Cascade Biotechnology Inc; Gilead Sciences, Inc.; GSK plc.;

Ipsen Biopharmaceuticals, Inc.; Mirum Pharma; and Zydus Pharmaceuticals, Inc.
Speakers Bureau participant with Amgen Inc.; Gilead Sciences, Inc.; GSK plc.;
Ipsen Biopharmaceuticals, Inc.; and Mirum Pharma.

Advisory Board for Gilead Sciences, Inc.; GSK plc.; Ipsen Biopharmaceuticals, Inc.;
and Mirum Pharma.

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34. PeerVoice

Pruritu

Tool

Pruritus NRS

ols

Items / Dimensions

1-item; measures itch
intensity over 24 hr

Scale

O (no itch) to 10 (worst
imaginable itch)

PBC WI NRS

1-item; measures itch
intensity over 24 hr

O (no itch) to 10 (worst
imaginable itch)

5-D Itch Scale

5 dimensions (duration,
degree, direction,
disability, distribution)

O (no itch) to 5 (worst
itch) for 4 dimensions
except for distribution

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35. PeerVoice

ELATIVE Study: Pru

us Outcomes

Baseline Pruritue Placebo | Elafibranor
(n= 53) (n=108)

WI-NRS Score

Mean 33228 32229

Moderate-to-Severe

Pruritus, % a 42

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LS mean change
from BL

Change in Score on the Worst Itch Numeric Rating
Scale (WI-NRS)
Patients With Moderate-to-Severe Pruritus

Elafibranor Placebo
— rez

25

0 4 3 2 20 24 28 32 36 40 44 48 52
Time, wk

The LS mean change did not differ
significantly between groups

(-1.93 vs -115; difference, -0.78;
95% Cl, -1.99 to 0.42; P= .20)

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36. PeerVoice

ELATIVE Study: Patterns of Pruritus Change

Change in 5-D Itch Scale Total Domain Scores Through Week 52 in
Patients With Moderate-to-Severe Pruritus
Proportions of patients with overall improvement or worsening through Week 52

Dogree Disability
100 100
# 00 5 80
5 3
¿o ¿so
$ >
2 40 $ 40
E 2 = 2
o o
Bosetne Week 52 Baseline Week 52 Baseline Week 52 Baseline Week 52
Elafibranor Placebo Elafibranor Placebo

Score Il

w> ms ma Ms

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37. PeerVoice

SPONSE Study: Pruritus Outcomes

Baseline Pruritus

Seladelpar
(n= 128)

Patients With BL Pruritus NRS Score 24
09

LSM Change

History of pruritus, % 738 nu
pe om soo 2028
Pruritus NRS 24, % 354 383

Pruritus NRS 24, lu en

mean + SD

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Time, mo

Seladelpar resulted in a greater reduction in score on
the pruritus numerical rating scale than placebo
(least-squares mean change from baseline, -3.2 vs

-17; least-squares mean difference, -1.5;
95% Cl, -2.5 to -0.5, P = .005)

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38. PeerVoice

RESPONSE: Patterns of Pruritus Change

Change in 5-D Itch Scale Total Domain Scores and Mean Scores Through Month 12 in
Patients With Baseline Pruritus NRS 24

Degree Disability

o à
(95% Cl)

LS Mean Change

LS Mean Change
(95% Cl) 5

Time, mo

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39. PeerVoice

Abbreviations and References

Pruritus-Specific Tools

Abbreviation(s): NRS: numeric rating scale; PBC: primary biliary cholangitis; Wk worst itch.
Reference(s): Ai X et al. Scand J Gastroenterol. 2022;57:333-339.

Alrubaiy L; UK-PBC Research Consortium. Aliment Pharmacol Ther. 2019;50:1223-1231.
Elman S et al. Br J Dermatol. 2010;162:587-593.

Jacoby A et al. Gut, 2005:54:1622-1629.

Montali L; Italian-Japanese PBC Study Group. Dig Liver Dis. 2010;42:718-723.
Schattenberg J et al. J Hepatol. 2023;78:S995,

ELATIVE Study: Pruritus Outcomes

Abbreviation(s): BL: baseline; LS: least squares.
Reference(s): Kowdley KV; ELATIVE Study Investigators’ Group. N Engl J Med. 2024;390:795-805.

ELATIVE Study: Patterns of Pruritus Change
Reference(s): Kremer AE et al. European Association for the Study of the Liver (EASL) 2024. LBP-028.

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40. PeerVoice

Abbreviations and References (Cont'd)

RESPONSE Study: Pruritus Outcomes

Abbreviation(s): LSM: least-squares mean; SD: standard deviation.

Reference(s): Hirschfield GM; RESPONSE Study Group. N Engi J Med. 2024;390:783-794.
RESPONSE: Patterns of Pruritus Change

Reference(s): Hirschfield GM; RESPONSE Study Group. N Engl J Med. 2024;390:783-794.

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41. PeerVoice

Part 6 of 7: Determining the Impact on Quality-of-Life Domains:
Can We Make a Difference in Day-to-Day Lives?

Stuart C. Gordon, MD

Professor of Medicine

Wayne State University School of Medicine
Michigan State College of Medicine

Grand Rapids, Michigan, USA

NE

Marco Carbone, MD, PhD
Professor of Gastroenterology
University of Milano-Bicocca
Milano, Italy

Copyright © 2010-2025, Pe

42. PeerVoice

Stuart C. Gordon, MD, has a financial interest/relationship or affiliation in the

form of:

Grant/Research Support from AbbVie Inc.; GSK plc.; Ipsen Biopharmaceuticals, Inc.;
and Mirum Pharma.

Speakers Bureau participant with Gilead Sciences, Inc.

Advisory Board for Gilead Sciences, Inc.; GSK plc.; and Ipsen Biopharmaceuticals,
Inc.

Marco Carbone, MD, PhD, has a financial interest/relationship or affiliation in the
form of:

Consultant for Cascade Biotechnology Inc; Gilead Sciences, Inc.; GSK plc.;

Ipsen Biopharmaceuticals, Inc.; Mirum Pharma; and Zydus Pharmaceuticals, Inc.
Speakers Bureau participant with Amgen Inc.; Gilead Sciences, Inc.; GSK plc.;
Ipsen Biopharmaceuticals, Inc.; and Mirum Pharma.

Advisory Board for Gilead Sciences, Inc.; GSK plc.; Ipsen Biopharmaceuticals, Inc.;
and Mirum Pharma.

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43. PeerVoice

PBC-Specific Tools for Measuring Health-Related QoL

PBC-Specific Questionnaires

(Number of questions per domain; answers are rated from 1-5,
where 1 = best possible answer and 5 = worst possible answer)

Domaine eis) (7 domain) (Soma)
Symptoms 7 3 =
Dryness = 2 =
Itch 3 3 1
Fatigue 1 E S
Cognitive 6 5 2
Social 10 3 E
Emotional 3 3 —

* Questions about dry mouth and dry eyes are included in the symptom domain.

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44. PeerVoice

ELATIVE OLE Study: Impact of Elafibranor on Fatigue

From Baseline to Week 104

From Baseline to Week 130
uw x 100
El 3
3 80 3 80 ze
& €
E 60 2 58
i 5 co so
E 8
zw Ê 40
5 2 3 20
& 5
2° so =
PESETA PBC-40 Fatigue = PFSF 7e PBC-40 Fatigue ESS
(n= 18) [Ren eo (n=9) Pass (n=8)
Patients with fatigue/ =
sleepiness at BL n/N 18/48 (38%) 24148 (50%) 16145 (53%) 9/26 (35%) 12/26 (46%) 8/26 (31%)

Patients included are those with non-missing data at baseline and week 104 and week 130. MCIDs defined as an improvement (decrease)
from BL 23, 25, and 23 for the PFSF 7a; PBC-40 Fatigue domain; and ESS, respectively. Moderate-to-severe fatigue defined as PFSF 7a
total score 260 or PBC-40 Fatigue domain total score 229 at BL, and excessive sleepiness defined as ESS total score 210 at BL.

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45. PeerVoice

ELATIVE Study: Impact of Elafibranor on Fatigue and Pruritus

Mean Score Change

Baseline Week 52 Baseline Weck 52

PFS 7a

Elafibranor n = 95
Placebo n = 46

-4 | Eafibranor n= 53
Placebo n= 26

PRC-40 Fat
ran

Moderate to severe All patients

fatigue ot BL

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Spearman's correlation None Weck Moderato Strong Perfect
coefficient: ES oF 7 7

Distribution of patients at baseline with moderate to severe fatigue and/or

pruritus

Sena praia
‘and moderate to
Severe aigue

‘Moderate to severe

|Moderate to severe pruritus and fatigue!
n=37

za

Correlation between fatigue (PFSF 7a) and pruritus (WI NRS) at baseline

Patients with moderate to severo fatigue at basal
pg

ELA‘P8O n= 68 085
Correlation between change from baseline in fatigue (PFSF 7a) and
pruritus (WINRS)

Allpatients

ELA = 80; ELASPBO n = 19 018020

Patients with moderate to severe fatigue at baseline
ELA n= SE ELASPBO n = 44 Re

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46. PeerVoice

RESPONSE Study: Quality-of-Life Measures in Patients With

Pruritus

PBC-40 Sleep Disturbance PBC-40 Fatigue

LS Mean Change
From BL, + SE
LS Mean Change
From BL, + SE
ÉS

Bi 8 6 9 nu
Time, mo

Time, mo

© Seladelpar 10 mg(n=45) e Placebo (n = 25)
of patients

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47. PeerVoice

Abbreviations and References

PBC-Specific Tools for Measuring Health-Related QoL

Abbreviation(s): PBC: primary biliary cholangitis; QoL: quality of life.

Reference(s): Ai X et al. Scand J Gastroenterol. 2022:57:333-339.

Alrubaiy L; UK-PBC Research Consortium. Aliment Pharmacol Ther. 2019;50:1223-1231.
Elman S et al. Br J Dermatol. 2010;162:587-593.

Jacoby A et al. Gut, 2005:54:1622-1629.

Montali L; Italian-Japanese PBC Study Group. Dig Liver Dis. 2010;42:718-723.
Schattenberg J et al. J Hepatol. 2023;78:5995

ELATIVE OLE Study: Impact of Elafibranor on Fatigue

Abbreviation(s): BL: baseline; ESS: Epworth Sleepiness Scale; MCID: minimum clinically important difference; OLE: open-
label extension; PFSF: patient-specific functional scale.
Reference(s): Swain MG et al. American Association for the Study of Liver Diseases (AASLD) 2024. Abstract 5042.

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48. PeerVoice

Abbreviations and References (Cont'd)

ELATIVE Study: Impact of Elafibranor on Fatigue and Pruritus

Abbreviation(s): ELA: elafibranor; NRS: numerical rating scale; PBO: placebo; WI: worst itch.
Reference(s): Jones DE et al. European Association for the Study of the Liver (EASL) 2025. Poster THU-294.

RESPONSE Study: Quality-of-Life Measures in Patients With Pruritus

Abbreviation(s): LS: least squares; SE: standard error.
Reference(s): Kremer A et al. AASLD 2024. Abstract 0167.

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49. PeerVoice

Part 7 of 7: Targeting Transplant-Free Survival:
Can We Improve Predicted Prognosis?

hy

Stuart C. Gordon, MD Marco Carbone, MD, PhD
Professor of Medicine Professor of Gastroenterology
Wayne State University School of Medicine University of Milano-Bicocca
Michigan State College of Medicine Milano, Italy

Grand Rapids, Michigan, USA

Copyright © 2010-2025, Peervoi

50. PeerVoice

Stuart C. Gordon, MD, has a financial interest/relationship or affiliation in the

form of:

Grant/Research Support from AbbVie Inc.; GSK plc.; Ipsen Biopharmaceuticals, Inc.;
and Mirum Pharma.

Speakers Bureau participant with Gilead Sciences, Inc.

Advisory Board for Gilead Sciences, Inc.; GSK plc.; and Ipsen Biopharmaceuticals,
Inc.

Marco Carbone, MD, PhD, has a financial interest/relationship or affiliation in the
form of:

Consultant for Cascade Biotechnology Inc; Gilead Sciences, Inc.; GSK plc.;

Ipsen Biopharmaceuticals, Inc.; Mirum Pharma; and Zydus Pharmaceuticals, Inc.
Speakers Bureau participant with Amgen Inc.; Gilead Sciences, Inc.; GSK plc.;
Ipsen Biopharmaceuticals, Inc.; and Mirum Pharma.

Advisory Board for Gilead Sciences, Inc.; GSK plc.; Ipsen Biopharmaceuticals, Inc.;
and Mirum Pharma.

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51. PeerVoice

ELATIVE Study: Mean Change in GLOBE and UK-PBC Scores

GLOBE UK-PBC

8 os wos

2 A

Fo ES

©. q

¿o $

2 02 © -01

5 -03 © 02

go 5 -03

8 os $ -04

o4 13 26 39 52 ES 0.4 13 26 39 52

Time, wk Time, wk

= Elafibranor 80 mg (n = 108) æ Placebo (n = 53)

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52. PeerVoice

ELATIVE Study: Long-Term Predicted TFS

Elafibranor (n = 108)

à: Baseline + Week 52
100 + (expected;n=108) (observed; n = 92)

Median Estimated TFS, %

10 years 15 years

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Placebo (n = 53)

a Baseline + Week 52
100 (expected; n = 53) (observed; n = 45)

Median Estimated TFS, %

10 years 15 years

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53. PeerVoice

SPONSE/ASSURE Study: Mean C

RESPONSE ASSURE

Mean Change From BL in
GLOBE Score + 95% Cl

-08 - - - —— - -
BI 3 6 9 1213 15 18 2 24
Time, mo

= Seladelpar 10 mg (n =125) -* Crossover to 10 mg (n = 52) 10 mg, 2-year completers (n = 27) -*- Placebo (n = 65)

One patient had their month 24 visit early and is not represented in the 2-year completers arm.

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54. PeerVoice

SPONSE Study: Predicted TFS

Continuous Seladelpar Placebo + Prior to treatment
100 100
3-month treatment
so —- 1-year treatment
+- 2-year treatment
80

Mean Predicted TFS
3

Mean Predicted TFS
Probability + 95% Cl

2
8

8

HRs calculated with survival estimates.

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55. PeerVoice

Abbreviations and References

ELATIVE Study: Mean Change in GLOBE and UK-PBC Scores

Abbreviation(s): PBC: primary biliary cholangitis; SE: standard error.

Reference(s): Kowdley VK et al. American Association for the Study of Liver Diseases (AASLD) 2024. Poster 5041.
ELATIVE Study: Long-Term Predicted TFS

Abbreviation(s): TFS: treatment-free survival.

Reference(s): Kowdley VK et al. AASLD 2024. Poster 5041.

RESPONSE/ASSURE Study: Mean Change in GLOBE Score

Abbreviation(s): BL: baseline.

Reference(s): Hansen B et al. European Association for the Study of the Liver (EASL) 2025. Abstract 1839.

RESPONSE Study: Predicted TFS
Reference(s): Hansen B et al. European Association for the Study of the Liver (EASL) 2025. Abstract 1839.

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