Document Details

BIOGEN 
THEMATIC PIPELINE SEMINAR
LUPUS
September 3, 2025
This presentation and the discussions during the related conference call contain forward-looking statements relating to, among others: our journey to build a new Biogen with an aim of long-term sustainable growth in our commercial
portfolio; the potential and expansion of our late-stage pipeline to support long-term growth; our potential to deliver medicines to patients of lupus; the potential benefits, safety and efficacy of litifilimab and dapirolizumab pegol (DZP,
developed in collaboration with UCB); the growth potential of lupus treatments into a larger multi-billion dollar market; the potential for lupus treatments to be a pillar of Biogen’s long-term growth; the anticipated benefits, risks and
potential of our collaboration arrangements with UCB and other partners; the innovation of our lupus and other pipeline products; the potential of Biogen’s pipeline in early-stage development, including felzartamab in lupus nephriti...

BIOGEN 
THEMATIC PIPELINE SEMINAR
LUPUS
September 3, 2025
This presentation and the discussions during the related conference call contain forward-looking statements relating to, among others: our journey to build a new Biogen with an aim of long-term sustainable growth in our commercial
portfolio; the potential and expansion of our late-stage pipeline to support long-term growth; our potential to deliver medicines to patients of lupus; the potential benefits, safety and efficacy of litifilimab and dapirolizumab pegol (DZP,
developed in collaboration with UCB); the growth potential of lupus treatments into a larger multi-billion dollar market; the potential for lupus treatments to be a pillar of Biogen’s long-term growth; the anticipated benefits, risks and
potential of our collaboration arrangements with UCB and other partners; the innovation of our lupus and other pipeline products; the potential of Biogen’s pipeline in early-stage development, including felzartamab in lupus nephritis and
BIIB142; how our proven track record in MS positions us to succeed in lupus; the risks and uncertainties associated with drug development and commercialization; our strategy and plans; potential of, and expectations for, our
commercial business and pipeline programs; clinical development programs, clinical trials, and data readouts and presentations; regulatory discussions, submissions, filings, and approvals and the timing thereof; the potential benefits,
safety, and efficacy of our and our collaboration partners’ products and investigational therapies; actions to improve the risk profile and productivity of our R&D pipeline, collaborations, and business development activities; expected
strong cash flow and our future financial and operating results and financial guidance. These forward-looking statements may be accompanied by such words as “aim,” “anticipate,” “assume,” “believe,” “contemplate,” “continue,”
“could,” “estimate,” “expect,” “forecast,” “goal,” “guidance,” “hope,” “intend,” “may,” “objective,” “outlook,” “plan,” “possible,” “potential,” “predict,” “project,” “prospect,” “should,” “target,” “will,” “would,” and other words and terms of
similar meaning. Drug development and commercialization involve a high degree of risk, and only a small number of research and development programs result in commercialization of a product. Results in early-stage clinical trials may
not be indicative of full results or results from later stage or larger scale clinical trials and do not ensure regulatory approval. You should not place undue reliance on these statements. Given their forward-looking nature, these
statements involve substantial risks and uncertainties that may be based on inaccurate assumptions and could cause actual results to differ materially from those reflected in such statements. These forward-looking statements are
based on management's current beliefs and assumptions and on information currently available to management. Given their nature, we cannot assure that any outcome expressed in these forward-looking statements will be realized in
whole or in part.
We caution that these statements are subject to risks and uncertainties, many of which are outside of our control and could cause future events or results to be materially different from those stated or implied in this document,
including, among others, factors relating to: our substantial dependence on revenue from our products and other payments under licensing, collaboration, acquisition or divestiture agreements; uncertainty of long-term success in
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compete, including increased competition from new originator therapies, generics, prodrugs and biosimilars of existing products and products approved under abbreviated regulatory pathways; our ability to effectively implement our
corporate strategy; the successful execution of our strategic and growth initiatives, including acquisitions; the drivers for growing our business; difficulties in obtaining and maintaining adequate coverage, pricing, and reimbursement for
our products; the drivers for growing our business, including our dependence on collaborators and other third parties for the development, regulatory approval, and commercialization of products and other aspects of our business, which
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These statements speak only as of the date of this presentation and the discussions during this conference call and are based on information and estimates available to us at this time. Should known or unknown risks or uncertainties
materialize or should underlying assumptions prove inaccurate, actual results could vary materially from past results and those anticipated, estimated or projected. Investors are cautioned not to put undue reliance on forward-looking
statements. A further list and description of risks, uncertainties and other matters can be found in our Annual Report on Form 10-K for the fiscal year ended December 31, 2024 and in our subsequent reports on Form 10-Q and Form 10-
K, in each case including in the sections thereof captioned “Note Regarding Forward-Looking Statements” and “Item 1A. Risk Factors,” and in our subsequent reports on Form 8-K. Except as required by law, we do not undertake any
obligation to publicly update any forward-looking statements whether as a result of any new information, future events, changed circumstances or otherwise.
FORWARD-LOOKING STATEMENTS
2
Priya Singhal, M.D., 
M.P.H.
Head of Development
CALL PARTICIPANTS
3
Daniel Quirk, M.D., 
M.P.H., M.B.A.
Chief Medical Officer, Head 
of Medical Affairs
Adam Meyers, 
M.B.A., M.S.
Head of Immunology and 
New Disease Areas Franchise
Diana Gallagher, 
M.D.
Head of Clinical Development, 
MS&I and AD
4
AGENDA
Opening Remarks
Lupus Overview
Late-stage Lupus Programs:
  Dapirolizumab Pegol in SLE
Q+A
Late-stage Lupus Programs:
  Litifilimab in SLE And CLE
Q+A
Concluding Remarks
Priya Singhal, M.D., M.P.H.
Head of Development
Daniel Quirk, M.D., M.P.H., M.B.A.
Chief Medical Officer, Head of Medical Affairs
Diana Gallagher, M.D.
Head of Clinical Development, MS&I and AD
All participants
Diana Gallagher, M.D.
Head of Clinical Development, MS&I and AD
All participants
Priya Singhal, M.D., M.P.H.
Head of Development
OPENING REMARKS
Head of Development
Priya Singhal, M.D., M.P.H.
WE ARE ON A JOURNEY WITH THE AIM OF BUILDING 
THE NEW BIOGEN
6
Salanersen^
(SMA)
Litifilimab
(SLE + CLE)
Zorevunersen*
(Dravet syndrome)
Dapirolizumab Pegol*
(SLE)
Potential 
Opportunities for 
Business Development
Other Pipeline
BIIB080^
(Early AD + dementia)
Felzartamab
(AMR + IgAN +
PMN +MVI + LN) 
Expected strong cash flow supports a balance sheet that allows for investment to augment growth
Maximize the profitability of the legacy 
MS business
Continue to build momentum of ongoing 
drug launches
Advance our high conviction late-stage 
pipeline to support long-term growth
Strategic Objectives
*
*
^
^
*Collaboration program; ^ Licensed from Ionis Pharmaceuticals, Inc. AD = Alzheimer’s disease; AMR = antibody mediated rejection; CLE = cutaneous lupus erythematosus; IgAN = IgA nephropathy; LN = lupus 
nephritis; MS = multiple sclerosis; MVI = microvascular inflammation in kidney transplant patients; PMN = primary membranous nephropathy; SLE = systemic lupus erythematosus; SMA = spinal muscular atrophy
PIPELINE NOW INCLUDES MULTIPLE HIGH SCIENTIFIC 
CONVICTION LATE-STAGE ASSETS
7
Alzheimer’s disease
Lecanemab (Aβ mAb)* – Preclinical AD
BIIB080 (tau ASO)^ – Early AD
Immunology
Dapirolizumab pegol (anti-CD40L)* – SLE
Litifilimab (anti-BDCA2 mAb) – SLE
Litifilimab (anti-BDCA2 mAb) – CLE
Felzartamab (anti-CD38 mAb)  – LN
BIIB142 (IRAK4 degrader)* – Autoimmune disease
Nephrology
Felzartamab (anti-CD38 mAb) – Late AMR
Felzartamab (anti-CD38 mAb) – IgAN
Felzartamab (anti-CD38 mAb) – PMN
Felzartamab (anti-CD38 mAb) – Late MVI
Neuromuscular
SKYCLARYS (Nrf2 activator) – Pediatric FA
Salanersen (SMN ASO)^ – SMA
Neurodevelopmental
Zorevunersen (SCN1A ASO)* - Dravet syndrome
Parkinson’s disease
BIIB122 (LRRK2 inhibitor)* – Parkinson’s
Multiple Sclerosis
BIIB091 (peripheral BTK Inhibitor) – MS
Phase 1
Phase 2
Phase 3
Phase 3 study now underway
Phase 3 study now underway
Phase 3 study initiation planned by early 2026 
Phase 3 study now underway
Randomized Phase 2 study planned
New asset with Phase 1 study initiation planned
Phase 3 study now underway
*Collaboration program; ^ Licensed from Ionis Pharmaceuticals, Inc. AD = Alzheimer’s disease; AMR = antibody mediated rejection;  ASO = antisense oligonucleotide; CLE = cutaneous lupus erythematosus; FA 
= Friedreich ataxia; IgAN = IgA nephropathy; LN = lupus nephritis; LRRK2 = leucine rich repeat kinase 2; MS = multiple sclerosis; MVI = microvascular inflammation in kidney transplant patients; PMN = primary 
membranous nephropathy; SLE = systemic lupus erythematosus; SMA = spinal muscular atrophy
OUR IMMUNOLOGY PORTFOLIO IS ANCHORED BY 
TWO PHASE 3 LUPUS ASSETS
8
Phase 1
Felzartamab
LN
• Prior CD38 data suggests activity in lupus nephritis
• Phase 1 data expected in 2026
Phase 3
Phase 3
Litifilimab
SLE
CLE
• Potential first-in-class once-monthly 
subcutaneous for CLE and SLE
• Phase 3 SLE data expected in 2026
Phase 3
Litifilimab
• Phase 3 CLE data expected in 2027
Phase 3
Dapirolizumab-pegol
SLE
• Third ever agent to successfully 
deliver positive Phase 3 data in SLE
• Confirmatory trial results expected 
in 2027-2028
Phase 3
Dapirolizumab pegol
SLE
Note: Dapirolizumab pegol is being developed in collaboration with UCB
CLE = cutaneous lupus erythematosus; LN = lupus nephritis; SLE = systemic lupus erythematosus 
OPPORTUNITY TO DELIVER MEANINGFUL NEW MEDICINES 
FOR PATIENTS WITH LUPUS 
We believe lupus is a highly underserved market with significant potential for market expansion
• One of only three drugs with positive Phase 3 data
• Compelling data across fatigue, reduction in flares 
and fewer steroids
• May support use in pregnant women due to 
limited placental crossing
• Confirmatory Phase 3 data expected 2027/2028
• Exciting Phase 2 data in both SLE and CLE 
published in NEJM
• Compelling data on skin, joint and overall 
disease control
• Monthly SC autoinjector
• First Phase 3 data expected next year
Phase 1 study underway for Felzartamab in LN
Dapirolizumab pegol
Litifilimab
Lupus is estimated to affect millions of patients globally*
Low treatment rates due to heterogeneity and lack of treatment options
9
Note: Dapirolizumab pegol is being developed in collaboration with UCB
*Lupus Facts and Statistics. Lupus Foundation of America, www.lupus.org/resources/lupus-facts-and-statistics.. Accessed 20 Aug. 2025
CLE = cutaneous lupus erythematosus; LN = lupus nephritis; NEJM = New England Journal of Medicine; SC = subcutaneous; SLE = systemic lupus erythematosus  
WE BELIEVE OUR PROVEN TRACK RECORD IN MS 
POSITIONS US TO SUCCEED IN LUPUS
Characteristics of MS also 
associated with Lupus1
~30 years in neuro-immunology pioneering 
the development of MS treatments
•
Heterogeneous disease and symptoms
•
Younger, predominantly female
•
Associated with flares, remission, and relapse
•
Driven by underlying immunologic pathology
10
Today, MS represents a ~$24B global market2
1. Dai, X., Fan, Y. & Zhao, X. Systemic lupus erythematosus: updated insights on the pathogenesis, diagnosis, prevention and therapeutics. Sig Transduct Target Ther 10, 102 (2025) 2. Total 2024 
global sales revenue of MS products; Data sourced from IQVIA Analytics Link
MS = multiple sclerosis 
WE HAVE AN OPPORTUNITY TO DELIVER EXCITING NEW 
MEDICINES FOR PATIENTS WITH LUPUS 
11
Lupus has the potential to grow into a larger multi-billion dollar 
market with new approved treatment options
We believe our proven track record in multiple sclerosis positions 
us to succeed in lupus
We have two Phase 3 assets that have demonstrated strong 
clinical data in lupus
LUPUS OVERVIEW
Chief Medical Officer, Head of Medical Affairs
Daniel Quirk, M.D., M.P.H., 
M.B.A.
LUPUS IS A VERY COMPLEX, HETEROGENEOUS 
SET OF DISEASES
Complex biology
Variability in patient experience
Multiple organs impacted
CNS
SKIN
HEART
BLOOD
JOINTS
KIDNEY
LUNG
SERUM
SPLEEN
13
• Involves both the adaptive 
and innate immune systems
• Tissue damage caused by 
multiple factors
• Symptoms vary by patient
• Response to therapy is highly 
variable between patients
• Ambiguity of symptoms can 
lead to delays in diagnosis
Figure adapted from Crampton SP, et al. Dis Model Mech 2014;7:1033–1046, licensed under CC BY 3.0 (http://creativecommons.org/licenses/by/3.0).
• Skin-based form of lupus with symptoms including rash, 
pain, hair loss, itch and photosensitivity
• Scarring and skin atrophy sometimes occur
• Patients also experience depression, anxiety and fatigue
• Can occur in either the presence or absence of SLE
~235k
~190k
~75k
~280k
~95k
~40k
LUPUS IS COMPOSED OF DISTINCT DISEASES WITH SLE 
AND CLE BEING THE MOST COMMON
Other indications include lupus nephritis, drug-induced lupus erythematosus and neonatal lupus
• Relapsing-remitting disease course with flares that can 
cause severe organ damage
• Patients experience fatigue, pain
• Multiple organs involved – skin, joints, brain, heart, 
lungs, kidneys 
SLE
CLE
U.S.
EU4+UK
Japan
14
Patient estimates based on Biogen 2025 Global Lupus Epidemiology Research
CLE = cutaneous lupus erythematosus; SLE = systemic lupus erythematosus  
SLE
SYSTEMIC LUPUS ERYTHEMATOSUS
Typical symptoms
Patient Population
SLE significantly reduces patients’ quality of life
Health impact
SLE IS A CHRONIC SYSTEMIC AUTOIMMUNE DISEASE WITH A 
BROAD RANGE OF CLINICAL MANIFESTATIONS
• Joint involvement observed in >90% of patients1
• Skin manifestations in up to 85% of patients7
• Symptoms from other organs including kidney, 
lung, heart, and spleen, and/or CNS and serum
• ~235k patients in the U.S.*
• Disproportionately affects younger women (15-55 
years of age) and those who are Black, Asian, Hispanic, 
or of Native American descent 4-5
• Uncontrolled SLE associated with mortality rates 
2-3x higher than those in the general population2
• At diagnosis, SLE associated with higher risk of 
comorbidities including depression, anemia,
CV disease, cancer, neurological disease, and 
organ damage3 
• Fatigue is reported by 50–86% of patients with SLE - 
many describe it as their most debilitating symptom6-12 
• Often accompanied by cognitive difficulties - 
commonly described as “brain fog” - that significantly 
impairs daily functioning and productivity
SLE patients are typically treated by rheumatologists with ~6k practicing in the U.S. today^
16
* Based on Biogen 2025 Global Lupus Epidemiology Research ^ Mannion ML, Xie F, FitzGerald JD, et al. Changes in the workforce characteristics of providers who care for adult patients with rheumatologic and musculoskeletal disease 
in the United States. Arthritis Rheumatol. 2024 July;76(7). 1. Data reported from multiple studies with up to 500 patients.HR-QoL, health-related quality of life; SF-36, 36-Item Short Form Survey. 2. Barber MR, et al. Nat Rev Rheumatol 
2021; 17:515-532 3. Fanouriakis A, et al. Ann Rheum Dis 2021;80:14–25  4. Barber MR et al. Rheumatology [Oxford];2023;62:i4–i9; 5. Manson JJ, Rahman A. Orphanet J Rare Dis 2006;1:6; Olesinska M & Saletra A. Reumatologia. 
2018;56:45–54; 4. McElhone K, et al. Lupus. 2006;15:633–43; 5. Bruce IN, et al. Ann Rheum Dis. 1999;58:379–81; 6. Zonana-Nacach A, et al. Lupus. 2000;9:101–9; 7. Krupp LB, et al. J Rheumatol. 1990;17:1450–2; 8. Wysenbeek 
AJ, et al. Br J Rheumatol. 1993;32:633–5; 9. Taylor J, et al. Rheumatology (Oxford). 2000;39:620–3 
CNS = central nervous system; CV = cardiovascular; SLE = systemic lupus erythematosus 
SLE IS CHARACTERIZED BY PHASES OF FLARES 
FOLLOWED BY LOW DISEASE ACTIVITY OR REMISSION 
SLE disease activity and 
inflammation
Damage accrual
Disease course
• SLE disease activity commonly 
fluctuates
• ~25% of patients flare within 
1–2 years after achievement 
of low disease activity or 
remission1
• Increased organ damage 
occurs as the disease 
progresses
• Disease is managed by therapy 
escalation and tapering
17
Figure adapted from: Barr SG, et al. Arthritis Rheum 1999;42:2682 and Fanouriakis A, et al. Ann Rheum Dis 2021;80:14–25. 1. Adamichou C, Bertsias G. Mediterr J Rheumatol 2017;28:4–12; 
SLE = systemic lupus erythematosus 
A CONVERSATION WITH 
DR. KAREN COSTENBADER, MD, MPH
18
Karen Costenbader, MD, MPH is Professor of Medicine at Harvard 
Medical School and holds the Michael E. Weinblatt, MD Endowed Chair in 
Rheumatology in the Division of Rheumatology, Inflammation and 
Immunity at Brigham and Women’s Hospital in Boston, Massachusetts, 
where she serves as Director of the Lupus Program and Chief of the 
Section of Clinical Sciences. Dr. Costenbader’s research investigates the 
epidemiology and pathogenesis of systemic lupus erythematosus and 
rheumatoid arthritis in particular. She is an experienced research mentor 
for medical students, residents, graduate students in epidemiology, and 
rheumatology fellows and junior faculty, having trained over 50 doctoral 
and post-doctoral fellows and faculty. She is PI of the Lupus Registry 
containing data on more than 3,000 patients. She is currently the Deputy 
Editor of Arthritis & Rheumatology. She has served as the Chair of the 
NIH’s ‘Arthritis, Musculoskeletal and Skin Disease’ Study Section, Chair 
of the Medical and Scientific Advisory Council for the Lupus Foundation of 
America, and as Faculty Director of the Office of Research Careers at the 
Brigham and Women’s Hospital.
SIGNIFICANT OPPORTUNITY TO EXPAND TREATMENT AND 
BENEFIT MORE PATIENTS WITH SLE
19
Disproportionately affects women aged 15-55 and people who are Black, 
Asian, Hispanic or Native American
Characterized by flares with potential for severe organ damage followed by 
periods of remission or low disease activity
Pregnant women often stop treatment
Most patients experience joint pain and skin involvement; quality of life 
severely impacted including with symptoms of fatigue
Lack of treatment options and heterogenous patient population limit biologic 
treatment rates today
CLE
CUTANEOUS LUPUS ERYTHEMATOSUS
• ~280k patients in the U.S.*
• Disproportionately women1 
• People who are Black or Hispanic have a higher risk 
of developing CLE. Black and Asian patients typically 
have greater disease severity2-3
• CLE is a distinct disease, but up to one-third of 
patients with CLE have, or will have, SLE4-5
• 70% of patients report painful skin7
• Patients report fatigue at 13x rates of healthy 
individuals8
• Significant impact on emotional and mental health9
CLE PRIMARILY MANIFESTS IN THE SKIN AND MUCOSAL TISSUES, 
WHICH CAN OCCUR WITH OR WITHOUT SYSTEMIC MANIFESTATIONS
CLE patients are typically treated by dermatologists but are referred to a rheumatologists if they also have SLE
• Photosensitivity
• Hair loss
• Pain
• Rash
• CLE associated with higher risk of 
comorbidities including hypertension, 
dyslipidemia, anxiety disorder, obesity, 
depression, T2D, and other conditions6
• Itch
• Scarring
• Dyspigmentation
Typical symptoms
Patient Population
CLE significantly reduces patients’ quality of life
Health impact
21
* Based on Biogen 2025 Global Lupus Epidemiology Research. 1. Petersen MP, et al. Lupus. 2018;27:1424-1430. 2. Izmirly P, et al. Lupus Sci Med. 2019;6:e000344. 3. Verma SM, et al. Br J Dermatol. 
2014;170:315-321 4. Petersen MP, et al. Lupus. 2018;27(9):1424-1430. 5. Vera-Recabarren MA, et al. Clin Exp Dermatol. 2010;35:729-735.  6. Merola JF, et al. Poster presented at EADV 2024 (Abstract 
841).  7. Ogunsanya ME, et al. Lupus. 2020;29:1691-1703 8. Tarazi M, et al. Br J Dermatol. 2019;180:1468-1472 9. Klein R, et al. J Am Acad Dermatol. 2011;64:849-858
CLE = cutaneous lupus erythematosus; SLE = systemic lupus erythematosus ; T2D = type 2 diabetes 
CLE IS DISTINCT DISEASE ASSOCIATED WITH SKIN 
MANIFESTATIONS
Disfiguring scars1,2,4
Photosensitivity2
Dyspigmentation1,2
Rash1
Itch2
Pain2
Hair loss3
Chronic Skin Manifestations
Image 1: erythema; image 2: erythema, scale, infiltration; image 3: alopecia; image 4: erythema, scale, edema; CLE = cutaneous lupus erythematosus. Images obtained for use with consent.
1. Drenkard C, et al. Front Med (Lausanne) 2022;9:897987; 2. Ogunsanya ME, et al. Int J Womens Dermatol 2018;4:152–158; 3. Ogunsanya ME, et al. Br J Dermatol 2017;176:52–61;
4. Drenkard C, et al. Arthritis Care Res 2019;71:95–103
22
A CONVERSATION WITH 
DR. JOSEPH MEROLA, MD, MMSc, FAAD, FACR
23
Joseph F. Merola, M.D. MMSc, FAAD FACR
Dermatologist, Rheumatologist
Medical and Scientific Board, Lupus Foundation
President Elect, Rheumatology – Dermatology Society
THERE IS A CLEAR OPPORTUNITY TO IMPROVE 
TREATMENT OPTIONS FOR CLE PATIENTS
24
Disproportionately affects women and people who are Black or Hispanic
Characterized by skin manifestations that are often painful and 
sometimes disfiguring 
Quality of life severely impacted including body-image concerns and 
symptoms of fatigue
There are no FDA approved treatments for patients with CLE
CLE = cutaneous lupus erythematosus
OUR LATE-STAGE SLE PROGRAMS
Head of Clinical Development, 
MS&I and AD
Diana Gallagher
DCs, 
Macrophages, 
and 
Monocytes
T cell
pDC
BDCA2
CD32a
(FcγRIIa)
Innate Immune System
Adaptive Immune System
BIOLOGY OF LUPUS INVOLVES SEVERAL REINFORCING PATHWAYS 
THAT PROVIDE DISTINCT OPPORTUNITIES FOR INTERVENTION
Type 1 
IFNs
Proinflammatory mediators 
(e.g., IFNs and cytokines)
Tissue 
damage 
caused by
2. T-cell infiltration
Direct tissue damage 
and release of 
proinflammatory 
cytokines
1. Cytokines
Promote inflammation 
and immune cell 
activation
3. Auto-antibodies and 
immune complexes
Trigger inflammation and 
activate the complement 
system
pDCs (plasmacytoid Dendritic Cells) 
produce excess IFN-I and other 
cytokines and activate antigen 
presenting dendritic cells
T-cells cause direct tissue 
damage and secrete 
proinflammatory signals and 
activate B-cells via CD40
B-cells generate autoantibodies 
that cause inflammation and 
tissue damage
Key 
Immune 
Cells
26
CD38
B-cell
T cell
B cell
Autoantibodies 
and Immune 
complexes
Graphic is intended to be a simplified schematic and does not include all cell types, or signaling pathways implicated in the pathogenesis of lupus
DC = dendritic cell; IFN = interferon
OUR PIPELINE SPANS MULTIPLE POINTS OF INTERVENTION 
IN THE LUPUS CASCADE
Immune Cells
Cytokines
Intercellular Signaling
• Litifilimab – pDCs
• Felzartamab – B-cells
• Belimumab – B-cells
• CAR-T and bi-specifics – T-cells & B-cells
• Obinutuzumab – B-cells
• Litifilimab – (upstream) Type 1 IFN
• Anifrolimab – Type 1 IFN
• TYK2 – (upstream) Type 1 IFN
• Dapirolizumab pegol – CD40L
DCs, 
Macrophages, 
and 
Monocytes
T cell
pDC
BDCA2
CD32a
(FcγRIIa)
Innate Immune System
Adaptive Immune System
Type 1 
IFNs
Proinflammatory mediators 
(e.g., IFNs and cytokines)
CD38
B-cell
B cell
Autoantibodies 
and Immune 
complexes
Note: Dapirolizumab pegol is being developed in collaboration with UCB
Graphic is intended to be a simplified schematic and does not include all cell types, or signaling pathways implicated in the pathogenesis of lupus. List of therapies is non-exhaustive. 
DC = dendritic cell; IFN = interferon
27
DAPIROLIZUMAB PEGOL IN SLE
FC-FREE PEGYLATED ANTIGEN-BINDING FRAGMENT
DCs, 
Macrophages, 
and 
Monocytes
B cell
T cell
pDC
Innate Immune System
Adaptive Immune System
CD40L IS A KEY TARGET TO DISRUPT CD40 SIGNALING 
AND INTERRUPT THE IMMUNOLOGIC CASCADE IN SLE
Type 1 
IFNs
Proinflammatory mediators 
(e.g., IFNs and cytokines)
• When CD40 binds to CD40L it signals the cell to activate 
• Therefore, preventing binding CD40 to CD40L blocks the downstream signaling that activates multiple cells 
in the SLE cascade (e.g. T-cells, B-cells, pDCs)
29
Note: Dapirolizumab pegol is being developed in collaboration with UCB
Graphic is intended to be a simplified schematic and does not include all cell types expressing CD40 or CD40-CD40L signaling components, including those relevant to lupus such as 
dendritic cells and antigen presenting cells 
DC = dendritic cell; IFN = interferon; pDC = plasmacytoid dendritic cells; SLE = systemic lupus erythematosus 
DAPIROLIZUMAB PEGOL IS DESIGNED TO DELIVER EFFICACY WITHOUT 
THE POTENTIAL FOR THROMBOSIS SEEN WITH OLDER CD40L AGENTS
30
• DZP is a pegylated antibody fragment 
designed to bind to CD40L
• Lack of functional Fc domain abrogates 
the potential risk of Fc-mediated 
platelet activation and aggregation
• Conjugation to PEG provides stability 
and increases circulation
Dapirolizumab pegol (DZP)
Fab’ fragment
PEG
FC-free
Note: Dapirolizumab pegol is being developed in collaboration with UCB
A PHASE 3 STUDY WAS CONDUCTED TO EVALUATE THE 
SAFETY AND EFFICACY IN PATIENTS WITH SLE
Note: Dapirolizumab pegol is being developed in collaboration with UCB; [a] Guidelines available at the time of study design; [b] Randomized set. 1. Fanouriakis A. Ann Rheum Dis 2019;78:736–45. 
BICLA = British Isles Lupus Assessment Group-based Composite Lupus Assessment; BILAG = British Isles Lupus Assessment Group; DZP = dapirolizumab pegol; EULAR = European Alliance of 
Associations for Rheumatology; iv = intravenous; LLDAS = lupus low disease activity state; OLE = open-label extension; PBO = placebo; Q4W = every 4 weeks; SFU = safety follow up; SLE = systemic 
lupus erythematosus; SLEDAI-2K = Systemic Lupus Erythematosus Disease Activity Index-2K; SOC = standard of care; SRI-4 = SLE responder index-4.  
2 : 1
Entered
OLE/SFU
Screening
Double-blind treatment period
N=321
randomizedb
DZP 24 mg/kg + SOC Q4W (iv)
PBO + SOC Q4W (iv)
n=213b
n=108b
−2
0
4
8
12
16
48
Week
20
54
24
28
32
40
44
36
Investigators were required to initiate glucocorticoid tapering for patients with a dose >7.5 mg/day 
prednisone with the goal of reaching ≤7.5 mg/day, in line with EULAR 2019 treatment 
guidelines,a,1 with tapering starting no later than Week 8
Mandatory corticosteroid tapering 
OLE/SFU
Moderate-to-severe disease 
activity defined as:
BILAG 2004 Grade B in ≥2 
organ systems and/or a BILAG 
2004 Grade A in ≥1 organ 
system at screening and 
baseline AND
• SLEDAI-2K ≥6 at screening
Patients were excluded if there 
was no history of persisting or 
relapsing-remitting disease 
course in the past 6 months 
and no risk factors for frequent 
flares
Disease activity 
inclusion criteria
BICLA response rate at Week 48
Primary objective1
• Achievement of BICLA response at Weeks 12 & 24
• Achievement of SRI-4 response at Week 48
Key secondary objectives1
31
• Severe BILAG flares through Week 48 
• LLDAS ≥ 50% postbaseline at Week 48
39.9
46.6
49.5
29.0
38.3
34.6
0
10
20
30
40
50
60
70
0
4
8
12
16
20
24
28
32
36
40
44
48
DAPIROLIZUMAB PEGOL IS ONLY THE 3RD AGENT TO MEET 
THE PRIMARY ENDPOINT IN A GLOBAL PHASE 3 STUDY
Note: Dapirolizumab pegol is being developed in collaboration with UCB; Full analysis set. Secondary endpoints were controlled for multiplicity using a hierarchical testing procedure. As the second step of the hierarchical testing 
was BICLA response at Week 24 and the p value was >0.05 for this time point, all other secondary endpoints cannot be considered statistically significant. A composite strategy was used for intercurrent events (escape 
treatment, premature withdrawal from the study, or permanent discontinuation of study medication while remaining in the study) and patients were assigned as a non-responder from the day after the intercurrent event 
occurred. After intercurrent event handling, any remaining missing data were handled using NRI. Difference in proportion responding between DZP+SOC and PBO+SOC, 95% CI for difference in proportions, and p-values were 
estimated and tested using the CMH risk difference estimate controlling for stratification factors (pooled region [North America vs Western Europe/Asia-Pacific vs Latin America/Eastern Europe], baseline disease activity pattern 
[chronic active vs acute flaring], and baseline SLEDAI-2K score [<10 vs ≥10]). [a] Of all randomized patients. BICLA = British Isles Lupus Assessment Group-based Composite Lupus Assessment; CI = confidence interval; CMH = 
Cochran-Mantel-Haenszel; DZP = dapirolizumab pegol; NRI = non-responder imputation; PBO = placebo; SLEDKAI-2K = Systemic Lupus Erythematosus Disease Activity Index-2K; SOC = standard of care. 
Dapirolizumab significantly improved disease activity in moderate to severe SLE
Difference in proportion
(95% CI): 
14.6 (3.3, 25.8) 
p=0.0110
Week
*
*
*
*
**
Difference in proportion (95% CI): 
10.8 (−0.1, 21.7)
p=0.0518
Primary endpoint
First
secondary endpoint
Patients achieving BICLA response (%)
Difference in proportion (95% CI): 
7.9 (−3.6, 19.4)
p=0.1776
100
**p<0.05
*Nominal p<0.05
DZP+SOC (n=208)
PBO+SOC (n=107)
32
DZP PATIENTS ACHIEVED A MEANINGFUL IMPROVEMENT IN 
STEROID USE AND REDUCTION IN FLARES
23.4
11.6
0
10
20
30
40
Difference in proportion (95% CI): 
11.5 (1.4, 21.6)
Nominal p=0.0257
Patients with severe BILAG flares 
through Week 48 (%)
100
DZP+SOC 
(n=208)
PBO+SOC 
(n=107)
50.4% reduction in proportion of patients receiving 
DZP+SOC with severe BILAG flares relative to patients 
receiving PBO+SOC
72.4
52.9
0
10
20
30
40
50
60
70
80
90
0
4
8
12
16
20
24
28
32
36
40
44
48
*
*
Week
*
*
*
*
*
*
*
Patients achieving reduction of 
corticosteroid dose from >7.5 mg/day to 
≤7.5 mg/day (%)
Corticosteroid tapering began no 
later than Week 8 
100
*
DZP+SOC (n=105)
PBO+SOC (n=51)
17% more patients on the DZP+SOC were able to 
reduce their steroids compared to PBO+SOC
33
Note: Dapirolizumab pegol is being developed in collaboration with UCB
*Nominal p<0.05
CI = confidence interval; DZP = dapirolizumab pegol; PBO = placebo; SOC = standard of care
*
Note: Dapirolizumab pegol is being developed in collaboration with UCB; 1. Touma et al., Lupus, 2025; 2. Parodis et al., EULAR, 2025; 3.Morand et al., EULAR, 2025; *Nominal p<0.05
DZP = dapirolizumab pegol; FACIT = Functional Assessment of Chronic Illness Therapy; HRQoL = health-related quality of life; SoC = standard of care
34
DATA HIGHLIGHTS THE POTENTIAL OF DAPIROLIZUMAB PEGOL TO ALLEVIATE 
FATIGUE, REDUCE DISEASE ACTIVITY AND IMPROVE QUALITY OF LIFE IN LUPUS
Dapirolizumab pegol showed efficacy across multiple clinical endpoints in the positive PHOENYCS GO 
Phase 3 study, including fatigue, measures of disease activity and patient reported outcomes
•
Improvements from baseline to week 48 in 
LupusQoL scores across all domains1
• Improvements across multiple domains of fatigue 
measured by both FACIT and FATIGUE-PRO2
•
Measures of disease activity and remission, 
improved over time through 48 weeks of treatment3
PHOENYCS GO data at EULAR 2025 show that* 
compared to SoC alone, DZP + SoC resulted in:
Worse HRQoL
Better HRQoL
0
100
Change in LupusQoL scores from baseline to Week 48
PBO+SOC (n=107) 
DZP+SOC (n=208)
DAPIROLIZUMAB PEGOL WAS GENERALLY WELL 
TOLERATED IN THE PHASE 3 STUDY
35
Note: Dapirolizumab pegol is being developed in collaboration with UCB; Safety set. MedDRA v24.0. [a] The two events were reported as “herpes zoster over left eyelid and forehead, V1” and “left 
herpes zoster ophthlamicus (dermatome V1/V2)”; [b] Reported as “herpetic queratitis”. DZP = dapirolizumab pegol; MedDRA = Medical Dictionary for Regulatory Activities; PBO = placebo; SLE = 
systemic lupus erythematosus; SOC = standard of care; TEAE = treatment-emergent adverse event. 
n, (%)
DZP+SOC
n=213
PBO+SOC
n=108
Any TEAE
176 (82.6%)
81 (75.0%)
Serious TEAEs
21 (9.9%)
16 (14.8%)
Permanent discontinuation of drug or study discontinuation due to TEAEs
10 (4.7%)
4 (3.7%)
Hypersensitivity TEAEs starting on the day of or the day after an infusion
6 (2.8%)
0 (0.0%)
Infections and infestations 
131 (61.5%)
56 (51.9%)
Mild
95 (44.6%)
35 (32.4%) 
Moderate 
66 (31.0%)
36 (33.3%)
Severe
3 (1.4%)
4 (3.7%)
Serious
8 (3.8%)
6 (5.6%)
Herpes viral infections 
13 (6.1%)
14 (13.0%)
Herpes zoster
4 (1.9%)
7 (6.5%)
Ophthalmic herpes zoster
2 (0.9%)a
0 (0.0%)
Herpes ophthalmic 
1 (0.5%)b
0 (0.0%)
Thromboembolic TEAEs confirmed by an adjudication committee
1 (0.5%)
0 (0.0%)
Acute myocardial infarction
1 (0.5%)
0 (0.0%)
Deaths
1 (0.5%)
0 (0.0%)
Gangrene-related sepsis
1 (0.5%)
0 (0.0%)
PRECLINICAL FINDINGS IN PREGNANCY SUPPORT 
A POTENTIALLY DIFFERENTIATED PROFILE
36
Note: Dapirolizumab pegol is being developed in collaboration with UCB.
DZP = dapirolizumab pegol
In primates:
• DZP caused no adverse outcomes on pregnancy or infant development
• Placental transfer of DZP from mother to infant during pregnancy was 
very low, as was transfer of DZP into milk
In the human ex vivo placental model:
• DZP transfer was below the level of detection in all but one experiment
(21 out of 22 experiments )
Based on current findings, DZP is not anticipated to cross the placenta to significant 
levels and supports further investigation in pregnant women
SECOND CONFIRMATORY PHOENYCS FLY PHASE 3 
STUDY ONGOING 
Dapirolizumab pegol is being developed in collaboration with UCB [a] Estimated enrollment; [b] For patients not entering open-label extension; [c] For patients receiving >7.5 mg/day prednisone 
equivalent at baseline, tapering will be initiated no later than Week 8 to reach a target of 7.5 mg/day or below by Week 18.
BICLA = BILAG-Based Composite Lupus Assessment; BILAG = British Isles Lupus Assessment Group; DZP = dapirolizumab pegol; GC = glucocorticoid steroids; IV = intravenous; SLEDAI-2K = 
Systemic Lupus Erythematosus Disease Activity Index – 2000; SoC = standard of care; q4w = every 4 weeks.
BICLA response rate at Week 48
Primary objective
Placebo (SoC only) (n=150)a
0
24
48
DZP 24 mg/kg + SoC q4w (n=300)a
4
8
12
16
20
IV infusion:
28
32
36
40
44
Primary 
endpoint
Week:
–2
Double-blind 
period
54
Safety 
follow-upb
GC taperc
Moderate-to-severe disease activity defined as:
• BILAG 2004 Grade B in ≥2 organ systems and/or a BILAG 2004 Grade A
in ≥1 organ system at screening and baseline AND
• SLEDAI-2K ≥6 at screening
Screening
Key objectives
37
DAPIROLIZUMAB PEGOL HAS THE POTENTIAL TO HAVE 
A MEANINGFULLY POSITIVE IMPACT ON PATIENTS
38
Ongoing Phase 3 study designed to confirm the first successful
Phase 3 with data expected in 2027-2028
DZP is only the 3rd agent to show a positive global Phase 3 study in SLE
Preclinical findings in pregnancy support a potentially differentiated profile
Data show a 50% reduction in flares, meaningful reduction in corticosteroid 
use, as well as a quality-of-life improvement, including fatigue
Note: Dapirolizumab pegol is being developed in collaboration with UCB
DZP = dapirolizumab pegol; SLE = systemic lupus erythematosus
QUESTION & 
ANSWERS
LITIFILIMAB IN SLE
BDCA2 INHIBITOR
• Production of IFN-I in pDC cells is 
inhibited by internalization of 
BDCA2 into the cell
• This makes BDCA2 an attractive 
target to inhibit the production of 
IFN-I and other cytokines and 
chemokines 
ANTI-BDCA2 IS A POTENTIALLY ATTRACTIVE APPROACH FOR 
REDUCING  PRODUCTION OF IFN-I, CYTOKINES AND 
CHEMOKINES IN LUPUS
41
1. Ye Y, et al. Clin Transl Immunology 2020;9:e1139; 2. Dzionek A, et al. J Immunol 2000;165:6037–6056; 3. Liu T, et al. Sig Transduct Target Ther 2017;2:17023; 4. Blomberg S, et al. Arthritis Rheum 
2003;48:2524–2532; 5. Kaul A, et al. Nat Rev Dis Primers 2016;2:16039; 6. Sozzani S. Trends Immunol 2010;31:270–277; 7. Vermi W, et al. Immunobiology 2009;214:877–886; 8. Cao W, et al. PLoS Biol 
2007;5:e248; ; 9. Swiecki M & Colonna M. Nat Rev Immunol 2015;15:471-485. BDCA2 = blood dendritic cell antigen 2; IFN-I = interferon type I; pDC = plasmacytoid dendritic cell
BDCA2
1. Pellerin A, et al. EMBO Mol Med. 2015;7(4):464-476. BDCA2 = blood dendritic cell antigen 2; IFN-I = interferon type I; pDC = plasmacytoid dendritic cell
• Litiflilimab is a monoclonal antibody that is 
designed to bind to BDCA2
• Binding of litifilimab to BDCA2 leads to:
— Rapid internalization of BDCA2 from 
the cell surface of pDCs
— Thereby inhibiting the production of 
pDC-derived IFNs, IFN-l, cytokines, 
and chemokines1 
Litifilimab is formulated as a once-monthly SC injection
42
LITIFILIMAB IS DESIGNED TO BIND TO BDCA2 THEREBY 
INHIBITING THE PRODUCTION OF IFN-I
Two OCS rescues allowed
OCS
stable
OCS taper to
≤10 mg/day
OCS 
stable
OCS 
stable/↓
OCS
stable
0
2
4
8
11
12
16
20
24
LILAC WAS A TWO-PART, PHASE 2, RANDOMIZED, 
DOUBLE-BLIND STUDY OF LITIFILIMAB
43
Part A study design in participants with SLE and active skin disease and joint involvement1
*Sum of swollen joints and tender joints as measured on a 28-joint assessment. A joint that was both swollen and tender was counted twice
AE = adverse event; ANA = antinuclear antibody; CLASI-50 = ≥50% improvement from baseline in Cutaneous Lupus Erythematosus Disease Area and Severity Index – Activity Scale; dsDNA = double-
stranded DNA; OCS = oral corticosteroids; Q4W = every 4 weeks; SAE = serious adverse event; SC = subcutaneous; SLE = systemic lupus erythematosus; SLEDAI-2K = Systemic Lupus Erythematosus 
Disease Activity Index 2000; SoC = standard of care; SRI-4 = Systemic Lupus Erythematosus Responder Index-4
1. Furie RA, et al. N Engl J Med 2022;387:894–904
Randomization (1:1)
Double-blind, placebo-controlled treatment period
• ANA and/or anti-dsDNA 
antibody positive
• Stable lupus SoC
• Stable OCS (≤20 mg/day)
• Joint count:
– ≥4 tender joints
– ≥4 swollen joints
• Active skin disease 
(SLEDAI-2K)
Litifilimab 450 mg SC Q4W +/− SoC (n=64) 
Placebo SC Q4W +/− SoC (n=56) 
Primary efficacy
• Change from baseline 
in total active joint 
count at Week 24*
Secondary efficacy
• SRI-4
• SLEDAI-2K
• CLASI-50
Safety
• AEs and SAEs
Follow up 12 weeks
28-DAY SCREENING 
PERIOD
SELECT 
ENDPOINTS
Efficacy and safety
PART A OF THE PHASE 2 LILAC STUDY MET ITS 
PRIMARY ENDPOINT
44
Improved Joint Activity: Litifilimab significantly reduced the mean total number of active joints vs placebo
*Sum of swollen and tender joints, as measured on a 28-joint assessment. A joint that was both swollen and tender was counted twice; †A post-hoc analysis to account for an imbalance in the sex of 
patients between the study groups provided results in the same direction as those of the primary analysis, but with smaller endpoint differences between groups. However, no formal inferences can be 
made. ‡Data from 12 patients who received litifilimab at doses of 50 and 150 mg were not reported
CI = confidence interval; LSM = least squares mean; SC = subcutaneous; SLE = systemic lupus erythematosus; SoC = standard of care
1. Furie RA, et al. N Engl J Med 2022;387:894–904
Total active joint count*† in patients with SLE and active skin disease and joint involvement 
(N=132‡) (primary endpoint at Week 24)1
LSM difference vs placebo at Week 24
 −3.4 (95% CI −6.7, −0.2); P=0.04
Placebo + SoC (n=46)
Litifilimab 450 mg SC 
+ SoC (n=56)
LSM absolute
change from baseline
−20
−15
−10
−5
0
0
2
4
8
12
16
20
24
−11.6 
−15.0
Week
SECONDARY ENDPOINTS IN LILAC ALSO SHOW IMPORTANT 
RESPONSE IN SKIN AND OVERALL SYMPTOMS
0
20
30
50
Patients, %
0
2
8
12
16
20
24
10
40
60
90
4
CLASI-50 responses* (secondary endpoint at Week 24)1
Placebo + SoC (n=38)
Litifilimab 450 mg SC + SoC (n=39)
Week
100
LSM difference (95% CI) 
20.0% (−1.3, 41.3)1,2
This study was not powered to detect statistical differences in secondary endpoints. CI = confidence interval; CLASI = Cutaneous Lupus Erythematosus Disease Area and Severity Index, CLASI-50 = ≥50% 
improvement from baseline in CLASI – Activity score; LSM = least squares mean; SC = subcutaneous; SoC = standard of care; SRI-4 = Systemic Lupus Erythematosus Responder Index-4
*Assessed in patients with CLASI-A activity ≥8 at baseline
1. Furie RA, et al. Arthritis Rheumatol 2022;74(Suppl. 9):0364 (Abstract); 2. Furie RA, et al. N Eng J Med 2022;387:894–904; 3. Furie RA, et al. N Engl J Med 2022;387:894–904 (Suppl)
Placebo + SoC (n=56)
Litifilimab 450 mg SC + SoC (n=64)
0
20
30
50
100
Patients, %
0
4
8
12
16
20
24
10
40
60
90
LSM difference (95% CI) 
26.4% (9.5, 43.2)3
SRI-4 responses (secondary endpoint at Week 24)3
Week
Saw a meaningful improvement in
skin manifestations
➢Majority of patients saw 
resolution in more than half of 
their affected skin
Saw a meaningful improvement in 
systemic symptoms
➢Responses observed 
irrespective of baseline disease 
activity and steroid use
45
LITIFILIMAB HAD AN ACCEPTABLE SAFETY PROFILE WITH 
NO INCREASED RISK OF INFECTION IN LILAC PART A
*The pooled litifilimab population included patients who received litifilimab at doses of 50 mg (6 patients), 150 mg (6 patients) and 450 mg (64 patients); The most common AEs were 
diarrhea, nasopharyngitis, UTI, fall, and headache1 
AE = adverse event; SC = subcutaneous
1. Furie RA, et al. N Engl J Med 2022;387:894–904; 2. Furie RA, et al. N Engl J Med 2022;387:894–904 (Suppl)
Event, n (%)
Placebo (n=56)
Pooled litifilimab SC (n=76)*
Patients with any AE
38 (68)
45 (59)
Mild AE
14 (25)
27 (36)
Moderate AE
18 (32)
15 (20)
Severe AE
6 (11)
3 (4)
Serious events
6 (11)
4 (5)
Events leading to drug withdrawal
3 (5)
2 (3)
Events leading to study withdrawal
3 (5)
0
Death
3 (5)
0
Infections and infestations 
22 (39)
27 (36)
Phase 2 LILAC Part A1,2
46
TWO PHASE 3 STUDIES ONGOING IN SLE WITH FIRST 
DATA EXPECTED IN 2026
TOPAZ-1 and TOPAZ-2 are two identically designed multicenter, randomized, double-blind, placebo-
controlled Phase 3 studies to evaluate the efficacy and safety of litifilimab in patients with SLE receiving 
non-biologic SoC that are actively recruiting participants1–3*
One OCS rescue
Stable
Taper
to target
Stable at
target / ↓
Stable at target
or Week 32 dose
0   2   4       8      12      16      20      24      28      32      36      40      44      48      52 
Estimated primary/study completion date: 
TOPAZ-1: 2025; TOPAZ-2: 2026
•
Aged ≥18 years
•
SLE diagnosis† ≥24 weeks prior to 
screening
•
Modified SLEDAI-2K ≥6‡
•
Modified cSLEDAI-2K ≥4§
•
BILAG A in ≥1 organ system or 
BILAG B in ≥2 organ systems
•
Stable (≥4 weeks) non-biologic SoC 
for ≥12 weeks
•
≤20 mg/day prednisolone 
equivalent
KEY INCLUSION 
CRITERIA
Key secondary efficacy
•
SRI-4 (Week 24)
•
Joint-50 response 
•
Steroid-sparing effects 
•
CLASI-50 response 
•
Annualized flare rate 
Exploratory endpoints
 PROs
•
LupusQoL, SF-36, FACIT-Fatigue, 
PHQ-9, WPAI:Lupus
 Safety
•
AEs and SAEs
SELECT
ENDPOINTS
Follow up 12 weeks (or LTE)
52-week double-blind, placebo-controlled treatment period
High-dose litifilimab SC Q4W + SoC
Low-dose litifilimab SC Q4W + SoC
Placebo SC Q4W + SOC
Randomization¶ 
(1:1:1)
Primary endpoint
SRI-4 at Wk 52
N≈540
Currently recruiting
*TOPAZ-1 and -2 have different geographical recruitment sites; †EULAR/ACR criteria; ‡excluding alopecia, fever, lupus-related headache, and organic brain syndrome; §excluding anti-dsDNA, low complement C3 and/or C4, alopecia, 
fever, lupus-related headache, and organic brain syndrome; ¶stratified based on OCS use, CLASI-A score, and geographic region. ACR, American College of Rheumatology; AE = adverse event; BILAG = British Isles Lupus Assessment 
Group; CLASI = Cutaneous Lupus Erythematosus Disease Area and Severity Index; CLASI-50 = ≥50% improvement from baseline in CLASI – Activity score; CLASI-A = CLASI – Activity; cSLEDAI-2K = clinical SLEDAI-2K; dsDNA = double-
stranded DNA; EULAR = European Alliance of Associations for Rheumatology; FACIT-Fatigue = Functional Assessment of Chronic Illness Therapy – Fatigue Scale; LTE = long-term extension; LupusQoL = Lupus Quality of Life; OCS = 
oral corticosteroids; PHQ-9 = Patient Health Questionnaire 9; PRO = patient-reported outcome; Q4W = every 4 weeks; SAE = serious adverse event; SC = subcutaneous; SF-36 = Short Form 36; SLE = systemic lupus erythematosus; 
SLEDAI-2K = Systemic Lupus Erythematous Disease Activity Index 2
1. NCT04895241. Updated. January 17, 2024. Available from: https://clinicaltrials.gov/ct2/show/NCT04895241 (Accessed June 28, 2023); 2. NCT04961567. Updated. January 17, 2024. Available from: 
https://clinicaltrials.gov/ct2/show/NCT04961567 (Accessed June 28, 2023); 3. van Vollenhoven RF, et al. Lupus Sci Med 2023;10:LP-184 (Abstract)
47
LITIFILIMAB IN CLE
BDCA2 INHIBITOR
BIOPSIES SHOW PLASMACYTOID DENDRITIC CELLS ACCUMULATE IN SKIN 
LESIONS HIGHLIGHTING THE POTENTIAL FOR BDCA2 IN TREATING CLE
pDC infiltration (measured by CD123 expression)
Cutaneous distribution of pDC in LE. Skin serial sections are obtained 
from a pDC-rich LE case (pDC content score = 3 [> 50% of positive cells 
in total mononuclear infiltrate]) and immunostained for CD123
LE = lupus erythematosys
1. Sozzani S, et al. Trends Immunol. 2010;31(7):270-277; 2. McNiff JM, Kaplan DH. J Cutan Pathol. 2008;35(5):452‐456; 3. Vermi W, et al. Immunobiology. 2009;214(9-10):877-886;   
4. Rakhshan A, et al. An Bras Dermatol. 2020;95(3):307-313
• In CLE, pDCs migrate to the 
skin1 and frequently 
comprise 20–30% of dermal 
infiltrates2-4 
• Therefore, anti-BDCA2 has 
the potential to reduce IFN-I 
in the skin of CLE patients
49
LILAC WAS A TWO-PART, PHASE 2, RANDOMIZED, 
DOUBLE-BLIND STUDY OF LITIFILIMAB
50
Part B study design in participants with CLE, with or without systemic manifestations1
Randomization (1:1:1:1)
Double-blind, placebo-controlled treatment period
• Histologically confirmed CLE 
diagnosis
• Active CLE: CLASI-A ≥8
– Subacute CLE: CLASI-A ≥2 
and/or
– Chronic CLE: CLASI-A ≥2 
and CLASI-D ≥1
• Stable OCS (≤15 mg/day)
Litifilimab 450 mg SC Q4W ± SOC (n=48) 
Litifilimab 150 mg SC Q4W ± SOC (n=25) 
Primary efficacy
• Percent change in CLASI-A from 
baseline to Week 16
Secondary efficacy
• CLASI-50 response rate at 
Weeks 12 and 16
• CLASI-A  percent change from 
baseline at Week 12
• ≥7-point reduction in CLASI-A 
score from baseline at Weeks 
12 and 16
Safety profile
• AEs and SAEs
12-week follow-up period
28-DAY SCREENING 
PERIOD
SELECT 
ENDPOINTS
Efficacy and safety 
profile
Litifilimab 50 mg SC Q4W ± SOC (n=26) 
Placebo SC Q4W ± SOC (n=33) 
0
16
2
4
8
12
AE = adverse event; CLASI-50 = ≥50% improvement from baseline in Cutaneous Lupus Erythematosus Disease Area and Severity Index–Activity; CLASI-A = Cutaneous Lupus Erythematosus Disease Area 
and Severity Index–Activity; CLASI-D = Cutaneous Lupus Erythematosus Disease Area and Severity Index–Damage; CLE = cutaneous lupus erythematosus; OCS = oral corticosteroid(s); Q4W = every 4 
weeks; SAE = serious adverse event; SC = subcutaneous; SCLE = subacute cutaneous lupus erythematosus; SOC = standard of care; SRI-4 = Systemic Lupus Erythematosus Responder Index-4
1. Werth VP, et al. N Engl J Med 2022;387:321–331
PART B OF THE PHASE 2 LILAC STUDY MET ITS PRIMARY ENDPOINT 
IN CLE PATIENTS WITH OR WITHOUT SYSTEMIC MANIFESTATIONS
51
Percentage change in CLASI-A score from baseline over time 
(primary endpoint at Week 16)*
–14.5 (6.4)
–38.8 (7.5)†
–47.9 (7.5)‡
–42.5 (5.5)‡
Placebo (n=33) 
Litifilimab 50 mg (n=26) 
Litifilimab 150 mg (n=25) 
Litifilimab 450 mg (n=48) 
LSM difference versus 
placebo, % (95% CI)
P-value
−24.3 (−43.7, −4.9)
P=0.015
−33.4 (−52.7, −14.1)
P=0.001
−28.0 (−44.6, −11.4)
P<0.001
-60
-40
-20
0
Week 0
Week 2
Week 4
Week 8
Week 12
Week 16
Percent change LSM (SE)
−20
−40
−60
*Mixed-effects model for repeated measurements; †P<0.05 versus placebo; ‡P≤0.001 versus placebo
CLASI-A = Cutaneous Lupus Erythematosus Disease Area and Severity Index–Activity; CLE = cutaneous lupus erythematosus; CI = confidence interval; LSM = least squares mean; SE = standard error
1. Werth VP, et al. N Engl J Med 2022;387:321–331
Litifilimab significantly reduced skin disease activity vs placebo, on top of standard of care
Observed consistent safety profile with no new safety signals
LITIFILIMAB ALSO SHOWED SIGNIFICANT DEPTH 
OF RESPONSE IN CLE
The study was not powered to assess the secondary endpoints, and no definitive conclusions can be drawn from these results.
CI = confidence interval; CLASI-50 = ≥50% improvement from baseline in Cutaneous Lupus Erythematosus Disease Area and Severity Index–Activity; CLE = cutaneous lupus erythematosus;; LSM = least squares mean
1. Werth VP, et al. N Engl J Med 2022;387:321–331; 2. Werth VP, et al. Oral presentation at ACR 2020 (Abstract 0986)
0.0
6.1
9.1
12.1
21.9
7.7
19.2
26.9
38.5
38.5
4.0
28.0
32.0
48.0
44.0
8.3
22.9
37.5
37.5
46.5
0
20
40
60
Week 2
Week 4
Week 8
Week 12
Week 16
Participants responding (%)
LSM difference (95% CI) 
23.3% (2.9, 43.6)1
CLASI-50 responses (secondary endpoint)
Almost half of all patients at the two highest doses showed greater than 50% improvement in skin manifestation at 16 weeks
100
52
Placebo (n=33) 
Litifilimab 50 mg (n=26) 
Litifilimab 150 mg (n=25) 
Litifilimab 450 mg (n=48) 
PATIENT EXHIBITED REDUCED ERYTHEMA, SCALES, 
AND SWELLING ON THE FACE
53
Images obtained with consent from the patient
DLE = discoid lupus erythematosus; Q4W = every 4 weeks; SC = subcutaneous; SLE = systemic lupus erythematosus
After 24 weeks of litifilimab SC Q4W treatment:
Patient with SLE and DLE exhibited reduced erythema, scales, and swelling on the face
AMETHYST IS INTENDED AS A REGISTRATIONAL STUDY 
TO EVALUATE LITIFILIMAB IN CLE
54
AE = adverse event; CLA-IGA-R = Cutaneous Lupus Activity of Physician’s Global Assessment–Revised; CLASI-50/70 = ≥50/70% improvement from baseline in Cutaneous Lupus Erythematosus Disease 
Area and Severity Index–Activity; CLASI-A = Cutaneous Lupus Erythematosus Disease Area and Severity Index–Activity; CLASI-D = Cutaneous Lupus Erythematosus Disease Area and Severity Index–Damage; 
CLE = cutaneous lupus erythematosus; CLEQoL = Cutaneous Lupus Erythematosus Quality of Life; DLQI = Dermatology Life Quality Index; PRO = patient-reported outcome; Q4W = every 4 weeks; ROW = rest 
of the world; SAE = serious adverse event; SC = subcutaneous; SCLE = subacute cutaneous lupus erythematosus; SELENA = Safety of Estrogens in Lupus Erythematosus National Assessment; SFI = 
Systemic Lupus Erythematosus Disease Activity flare index; SOC = standard of care
1. Werth V, et al. J Invest Dermatol. 2023;143(5 Supp):S100 (Abstract 583). 2. NCT05531565. Updated July 8, 2024. Available from: https://www.clinicaltrials.gov/ct2/show/NCT05531565 (Accessed 
September 20, 2024)
•
Age ≥18 years
•
Histologically confirmed CLE 
± systemic manifestations
•
CLASI-A score ≥10 
•
Refractory/intolerant to 
antimalarials
KEY INCLUSION 
CRITERIA
Key secondary efficacy
• CLASI-50 response
• CLASI-70 response
PROs
• CLE QoL, DLQI
Safety profile
• AEs and SAEs
SELECT
ENDPOINTS
N=474
Part A (Phase 2) and Part B 
(Phase 3) have identical 
dosing and treatment period 
durations
Study visit
Study visit and 
treatment administration
Litifilimab SC Q4W + SOC 
(placebo at Week 26)
Litifilimab SC Q4W + SOC
Placebo SC Q4W + SOC
20
52
48
44
40
36
32
28
24
16
12
8
0
2
26
Double-blind, 
placebo-controlled 
treatment period
Extended 
treatment period
4
Randomization
Primary endpoints
Part A (USA and ROW) and Part B (USA): proportion achieving CLA-IGA-R 
erythema score of 0 or 1 at Week 16 
Part B (ROW): proportion achieving CLASI-70 response at Week 24
AMETHYST study design1,2
THE LILAC STUDIES SUPPORT COMPELLING PROOF OF 
CONCEPT FOR LITIFILIMAB IN BOTH SLE AND CLE
55
CLE (Lilac B)
Published September 7, 2022 N Engl J Med 2022;387:894-904  DOI: 
10.1056/NEJMoa2118025
Further supported by investment partnership with Royalty Pharma
Published July 27, 2022 N Engl J Med 2022;387:321-331 DOI: 
10.1056/NEJMoa2118024
SLE (Lilac A)
LITIFILIMAB HAS THE POTENTIAL TO TREAT PATIENTS 
IN BOTH SLE AND CLE
56
Litifilimab targets BDCA2 as a once-monthly subcutaneous injection focused on 
modulating expression of IFN-1 as well as other pro-inflammatory cytokines
Delivered successful Phase 2 Proof of Concept trials in both SLE and CLE; 
both published in the New England Journal of Medicine
Investment partnership for Phase 3 studies with Royalty Pharma in 2025
Meaningful data across joint, skin and overall symptoms
Running two Phase 3 studies in SLE and a third in CLE
First SLE data expected in 2026 with CLE data expected in 2027
BDCA2 = blood dendritic cell antigen 2; CLE = cutaneous lupus erythematosus; IFN-I = interferon type I; pDC = plasmacytoid dendritic cell; SLE = systemic lupus erythematosus
CONCLUDING REMARKS
Head of Development
Priya Singhal, M.D., M.P.H.
LUPUS IS A KEY COMPONENT OF A STRENGTHENING 
PIPELINE TO SUPPORT OUR LONG-TERM GROWTH OBJECTIVE
Phase 1
Phase 2
Phase 3
Regulatory Review in 
Certain Markets
BIIB142 (IRAK4 degrader)* – 
Autoimmune disease
Phase 1 planned
BIIB080 (tau ASO)^ 
Early AD
Lecanemab (Aβ mAb)* 
SC-AI Initiation 
Early AD
Felzartamab 
(anti-CD38 mAb) – AMR
Lecanemab (Aβ mAb)* SC-AI 
Maintenance  
Early AD
Now FDA approved
Felzartamab 
(anti-CD38 mAb) – LN
BIIB122
(LRRK2 inhibitor)* – PD
Lecanemab (Aβ mAb)* 
Preclinical AD
Felzartamab 
(anti-CD38 mAb) – IgAN
HD Nusinersen 
(SMN2 splice modulator) 
SMA
PDUFA Sept 22
BIIB091 (peripheral BTK 
Inhibitor) – MS
Dapirolizumab pegol 
(anti-CD40L)* – SLE
Felzartamab 
(anti-CD38 mAb) – PMN
Zuranolone
(GABAA PAM)* – PPD
Now approved in U.K.
Positive CHMP opinion in E.U.
Felzartamab 
(anti-CD38 mAb)  
DSA- MVI
Phase 2 planned
Litifilimab 
(BDCA2 mAb) – SLE
SKYCLARYS (Nrf2 activator) – 
Pediatric FA
Litifilimab 
(BDCA2 mAb) – CLE
Zorevunersen
(SCN1A ASO)* – Dravet syndrome
Salanersen (BIIB115) 
(SMN ASO)^ – SMA
Phase 3 planned by early 2026
Immunology
AD and Dementia
Neuropsych
Parkinson’s disease
MS
Neuromuscular disorders
Pipeline Updates: Added = BIIB142 in autoimmune disease *Collaboration program; ^ Licensed from Ionis Pharmaceuticals, Inc.; AD = Alzheimer’s disease; AMR = antibody mediated rejection;  ASO = antisense 
oligonucleotide; CLE = cutaneous lupus erythematosus; FA = Friedreich ataxia; GABA = γ-Aminobutyric acid; HD = higher dose; IgAN = IgA nephropathy; LN = lupus nephritis; LRRK2 = leucine rich repeat kinase 2; MS 
= multiple sclerosis; DSA- MVI = donor specific antibody negative microvascular inflammation; PAM = positive allosteric modulator; PD = Parkinson’s disease; PMN = primary membranous nephropathy; PPD = 
postpartum depression; SC-AI = subcutaneous autoinjector; SLE = systemic lupus erythematosus; SMA = spinal muscular atrophy
Neurodevelopmental 
58
Nephrology 
OUR DISCIPLINED SCIENTIFIC APPROACH IS POISED TO DELIVER 
KEY EXPECTED MILESTONES OVER THE NEXT 18 MONTHS
LEQEMBI (lecanemab-irmb) is being developed in collaboration with Eisai Co; BIIB080 is licensed from Ionis Pharmaceuticals, Inc.; Zorevunersen is being developed in collaboration with Stoke therapeutics
AD = Alzheimer’s disease; AI = autoinjector; CLE = cutaneous lupus erythematosus; DS = Dravet syndrome; FA = Friedreich’s ataxia; IgAN = IgA nephropathy; LN = lupus nephritis; PD = Parkinson’s disease; 
PPD = postpartum depression; PMN = primary membranous nephropathy; SC = subcutaneous; SLE = systemic lupus erythematosus; SMA = spinal muscular atrophy; 
Study Starts
Clinical Trial Readouts
Regulatory Decisions
• Felzartamab Phase 3 in IgAN
• Felzartamab Phase 3 in PMN
• SKYCLARYS Phase 3 in pediatric FA
• Zorevunersen Phase 3 in DS
• Salanersen Phase 3 in SMA
• Felzartamab registrational          
Phase 2 in DSA negative MVI 
• BIIB142 Phase 1 in autoimmune 
disease
• Salanersen Phase 1b interim in 
SMA
• Litifilimab Phase 3 in SLE
• Litifilimab Phase 3 in CLE
• BIIB080 Phase 2 in Early AD
• Felzartamab Phase 1 in LN
• Zuranolone in PPD 
• LEQEMBI SC-AI maintenance in 
Early AD
• LEQEMBI SC-AI initiation in Early AD 
• Nusinersen (SPINRAZA) higher dose 
in SMA
3
4
2
59
First Phase 3 by end of 2026
Late 2026 to early 2027
By mid-year 2026
2026
Now approved in U.K. & 
Positive CHMP opinion in E.U.
Now FDA approved
FDA Rolling Submission initiated
FDA PDUFA: September 22, 2025
QUESTION & 
ANSWERS